Final draft, uncorrected proof version. Copyright 26 September 1999


Psychiatry and the Human Condition by Bruce Charlton
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Radcliffe Medical Press: Oxford, UK, 2000
Pages: xiv, 250. ISBN: 185 775 314 3


A radical reappraisal of the nature, classification and treatment of mental illness



Bruce Charlton


Psychiatry and the Human Condition provides an optimistic vision of a superior alternative approach to psychiatric illness and its treatment, drawing upon modern neuroscience and evolutionary theory. Psychiatric signs and symptoms - such as anxiety, insomnia, malaise, fatigue - are part of life for most people, for much of the time. This is the human condition. But psychiatry has the potential to help. In particular, psychotropic drugs could enable more people to lead lives that are more creative and fulfilled. Current classifications and treatments derive from a century-old framework which now requires replacement. Available psychotropic drugs are typically being used crudely, and without sufficient attention to their psychological effects.

We can do better. This book argues that obsolete categories of diseases and drugs should be scrapped. The new framework of understanding implies that clinical management should focus on the treatment of biologically-valid symptoms and signs, and include a much larger role for self-treatment.

Psychiatry and the Human Condition is a referenced work of medical science by an experienced researcher, but written in a clear and vivid style so as to be accessible to a general audience. Since its publication the book has divided opinion very sharply - attracting both strong praise and vitriolic criticism in roughly equal proportions.

Bruce G Charlton  MD

Reader in Evolutionary Psychiatry

Department of Psychology

Henry Wellcome Building

Medical School

University of Newcastle upon Tyne


Editor-in-Chief, Medical Hypotheses


Tel:      0191 222 6247

Fax:     0191 222 5622


Home Page: Index



The understanding of nature has as its goal the understanding of human nature, and of the human condition within nature.


Jacob Bronowski



Psychiatry and the Human Condition

Bruce Charlton




Reading this book




Chapter 1 - Psychiatry and the Human Condition

The endemic nature of psychiatric illness

Disease as the norm? An evolutionary perspective

Three types of society

The nomadic, foraging life

Egalitarian economics

Degrees of happiness

Improving human happiness?


Chapter 2 - Social Intelligence and the Somatic Marker Mechanism

Social intelligence

The somatic marker mechanism - what you need to know to read the rest of this book


Chapter 3 - Psychiatric Classification

Current diagnostic practice - pragmatism

Categorical thinking

A new nosology needed


Chapter 4 - The delusional disorders

Case history of a persecutory delusion - the story of Bill

Delusions and other false beliefs

The ‘theory of mind’ mechanism (ToMM) and delusions

Psychopathology of theory of mind delusions

            1. Subject matter of delusional disorder

            2. False beliefs are unavoidable in mental state inferences

            3. Beliefs concerning ToM inferences will be resistant to counter-argument

            4. Delusions are encapsulated due to the nature of the ToMM

The example of morbid jealousy

            A jealous delusion - Edward

Theory of mind delusions are part of ‘normal’ life


Chapter 5 - Bizarre delusions

Two kinds of delusions : ToM delusions and bizarre delusions

Impaired thinking leads to bizarre beliefs

Bizarre beliefs: a sign of madness

Bizarre delusions contrasted with ToM delusions

            1. Subject matter of bizarre delusions- anything

            2. Bizarre beliefs may survive objective refutation

            3. Bizarre delusions are not encapsulated by social category

4.Pure cases of bizarre delusions will not exist  

Bizarre delusions are caused by organic brain impairment


Chapter 6 - Delirium and Brain Impairment

Definition of delirium

The critical role of delirium in neo-Kraeplinian diagnosis

But if acute psychotic patients are delirious…

Testing the delirium theory of psychotic symptoms

Clinical implications of the delirium theory of psychosis

Implications for nosology


Chapter 7 - The ‘anti-delirium theory of electro-convulsive therapy (ECT) action

The mysterious nature of ECT

The effects of ECT - a sleep surrogate or sleep-inducer


Chapter 8 - The malaise theory of depression

Depression - the need for a fundamental re-appraisal

The nature of mood and emotions

Deficiencies in current understanding

Emotions and the somatic marker mechanism


Major depressive disorder is sickness behavior

Cytokines as mediating factors of sickness behavior

Mood changes are secondary to sickness behavior

Implications of the malaise theory of depression

Autoimmune disease suggested as a cause of depression?



Chapter 9 - Antidepressant drug action

Antidepressants as analgesics

Speed of response to antidepressants

Future research into depression and antidepressants

Analgesics as antidepressants

Action of SSRIs?

Summary - the nature of depression

Mood management and self-help


Chapter 10 - Mania

Problems with current concepts

Arousal and analgesia

Endogenous opiates as anti-fatigue analgesics in mania

The arousal-analgesia model for hypomania leading on to full mania

Chronic, severe sleep deprivation as the cause of manic psychotic symptoms

Recovery - mania terminated by deep sleep

The traditional interpretation

Other anti-fatigue endogenous analgesics in mania?

Psychopharmacological analgesia increases susceptibility to mania

Induced fatigue as therapy for mania?


Chapter 11- Neuroleptics

Mode of action of neuroleptics

Side effects or therapeutic effects?

Action on the basal ganglia

Neuroleptics and the somatic marker mechanism

Sedatives as a treatment for mania - the ‘atypical’ neuroleptics

The wheel turns? Anti-epileptic sedatives and mania

Lithium - a different kind of ‘neuroleptic’


Chapter 12 - Schizophrenia

The nature of schizophrenia

Schizophrenic delusions - theory of mind delusions

Schizophrenic delusions - bizarre delusions

Schizophrenic hallucination

Acute schizophrenia is a delirious state

Negative symptoms

Schizophrenia is not a unified biological entity


A new psychiatric nosology needed

Time to discard the diagnostic category of schizophrenia

Factors blocking change

Schizophrenia and the human condition

            1. Research

            2. Treatment

            3. Links to normal behavior


Chapter 13 - Psychopharmacology and the human condition





APPENDIX 1 - Evolution and the cognitive neuroscience of awareness, consciousness and language

Evolution of awareness

Function of awareness

Awareness is located in working memory


Evolution of consciousness

Awareness of body states

Working memory as a convergence zone for emotions and perceptions

Why can we be aware of body states?

Consciousness is sufficient to perform its adaptive function, but not necessary


The somatic marker mechanism

Emotions and feelings

Theory of mind and the somatic marker mechanism

Internal-modeling of behavior by the SMM

Tactical and strategic social intelligence

Humans are essentially social creatures



Defining ‘language’ as displacement-communication

Displacement is necessary, but not sufficient, for the definition of language

Why displacement evolved - role and adaptive benefits

Constraints on the evolution of displacement language

Displacement, group size, and the sexual division of labour

Displacement in WM depends on sufficient spatial capacity for complex representations

Limits of working memory

Some consequences and predictions

            1. Enhancing chimpanzee working memory

            2. Humans with low capacity WM may lack language (ie. lack displacement)

            3. The social structure of language


Language and the human condition


APPENDIX 2 - Human creativity and the Col-oh-nell Flastratus phenomenon

Creativity and culture

A dream

Peak experiences

Peak experiences in science

A personal example

The nature of the scientific peak experience

Limitations of the PE

The meaning of the PE

Delirious delights

Sorry to be boring, but…

Consciousness as a storyteller

The social nature of scientific models





Further Reading and References

Reading this book

The main argument of this book is presented such that the book can be read straight through. There is also an attempt at making the chapters relatively autonomous, by allowing a small degree of explanatory repetition, such that each topic could be read in any order. Further reading and references are listed at the end of the volume, and this section also presents the intellectual background to the ideas. Appendix one contains technical theoretical material which may be omitted, but which is necessary for a full understanding of the main argument, and ideally should before commencing Chapter 3. Appendix two concludes this book in what I hope is an optimistic spirit, by considering some of the most positive aspects of the human condition. It adopts a similar evolutionary and cognitive neuroscience-based approach to that used in the main argument of the book, but this chapter is a more easy-going meditation on the topics of ecstasy and creativity.



Chapter 1

Psychiatry and the human condition


The endemic nature of psychiatric illness

Imagine a world in which many of the people suffer from psychiatric symptoms for most of the time and very few live out their lifespan without suffering periods of significant psychiatric illness. I am describing the world we live in.

If this seems far fetched, start adding up the numbers. In the first place there are the obvious people who suffer from the formally diagnosed psychiatric diseases such as major depressive disorder, schizophrenia, Alzheimer’s dementia.

There is the vast army of the anxious; people who go through life in a state of gnawing angst, perhaps seeking temporary relief from alcohol, perhaps stoically enduring.

Then there are those suffering from sleep deprivation for a multitude of reason - shift work, overwork, jet lag, young children, obstructed airways - or just chronically poor sleepers no known reason.  Then there are the more or less miserable people who are ill and in pain - with colds, flu, hay fever, gastroenteritis, irritable bowels, headaches, back aches, inflammations. And the patients with life-threatening diseases like cancers, heart disease, stroke, AIDS - who often have significant ‘psychiatric’ symptoms that may amount to a formal psychiatric diagnosis.

Of course, huge numbers of people at any one time will be either intoxicated and brain impaired from alcohol, opiates, uppers, downers, solvents and the like - or else are ‘hung over’ and brain impaired as an after effect of such intoxication. It must not be forgotten that prescribed drugs often have undesirable and sometimes unavoidable side effects of a psychiatric nature - sedation, headaches, mental clouding… Then there are people without a psychiatric diagnosis but taking prescribed psychoactive medication: tranquilizers, antidepressants etc. These represent only a proportion of those whose state of mental health or well-being depends upon taking drugs.

When considered in this way, it is clear that few people are free of psychiatric symptoms for sustained periods of time. And if psychiatric symptoms are a matter of everyday life, then so - potentially - is their treatment. Such is the scale that professional management is inconceivable, as well as undesirable. Logistically, this means an expansion in psychiatric self-help - which entails expertise in self-diagnosis, self-treatment and the self-evaluation evaluation of this process.

The human condition, as we experience it in contemporary life, is one where psychiatric symptoms are endemic, being constantly present in the population - and present at a remarkably high prevalence.


Disease as the norm? An evolutionary perspective

There is little doubt that, conceived in this way, psychiatric impairment is the norm. Mental health and well being are so rare as to be remarkable. For most people, even a single day of unalloyed well-being is a rare event. Some unfortunate people probably never experience even a day of well-being, at best managing a few minutes as a kind of glimmering of what is possible.

But why should this be? Why should the world be a place of illness and drugs - surely that is unnatural? The answer is that the modern world is indeed unnatural and has been so, for the majority of humankind, for many thousands of years. Unnaturalness is profound, inevitabl, unavoidable. It is time that we recognized that ‘naturalness’ is not an option, and worked hard on how best to cope with it.

People are not biologically designed to be happy as such. From an evolutionary perspective happiness is an incentive for action, not a steady state of being - a means to the end of reproduction. This is fundamentally why it is so difficult to attain happiness, and why having attained happiness it is virtually impossible to maintain.

Humans are living in a world very different from that which shaped their bodies and minds during their evolutionary history. Ultimately health is based upon biology - and this applies to humans just as much as to any other biological entity. Our destiny as individuals is shaped by biology. We have not transcended our dependence upon our bodies; and our minds - with their motivations, satisfactions and pains - are rooted in our bodies.

Humans are animals, like all animals they evolved, and the circumstances under which they evolved shaped their minds and bodies. The evolution of complex adaptations typically requires an accumulations of several coordinated genetic mutations, is gradual and takes place over many hundreds or thousands of generations. Since humans take many years to reach sexual maturity and reproduce infrequently, the evolution of new mental capacity will have required selection pressures that were stable and sustained over time scales measurable in tens of thousands of years.

It was the ecological and social conditions of human prehistoric past that shaped the minds and bodies of modern humans. Our minds were ‘made-up’ before the invention of agriculture, and there has been insufficient time for natural selection to change them. And the evolutionary past was one in which human society was small scale, face-to-face, nomadic and based upon foraging, hunting and gathering.


Three types of society

For reasons which are accidental - in the sense that they were historically contingent and might easily never have happened - humans have created a range of agricultural and industrial societies with conditions that differ profoundly from the conditions under which humans evolved. Natural selection is not fast enough to keep pace with the historical rate of cultural change. All across the planet, humans are dwelling in environments that, although created by humans, have aspects that are fundamentally at odds with the biological attributes with which humans have been equipped by natural selection.

The Golden Age for humans - such as it was - was the life of a nomadic hunter gatherer. Evidence for this statement is scanty, but what evidence there is (see below) is consistent and unambiguous. This was the time when more of the people were happier for more of the time than at any other point in human history. It seems probable that ‘modern’ humans (Homo sapiens sapiens), our hominoid ancestors, and also the great ape human ancestors (including those similar to modern chimpanzees) lived for the great majority of their history as nomadic foragers with various combinations of gathering vegetables and hunting meat. Indeed, foraging was ubiquitous until some societies adopted village life as ‘sedentary’ hunter gatherers or agriculturalists - from around fifteen thousand years ago.

The agrarian way of life - a life based on agriculture, herding and storage of hunted food - gradually spread to cover the whole planet. Agrarian cultures spread not because the people were happier or healthier, but by a combination of military conquest and conquest by disease. The same land could support a much greater population, specialization of labour to enhance productivity, and concentration of people and proximity of animals led to diseases that would almost wipe-out naïve populations.

Over the past few centuries the agrarian way of life is being replaced by increasingly industrial and mercantile forms of organization. In other words, contemporary ‘Western’ type societies are dominated by production and exchange rather than by agriculture.

So there are three essential types of society: nomadic-foraging societies; agrarian societies (which include herding and hunting societies that use storage of food); and industrial-mercantile societies. Gellner has described the political characteristics of each of these three basic types. Essentially, nomadic-foraging societies are anarchistic democracies, agrarian societies consist of a mass of semi-starved peasants ruled by a small minority of relatively wealthy warriors with the assistance of a priesthood who propagandize on their behalf, while industrial-mercantile societies such as our won are dominated by the controllers of the wealth-creation apparatus - the business and money interests.


The nomadic, foraging life

Humans evolved in a society of nomadic foragers. This constitutes most of the history of the species. Most of the humans who have ever lived were hunter-gatherers. Most importantly, there has not been enough generations since humans stopped living the life of nomadic foragers for significant psychological or physical evolution to occur (although a few adaptations have evolved - such as the ability of adults to digest agricultural products such as milk, and some types of resistance to diseases of ‘civilization’ such as the sickle cell anaemia gene giving resistance to malaria). An understanding of the conditions of ancestral hunter gatherer life is therefore extremely useful in understanding the biological basis of human behavior.

While the life of ancestors cannot be observed directly, there are indirect routes to this knowledge. Our understanding of the ancestral hunter-gatherer life is derived from a variety of sources. Naturally, this evidence is incomplete, but a great deal can be learned by combining many sources such as archaeological evidence from relics and remains, the anthropological study of modern nomadic hunter-gatherers who - at least until recently - lived in places such as Africa, New Guinea, and South America. Observations of the behaviour of great apes and other primates and archaeological evidence of primate ancestors has also been highly enlightening. This is supplemented by information on the history of climate, vegetation and fauna. Psychological and neurological study of modern humans, including the identification of cross-cultural cognitive patterns, can be used to explore universal and evolved mechanisms. Furthermore, mathematical modeling can be a useful way of determining the effects of theoretical changes in genes and behaviours.  

A composite sketch of the hunter-gatherer life of human ancestors can be constructed - bearing in mind that humans did not evolve in all at once, or at one place or at one time. The ancestral society was probably composed of extended family ‘bands’ of some twenty-five to forty members. These extended families were based around male blood relatives, and females joined from other bands of more remote relatives - probably by adolescent girls ‘marrying’ into the group. The bands were part of larger, looser alliances (‘clans) of around one or two hundred more-or-less related members with whom individuals were exchanged with some fluidity. The largest form of human organization was the ‘tribe’ of perhaps one or two thousand people sharing a common language. The tribe, in many instances, constituted the entirety of known humanity.

Perhaps the most surprising aspect of simple hunter gatherer societies (as exemplified by the Kung San Bushmen, or the Hazda of Tanzania) is that they are highly leisured and affluent. Leisured in the sense that there is plenty of time for the social activities involved in preparing and consuming food, and generally gossiping, discussing and debating, cooperating and competing socially. Affluent in the sense that the survival tasks of hunting and gathering only take up on average about half of the day (say, 4 hours). It is the typical peasant labourer in an agrarian society whose almost every day is composed of grinding, round-the-clock work, and whose life deserves the phrase ‘nasty brutish and short’. By contrast with a peasant’s the life of a nomadic forager is little short of idyllic.

Most people’s ideas of ‘primitive’ or ‘tribal’ life is based on agricultural or herding modes of production. In such societies there is invariably domination of the mass of people by a ‘chief’ (plus henchmen) who appropriate a large share of resources. But in an ‘immediate return’ or ‘simple hunter-gatherer’ economy there is an extremely egalitarian social system, with very little in the way of wealth differentials. Food is gathered on a roughly daily basis for rapid consumption, and tools or other artifacts were made as required. There was no surplus of food or material goods, no significant storage of accumulated food or other resources, and the constraints of nomadic life meant that artifacts can not be accumulated.


Egalitarian economics

One of the most distinctive features of foraging societies, as contrasted with human societies that currently exist, was that ancestral societies were to a high degree egalitarian and without significant or sustained differentials in resources among men of the same age. There were indeed differentials in resource allocation according to age and sex (eg. adults ate more than children, men ate more than women) - but there was not a class or caste system, society was not stratified into rich and poor people who tended to pass their condition on to their children.

This equality of outcome is achieved in immediate-return economies by a continual process of redistribution through the sharing of food on a daily basis, and through continual equalizing redistribution of other goods. The sharing may be accomplished in various ways in different societies, including gambling games of chance or the continual circulation of artifacts as gifts. But the important common feature is that sharing is enforced by a powerful egalitarian ethos which acts to prevent a concentration of power in few hands, and in which participants are ‘vigilant’ in favour of making sure that no-one else takes more than themselves. If each individual person ensures that no-one else gets more than they do, the outcome is equality.

Diet for nomadic foragers was very different from the modern idea of a ‘natural’ diet, and equally different from the diet of agrarian peasants. For hunter gatherers was no ‘staple’ carbohydrate such as rice, wheat, oats, yams, potatoes, maize or millet - the kind of food that provides the bulk of calories in agrarian societies. Such items would if available - have been only a small element of a range of dozens or hundreds of vegetable foods, mainly drawn from the categories of fruits, berries, roots, tubers and nuts. This variety and the large area over which nomads could range, meant that food would seldom have been in short supply, and foragers would not often have experienced the severe famines and chronic malnutrition that typify agrarian societies - even today.  For hunter-gatherers meat probably made up around half of the calories, depending upon place and season. But hunted meat differs from that we eat today - wild game is stringy, fibrous, high in protein and low in saturated fats. By contrast domesticated meat produced agriculturally is often tender and fatty, which is more palatable although probably less nourishing.

The hunter gatherer diet was therefore extremely varied, abundant and much more nutritious than the diet of agrarian peasant societies. And this was reflected in the health and life-expectancy of foragers - who were taller, lived longer, suffered much less malnutrition or starvation and had fewer diseases than peasants. Infectious disease was rare, due to the low population densities - although chronic and low-virulence infections such as syphilis and tuberculosis were a feature. But, nonetheless the nomadic foragers who were our ancestors were probably as tall and as long lived as almost anyone in human history - except for the most prosperous classes of twentieth century Western societies.


Degrees of happiness

The lifestyle of nomadic foragers involve little forward economic planning beyond the communal decisions over when and where to move camp, and the logistics of hunting and gathering. This means that most problems of life related to the social realm - especially around the question of competition for mates - and this lay behind the power struggles, disagreement, discussions and violence. And the primacy of social life in hunter gatherer societies is what has been the decisive force in human evolutionary history - the main focus for natural selection is within-species, human versus human competition.

In summary, the ancestral hunter gatherers experienced a way of life that was - in world historical terms - leisured and egalitarian, and enjoyed health and life expectancy at a high level. Of the three kinds of society as described by Gellner: hunter-gatherer, agrarian, and mercantile, it is probable that hunter-gatherers had the best life, overall. Hunter gatherer societies are the happiest and peasant societies are the most miserable - while industrial-mercantile societies such as our own lie somewhere in between.

That, at any rate, is the conclusion of anthropologist Jerome Barkow - and his opinion is widely confirmed by the reports of many independent anthropologists who have experienced the alternatives of foraging, agrarian and industrial society. The ‘naturalness’ of nomadic foraging is also shown by differences in the harshness of child rearing practices in different types of society. Child rearing involves varying elements of forcible training that are necessary to prepare children for their social role. Peasant societies typically employ extremely repressive forms of socialization, extreme discipline, restriction, and the use of child labour. Industrial mercantile societies (such as our own) are much less tough on children - but still require many unnatural behaviors (eg. sitting in classrooms or examination halls for long periods of time without speaking or moving). But nomadic foragers are able and willing to give their children even more freedom than the most liberal ‘modern parent’ - and such a relaxed upbringing of unstructured interaction with peers apparently prepares the child properly for the adult life to come.

Another line of evidence is patterns of voluntary migration. When industrial mercantile societies develop, they are popular with the miserable peasantry of agrarian societies who flee the land and crowd the cities, if given the chance. Not so the happier hunter gatherers who typically must be coerced into joining industrial life. My great grandparents left their lives as rural peasants and converged from hundreds of miles and several countries to work the coal mines of Northumberland. They swapped the open sky, fields and trees for a life underground and inhabiting dingy rows of colliery houses. Being a miner in the early twentieth century must have been grim, but apparently it was not so bad as being an agricultural laborer. 

From a psychiatric perspective, then, there are sharp differences between ancestral societies and modern societies. In terms of their general social situation modern humans are faced with a wide range of new problems - although we console ourselves that for the bulk of the population life is much better in an industrial mercantile society than in a warrior-dominated medieval peasantry. Nevertheless we now live in a mass society, full of strangers who there is no reason to trust since they are neither family nor friends. Although resources are vastly more abundant, resources are linked to status and there are massive inequalities in their distribution.

This means that there is a much higher proportion of intractably low status people in modern societies than in the societies in which humans evolved. Since status is the most important factor in determining a man’s sexual attractiveness, this is a major source of dissatisfaction. Men will devote enormous effort and take great risks in pursuit of the highest status, but for most people in delayed return economies the odds are stacked heavily against them succeeding. 


Improving human happiness?

Even if, somehow, the impossible were achieved and humans returned to the kind of egalitarian, immediate return, foraging societies in which we spent much of our recent evolutionary history - then unhappiness would still be common and intractable.  Humans did not evolve to be happy - natural selection rewards reproductive success, not happiness. Happiness is - from this perspective - merely the ‘carrot’ which compliments the ‘stick’ of pain - a lure to draw us onwards, to make us strive - but happiness is a reward that we can never permanently grasp nor enjoy at leisure.

So much for the bad news. Happiness drives us, it is not a permanent state. And this really is bad news because there is little we can do about it, short of changing human nature.  The good news is that this might prove possible - at least to some extent. Just as human ingenuity has landed us in the predicament of a sub-optimal modern human life, so the same ingenuity has proved a range of technologies of gratification through which we can attain a variety of surrogate satisfactions. - something that will be discussed more towards the end of this book .

Essentially the broad shape of society and its possibilities for happiness are the way they are for reasons that are accidental, unplanned, and intractable. We inhabit a society that grants few satisfactions and offers limited possibilities of fulfillment. It is also a society in which psychiatric symptoms are endemic and a major cause of human misery. In our favour we have increasing knowledge of the causes of human misery, including the understanding of psychiatric illness, and increased power to alleviate that misery provided by the armamentarium of psychopharmacology. All this understanding and therapeutic potential has arisen within the past few decades, and we have hardly learned how to use it.

My point is that the human condition of Western man is intractable in its fundamentals, but amenable to improvement in important ways. Things are worse than they might be. One aim of this book is to explore some of these means of improvement, and to do this will require an evaluation of the extent and nature of psychiatric illness.

The purpose of this book is therefore to suggest how knowledge and technology might be deployed to ameliorate the human condition. We are not talking about utopia, but we are talking about the potential for significant and worthwhile improvements in well-being for substantial numbers of people. However, power can be used for many purposes. And potential agents for good are almost inevitably also potential agents for harm. The possibilities for benefit from psychopharmacology is, although not universal, nevertheless immense. Whether these benefits can be realized under prevailing social conditions is altogether a different matter.


Chapter 2

Social intelligence and the somatic marker mechanism

Social intelligence is the basis of distinctively human thinking, and the somatic marker mechanism is the major embodiment of social intelligence. 

What follows is a brief account of Social Intelligence and the Somatic Marker Mechanism (SMM) which will suffice for reading the remainder of this book. However, the evidence and uncertainties which underpin these key concepts is more fully set out in the Appendix. Anyone who wishes fully to understand the background to the ideas of this book, and to know their links with human consciousness and language, will need to grapple with the conceptual difficulties of the Appendix.

In a nutshell, human intelligence is essentially an adaptation of social intelligence, and social intelligence comprises mechanisms that evolved for the primary purpose of dealing with other human beings. Most uses of human intelligence (watching football, doing science, playing chess, reading newspapers etc) are accidental by-products of this evolved ability to interpret social situations. The Somatic Marker Mechanism (SMM) is the brain system which supports much of what is distinctive about human social intelligence: it is the way in which the brain uses emotions to interpret the meaning of social situations. ‘Somatic’ refers to the body, and emotions are actually the brain’s interpretation of body states.

The Somatic Marker Mechanism is so called because it is a brain mechanism that integrates body (ie. somatic) states that correspond to emotional responses, with the social situations that triggered those emotional responses. This means that emotions are used to evaluate social situations: in other words, perceptual information from within the body ‘soma’ is used to ‘mark’ sensory perceptual information from outside the body.


Social intelligence

The general nature and mechanism of consciousness - what it is, what it is for, and how it works  has now been largely established, at least in outline. The main protagonist in this major breakthrough has been Antonio Damasio and his colleagues. Consciousness is now situated firmly within a framework of mainstream biological research into cognitive neuroscience and evolutionary psychology. There is nothing weird or special about the brain that is involved - just normal bits of primate cerebral cortex which evolved because they benefited the organism’s reproductive success.

Perhaps the most crucial advance towards a biological understanding of ‘consciousness’ was the development of the concept of social intelligence. This is the idea that the main problem which human ancestors faced, the problem that most affected human ancestors differential chances of reproductive success, was competition with other people. The social environment of the group was therefore of primary importance, not the physical environment in which the group lived. The rapid evolutionary growth of human brain size, and the distinctive aspects of human intelligence over the past few million years of evolutionary history, have occurred in response to selection pressures from conspecifics (members of the same species) consequent upon social living

Since human consciousness and human language evolved recently, they are assumed to be aspects of social intelligence. This means that human consciousness and human language evolved and are adaptive for the social tasks specifically, and for those social conditions which prevailed at the time of rapid frontal cerebral cortex expansion. Consciousness was ‘designed’ by natural selection for dealing with other people.

But consciousness and language are now used for many other non-social purposes, and in circumstances very different from those that prevailed during the human evolutionary history. The myriad other functions and uses of consciousness and language are therefore epiphenomena.  These non-social functions are accidental by-products, rather than capacities for which the consciousness or language actually evolved. In other words, consciousness evolved to be an aspect of social intelligence, but is used for other things - just as the hand evolved its precise grip and manipulative ability to use tools, but the same ability enables some people to play the piano. Similarly, although consciousness and language are necessary for both organized religion and for science - this is accidental, and the results are not necessarily adaptive.

Because of our evolutionary history, human consciousness confronts the world primarily as an instrument designed for social tasks. We tend to interpret the conscious world and the world of language as if they were inevitably social phenomenon.


The Somatic Marker Mechanism

- what you need to know to read the rest of this book


                The Somatic Marker Mechanism (SMM) gets its name because changes in the inner environment of the 'soma' (body) are used to ‘mark' perceptions and sensory information coming in from the external environment. This integration of bodily and environmental information occurs in Working Memory, probably situated in the upper-outer areas of the frontal lobe of the cerebral cortex.

                Emotions are body states as they are represented in the brain. For example, when confronted with a threat to survival an animal enacts a body state of physical arousal to prepare for action: eg. heart beating fast, blood being diverted to the muscles, hairs standing on end etc. The brain continuously monitors the body and receives feedback from nerves and chemicals in the blood. Fear is the emotional state which occurs when the brain recognizes the physical state of arousal and adapts behavior appropriately - for example generating fight or flight. Most large animals experience emotions.

                While most animals have emotions, only humans (and perhaps a few other complex social animals such as chimpanzees) are capable  of being aware of emotions. We become aware of our emotions when our attention is drawn to them, but by contrast a mouse can experience fear, but it is can not become aware of its own state of fear. Feelings is the term for emotions of which we are aware, and we are aware of them because the emotions are represented in working memory.

                Working memory (WM) is the site of awareness, located in the prefrontal lobe of the cerebral cortex. WM functions as an integration zone of the brain, where representations from different systems converge and where several items of thought to which we are attending can simultaneously be sustained and manipulated. When we deliberately grapple with a problem and try to think it through - this process is happening in working memory, when we are aware of something it is in working memory, when we wish to attend to a specific stimulus, we represent it is WM.

                The somatic marker mechanism (SMM) is fund only in humans and a few other social animals. The SMM integrates perceptions of social situation with the emotions that occur in response to this situation. For example a particular person with the emotions that they make us feel - fear, lust, surprise or whatever. The SMM is able to do this because both perceptions and emotions are represented in working memory.

                For instance, when a rival male provokes fear, the bodily state of fear (emotion) links with the identity of the male rival (perception). So the SMM creates an in working memory. This emotional-perceptual representation can be stored in long term memory, and when recalled it has the potential to provoke both recognition (of the male rival) and evoke an emotion in the body (fear). Thinking about the male rival (even when he is not present) therefore replays the emotion of fear which means that the body is stimulated to reenact the same body state that was experienced at the time the perception was laid down in memory.

                The somatic marker mechanism is here considered to be the basis of the 'Theory of Mind' mechanism. Theory of mind is the name often given to the ability that humans have of making inferences ('theories') about the contents of other peoples' minds. For example, knowing that someone else does not have the same ideas as I do, and instead that each person has knowledge and desires that are frequently different from one's own.

                The somatic marker mechanism uses the emotional response to a social situation to make inferences about the dispositions, intentions and motivations of the people involved in that social situation. For instance, if a male rival induces the emotion of fear, then the inference might be that the male rival is hostile and aggressive. Whenever I think about that man I replay the emotion of fear, and I reason that he is intending to harm me. This is equivalent to my having a 'theory of mind' about the male rival, since it involves making an inference about what he is thinking.

                Since the somatic marker mechanism underpins human social intelligence,, and since social intelligence underpins much that is distinctive about human thinking,  the physical attributes of the SMM have implications for human behavior.

                For example the categories of distinctively human intelligence are seen to be social categories and emotional categories. It would be expected that these categories would underlie much human thought, even when the subject matter is abstract.

                The fact that the SMM is located in working memory means that the conscious human world is essentially a social world, permeated with social categories, orientated toward social matters. Humans see the world through social lenses.



Chapter 3

Psychiatric classification


Current diagnostic practice - pragmatism

Psychiatric illnesses and diseases are classified into a diagnostic scheme or ‘nosology’. The prevailing ideas are exemplified in the United States and research communities by the regularly updated editions of the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association and in Europe (and for more epidemiological purposes) by the International Classification of Disease (ICD).

The commonly used diagnostic scheme in clinical practice owes much to DSM and ICD, but also continues to make other distinctions which lack ‘official’ sanction. So the systems in practice includes some of the familiar (although controversial) distinctions between organic and ‘functional’ psychoses; between schizophrenia and the ‘affective’ disorders; between unipolar and bipolar (manic-depressive) affective disorders; psychosis and neurosis and the personality disorders.

These diagnostic systems employ a syndromal system of classification that derives ultimately from the work of the psychiatrist Emil Kraepelin about a hundred years ago, and is therefore termed the ‘neo-Kraeplinian’ nosology. Whether or not a psychiatrist uses the formal diagnostic criteria, the neo-Kraeplinian nosology has now become ossified in the DSM and ICD manuals. Over the past few decades the mass of published commentary and research based on this nosology has created a climate of opinion to challenge which is seen as not so much mistaken as absurd.

Yet the prevailing neo-Kraeplinian nosology is a mish-mash of syndromes that have widely varying plausibility and coherence. Some diagnoses are probably indeed biologically valid - having perhaps a single cause, occurring in a single psychological functional system, or having a unified pathology (some of the anxiety disorders, for instance, such as generalized anxiety, panic and simple phobias) But from the perspective of providing a sound basis for scientific research, especially for the core diagnoses of the ‘functional psychoses’, the whole thing is a terrible, misleading mess.


Categorical thinking.

It might be thought that the current diagnostic schemes are supported by a wealth of scientific research. But almost the opposite is the case. Despite widespread skepticism in the research literature about the validity of the current diagnostic categories, it is still the case that almost all biological research is based upon neo-Kraeplinian diagnoses, them rather than neo-Kraeplinian diagnoses being based on research.

A typical research project will involve comparing a group of subjects diagnosable in a DSM or ICD category with normal controls with respect to some measurable parameter - biochemical, hormonal or some aspect of brain imaging. The biological validity of the diagnostic categories is implicitly assumed, and all information gathering is structured around this assumption. Whether the results means anything at all entirely depends on the validity of the comparison groups. For example, although hardly anybody believes that schizophrenia is a single disease entity, vast amounts of research is funded, conducted and published on the causes, correlates and cures of ‘schizophrenia’ and based upon gathering groups of ‘schizophrenic’ patients and comparing them with other diagnoses and controls. Conferences, journals and societies are based on the diagnosis. 

This has created and sustained the illusion that current psychiatric practice is a matter of diagnosing biologically individuated diseases and treating them with specific agents: the diseases are in categories such as depression, mania and schizophrenia while the treatments are seen in categories such as anti-depressant, anti-manic and anti-schizophrenic. This is categorical thinking - diseases and drugs are put into categories whether or not the categories are valid, and whether or not the individual people and drugs comfortably fit the categories. Having classified everything creates an illusion of understanding.

However, when the neo-Kraeplinian diagnostic schema has been analyzed it has typically been found that the standard diagnostic categories have less predictive validity than a symptomatic approach. In other words treating a patient with the diagnosis of depression is really much the same as (or worse than) treating a patients symptoms of depression, treating the diagnostic category of schizophrenia is really more akin to treating the symptoms of hallucinations and bizarre delusions. And the treatment of a symptom such as auditory hallucinations is the same whether the symptoms occur in schizophrenia, mania or psychotic depression.

The same applies with psychiatric drugs. In reality the categories such as ‘anti-depressant’ and ‘anti-psychotic/ neurolpetic’, ‘anxiolytic’ and ‘mood stabilizer’ are neither distinct nor autonomous. Psychiatric drugs (like most drugs) have broad and non-specific pharmacological and clinical actions. To take the example of the ‘anti-psychotic’ chlorpromazine: this has powerful anti-dopamine, anti-histamine and anti-cholinergic actions. And its clinical actions - as well as the ‘anti-psychotic control of hallucinations and delusions, also include sedation and anxiolysis, a kind of a general ‘strait-jacketing’ behavioural control in high doses, control of mania, anti-depressant activity (especially in sever psychotic depression), anti-nausea and anti-emetic actions (for which it was originally licensed in the USA), and control of hay fever and hiccups. Indeed chlorpromazine is just about the least specific drug ever invented, so to regard it as a member of the class of neuroleptics of anti-psychotics is particularly absurd.


A new nosology needed

The continuation of the current diagnostic system has therefore little or no scientific justification, and is only supported by the pharmacological evidence by an extra-ordinary habit of regarding psychiatric drug activity in distinct categories. Indeed, it would probably be true to say that we know enough to know that the current nosology is untrue.

Certainly this holds in important respects - for instance that schizophrenia is definitely not a valid biological category. The diagnostic category of schizophrenia  is hardly at all predictive of prognosis, or specific treatment response, displays no specific psychological abnormalities, has no distinctive or characteristic physical pathology, and in general does not make sense from a biological perspective. This is hardly surprising since the current concept of schizophrenia is a modification of ideas that are a hundred years old which has never been revised in the light of modern knowledge. How many other century old diagnostic schemes are still regarded as valid?

The only proper justification for continuing the neo-Kraeplinian approach is that it is much better than no classification at all, and that no other system is as well validated. These are compelling pragmatic reasons, and I certainly would not advocate dropping the current nosology from clinical practice until something better comes along and has been thoroughly researched. However, there is no reason why a new nosology should not immediately guide research (as opposed to clinical practice). All rationality points to the urgent need for researchers to drop the current classification at once and set to work to try to discover something better.

That is the project I will begin in this book: the search for a better nosology, a better system of disease classification that is more biologically coherent and will serve as a basis for research. I will suggest several psychiatric diagnostic categories, based upon cognitive neuroscience informed by a perspective from evolutionary psychology. And I will reinterpret psychiatric drugs in terms of their actions upon these psychological variables. The first will draw upon the concept of theory of mind as being based upon the ‘somatic marker mechanism’ which was expounded in the previous chapter.  


Chapter 4

The delusional disorders

One of the classic symptoms of ‘madness’ is to have false but strongly held beliefs that have a powerful effect on behavior. Such beliefs are termed delusions - at least they are termed delusions when they are taken to be a symptom of psychiatric illness. Many people who have delusions also have other symptoms of ‘madness’ - they hear voices, have incoherent speech, display strange or inappropriate moods or adopt bizarre postures and are immediately recognized by the general public as ‘mad’.

But some people with delusions are entirely ‘normal’ except for the false belief, and the belief itself is neither impossible nor outlandish. Any other unusual behaviors can be traced back to that false belief. For instance, a man may have the fixed, false and dominating belief that his wife is having an affair with a neighbour. This belief may be so dominating as to lead to a large program of surveillance  - spying on his wife, searching her handbag, examining her clothes etc. Yet the same man may show no evidence of irrationality in other areas of his life, being able to function normally at work and socializing easily with acquaintances, so that only close friends and family are aware of the existence of the delusion. In such instances the delusion is said to be ‘encapsulated’, ie. sealed-off from other aspects of mental life, and these people are said to have a delusional disorder.


Case history of a persecutory delusion - the story of Bill

Bill is an unemployed man in his early thirties, happily married with children. Bill’s delusion began two years before the interviews. He believes that a gang of criminals think that he informed on them. These men want to hurt or kill him; and will do so if they see him. As a consequence, he rarely leaves the house.

One of Bill's old friends was a shopkeeper who was burgled several times over a short period. Bill knew no details about the crimes; however, he coincidentally went to visit shortly after a burglary had occurred, and stood outside the shop talking for a while with his friend. On the same day the shopkeeper happened to discover the burglar’s identity, and Bill believes that the shop assistant will have assumed that this information had been passed-on by Bill during his conversation outside the shop. Since the burglars were frequent customers at the shop, the assistant will (Bill thinks) probably have told them that Bill was the informant. Bill believes that these criminals now want revenge, and may want to kill him.

Two pieces of supposed evidence have confirmed this theory. Bill was waiting in a car when he saw some men pointing at him and overheard them saying ‘that's him in the car’. And at about the same time Bill also began to notice that old friends seemed to be ignoring him in the street, and were behaving in a manner similar to that directed at someone known to be a ‘grass’. To avoid meeting the burglars, Bill stays at home as much as possible. If he finds it necessary to go out, he runs between his house, the car and his destination. This has stopped him having a job and being able to take his children to school, and has led him to be referred to a psychiatrist. He was diagnosed as having ‘acute paranoid disorder’, prescribed anti-depressants and neuroleptics, and he continues as an outpatient.

Bill’s case is a true story, although names and identifying details have been changed. Yet the striking thing about Bill was how ‘normal’ he was. Even on detailed interviewing he did not appear in any way ‘mad’, he presented socially as a very ‘down to earth’, plain-speaking, solid working man. He had no evidence of other psychiatric illness, nor of intellectual damage. Off the subject of his delusions he could converse with interest and animation in a manner indistinguishable from other men of his age and background. His persecutory beliefs were false, and were based on what seemed to most people to be inadequate evidence - yet they were not bizarre beliefs, nor was his reaction to them hard to understand. If Bill had been correct about being persecuted, then his interpretations and actions were perfectly understandable and reasonable.


Delusions and other false beliefs

Delusions are typically stated to have three major defining characteristics. Firstly that a delusional belief is false, secondly that this false belief is behaviorally dominant, and thirdly that the false belief is resistant to counter-argument. All these characteristics are shown by delusional disorders, yet they occur in a context of generally non-pathological cognitive functioning. 

Humans are extremely prone to ‘false’ beliefs, or at least beliefs that strike many or most other people as false. Some of these false beliefs are strongly held and dominate behavior. It is trivially obvious that humans are imperfect logicians operating for most of the time on incomplete information, so mistakes are inevitable. But it is striking that although everyone would acknowledge the imperfections of human reasoning, many of these false beliefs are not susceptible to argument. For example, deeply cherished religious and political beliefs are nonetheless based on little or no hard evidence, vary widely, yet may dominate a person’s life, and are sometimes held with unshakeable intensity. And religious and political beliefs may strike the vast majority of other people as obviously false.

What about beliefs concerning the racial supremacy of people with white skins or the racial inferiority of Jews? Such beliefs have been common in many times and places, they are certainly strongly held, affect behaviour, and a person who holds them may not be persuadable to the contrary. Although we consider them false as well as wicked, there would seem to be no compelling evidence with which we might have confronted, say, Adolf Hitler that would have persuaded him to admit he had been wrong about the Jews. Even if Hitler may be considered an insane individual, that could not apply to all the millions of people who agreed with him.

On reflection, we all harbor beliefs that may strike other people as false, even abhorrent, yet they could not persuade us out of them, at least not over a short timescale. Deeply felt beliefs do sometimes change over a lifetime but not necessarily as a consequence of compelling evidence - people sometimes change their political views, convert to a new religion or to agnosticism, and in their personal lives go through several revisions of their opinion about who is the most beautiful and desirable woman/ man in the world.

In other words, delusions are a part of everyday life - but all these everyday delusions are of a particular sort. They are all delusions in relation to social intelligence. At root, all these false, or at least unjustifiable, beliefs are based upon interpretations of the human world. Even some of the more strange beliefs people have about cosmology and metaphysics often boil down to beliefs about agency - the power and influence of powerful and influential agents - whether human or supernatural.

These everyday delusions can be interpreted alongside a formal psychiatric diagnosis called delusional disorder. The category of delusional disorder describes a psychiatric syndrome characterized by non-bizarre, chronic and content-encapsulated false beliefs in a context of generally intact affect, speech and general behavior. In other words, a person with delusions disorder is essentially normal except for the subject matter of their delusions, all other abnormalities of their behavior can be traced back to that cause.

Subject matter is variable; with persecutory, jealous, grandiose, erotomaniac and somatic subtypes. A persecutory delusion might involve a fear that one is being hunted by a hostile gang, such as the mafia; jealous delusions involve a belief in the sexual infidelity of a partner; grandiose delusions involve the false belief that one is of higher status than one’s actual status, or perhaps that one possesses exceptional powers or skills; a person subject to erotomaniac delusions will believe that someone is in love with them when that person is not; and somatic delusions involve false beliefs about parts of one’s body - such as that one has a large ugly nose when it is actually normal. 

It will be suggested that many delusional disorders can plausibly be interpreted as ‘theory of mind-delusions’  - false beliefs whose formal characteristics are consequences of the theory of mind mechanism, and whose subject matter reflects social selection pressures that were important during human evolutionary history.  This analysis will in turn throw light upon the nature of human thinking about social interactions, and will demonstrate the dependence of social judgment upon emotions and feelings.


The ‘theory of mind’ mechanism (ToMM) and delusions

It is striking that the subtypes of delusional disorder represent fundamental aspects of human social functioning; being related to sexual attractiveness (erotomaniac and somatic types), sexual reproduction (morbid jealousy), status (grandiose) and personal survival (persecutory delusions).

Human social intelligence has arisen in order to understand, predict and manipulate the behavior of other people - a task that places exceptional demands on cognitive processing. It is believed that social competition between humans provided the most important constraint on survival and reproduction under recent ancestral conditions.

Social intelligence interprets behavior in the light of inferred mental states. In other words the mechanism of social intelligence makes ‘theories’ of mind; which are inferences about what other people are thinking - their motivations, intentions and dispositions. These inferences concerning mental states affect the interpretation of behavioral cues. For instance, a clenched fist might be interpreted either as a threat of violence or as an encouraging gesture of support, according to whether the motivational mental state was inferred to be hostile or friendly. It is this evolved adaptation by which states of mind are inferred and deployed in human reasoning has been termed the ‘Theory of Mind Mechanism’ (ToMM).

The neural mechanism for the ToMM has recently been elucidated by Antonio Damasio and his colleagues and termed the somatic marker mechanism (SMM;). As described previously, in essence the SMM involves using one’s own emotional reactions as indicators of another person’s mental state; then using this ‘cognitive representation’ of person plus mental state to perform internal modeling of behavioral consequences. For example, if the approach of a stranger induces an emotional response of fear, a combined emotional-perceptual representation of a ‘fear-inducing’ (or ‘hostile’) stranger is created in ‘working memory’. If the perceptual representation of the stranger is reactivated from memory, as well as recognition of the individual the linked emotion of fear will also be re-deployed in the body and physically re-experienced. The function of the perception-emotion linkage in ToM is therefore to evaluate the significance of internally-modeled social situations.

Our attitude to a social situation is profoundly affected by the emotions that occur as a consequence of that social situation. This attitude is re-evoked and re-experienced as an emotion when that social situation is recollected or anticipated. So, the social category to which the original social situation was assigned becomes capable of creating a particular emotion - every time you think of the prospect of meeting Big Al you feel fear, every time you think of Big Alison the recollection evokes a stirring of desire…


Psychopathology of theory of mind delusions

Since it is argued that delusional disorders are aspects of social intelligence, and social intelligence involves the ToMM, then the structure and function of the Somatic Marker Mechanism should be able to explain many of the clinical and phenomenological features of delusional disorder.

The suggestion is that delusional disorders are a consequence of normal, logical reasoning from false premises concerning other peoples’ mental states. The false beliefs are based on false assumptions about motivations, intentions and dispositions rather than being a consequence of strictly logical errors.

The assumption here is that the delusional disorders occur in a context of non-pathological, adaptive cognitive processes, including an intact ToMM - and that their characteristic false beliefs are an outcome of the nature of psychological mechanisms operating on a particular personality-type and social circumstances. A further factor is probably that human psychological mechanisms evolved under tribal conditions but now operate in a mass social environment populated mainly by strangers performing unobserved acts - what was adaptive may become pathological under modern circumstances.


1. Subject matter of delusional disorder

Humans are social animals, and the reproductive success of our ancestors depended crucially upon their ability to negotiate the social milieu and compete with members of their own species. Beliefs in the social domain therefore tend to have a strong effect on behavior (ie. beliefs tend to be behaviorally dominant) because the social arena is crucial to human survival and reproduction.

The subject matter of delusional disorder bears a striking resemblance to the principal categories of social interaction that have evolutionary importance and require mental state inferences. In other words, delusional disorders apparently reflect the nature of social selection pressures in an ancestral environment. For example, homicide is a major cause of premature male death (hence, failure to reproduce) under tribal conditions, and many homicides are the result of ‘gangs’ of males. The same phenomenon has been reported in common chimpanzees, where ‘gangs’ from one troop will seek and kill isolated males from another troop. Persecution by hostile alliances of unrelated males was probably a significant feature of ancestral social life, and it makes sense that inferences concerning persecution by male alliances have the potential to act as a powerful influence on behavior.

Similarly, a conjectural evolutionary scenario to account for erotomaniac and some somatic delusions can be derived from sexual selection theory. The major variable that influences a man’s attractiveness to women is status; and erotomania can be seen as a condition in which a woman becomes delusionally attracted to an unattainable but high status male whom she believes returns her love). By contrast, a woman’s physical attractiveness to men is primarily a matter of physical beauty (cues of youth and health) and in the somatic type of delusional disorder (ie. a delusions related to the body or ‘soma’) a common presentation is in a hypersensitive, insecure woman of reproductive age who has become preoccupied that she is physically unattractive due to some bodily impairment (such as a foul odor) or personal ugliness (eg. blemished skin, large nose). Somatic delusions of this type are reported to be unusual in women beyond reproductive age. And when somatic delusions of this type are found in men, it could be predicted that they will be more common among those who rely on their appearance for attracting sexual partners - for example homosexual men, or men of lower social status.


2. False beliefs are unavoidable in mental state inferences

The false beliefs found in delusional disorder are social, and inevitably involve making mental state inferences - ie. judging the dispositions, motivations and intentions of other people. Mistakes in evaluating dispositions, motivations and intentions are inevitable. Beliefs concerning the mental state of others are always inferences based upon insecure (emotionally-derived) assumptions, they cannot always be true because beliefs cannot be checked against objective criteria - there is no direct access to other minds.

Inferences concerning the state and content of other minds depend upon information from one’s own subjective emotional responses, as well as from observed behavioral cues. When subjective emotional response is inappropriate, then the inference of mental state will be wrong. For example, inappropriate fear may lead to a false belief concerning the hostile intentions of a male stranger, and this may emerge as a persecutory delusion. There is no secure way of checking whether fear of another person is appropriate, whether Big Al really is as aggressive as he makes you feel, or whether beneath the granite exterior beats a heart of gold. The link between emotions and delusional disorder may also be seen in the reported association between low self-esteem (ie. perceived low status) and morbid jealousy. If a man believes he is unattractive to his wife and other women, he is more likely to believe that his wife is motivated towards having a sexual relationship with another and more attractive man.


3. Beliefs concerning ToM inferences will be resistant to counter-argument

Beliefs concerning the state of mind of other people may be resistant to counter-argument since the human social domain is intrinsically competitive. We would be foolish always to be persuaded by the arguments of other, since everybody is ‘in competition’ with everybody else to a greater or lesser extent - even close family members will lie to one another (whether ‘for their own good’ or to shape behaviour in a more personally advantageous direction).

Indeed, it is suggested that the ToMM evolved as a direct consequence of human versus human competition. We base our assessments of others upon the emotions they evoke in us, ‘I know everybody says he is nice, but I don’t trust him - he makes me feel uncomfortable’. These feelings have adaptive significance. Deception and concealment of hostile motivations and damaging intentions can be expected in the social domain.

Mistrustfulness concerning the reassurances of others is - in this sense - adaptive. Dishonesty from other people - in these matters - is to be anticipated. Would your best friend really tell you if your wife was having an affair? Many people lie in such circumstances, for all kinds of reasons. Especially when it might be your best friend that is having the affair… It therefore makes sense that - despite their being based upon insecure inferences - beliefs concerning theory of mind will neither be labile nor readily abandoned. In a rivalrous social world where no-one can wholly be trusted, each person must reach their own conclusions about the motivations, disposition and relationships of other people.


4. Delusions are encapsulated due to the nature of the ToMM

When mental state delusions are a consequence of the ToMM (ie. the SMM) they depend upon a cognitive representation that incorporates a social identity with an emotion. In other words, an body state is linked specifically with a particular category of social interaction. So, the social category of a particular gang may be linked with the emotion of fear, and whenever the gang is thought about then the body will enact the emotion of fear - and this state of fear will influence interpretation of social events. Other social categories might be kinship categories (mother, father, spouse, son or daughter etc.), groups in our immediate environment, or any other grouping which we (rightly or wrongly) subjectively consider to be cohesive - such as ‘the Irish’, ‘the communists’, or ‘the managers’.

But other social categories are not linked to fear. Mental state inferences will therefore be restricted to the particular person or group described by that social category.

This potentially explains why pure cases with delusions of persecution can nevertheless maintain friendly and cooperative social relationships with people outside of the social category of their presumed persecutors. Female persecutory delusions usually relate to familiar people, while male delusions relate to strangers. In both cases, the delusion is encapsulated according to social category.


The example of morbid jealousy


A jealous delusion - Edward

What follows is a true story - names and identifying details have been changed.

Edward is a man in his mid-twenties. He had an uneventful childhood, was an average pupil and left school without taking examinations to serve an apprenticeship. Edward’s personality is cautious and careful, and people have commented on his neatness, punctuality and conscientiousness. Although somewhat shy, he has plenty of friends and an active social life. Indeed, he has strong attachments to his family, and a powerfully developed sense of personal responsibility. There is no history of psychiatric illness, nor current sign of psychiatric illness.

In his early twenties, Edward began a relationship with a younger girl called Frances that lasted several years. As the relationship progressed it became more stormy, with arguments centering around Frances’s desire for more freedom to go out with friends, and Edward’s increasingly possessive attitude to her and his criticisms of her sexually provocative style of dress. Edward became increasingly worried that Frances might be ‘seeing other boys and having sex. If she had sex with anyone else I could never have her back’. The worry escalated into a tormenting pre-occupation, and on one occasion Edward was driven to phone one of Frances’s friends to check that she was not seeing anyone else; on another occasion he went around the local night clubs to check on her whereabouts.

The situation became so bad that the relationship split up (a ‘trial separation’). However, Edward became even more distressed. One evening, Edward saw Frances in a bar, talking to a group of men and dancing in what seemed a provocative fashion. He left the bar ruminating on the possibility that she was seeing other men, and the thought ‘jumped through’ his mind that she may have had sex with them - although he pushed the thought aside. In an overwrought mood, he waited outside Frances’s home in a car to discuss their relationship. She sat by him in the car, an argument broke out and Francis tried to make it up by kissing Edward; but Edward exploded into sudden anger at her sexually provocative manner - and he strangled Frances to death.

Edward was immediately overwhelmed with remorse, drove for miles, and made a determined attempt at suicide. The interview took place in prison where Edward was awaiting trial for murder.



Jealousy in humans is a cultural universal, a complex and characteristic pattern of behavior in response to specific cues, which serves an adaptive function concerned with paternal investment in offspring. Across the animal kingdom, jealous behavior is found only when males contribute resources to their offspring (especially after birth) and is a response to the problem of uncertain paternity in species where females potentially mate with more than one male. Jealousy in men can be seen as an evolved ‘instinct’ that operates to reduce the chance of sexual infidelity in a partner, and reduce the chance of misdirected investment. If a male were to tolerate sexual infidelity and continue to invest resources into a rival male’s offspring, he would incur the ‘double’ genetic penalty of both failing to reproduce and ‘wasting’ resources on assisting a rival’s reproduction. Humans have few offspring, each requiring a substantial investment of resources - any child sired by another man represents the loss of a substantial proportion of expected reproductive capacity.

Jealousy in women is significantly different in its motivation and intentions since female mammals do not suffer from uncertainty as to the identity of their offspring, and sexual infidelity per se is not a problem. The problem for a female is to secure investment to help in rearing offspring, and jealousy is primarily concerned with ensuring that the male partner directs his investment efforts towards the woman’s own offspring. So female jealousy is less concerned with the act of sexual infidelity and more with the danger of a male partner transferring his affections (and resources) to another female. Hence selection pressures have led to different cues that stimulate the emotion of jealousy in men and women: men primarily fear physical infidelity (the partner having sexual intercourse with another man) while women primarily fear emotional infidelity (the partner falling in love with another woman).

‘Morbid jealousy syndrome’ describes a condition of inappropriate or excessive jealousy, specific to the sexual partner, and which dominates behavior; this becomes delusional when it involves a false belief in the sexual infidelity of the spouse or sexual partner. Morbid jealousy can occur in a pure form (ie. without the presence of another psychiatric diagnosis), in both males and females; although it is commoner in males. The extreme of morbid jealousy itself would not usually be considered adaptive since it could severely damage reproductive success: for example when it causes the breakup of a relationship, or death of one or both partners by homicide. However, it remains possible that the threat or possibility of such extreme sanctions may serve as an effective deterrent; hence even intense jealousy may be adaptive on average or under ancestral conditions.

Delusions of sexual infidelity can be considered as consequences of the ToMM and strategic social intelligence, since they are concerned with internally modeled social relationships and mental state inferences. Jealous delusions are not about what is happening here-and-now (since that is a matter for direct observation); but instead about what did happen, is happening elsewhere, or might happen in the future. False positive or inappropriate jealousy is inevitable at a certain frequency since imaginative construction of possible scenarios cannot always be based-upon or checked-against reality. Also, inferences concerning the intentions of a sexual partner are not directly accessible but can only be checked against behaviors whose interpretation is ambiguous.

Jealousy is notoriously resistant to reassurance or counter-argument. There is often no objectively convincing way to contradict the delusional belief. This arises from the fact that jealousy evolved in a context of social competition where deception is expected as an element of that competition. Nonetheless, false beliefs of sexual infidelity are compatible with being encapsulated and specific to the sexual partner. The encapsulation occurs on the basis that the ToMM involves a cognitive linkage between a particular social category and the particular emotions associated with jealousy. Outside that subject matter and that emotion, cognitive life may proceed relatively unaffected.

So, the emotion of jealousy may be ‘attached’ to the social category of ‘my wife’ and confined to that category - a man who is jealous of his wife need not be jealous of any other woman (‘he always seemed charming to me…’), nor of women in general, nor of men, nor of inanimate objects. Sexual jealously is probably always confined by category - although the category will vary between individuals and may be more extensive than just wife (eg. sexual jealousy may apply to any women with whom the man has had sexual relations, or any woman with whom he wishes to have sexual relations). The point is that, due to the SMM, the emotion is linked to a perceptual category such that evocation of the perceptual category triggers the emotion.

Patients with delusions show varying degrees of rational ‘insight’ into the possibility of error in their inference, and ToM delusions including non-delusional morbid jealousy may respond to reasoning techniques such as Cognitive-Behaviour therapy. However, a fundamental problem for cognitive therapy of delusional disorders concerns the intractable inaccessibility of the true intentions and motivations of others. It may be impossible in practice to prove a negative; eg. that a partner has not been sexually unfaithful or that there is no gang trying to kill you, or that secretly men find you repulsive and stare at your big nose - or for that matter that Big Alison finds you almost overwhelmingly attractive and has to fight very hard to avoid showing the fact….


Theory of Mind delusions are part of ‘normal’ life

In these ToM-delusions relating to social instincts, the delusional quality (ie. its dominating and intractable nature) is a consequence of the evolutionary importance of the subject matter combined with the frequently insurmountable difficulty of verifying mentalistic inferences. The intensity of a false belief may wax and wane quantitatively between morbid pre-occupation and frank delusion according to personality and social circumstances, and will typically persist in the long-term. It follows that the exact dividing line between a ToM-delusion and a strongly held and dominating ‘overvalued idea’ is of little pathological or diagnostic significance.

The suggestion is that delusional disorder is understandable in terms of evolved psychological mechanisms for making mental state inferences. ‘Theory of mind delusions’ are an inevitable consequence of the ToM depending upon subjective emotional states for internally modeling the mental states of other people; they are the consequence of reasoning logically from false premises about dispositions, motivations and intentions. This general process interacts with individual personality and circumstance to create specific delusional contents.

The conclusion would be that many of the social phenomena mentioned earlier - such as racism, and strongly held political and religious views - can be conceptualized as operating with the same features of psychological organization as delusions disorder. It is yet another example of the way in which emotions interact with cognition, so that perceptions are coloured by mood. Emotion shapes reasoning in a profound fashion, and because of the somatic marker mechanism emotional colouring may be focused on particular social categories.

This is a way in which preconceptions may shape reasoning such that beliefs become almost unshakeable. When specific social categories become associated with certain classes of emotion, this constitutes what might be termed ‘prejudice’ in the exact sense of pre-judging. If perceptions or recollections of Jew or black people cause the enactment of aversive emotions, then these will affect the evaluations of social situations. A belief that ‘the Jews’ form  a sinister, international conspiracy - powerful yet covert - may be strongly-held, dominating, and in practice impossible to refute by argument. The belief is not illogical, but is based upon inference from indirect evidence.

Few people are immune to this kind of thinking, since the alternative to having strongly held beliefs on insufficient evidence is to have no strongly held beliefs at all - which is not an option: we must make judgments. Something similar happens, I suggest, with other social categories such as political parties. In a two-party political system there is a tendency to assume that one of the parties is basically well-motivated although susceptible to mistakes, while the other party is basically wicked although capable of producing the occasional good policy - albeit for the wrong reason. People who support the same political party as I do are basically decent, while people who support the other party are basically selfish, stupid or misinformed. And there is no neutral ground upon which this disagreement can be settled, no way of determining which party really is the best because all the ‘facts’ are interpreted in the light of assumptions about motivations. It is no easier to persuade someone to change their political allegiance than it is to persuade someone with persecutory delusions that their beliefs are unfounded.

Although such social groupings as ‘races’, political parties or religions are so large and unorganized as to be abstract and amorphous, the structure of human intelligence is such that even when it is meaningless to attribute dispositions, intentions and motivations, human group categories gather to themselves emotions that are appropriately meant to be attached to individuals. As stated above, since we are social animals we must make judgments about who are our allies and who our enemies - even when secure grounds for this decision are lacking and we cannot always tell the one from the other. But for modern humans in mass societies the problem is impossible. We make judgments, and we stick by them and are dominated by them - even though that which we are judging is an artifact - a mere word that stands for something that may not exist, and if it does exist may lack coherence and structure.

In effect, modern humans continue to anthropomorphize the social scene, to personalize the impersonal, however inappropriate this may be. We naturally tend to make everything into a ‘human interest story of heroes and villains - which is why tabloid journalists are so successful when they present issues in this fashion. But having simplified life into a soap opera we become captive to our own assumptions and preconceptions.  In this sense, delusional disorder is part of the human condition, and its importance increases with every passing year.



Chapter 5

Bizarre delusions


Two kinds of delusions: ToM delusions and bizarre delusions

Delusions, I suggest, fall into two categories: theory of mind delusions, and bizarre delusions.

A theory of mind delusion is a false belief which is the logical outcome of a false premise. The processes of reasoning are intact and unimpaired, but operating on incorrect assumptions.  For Edward, the jealous murderer, two plus two still equals four and the sun still rises in the East. Edward remained able to give accurate accounts of direct observations of objective data. However, his assumption that his girlfriend was having an affair was based upon an incorrect interpretation of indirect inferences concerning her state of mind Although her behavior appeared to be consistent with the assumption of her sexual infidelity, the fact of the matter was that Edward’s girlfriend was not actually having an affair.

But false beliefs might also be the outcome of impaired thinking, of ‘illogical’ reasoning. Even correct premises would not necessarily led to correct conclusions since thinking is impaired. When reasoning is illogical, two plus two would not necessarily equal four, but might instead equal three, or five, or Adolf Hitler. The sun may rise in the West tomorrow, fail to rise at all, or have turned into a balloon.


Impaired thinking leads to bizarre beliefs

We are all familiar with this kind of illogical reasoning that leads to bizarre delusions since the illogical progression of ideas by association is the sort of thing that happens in dreams: ‘I walked into the street and saw a lion and realized that to escape I needed to open a trapdoor hidden underneath the hedge, and the trapdoor opened onto another planet with purple skies and no gravity, but the lion had changed into a flowerpot…’

If we are awaken from a doze, or just as we are dropping-off to sleep, we may recall that our thoughts were ‘falling apart’ and becoming illogical. The release from a normal coherent progression to an unpredictable association of ideas varies in severity on a continuum from occasional mistakes to gross incoherence. And the process can be observed from the outside when a delirious patient exhibits a fluctuating state of consciousness, lucid intervals interspersing periods of incoherence. 

Incoherent thinking and illogical reasoning is therefore often a consequence of ‘clouded’ consciousness, or brain damage. And whenever thinking is impaired by ‘organic’ insult to the brain - when consciousness is clouded, when we are sleepy, when the brain is reversibly impaired by drugs or alcohol or permanently impaired by dementia or other forms of brain damage - then under such circumstances there is a greatly increased potential for impaired reasoning to lead to false beliefs.

Beliefs resulting from illogical thinking can be extremely bizarre, especially since the mechanism for testing ideas for plausibility and consistency with other ideas is exactly what is damaged.



Bizarre beliefs: a sign of madness

All delusions are not the same. While false beliefs about other people - about sexual infidelity or persecution, for instance - can be seen as variants of normal behavior and based on rational reasoning, other false beliefs are based on irrational thinking, and only occur in ‘mad’ people who are suffering from a general form of impairment in brain function, and who will exhibit a variety of symptoms. These are the bizarre delusions.

There has long been a recognition, albeit vague, that some ‘bizarre’ beliefs have a different pathological significance from false beliefs that stem form misinterpretation of real phenomena. Bizarre beliefs are evidence of mental illness in a way that ToM delusions are not. Indeed, I suggest that it is a feature of bizarre beliefs of a delusional nature that they are never the only sign of mental illness, but that bizarre delusions are invariably part of a clinical picture which includes a range of other ‘psychotic’ symptoms such as hallucinations, or illogical and incoherent speech (so-called ‘thought disorder’). 

Bizarre delusions include many of the most typical delusions seen in classic ‘schizophrenic’ patients. For example those ‘primary’ delusions in which a person suddenly becomes convinced of something false without any understandable logical link - ‘the traffic lights turned green and I knew I was the son of God’, or ‘My thoughts stopped and I realized that they were being drawn out of my head by X-rays’.

Some bizarre delusions arise from hallucinations or other abnormal bodily or mental experiences - for example ‘the voices’ may have told the patient that he was the son of God, or he believes that the funny feelings in his belly were caused by a satellite. These are bizarre ways of explaining bizarre experiences - and both experience and explanation probably share a common source in brain impairment.


Bizarre delusions contrasted with ToM delusions


1.   Subject matter of bizarre delusions - anything

While theory of mind delusions are always about social phenomena, bizarre delusions might be about anything: social or environmental, physical or metaphysical, natural or supernatural. 


2. Bizarre beliefs may survive objective refutation

Theory of mind delusions stem from inferences concerning the mental states of other people, in other words from indirect inferences about entities which are not directly observable. But bizarre delusions may be held despite the evidence of direct observation.

Evidence that a normal person would find compelling is not necessarily persuasive to someone with bizarre delusions. Because the reasoning processes are impaired in bizarre delusions, then a chain of argument that would usually be considered to be conclusive evidence against a belief does not have the force it usually would.

For instance, a person with psychotic depression and nihilistic delusions may believe that their internal organs have rotted away leaving them hollow. Such a person is holding a belief in the existence of a state of affairs that is incompatible with human life - yet this ‘fact’ of the delusion being impossible is not taken to be compelling. Indeed, this kind of patient may deny that they are alive at all - which again contradicts what would be considered to be the possibilities of objective fact. After all, one does not hold conversations when one is dead.

Whatever arguments or evidence that are brought to bear, the bizarre delusional belief may unshaken because, when brain function is impaired we cannot follow logic, and so logical argument does not have the power to persuade.


3.   Bizarre delusions are not encapsulated by social category

ToM delusions are characterized by false beliefs confined to a particular social category - as when the deluded person is only jealous of his wife (but not his sister), or only afraid of the local drug Mafia (but not the Freemasons). But since bizarre delusions are caused by impaired reasoning, bizarre delusions are not restricted to particular social categories, and delusional thinking is liable to be a feature of many domains of discourse.


4.Pure cases of bizarre delusions will not exist

While ToM delusions can occur as ‘pure cases’ in people who are otherwise normal it would be predicted that there will be no pure cases of bizarre delusions. That is to say there will be no cases of people who have an encapsulated bizarre delusion with otherwise wholly normal psychological functioning. In lay terms, all people with bizarre delusions will be overtly ‘mad’ or in some other way suffering from brain impairment leading to a variety of psychological symptoms.

To put it another way, bizarre delusions are assumed to be a consequence of impaired reasoning processes, and reasoning processes are assumed to be abnormal as a consequence an organic brain impairment such as delirium or dementia. And if delirium or dementia are present then there will inevitably be a widespread impairment in brain function which will produce not just a single false belief, but a variety of psychological symptoms typical of that form of impairment. A delirious patient will not merely have a false belief, he will also exhibit impairments in concentration, altered mood and poor performance on short term memory tasks.

So, it is firmly predicted that bizarre delusions would only be found as part of a psychiatric syndrome - never as pure cases.


Bizarre delusions are caused by organic brain impairment

In other words, the category of bizarre delusions are not explicable in terms of rationally misinterpreting normal perceptions on the basis of mis-attributed intentions, motivations, or dispositions. Bizarre delusions either require that the patient is rationally misinterpreting pathological psychological features such as hallucinations, or else the actual thought processes are irrational due to pathology and the chain of inference is itself illogical: ‘they threw an egg at my window, and this meant I was a homosexual, so I switched on my radio’. The chain of inference is illogical by normal standards of language as a medium of communication - although the story may well be explicable as a consequence of personally-significant ‘associations’ in just the same way as dreams can make a kind of subjective sense.

The exact psychopathological mechanisms by which bizarre delusions arise cannot be known until the processes of normal, non-pathological thinking is understood - and this is not understood at present, we just do not know the ways in which inferences are made.  However, it is uncontroversial that irrational thinking and abnormal psychological experiences are a common feature of organic brain disease - such as delirium, epilepsy or dementia. In other words, when a brain is dysfunctional or damaged then it is unsurprising that the brain cannot perform cognitive processing in the normal fashion. The same applies to sleep or near sleep states. False beliefs are to be expected in a circumstance when brain impairment has affected the cognitive processes by which beliefs are generated.

Although epilepsy and dementia may have a significant role to play in generating psychiatric illness, it is delirium that is the most interesting as a possible cause of bizarre delusions. Interesting because delirium is a concept of critical importance in the neo-Kraepelinian diagnostic system - indeed delirium could be described as the keystone of the whole nosology.

If current concepts of delirium are inadequate, and if the keystone at the heart of neo-Kraepelinian nosology is defective, then the current classification of psychiatric disorders will collapse like a packhorse bridge crumbling into the chasm beneath.


Chapter 6

Delirium and brain impairment


Brain impairment is another fact of everyday life. Many people are brain impaired for much of the time, few will avoid impairment for very long - and a substantial number of people are impaired on a permanent basis. One of the critical concepts in psychiatry is that of reversible cognitive impairment - in other words impairment of brain function without any permanent changes in structure. The most convenient term for clear-cut impairment of brain function is delirium. Other terms for delirium include acute organic syndrome and acute or toxic confusional state - or simply ‘confusion’.

The causes of delirium are many fold. As well as toxic levels of intoxication with alcohol or other ‘drugs’, delirium can be induced by withdrawal of alcohol and other intoxicating drugs (eg. in delirium tremens). Children and elderly people may suffer delirium when running a high fever, after an operation or severe trauma, or after any significant ‘insult’ to the brain (such as an acute illness or trauma).

But perhaps the most common type of delirium is the state between sleeping and waking in which ‘hypnogogic’ hallucinations can occur, and in which people may temporarily not know where they are or what day it is. People dropping off to sleep may hear voices, noises, see things - and the same thing may happen when waking (or being half-awake and suffering sensory deprivation in the dark). Who has not awoken to experience a bizarre (albeit transient) belief hanging-over from a dream? These are ‘normal’, everyday experiences of psychotic phenomena, and they are due to reversible functional brain impairment.

The fact that delirium causes psychotic symptoms such as hallucinations and bizarre delusions has been a well established fact for some centuries. But what is the definition of delirium - what is the threshold at which it can be diagnosed? Upon this definition depends whether or not the psychotic symptoms in a particular patient can be attributed to delirium.


Definition of delirium

Traditionally, the term delirium has been reserved for only the most severe end of the spectrum characterized by disorientation (ie. not knowing when it is, where you are, who you are, or what is going-on). The other feature of delirium is ‘clouding’ of consciousness; which is defined as drowsiness, reduced awareness of the environment, poor concentration and distractible attention - a state compatible either with sleepiness or with excitable agitation.

This definition on the basis of disorientation is quite clear cut, and prevents the over-diagnosis of delirium. But this categorical, yes or no definition obscures the fact that brain impairment is a continuum, not simply something that is present or absent. Furthermore, to equate delirium with disorientation produces the problem that mild (but significant) delirium is under-diagnosed. More sensitive and objective measures, in particular such as the electroencephalogram (which measures ‘brainwave’ electrical activity across the brain surface) demonstrate that delirium can occur in the absence of disorientation. Making the diagnosis of delirium depend upon disorientation produces false negatives - in other words people who would have solid EEG evidence of delirium but whose cognitive impairment is missed by the crude disorientation test.

The reality seems to be that delirium is not all of one kind - different impairments produce different symptoms and signs. Delirium tremens as a result of acute alcohol withdrawal, often causes terrifying visual hallucinations - traditionally of pink elephants or snakes. But psychedelic drugs may induce a delirium characterized by pleasant emotional and sensory experiences. Presumably these differences reflect the nature of the chemical insult, and differences between those parts of the brain they affect. But both are still classifiable as delirium.

In summary there is need for a sub-classification of  delirium, as well as a re-definition in order to diagnose the condition with greater sensitivity.


The critical role of delirium in neo-Kraeplinian diagnosis

If we recognize that delirium is common, varied in form, on a continuum of severity, and is not restricted to people who are disorientated - then the role of delirium in psychiatric illness needs to be re-evaluated. This is particularly important since it is recognized that delirium can lead to almost any kind of psychiatric abnormality. Because of the ability of the various types of delirium to generate multifarious psychotic symptoms, the early psychiatrists involved in classifying mental illness needed to differentiate when delirium was, and when it was not, present. Because when delirium was there was no mystery about the cause of psychotic symptoms (a globally malfunctioning brain will obviously produce abnormal cognitions of one sort or another).

But if psychotic symptoms could occur in the absence of delirium, then this represented a fascinating enigma - a whole new category of diseases - characterized by psychotic symptoms in clear consciousness. These were termed the ‘functional psychoses’ and comprised schizophrenia, mania and depression (and, in the early days, ‘paranoia’ - a category that has been replaced by the delusional disorders).  One could speculate that a great deal of the mystique about the functional psychoses - the ‘core syndromes’ of psychiatry, the special preserve of psychiatrists, the heart of the discipline of psychopathology - this whole edifice of psychiatry rests upon the simple assertion that here we have syndromes characterized by psychotic symptoms in the absence of delirium. 

Yet, the symptoms of delirium are strikingly similar to those of acute schizophrenia or mania. Emotions are perplexed, fearful, paranoid, and labile; attention is distractible; speech may be jumbled and illogical; behavior may be inappropriate;  hallucinations, persecutory delusions, and other bizarre delusions may be common. Indeed, the presence of disorientation and ‘clouding’ of consciousness may be the only parameters that differ between delirium and acute psychosis.

This is very important: schizophrenia and delirium may be symptomatically identical, with the only difference between them being the presence or absence of clouding of consciousness. Yet even that criterion is not considered to make a decisive or clear cut difference in all patients. Clouding can occur in what are diagnosed as acute psychotic states (mania or schizophrenia), and as suggested above the more subtle signs of mild delirium are very common in psychosis.

So, apparently, in practice there may be no difference at all between - say - mania and an agitated delirium. Which is to say that mania and delirium are identical. Traditionally, organic psychosis (dementia, delirium, epilepsy etc) in which there is ‘coarse’ brain damage are assumed to be qualitatively different from ‘functional’ psychoses such as schizophrenia and the affective disorders in which brain damage is assumed to be much more subtle. The differential diagnosis is not made on the basis of clinical symptoms, but long term prognosis - a delirious state is assumed to be short lived and a consequence of physical illness or some other form of brain insult - whereas mania is assumed to be a mood disorder which is a disposition  of the individual and which may or may not lead to delirium as a secondary feature. This is probably quite true, but serves to obscure the apparent fact that an acute manic, schizophrenic or other psychosis is often an episode of delirium. The reason for this delirium is a legitimate source of inquiry, but that the state is delirium seems quite straightforward.

So if the presence of disorientation and clouding of consciousness are not sufficiently sensitive measures of delirium - then the boundaries between acute functional psychosis and acute organic states are breached. In other words, delirium is the key concept that stands at the boundary between ‘organic’ and ‘functional’ psychoses. This distinction is the fundamental basis of the whole Kraeplinian and neo-Kraeplinian nosology.  If absence of delirium does not characterize the functional psychoses, then there is very little basis for the diagnostic categories and the whole implicit aetiological distinction between mania and delirium is thrown into doubt.


But if acutely psychotic patients are delirious…

The whole of modern diagnostic practice therefore hangs upon the definition of delirium. And if - as I have argued - the threshold for diagnosing delirium has been set at too insensitive a level, then the whole of modern diagnostic practice, and consequently a great deal of the research literature, requires substantial re-appraisal. This is serious stuff.

For example, hallucinations - another of the classic symptoms of ‘madness’ when they occur in ‘clear consciousness’ - in other words in the absence of delirium. Supposing ,after all, consciousness is clouded and delirium is not absent? This would certainly solve a long standing mystery concerning the mechanism by which hallucinations are produced. There is a considerable speculative literature which tries to explain the psychological mechanisms by which auditory hallucinations occur. Ingenious though this literature is, I find it extremely unconvincing. Again the main problem is that we do not have any convincing models of normal cognitive activity, so the task of explaining abnormal cognitive activity by reference to breakdowns in the normal process is an extremely long shot.

But if patients with hallucinations are actually delirious, then there is no problem. Everyone knows that delirious patients hallucinate. Although we do not know exactly why they hallucinate, it is no great mystery. A damaged or deranged brain does things like that. We have experienced it ourselves when dropping off to sleep - or seen it in our children or grannies when they had a high fever.

This is perhaps every much like hypnagogic hallucinations would be if we were at a sustained level of consciousness that was poised at the verge of sleep, not quite falling asleep, not quite becoming fully awake. This explains the distractibility, poor concentration and poor cognitive performance of actively hallucinating patients. It is not so much that such patients are ‘attending to hallucinations’ - as they are frequently described as doing - but rather that they are delirious. Like other delirious patients they have a fluctuating and frequently impaired conscious level, indeed this is taken to the extreme.

To summarize: a hallucinating person is partially dropping-off to sleep, dreaming , then awakening - repeatedly, so that the dreams are remembered.


Testing the delirium theory of psychotic symptoms

If hallucinations in schizophrenia, mania and depression are actually caused by delirium, there is no need to posit any special or exotic mechanism for hallucinations. These are not ‘functional psychoses’ without organic features, rather they are organic syndromes in which the consciousness is at a level intermediate between ‘clear’ consciousness and the ‘organic’ level of impaired consciousness that has disorientation as its hallmark.

The proposition is readily testable, because it implies that any actively hallucinating patients will have brain changes compatible with delirium - and these changes should be detectable by using electroencephalogram (EEG) or any other valid, sensitive and convenient measure of brain function. Similarly with bizarre delusions, and with the phenomena of ‘thought disorder’ phenomena such as incoherent speech, thought-insertion or thought-stopping - these patients should exhibit delirium. A study of EEGs on actively psychotic patients is logistically difficult to perform. Nonetheless it may be worth the effort. Patients with hallucinations, bizarre delusions or thought disorder should exhibit delirium. If they do not, then my theory is wrong.

Electroencephalograms exhibit a wide range of normal variations, so that in order to detect EEG changes it would probably be necessary to perform serial measurements. Fluctuating conscious level is the key - the hallucinating patient dips into, and out of, dreams. The prediction is that if, for example, EEG measurements were taken both during the hallucinations, and following recovery from hallucinations (logistically difficult, but perfectly achievable given the time and resources) then there should be evidence of pathologically significant change during the psychotic episode. Since (as suggested below) it is probable that interference with working memory is the predated cause of symptoms, then EEG changes should be sought in the prefrontal cortex, especially the dorso-lateral (upper-outer) regions.

During the episode of hallucination there should be evidence of fluctuating conscious levels, and a correlation between the actual experience of hallucination and an immediately preceding dip in conscious level. By contrast, and as a possible control group, pure cases with ToM delusions would not be predicted to demonstrate EEG abnormalities, because they do not have abnormal brain function. 


Clinical implication of the delirium theory of psychosis

Electroencephalogram changes are currently the most sensitive markers of delirium. But EEG’s are inconvenient, inaccessible, expensive and some patients may be unable or unwilling to cooperate with the procedure. So it is important to generate data on the correlations between clinical symptoms and the objective measures of EEG so that the clinical symptoms might eventually be used as a guide to diagnosis and treatment.

What follows are little more than hunches or intimations, but possible clinical criteria for delirium might include the known ‘prodromal’ affective changes which are part of the spectrum of impending delirium.

I suspect that a fearful perplexity may turn out to be the characteristic mood which is indicative of subtle functional impairment of the brain. Perplexity is the sense that something is amiss, but we do not know what. I suggest that perplexity might be indicative of a state in which there is something wrong with the brain, and the brain is able to sense this impairment, but due to its impairment (especially the fluctuating conscious level) the brain cannot work-out what it is that is wrong. In other words, this is probably a defect in the operation of working memory, which is necessary for the conscious mental manipulation of representations involved in ‘working out’ the meaning of events. The prediction is that acutely psychotic patients will be perplexed as their general affect - although this may not apply to chronically psychotic patients all of the time when brain damage may also have damaged emotional expression.  

Distractible attention is probably the first cognitive deficit to emerge with delirium. The patient cannot concentrate for very long on any single line of reasoning and is readily diverted from any particular line of thought or attempted task. Poor attention also affects the laying down of memory. I suggest that attention deficits might emerge as the key basic psychological variable (or sign, since it is more apparent to an observer than to the patient). Neurologically, poor attention is probably also a consequence of disrupted working memory, with interruption to the progression of associated representations.

Perhaps the action of working memory is repeatedly being disrupted by micro-sleeps, producing lapses of attention and loss of the sustaining of cognitive representations upon which WM depends. To speculate, sometimes the micro-sleeps could produce dreams (perhaps leading to hallucinations), sometimes they might lead to bizarre associations of ideas typical of ‘dream logic’ (perhaps leading to bizarre delusions), and sometimes they interrupt the train of thought (perhaps leading to thought-stopping or sudden changes of subject). Attention cannot be focused under these circumstances, but wanders according to strength and novelty of stimulus - leading to distractibility, and the associations of ideas which occur in states of clouded consciousness.              


Implications for nosology

A picture of emerging which interprets the classic ‘mad’ symptoms of the functional psychosis (schizophrenia, mania and psychotic depression) as being caused by delirium - clouding of consciousness. This stands in total contrast to the traditional view of ‘functional psychoses’ being defined as phenomena that occur in clear consciousness. The discrepancy is asserted to be due to an excessively insensitive definition of delirium and clouding.

But even after this has been taken into account it is important to note that although the functional psychoses are associated with delirium - it is delirium of a distinctive kind. After all, these are delirious people who have a remarkably high level of cognitive functioning. The leads us to ask about the pathological causes of delirium in those psychiatric diagnoses usually considered to be ‘functional’ rather than organic. The pathology must be reversible, because patients usually get better or at least improve substantially. The answer is presumably that acute psychotic states have the same kinds of pathology that can cause reversible delirium of other kinds. Exactly which kind remains to be established, and would probably require specific enquiry in each patient.

In this context it is especially interesting to consider sleep-deprivation.  Chronic severe sleep deprivation is a feature of many psychotic patients - and whether this a cause or an outcome of pathology (it could be different for different cases), chronic , severe sleep deprivation could certainly cause delirium. I will be exploring the possible role of sleep deprivation to psychopathology in depression, mania and schizophrenia in the chapters devoted to those putative diagnoses.


To reiterate, hallucinations, bizarre delusions, thought disorder and other ‘psychotic’ phenomena are a consequence of delirium - and delirium is a state of reversibly impaired brain function we have re-defined in a more sensitive, as well as scientifically objective, fashion.

Delirium is a therefore basic phenomenon of psychiatry which occurs in many circumstances, and leads to many of the most striking psychiatric symptoms. The pathologies of psychotic delirium is simply the normal causes of cerebral impairment, and delirium is found at a wide range of severities, and interacting with individual differences in disposition to produce different clinical phenomena.

Psychiatric nosology will need to find a much larger place for delirium,  a classification of the types of delirium, and scales for measuring the severity of delirium. A great deal of work needs to be done.


Chapter 7

The ‘anti-delirium’ theory of electro-convulsive therapy (ECT) action


Having clarified the nature of delirium allows us to approach some of the major phenomena of psychiatry with a fresh eye. It turns out that some of the long-standing enigmas of psychiatry are less enigmatic than usually supposed. This applies not only to the diagnostic categories, but also to the major treatments. And of all the enigmas of psychiatry the one that stands most in need of explanation and understanding is probably electro-convulsive therapy - ECT.



The mysterious nature of ECT

Electro-convulsive therapy (ECT) is one of the most rapidly acting and powerful treatments used in psychiatry - its effects on severe depression (melancholia) are extensively documented, but ECT is also an effective therapy in many cases of mania, acute schizophrenia, delirium and Parkinson’s disease. However, the lack of a convincing physiological rationale for its effectiveness has served to cast a cloud over the use of ECT in psychiatry, which is under endemic threat from those who perceive it to be intrinsically invasive and coercive.

ECT involves putting the patient to sleep with anaesthetic, giving a muscle relaxant, applying electrodes to the scalp and inducing a ‘grand mal’ epileptic fit by passing direct current electricity through the brain in the minimum dose necessary to induce the seizure.  The muscle relaxant prevents the patient damaging himself by violent movements during the fit. After the fit, the muscle relaxant quickly wears-off, then the anaesthetic wears off and the patient awakens.

It is generally agreed that the therapeutic effect of ECT comes from the grand mal convulsion (rather than from the anaesthetic, the passage of electricity through the skull and brain, or other aspects of the maneuver). Hence any means of inducing a generalized epileptic seizure (eg. inhalation of camphor or injection of leptazol) is considered to be equally effective. ECT just happens to be the safest and most reliable means to this end.

This suggests that ECT action involves large volumes of brain tissue, since it is highly implausible that a generalized fit would have a highly focused effect on a specific brain region. It also suggests that the therapeutic action of ECT is ‘simple’, in the sense of working by its effect on basic biological variables such as arousal rather than acting on specific regions or detailed aspects of brain function. Furthermore, any explanation of the effectiveness of ECT should account for the broad spectrum of diagnostic categories in which it is effective. As described above, the potential indications go beyond the most common usage of ECT in severe major depression with biological features. 

My suggestion is that the primary therapeutic physiological effect of ECT is in the treatment of delirium; probably by means of simulating or inducing physiologically ‘natural’ and restorative sleep. The beneficial effect of ECT might be achieved either by the epileptic seizure itself mimicking sleep, or the benefit might be caused by the ‘post ictal’ sleep which occurs after an epileptic seizure.

One line of evidence for this is that a course of ECT cumulatively leads to electroencephalogram (EEG) changes characterized by increased amplitude and reduced frequency (‘delta’ activity). These changes produce an EEG trace somewhat similar to that seen in normal sleep. According to some research a east, it is likely that the presence of such EEG changes in a patient are correlated with improved clinical response to ECT and reduced likelihood of relapse.


The effects of ECT - a sleep surrogate or sleep-inducer

If the account of delirium as any significant functional brain impairment is accepted, it can be seen that by the time psychiatric patients are considered for ECT they will typically have suffered several months of altered sleep habit, amounting to chronic severe sleep deprivation (often combined with a shift in diurnal rhythm seen in early-morning awakening). Significant impairments in brain function would be expected. It is possible that delirium secondary to sleep deprivation is the cause of the mental and physical slowing (’psychomotor retardation’) that is a frequent and importantly diagnostic feature of major depression.

Severe sleep disturbance is also a feature of mania, in which a period of several days totally without sleep often precedes an acute breakdown; and where inability or unwillingness to sleep is a major clinical symptom. In this respect depression may resemble the somnolent form of delirium (characterized by EEG slowing) and mania the agitated form of delirium (characterized by rapid EEG traces). This prediction is readily susceptible to empirical testing.

In mania and delirium even a single ECT treatment may serve to disperse an excited, insomniac, hyper-active state. When ECT is effective in depression, the patient often wakes from the first treatment feeling symptomatically improved and further improvement may follow sound sleep during the following nights.

I suggest that ECT is a specifically effective treatment for depression only in those depressed patients who are at an advanced stage of their illness, and in whom delirium (and the putative delirium-related symptoms such as psychomotor retardation, hallucinations and delusions) is a feature. Stressors such as insomnia and acute weight loss might further be expected to lead to changes in physiological and metabolic status which amount to a systemic illness with immune activation. As I have argued in the chapter on depression, the specific mood of depression may be a secondary consequence of a cytokine-mediated psychological and physical malaise including the typical pattern of ‘sickness behavior (including demotivation, inertia, anhedonia, exhaustion, anorexia and sleep disturbance) - sleep deprivation might be expected to synergize with any pre-existing systemic illness in the production of delirium.

ECT breaks this vicious circle by inducing a generalized epileptic seizure which acts upon the brain like a deep and restorative sleep - the distinctive features of which require further investigation. It is possible that the grand mal is itself functionally akin to deep sleep, or it may be that the post-ictal state following the fit acts as a surrogate for sleep. And 'sleep' - in the sense of a physiologically restorative process - must also be differentiated from 'unconsciousness'. It is clear from trials of 'sham' ECT that a general anaesthetic alone is not equivalent to ECT in its specifically therapeutic effect. This is also consistent with the lack of a subjectively restorative effect from general anaesthesia. Physiological sleep is clearly a  more complex phenomenon than mere unconsciousness, and an ECT surrogate would need to replicate the physiological state of natural deep sleep.




While ECT exerts its major effect upon sleep, there may be other effects of the treatment - indeed it is the usual situation for effective psychoactive interventions that they have several effects, some useful some unwanted. It may (for example) be that repeated ECT may have effects for example on entraining circadian rhythmicity (the sleep-wake cycle), or on raising the threshold to pain and other forms of aversive sensation - and these effects may result from quite different causes such as hormone release. But the effect on delirium seems to be the most striking and rapid action of ECT. 

The sleep theory of ECT action makes several radical predictions. Most strikingly, and in contrast to current conceptualizations, ECT is not seen as a specifically anti-depressant or mood-elevating intervention - despite being most commonly used as a treatment for severe depression. Indeed, as I argue in the chapter on depression, I do not regard any of the traditional antidepressants as being primarily active upon mood - mood is an end state or  consequence of emotions, and not a primary psychological variable. The prediction is therefore that ECT should not be specifically effective (ie. over and above placebo) when delirium is absent. This is consistent with ECT being be more effective in late and severe depression in in-patient populations than it is when used for early, mild or out-patient cases.

It seems probable that late depression has entered a self-perpetuating, positive feedback stage in which the original cause is no longer operating and the symptoms are mutually reinforcing and sustaining. Perhaps delirium maintains a pattern of insomnia and anorexia which, in turn, sustains delirium. The intervention of ECT breaks this positive feedback loop, clears delirium with deep sleep, resolves hallucinations and delusions, and allows a normalization of sleep and appetite which restores physiological normality. Eventually mood recovers and stabilizes. 

Secondly, properly-administered ECT, with a confirmed grand mal seizure, should be rapidly effective if it is going to be specifically effective. Cases which apparently improve only after many treatments over long periods of time would be expected to be responding to placebo effects, coincident therapeutic treatments (e.g. ongoing pharmacological or psychological therapies), or undergoing a natural remission. It would be predicted that if ECT responsivity was rigorously defined as only occurring in those patients with a rapid response (after one or two treatments), the presence of delirium (as defined by EEG) would be seen to be a major factor in defining the population liable to benefit from ECT.  

Thirdly, improvement in ‘delirious symptoms’ such as psychomotor retardation, hallucinations and bizarre delusions may be immediate; but full resolution of the affective component of the illness would typically take longer. This staged improvement may be missed by the employment of generalized depression scales that measure global improvement in the depressive syndrome (such as those by Hamilton or Beck). Instead clinicians should adopt a line of questioning directed at discovering the first signs of clinical improvement. (For instance, observers often notice objective improvements in activity, appetite or sleep several days before the patient reports an improvement in subjective mood.)

The delay in affective response to ECT may be explained on the general model that mood is a secondary consequence of cognitive functioning, and recovery of mood builds-up following an accumulation of positive cognitions. Sleep patterns and appetite are restored, and gradually the accumulated exhaustion of several months is repaired. Just as full recovery from influenza takes a few weeks, so the process of recovery from depression (which probably shares many common phenomenological, and probably pathological, features with influenza) would be expected to proceed over a similar timescale.

It seems that ECT is not primarily or specifically an antidepressant treatment. Instead ECT exerts its therapeutic effects on mood indirectly by simulating or inducing deep sleep to resolve delirium. Subjectively satisfying and objectively physiologically-normal sleep is not always easily attained by pharmacological means, and ‘hangover’ effects from sedatives may cause troublesome daytime somnolence which further disrupts circadian rhythms - yet the benefits of sleep may be rapid and profound. If a less invasive substitute for ECT were desired, the priority to would be to devise an equally powerful and rapid means of inducing physiologically restorative sleep.



Chapter 8

The malaise theory of depression


Depression - the need for a fundamental re-appraisal

Depression is probably the commonest of the formally diagnosed psychiatric illnesses - ‘the common cold of psychiatry’. Certainly depression is so frequent as to be a substantial element in the human condition - many people will be diagnosable as depressed at some point in their lives, and almost everybody will have a close relative or friend who suffers from depression.  And the diagnosis and treatment of depression is one of the great success stories of postwar psychiatry - with greatly improved detection of the disorder and a wide range of effective antidepressant interventions available that have enormously improved the outcome.

Nonetheless depression is not well understood. The word ‘depression’ is a problem. There is continued confusion in the mind of the general public about the relationship of ‘everyday’ sadness to the syndrome of ‘major depressive disorder’ (MDD). Within MDD is a huge range from patients who are able to hold down a job and function at a high level down to those who do not eat or drink, cannot speak or move and are candidates for emergency ECT. The syndromal diagnosis of MDD does not explain what depression is, it merely offers a thumbnail sketch of the kind of person that gets diagnosed as suffering from MDD - and as described, these vary extraordinary widely.

To exacerbate matters, there is a problem in explaining how antidepressant drugs work - in explaining why a chemical is apparently sometimes the best way of removing sadness and restoring ‘normal’ a mood state. No amount of proof of the effectiveness of antidepressants or ECT seems able to remove the suspicion of these treatments (especially among the more educated part of the population, who persistently favour psychological explanations and treatments of depression; even when these are wholly lacking any specific evidential base). The usual ‘scientific’ explanations about specific brain chemicals being abnormal in depression (eg. low levels of brain serotonin), and this being corrected by antidepressants (a few of which supposedly have specific influence on brain serotonin) is probably untrue, and certainly unproven.

The abnormal neurochemistry story is also more frightening  to lay people than most psychiatrists realize. Brain damage is one of the most dreaded conditions. To say that someone has an abnormal brain chemistry is to say they have brain damage - albeit mild and temporary - and this is probably even more stigmatizing and scary that the lay story of depression happening as a consequence of stresses and vulnerabilities. Ask yourself - would you employ, or leave your children with, or marry, someone who has ‘abnormal brain chemistry’? It sounds terrible - how could such people be responsible for their actions? Although the neurotransmitter story removes blame from patients it also removes rationality. And if depression is re-classified from a response to misfortune to a form of reversible brain damage. then anti-depressants are seen as mind manipulators.

Yet of course many depressed patients are able to perform work and parenting to a high level, and to sustain human relationships, and the demonstrated effects of antidepressants on brain neurotransmitters are weak or perhaps non-existent.

It is hardly surprising that despite a mass of would-be commonsense and demystifying propaganda, the public remains frightened and unconvinced by the prevailing explanation of depression - what is it, what is wrong, and how antidepressants work. It is time for a fundamental reappraisal of the nature of depression.


The nature of mood and emotions

Major depression is one of the ‘affective’ or ‘mood’ disorders, which are psychological illnesses that are seen as having mood changes as their core symptom. Yet despite this central role of mood in psychiatry, mood is itself poorly conceptualized. What is mood? Is it a cause or an effect of behavior, how is it represented in the brain, how does it interact with other forms of cognition - what kind of a thing is mood? Before trying to unravel the nature of depression and major depressive disorder it is important to attain some conceptual clarity about affect.

As a starting point, mood has something to do with emotions. But, according to my understanding of contemporary cognitive psychology, mood is not a primary variable of psychological life. Sadness is not like fear - sadness is an end-product - not a primary cause but a secondary consequence of other variables, particularly of emotions. Although moods are recognized by characteristic facial expressions, brain centres for emotions such as fear and disgust have been found, but not for happiness or sadness. Fear and disgust are emotions but happiness and sadness are moods.

I suggest that mood is used, and should be used, as nothing more than a summary term. To say a depressed person ‘is sad’ has no more depth or significance than to say that summer ‘is warmer’ than winter. Terms like happiness, sadness and perplexity implicitly take an average of a subjective state over a period of time. A person’s ‘mood’ might be conceptualized as shorthand for the modal or mean average of their emotional states with respect to the very general categories of gratification or aversion, pleasure or pain, attraction or repulsion, action or inaction, exploration or withdrawal.

There are two ways to have a ‘depressed' mood: to be sad all the time, or never to be happy. So a person with a depressed mood might be someone whose usual mood is misery, or alternatively someone whose range of emotions is shifted such that they very seldom feel gratified. Similarly, a winter day is usually colder than a summer day, and even on the hottest winter day it never gets as warm as the hottest summer day. Happiness is therefore just a word to summarize the many ways in which a person may experience gratification as their usual emotion, while sadness is a term for the state caused by aversive emotions. The ascription of mood does no more than indicate the characteristic emotion.

Someone's characteristic emotion will define a characteristic ‘cognitive style’, a way of interpreting and responding to stimuli. The happy man sees a different world from the world of the unhappy man. Each attends to different stimuli, perceptions are differently processed, and there are different responses to the same stimuli.   

Depression is not a valid aetiological category nor does it describe a unified cause; rather 'depression' describes an end-state, a characteristic emotional range. More exactly, depression is a state of the body (and mind) composed of other more primary emotions. There are as many causes of ‘depression’(in the sense of sadness or misery) as there are causes of aversive states; there are as many ways of being sad and miserable as there are differences in personality and experience. So there is no clear single category relating to the mood of depression, sadness or misery. One person's low mood may be entirely different in cause and quality from any other; one person may be fearful and anxious, another feel hopeless, a third subject to severe downward mood swings, a fourth may be 'unable to feel'. And all of these and other types of misery may represent different pathologies, rather than being 'subtypes' of depression. 

But among this potentially limitless diversity of negative human states, there does appear to be a specific syndrome which is approximated by the diagnostic category of Major Depressive Disorder (MDD). I suggest that MDD is a cross-culturally observed syndrome which forms a reasonable basis from which to look for an illness with a genuine psychological unity. I will argue that MDD is not an affective category, ie. not a ‘mood disorder’, but instead MDD is a behavioral outcome that approximates to a legitimate unified and underlying biological ‘core’ emotional state that will be termed malaise.


Deficiencies in current understanding

My stance will be that the diagnostic syndrome of major depressive disorder (MDD) is broadly along the right lines. However MDD should not be considered as an ‘affective disorder’ (an illness primarily of mood). Instead MMD should be reinterpreted as summarizing the behavioural outcome of a unified aversive malaise state called ‘sickness behavior’ that is caused mainly by immune chemicals such as cytokines.

One problem with conceptualizing MDD is an affective disorder is that there is no consistent affect. Many MDD patients deny that they feel sad or miserable, and the diagnostic schemas (such as DSM-IV and ICD-10) specify a variety of supposedly ‘characteristic’ mood states such as hopelessness, ‘anhedonia’ (reduced or absent capacity to experience pleasure), anxiety, distress and irritability. This variety of dissimilar moods seems excessively imprecise to be a primarily ‘affective’ diagnostic category.

It has proved difficult to conceptualize how ‘sadness’ could constitute an illness, and even harder to understand how ingesting a simple chemical could specifically alleviate sadness and restore normal ‘euthymic’ mood. Antidepressants are not euphoriants like amphetamine, not do they intoxicate like MDMA (‘ecstasy’), nor are antidepressants considered to be addictive or dependence-inducing - recreational abuse is very rare. So what antidepressants do not do is well established - yet their positive psychological action remains obscure. Also, antidepressants are commonly supposed to have a delay of two to six weeks before the onset of therapeutic action. If true, this would make antidepressants unique in the whole of pharmacology, since even the slowest of other agents (eg. hormones that affect DNA transcription, such as cortisol or thyroxine) have a measurable onset of action within just a few days.

The problem here is that since the psychological nature of depression is unclear, the way in which antidepressants act upon depression is also unclear.


Emotions and the somatic marker mechanism

When emotions reflect pathological states, they can have damaging effects on behavior - in this case emotions are maladaptive. For example, fear is adaptive when fight or flight is appropriate. But when a person’s physiological state of fear is excessive, or without adequate cause - when fear is pervasive and chronic rather than being related to specific dangerous situations, then the emotion is no longer a good guide to behavior. In such pathological states, a person may be described as locked-into the emotion. When locked into a pathological emotional state the emotion is not activated when needed and as appropriate, but instead distorts behavior in ways that may be unpleasant and/ or harmful.

When pathological, fear becomes associated with all perceptions instead of just those ones that are potentially dangerous. We do not just feel fear on perceiving a lion, but also on perceiving a mouse.  This inappropriate fear feeds into working memory and interacts with perceptions by the somatic marker mechanism. These perceptual-emotional representations are stored in long term memory.

The here-and-now primary emotions of which we are aware are fearful, and this means that incoming perceptions are interpreted as anxiety-provoking (ie. we feel fear and 'therefore' infer that the stimuli in our environment must be frightening us). But the effect of being locked into a state of fear also affects secondary emotions via the somatic marker mechanism. When we recall perceptual information from long term memory, the cognitive representation also causes us to ree-experience the emotional state that was laid down with it. So that when fear-marked cognitions are laid down as long term memories, they accumulate to become a disposition or characteristic way of appraising and reacting to the world. More and more things are fear provoking to us.

If a person in a state of anxiety sees a mouse then the somatic marker mechanism may record the anxiety along with the memory of the mouse. When the identity of the mouse is recalled from long term memory the these memories may be perceived as fear provoking.  We think of a mouse, and the fear which ‘marked’ this representation is re-enacted in our body.

So, memories that are laid down when a person is locked-into a pathological emotional state may become coloured by that emotion. If the emotion was fear, then anticipated situations evoke dread. In such a fashion long-term psychiatric illness cumulatively affects personality by impressing characteristic emotional states onto the content of long term memory.

But, whatever the original causes of fear in the past or present, anxiolytic drugs may be effective at alleviating the physical state of current anxiety, diminishing the manifestations of fear. For example, propranolol may act to diminish the peripheral manifestations of anxiety such as accelerated heart rate, diazepam may diminish muscular tension. This reduces the primary emotion of fear in the here and now, as it is interpreted by the brain on the basis of monitoring the state of the body. But the secondary emotion of fear is also affected. So we think of the mouse, and recall to awareness in working memory the long term memory that contains both perception and emotion; but we do not feel anxious because the anxiolytic drug blocks the bodily response to this memory. The anxiolytic prevents the body from enacting the emotion of fear - the heart rate does not increase, we do not break into a sweat, the muscles do not become tense. 

In other words anxiolytics treat the proximate mechanisms of fear, the mechanism by which fear is physically manifested. And I will argue that the situation for fear and antidepressants finds a close parallel in the situation relating to major depressive disorder and antidepressants. Antidepressants block the proximate mechanisms that cause the characteristic emotion of depression.



Major Depressive Disorder is sickness behavior

The emotional state of ‘depression’ can be approached in a manner closely analogous to that emotional state of fear, which is so well characterized. In other words by seeking the adaptive function of the pattern of behavior termed ‘major depressive disorder’, elucidating the factors which mediate these behaviors, and analyzing the ways in which pharmacological and other interventions might have beneficial effects upon different components of the system. Just as the evolutionary function of human fear can be seen by a comparison with the behavioral pattern with that of other animals, so the behavioral pattern of major depressive disorder.

Remarkably, it turns out that the syndrome of MDD is virtually identical with a syndrome seen in animals. The animal equivalent of MDD is the adaptive state termed sickness behavior (SB). Sickness behavior is the characteristic behavior pattern of a sick animal, and was first described by a veterinarian as a physiological and psychological adaptation to acute infective and inflammatory illness in many mammalian species. Major depressive disorder is sickness behavior - inappropriately-activated or excessively sustained.

The characteristic pattern of sickness behavior comprises pyrexia, fatigue, somnolence, psychomotor retardation, impaired cognitive functioning and demotivation with respect to normal drives such as appetite for food and sex (this probably corresponds to anhedonia in humans, which is the inability to experience pleasure). In other words, the syndrome of SB is almost exactly the same as the standard diagnostic descriptions of MDD. The only apparent differences - somnolence and pyrexia - are explicable given that daytime somnolence typically leads to secondary insomnia and nocturnal sleep disruption, and that the presence of pyrexia has not been evaluated in MDD (it may be that patients with MDD do have a raised temperature in the early stages of the illness, but that this state has resolved by the time they are seen by psychiatrists or get admitted to hospital).

The evolved function of SB is to act as an energy-conserving, risk-minimizing, immune-enhancing state appropriate for a body mounting a short-term, all-out attack on an invading micro-organism. Major depressive disorder is therefore the behavioral response to a physical illness - it is a syndrome in which low mood is the product of malaise; where malaise describes the symptom of ‘feeling ill’. By this account, the feeling of malaise should be regarded as the core emotion of depression.

Malaise is an emotion because it is based upon a characteristic physiological disposition as represented in the brain. In other words, the brain receives feedback on certain aspects of the body state - especially the presence of increased concentrations of circulating cytokines and similar immune products - interprets these as evidence of sickness requiring adaptive behavioral changes to conserve energy, minimize risk and fight the disease.

Therefore major depressive disorder is not primarily an affective disorder, the syndrome is not driven by a change in mood. Instead the primary pathology in major depressive disorder is somatic (ie. of the body), and mood is a secondary and variable response to this disordered physical state. And the major psychological change involves an emotion  (ie. malaise) rather than a mood (such as sadness).


Cytokines as mediating factors of sickness behavior

The emotion of fear is mediated by the sympathetic nervous system. The analogous mediating factor for depression seems to be hyper-activity of the immune system in response to ‘non-self’ antigenic challenge (for example, inflammation due to infection, carcinoma or ‘autoimmune’ disease). The chemical factors responsible for mediating sickness behavior appear to be the class of immune active agents known as cytokines (eg. interleukins and interferons). Indeed, SB is best considered as an integral and adaptive part of the pyrexial response, SB is the behavioral change that assists in the generation and maintenance of raised body temperature, and is appropriate to general immune activation.

There is abundant evidence to support the contention that malaise is mediated by cytokines. For instance, administration of cytokines to mammals provides a model for depression: an intravenous infusion of interferon into humans rapidly produces a syndrome that is psychologically and physically identical with MDD. And the high incidence of depression and other aversive psychiatric side effects are well-recognized as perhaps the most significant clinical limitation unwanted on the therapeutic use of cytokines (such as interferon and the interleukins) for the treatment of cancer and viral infections.

One important aspect of cytokines is that they produce hyper-algesia or increased sensitivity to pain. This provides a plausible mechanism for producing the physical symptoms of depression, and possibly contribute to the related illnesses of chronic fatigue syndrome. Ordinary bodily sensations, which would usually be ignored, rise above the threshold of awareness when cytokines are circulating. These aversive sensations - which really have no pathological significance, are then perceived as pains, aches, heaviness and fatigue. Like all aversive signals, these are hard to ignore since the body interprets them as a warning of pathology, usually altering the motivational state in the direction or rest and immobilization.  

The clinical evidence for cytokines being the cause of MDD is also powerful, since there is a substantial literature documenting significant immune activation in depression, with a wide range of abnormalities in cytokines and other acute phase proteins, correlating with the natural history of the illness and response to therapy. It would be predicted that cytokine abnormalities would be even clearer and more specific if studies were restricted to only those ‘depressed’ patients who exhibited the syndrome of sickness behavior with prominent symptoms of malaise.

As something of a sideline, there may also be an interesting relationship between cytokines and the ‘stress hormone’ system. The major stress hormone is cortisol, secreted from the adrenal gland. Some of the cytokines have a direct action in stimulating the secretion of ACTH which in turn stimulates cortisol. Cortisol is a powerful anti-immune and anti-inflammatory agent (cortisol or its analogues are often used for this purpose as a drug). What seems to be happening is that cortisol provides a negative feedback effect on cytokines, to suppress their secretion and suppress their immune effects.

Many depressed patients have a raised blood level of cortisol, and it is plausible that the raised cortisol is actually doing these patients some good - at least in the sense of diminishing some of the effects of raised cytokines. For example, cortisol has actions as a pain killer or analgesic, and this would be expected to combat (to some extent) the hyper-algesic effects of cytokines. Terminally ill patients with widespread malignancy are often given steroids to improve their mood and sense of well-being. Furthermore, many patients with symptoms of chronic fatigue appear to have raised blood cytokines but without raised blood cortisol. Raised cytokines but no cortisol analgesia is a plausible rationale for why chronic fatigue patients may suffer extreme symptoms of fatigue - they are suffering from the 'unopposed' action of cytokines. This suggestion is consistent with reports that chronic fatigue responds to low (ie. physiological, rather than pharmacological) doses of cortisol analogues.   

The bizarre conclusion seems to be that patients with chronic fatigue syndrome characterized by raised cytokines may be a subtype of ‘cortisol deficient’ major depressive disorder - and the addition of small doses of cortisol may make them just plain depressed (but without the overwhelming fatigue). This predication is so odd, that it just might be true - time will tell.

Having suggested the primary somatic (physical) pathology of MDD, the ‘characteristic’ psychological changes of this syndrome now require to be explained. What causes the depressed mood?


Mood changes are secondary to sickness behavior

Although animals demonstrate sickness behavior mediated by cytokines in the same way as humans, only conscious animals such as humans can suffer from the distinctive ‘existential’ state of depression, with feelings such as nihilism, worthlessness, guilt and suicidal ruminations. The locked-in state of malaise which prevails in sickness behavior interacts with memories of the past and anticipations of the future such that a demotivated, exhausted and profoundly dysphoric state of malaise fills and colors past, present, and the anticipations of future mental life.

Imagine a depressed person sitting on the edge of their bed, trying to get going. They think of breakfast, but have no appetite. Should they go for a walk? They feel exhausted. They are troubled by aches, pains, heaviness that force themselves on awareness - might this be evidence of disease, maybe cancer? How about visiting a friend - on recollecting the last conversation there is no sense of pleasure, what might they talk about today? Guilt - because I should be eating, I should be exercising, I should go and see my friend, but… Whatever can be imagined fails to produce a stirring of pleasant anticipation - the dull state of malaise continues.

Something like this is the state of a person with MDD, and describing it precisely in terms of mood is difficult (especially when you are demotivated and cannot see the point in making the effort). It may be describable as sad and miserable in one sense, but also dull, unresponsive, nothing. Nothing, because nothing seems to make a difference - action is tiring and unrewarding, inaction merely allows more time for brooding and feeling the unpleasant state of one’s own body. 

Prolonged sickness behavior therefore creates a nihilistic mental state where life seems devoid of gratifying possibilities (ie. pessimism) because feedback registers a physiological state that is locked-into SB and unresponsive to the usual appetites (ie. anhedonia). The sufferer cannot ‘pull themselves together’ or ‘snap out of it’ any more than a person with influenza can think themselves better, or be made better by psychotherapy - talking to a sick person may help make them feel better, it may improve their overall condition: but they will still be sick.

Another other factor is that, unlike the flu sufferer, the sufferer from SB does not know that they are sick, and often interprets their lack of energy, lack of motivation, and poor concentration as a moral failure - leading to feeling of guilt and unworthiness. And of course, although overwhelmingly real (no- I do not feel well - I feel sick), the physical state is vague, hard to formulate, hard to localize and pin down. This may even be exacerbated by the fact that psychiatrists are not interested in their physical symptoms, never ask about them, always explain them away as being secondary to mood. Given the nature of this subjective mental landscape, the high rate of suicide in MDD is unsurprising.

To put malaise at the core of the depressive syndrome may seem a radical inversion of the usually accepted causal interpretation, since symptoms of malaise have traditionally been interpreted as secondary to the mood change in MDD. Traditionally (eg. in DSM-IV) it is supposed that depressed people complain of tiredness and aching limbs because they are miserable - whereas the malaise theory suggest that they are miserable because they are tired and have aching limbs, until eventually chronic misery is learned and becomes habitual so that it may persist even after resolution of SB.

But to emphasize the physical symptomatology of the depressive is more of a re-emphasis than a novel discovery. Kurt Schneider considered the physical or ‘vital’ symptoms of depression to be of paramount diagnostic importance and the nearest approach to a ‘first rank symptom’ of affective disorders. Most comprehensive textbooks of psychiatry or psychopathology describe a range of typical ‘depressive’ physical symptoms such as exhaustion, washed-out feelings, aching, heaviness, or pain. The malaise theory of depression suggests that Schnieder’s tentative hints were correct, and that a more coherent and biologically valid concept of depression can be created with these physical symptoms as the unifying primary psychopathology, and affective changes as a secondary, contingent and variable consequence. 


Implications of the malaise theory of depression

If sickness behavior is equivalent to major depressive disorder, this implies that instead of ‘sad’ mood being regarded as the primary symptom of MDD, the state of malaise should be seen as the core symptom of MDD.

The depressed person is physically sick but does not know it. Because he does not know it, the depressed person blames himself for his symptoms - ‘Why am I so exhausted and do nothing? - Because I am useless, have no moral fibre, I am a failure as a husband, a bad father.’

This interpretation immediately suggests that knowledge of causes might have some therapeutic benefits to the depressed patient. To know that one is physically ill as a cause of malaise does not cure the problem, any more than knowing that one had influenza removes the physical suffering. But even if such knowledge does not make you feel less ill, it may make the state of malaise less depressing

As suggested above, past research into depression would need to be reinterpreted in the context of this new and more restrictive definition of major depressive disorder. According to the concept of MDD as SB, most previous studies of ‘depression’ can be seen to have contained heterogeneous diagnostic groups - comprising a mixture of some subjects with malaise and the other typical features of SB, and other subjects with few or no such features.

Since the malaise theory of depression has so many implications, it is readily testable. One startling implication is that the brain need not have any pathological involvement in the core syndrome of major depressive disorder (this may explain why robust evidence of a specifically depression-related cerebral pathology has proved elusive). It requires a profound conceptual shift to recognize that the syndrome of MDD may be the response of a ‘healthy brain’ to a ‘sick body’ - especially in the light of the hundreds of millions of pounds spent searching for a pathognomonic brain lesion in depression. While, of course, the brain may also be involved in any generalized inflammatory, immune or neoplastic pathology which is also associated with sickness behavior, and any change in motivational behaviour must be associated with changes in the brain; in the minimal or ‘core’ state of MDD the brain merely monitors, interprets and responds behaviorally to a pathological change in the body.

The cognitive impairment seen in ‘non-psychotic’ MDD (ie. symptoms such as poor concentration, reduced performance on short term memory tasks etc) is not qualitatively distinct from the psychological symptoms which commonly occur as a part of acute physical illnesses such as colds and flu, and colds and flu are not usually described as being associated with neurotransmitter abnormalities.

However, in the most severe and sustained cases of ‘psychotic’ MDD the brain as well as the body is involved. In such cases of brain involvement qualitative cognitive impairment is found (eg. psychomotor retardation, poor concentration and memory, hallucinations and delusions). These symptoms can be interpreted as instances of delirium (ie. functional, reversible brain impairment). This cerebral pathology might occur either as a secondary consequence of generalized immune activation from a generalized pathology, or as a consequence of SB-specific factors such as chronic, severe sleep deprivation and perhaps starvation and dehydration. It would be predicted that MDD patients with psychotic symptoms would show abnormalities on EEG - especially slowing relative to the EEG in the non-psychotic state. Psychotic MDD patients are most effectively treated by electro-convulsive therapy (ECT) and this is understandable on the basis that ECT may function as a sleep-surrogate and anti-delirium intervention rather than acting primarily as an ‘antidepressant’.


Autoimmune disease suggested as a cause of depression?

The malaise theory leads to a variety of immunological predictions. One helpful aspect is that the malaise theory points towards a useful animal model of depression - namely animals treated with cytokines to produce sickness behaviour. This could be very useful, since the lack of animal models of psychiatric disease has been a very important barrier to the development of new drugs.

There is also need for more precise understanding of the complex cytokine changes associated with sickness behavior in humans. In particular we need to search for any causal relationships between specific patterns of immune abnormality and specific psychological symptoms. For instance, specific cytokine abnormalities may cause specific psychological symptoms.

There is also the possibility of monitoring the depressive illness biochemically. Longitudinal changes in cytokines (or their surrogate indices - such as C-reactive protein) would be expected to mirror the progress and activity of major depressive disorder. Hence cytokine monitoring may provide a marker of treatment response, or a marker for remissions and relapses. At a more mundane and easy to test level - depressed patients would be expected to be pyrexial; at least in the early stages of the illness that leads to sickness behavior.

But perhaps the most important contribution that immunologists could make would be to elucidate the nature of the ‘hyper-immune states’ that are associated with MDD. What are the primary causes of MDD? It is probable that there are as many causes of MDD as there are causes of sickness behaviour - but it may also be that ‘classic’ MDD as seen by psychiatrists will correspond to a more specific pathological state.

The natural history of classic, psychiatrist-observed MDD is of a reversible illness with a natural history of several months eventually leading to a spontaneous remission and typically full recovery. Some people are more prone to this illness than others. Those patients with a family history of MDD, or a past history of MDD have an increased probability of relapse. This pattern of natural history and epidemiology is reminiscent of some of the ‘autoimmune’ diseases akin to rheumatoid arthritis.

It would therefore seem worthwhile testing the idea that ‘classic’ cases of MDD are caused by some kind of ‘autoimmune’ disease - a relapsing and remitting inflammatory disease which produces increased secretion of cytokines. Certainly the typical natural history is similar to that seen in a number of the autoimmune diseases such as rheumatoid arthritis - a typical timescale of weeks or months to an episode, spontaneous recovery between episodes and so on.

An autoimmune cause for MDD might explain the inherited genetic predisposition and the MDD trait such that one episode predicts an increased likelihood of others. Individual inflammatory episodes might then be triggered by a variety of environmental, pathological, behavioral or developmental precipitants, as with rheumatoid arthritis. All this is highly speculative, but some cases of major depressive disorder might end up being classified with the ‘connective tissue diseases’. 



It is important to emphasize that although sickness behavior is an evolved, adaptive response to infection, MDD is a maladaptive manifestation of sickness behavior. The analogy is with generalized anxiety - although fear is an adaptive behavioral pattern, when fear is continuously activated it becomes pathological.

Similarly when sickness behavior occurs as a short-term response to acute infection it is (on average) adaptive and may be life saving. But when SB is activated continuously and outside of the circumstance for which it evolved, SB is of course dysfunctional. In an acute infectious illness, the state of demotivation is valuable in conserving energy for an all-out fight against infection. But when sickness behavior is sustained or inappropriately evoked this long-term state of demotivation will be profoundly damaging - after all, animals must eventually eat and reproduce.

Hence MDD - although it is an evolved behavioral pattern - is indeed maladaptive and dysfunctional - in a nutshell pathological. Major depressive disorder should continue to be considered an illness: and undoubtedly one of the worst. Knowing that MDD is primarily a physical illness may in its own right be therapeutically beneficial. But the main role of the malaise theory is to improve treatment - and that is the next topic for consideration.


Chapter 9

Antidepressant drug action


If Major Depressive Disorder is Sickness Behavior, and depressed mood is best conceptualized as malaise due to physical illness, then what is the action of antidepressants and how do they improve depressed mood? In the first place, we must distinguish between specifically antidepressant drugs which act on malaise, and drugs that might in some other way be helpful in a depressive illness.

I suggest that since malaise is seen as the core symptom of depression, then a specifically antidepressant drug should have as its primary action the alleviation of malaise and the other ‘vital’ physical symptoms of MDD such as fatigue, heaviness, aches and pains. Of course psychiatric drugs are relatively non-specific, as are current diagnoses, and other drugs than specific antidepressants may be valuable in the treatment of other aspects of the MDD syndrome. For example benzodiazepines may alleviating symptoms such as insomnia or anxiety, and neuroleptic drugs may help with hallucinations and delusions in association with depression. But the core activity of antidepressants should refer to the core symptoms of depression - the primary, syndrome-creating physical symptoms associated with malaise.

When cytokine-induced fatigue, demotivation, aches and pains occur during acute infectious diseases such as influenza, these symptoms are usually treated by analgesia. For example, people usually take aspirin or paracetamol when they have flu - partly to bring the temperature down, and partly to relieve aching and washed-out feelings. I suggest that in this sense true antidepressants are analgesics - on the basis that any drug which alleviates subjectively dysphoric states can be considered an analgesic.

My assertion is that antidepressants are drugs whose specifically anti-depressant action is the treatment of an aversive physical state to make patients feel better - very much as aspirin can make patients with flu feel better. In other words, antidepressants are anti-malaise analgesics. When patients feel less ‘sick’, their mood will - usually - start to improve just as people usually start to feel more cheerful after they have recovered from flu. So, antidepressants do not ‘make people happy’ but (when effective) they remove a significant obstacle to happiness. It is easier to be happy without malaise although happiness is certainly not guaranteed.

Conceived in this fashion, the anti-malaise analgesic effect of antidepressants on mood is no more remarkable than the fact that it is easier to be happy without a chronic headache than with one. This is the simple answer to the puzzling fact that that a chemical such as an antidepressant can apparently treat so complex a thing as human misery. The true antidepressant is not a mind-manipulating drug, nor a happy pill. Antidepressants could be considered a kind of ‘mood aspirin’. When effective an antidepressant can alleviate aversive symptoms of pain and sickness, and give people a better chance of enjoying life.


Antidepressants as analgesics

There is conclusive evidence to support the idea that tricyclic antidepressants are analgesics when tested in both human and animal models. Tricyclics are increasingly used in the management of chronic pain, neurogenic pain, migraine, chronic fatigue, cancer pain, AIDS and arthritis. I suggest that analgesia is not just a lucky side-effect of tricyclics, but analgesia is the primary action of any specifically ‘antidepressant’ drug.

The analgesic effects of non-tricyclic classes of antidepressant are less clear. There is some evidence that fluoxetine (Prozac), for one example, is also analgesic in AIDS and some other conditions - however it is not certain which symptoms the drug is acting upon, and whether it is malaise that is being improved, or some other aspect of the MDD syndrome such as anxiety or insomnia that might be contributing towards a depressed mood. David Healy has argued that SSRIs may be primarily anxiolytic agents and some patients diagnosed as suffering MDD may have significant symptoms of anxiety. It is noteworthy that trials have also shown that benzodiazepines and neuroleptics are more effective than placebo when used as antidepressants - so the ability of a drug to produce significant clinical improvement in depressed patients is not very specific. 

Phenelzine, the commonest monoamine oxidase inhibitor, is probably an analgesic rather like the tricyclics - and it also has psychostimulant properties rather like amphetamine. Amphetamine itself is a very powerful analgesic. Amphetamine or some of the other psychostimulants may have a role as an antidepressant in carefully selected cases who would be at low risk of addiction and who were not troubled by the side effects.


Speed of response to antidepressants

It is traditionally said that antidepressants take from two to six weeks to have a therapeutic effect - when ‘effect’ is measured by global, averaged and mood-based scales such as the Hamilton Rating Scale. According to the above model, the apparently delayed effect of tricyclic antidepressants on mood arises because the response of mood to analgesia is less specific, slower and more unpredictable than the primary analgesic action on malaise symptoms. In physical medicine it may take some days or weeks for a patient's mood to improve after relief of long term pain or discomfort, since chronic misery may establish habits of gloomy rumination and an accumulation of sad memories. 

The analgesic activity of tricyclics - as for other analgesics - has a rapid onset within hours of reaching an effective dose. It is probable that the first observable effects of tricyclics (ie. an improvement of physical symptoms) would be found within hours of reaching an effective dose. It is also possible that the drugs are effective in smaller doses than usually given in psychiatric practice. General practitioners treating mild depression often obtain excellent results with smaller doses than are considered to be effective in the more severe cases seen in psychiatric practice. Probably, this is a dose effect, with severe malaise needing a higher dose to control it.

However, due to the long half-life of many tricyclics, and the problem of getting used to side-effects it is often the case that doses of tricyclics must be escalated slowly. This means that an effective therapeutic blood levels of drug may not be reached for several days or even several weeks. But this is not a slow onset of drug action, it is merely a delay in reaching therapeutic blood levels.

Following prolonged malaise, the accumulation of dysphoric memories might alter a person's habitual cognitive style - ie. their mood. This means that even when they have obtained relief from the current state of malaise, mood will not immediately improve, ,and it may not improve at all. This is quite frequently observed: a patient who ‘objectively’ has greatly improved in their level of activity, appetite, sleep etc - as a result of antidepressant treatment; but who still feels sad. The antidepressants have ‘worked’ in the sense that they alleviated the symptoms which they are effective at treating - but the patients mood has not have improved.

This happens because sadness has many causes as well as malaise - misery can be caused by anxiety, by emotional blunting, by motor side effects such as akathisia, indeed by any sustained aversive state.  And even when effective, antidepressants cannot transform a whole life and personality - they can at best only alleviate certain symptoms. By concentrating on measuring mood as an index of drug effectiveness, researchers on the mode of action of antidepressants have been studying the wrong outcome variable. This is almost as misguided as it would be to measure the effectiveness of aspirin by asking someone how happy they are, rather than asking them whether their headache had improved.

There is an urgent need for new and valid measurement scales to measure the severity of sickness behavior in order to evaluate the effectiveness of antidepressants. A specifically active antidepressant should have a significant effect on the core symptoms of malaise within hours of reaching an effective dose. Mood is a separate matter, and mood may take several weeks to lift, or may not lift at all if chronic low mood has lastingly affected the personality or if someone’s life circumstances are so miserable that they make sadness an inevitable response. 

This prediction that effective antidepressant activity depends upon an analgesic action which has rapid onset has important therapeutic implications. Current practice looks for lifting of mood as evidence of effectiveness and (correctly) assumes that it usually takes four to six weeks for mood to respond to antidepressants. This has been interpreted to mean that the doctor should wait for a couple of months before trying another drug.

But this is probably a wrong approach. Antidepressants work on malaise, not mood. So clinical attention should focus on malaise symptoms, not mood, and a very rapid improvement in symptoms of malaise would be expected as soon as an active drug level is attained. And if there is no improvement in malaise symptoms then another drug should be tried without delay.

If therapeutic trials could be shortened to a week at a therapeutic dose, or even shorter, it would mean that the ‘trial and error’ process of discovering an effective antidepressant would be much more rapid. Assuming that this strategy enabled a much more rapid identification of an effective therapeutic agent for each specific patient, then it might represent a major breakthrough in the treatment of depression.

The enormous length of time taken in current practice to conclude that a drug has not worked means that many patients will get better spontaneously during this period. This is especially the case considering that patients will usually be depressed for several weeks or months before ever seeing a psychiatrist, and most episodes of depression resolve without treatment after roughly six months. Many of the apparently ‘late responses’ to antidepressant treatment may therefore be natural remissions, unrelated to the drug - or due no non-specific factors such as the drug improving sleep and appetite.

Clearly these ideas need formal testing before being adopted, but unless antidepressants are different from any other kind of drug that I know of, they must act more rapidly than six weeks, even if their full effects take a longer time to become evident. The task is to devise a rating scale that detects the first signs of therapeutic response, rather than relying on ‘global’ scales (such as the Hamilton scale) which do not focus on core symptoms but tot-up all the aspects of depression into a single measure.

Clinicians need to recognize that mood is only indirectly related to drug effects. Enquiring about a patient's state of happiness is not a satisfactory way of establishing whether or not an antidepressant drug has worked - we need to know about the specific drug effect on symptoms of malaise.


Future research into depression and antidepressants

A consequence of the malaise theory is that prescribing of treatments for patients with MDD might be done on a more rational basis. Since MDD is a syndrome and not a disease state, and antidepressants are symptomatic treatments rather than disease-modifying agents, it makes sense to treat ‘depression’ in an explicitly symptomatic fashion.

At present it is usual to prescribe ‘an antidepressant’ for the diagnosis of ‘major depressive disorder’ in a black-box and categorical fashion. The drug is matched to the diagnosis and choice of drug depends on secondary factors such as side effects or cost. Instead, specific symptoms could be targeted by specific drugs which influence these particular symptoms. For instance, malaise might be treated with analgesics - trying out several until something effective was found to relieve the aversive feelings.

Patients with malaise and weight loss might be tried with tricyclics - and the choice between tricyclics made on the ground of whether sedation was wanted or not. Malaise with over-eating and weight gain might be treated with phenelzine, or possibly a psychostimulant such as amphetamine, pemoline or methylphenidate (Ritalin). Patients who are miserable without malaise, and whose dominating complaint is of anxiety might be treated with anxiolytic agents such as SSRIs and again the choice between them could be made on the grounds of whether stimulation or sedation was required.

Or anxious patients might benefit from benzodiazepines, if their potential for addiction was low. Sleeplessness could be treated with hypnotics - and more work needs to be done on the quality of sleep that hypnotics provide (it has been suggested that the ‘atypical’ neuroleptics such as risperidone and olanzepine may provide a better quality of sleep that the traditional sleeping tablets such as lorazepam). Psychotic symptoms such as bizarre delusions and hallucinations could be treated with anti-delirium treatments such as ECT or hypnotics. Agitated behavior driven by extreme emotions could be treated with neuroleptics. Of course, caution would need to be exercised over drug interactions, but this way of tailoring treatments to a specific patients symptoms has greater therapeutic potential than the simplistic idea of categorical prescribing for categorical diagnosis. Instead the aim is not to treat the syndrome of depression, rather to try and break down the syndrome into symptoms; and tailor the treatment to the symptom profile of each individual patient.

As a long term goal, it might be a reasonable strategy in treating the syndrome of Major Depressive Disorder to seek disease-modifying agents - which operate to normalize either the primary cause of sickness behavior, or the cytokines which mediate the sickness behavior. In this context it might be fruitful to explore the use of anti-inflammatory drugs in MDD - such as very low dose glucocorticoids which have recently been found effective in rheumatoid arthritis and chronic fatigue.


Analgesics as antidepressants

Since tricyclic antidepressants are analgesic, and that this is assumed to explain their therapeutic action, it would be predicted that traditional analgesics should also be effective as antidepressants. It is an intriguing possibility that ‘traditional’ analgesics such as paracetamol, aspirin or the NSAIDs might also be effective against the symptom of malaise which is at the core of depression. Indeed, it is an open question whether or not much of the self-medication with simple analgesics that goes on may actually be done for the purposes of mood-manipulation rather than pain relief. Certainly the belief that aspirin ‘picks you up when you are down’ is common enough.

My suggestion is that antidepressants should be targeted specifically at malaise symptoms. The prospects for drug development are intriguing. Tricyclics are not remarkable for their effectiveness as antidepressants (at least as presently prescribed). They also have unpleasant and sometimes dangerous side effects. There is certainly great scope for improvement in antidepressants.

It is quite possible that more specific and more effective and less toxic antidepressants could be engineered or discovered when the process was informed by increased precision in defining the nature of the target symptom of malaise, and when there was an improved understanding of the desired pharmacological effect in alleviating malaise.

Centrally acting analgesics of the opiate class should probably have a role in the management of Major Depressive Disorder when malaise symptoms are dominant. Before the advent of ECT and the discovery of tricyclics, opium was considered by many authorities to be the best and most specific treatment for ‘melancholia’. And in the nineteen seventies when the endogenous opiates (enkephalins and endorphins) were discovered there was a resurgence of interest in this question. Several studies were published which suggested a useful therapeutic role for opiates in depression. However, results were somewhat confusing, and the field seems to have been abandoned without the questions ever being properly resolved.

It seems highly likely that opiates would be effective anti-malaise analgesics, hence effective antidepressants. Certainly opiates such as codeine are commonly used and effective at improving symptoms in colds and flu, which implies that the same would probably be true to MDD. At least opiates would be worth trying in malaise-dominated depressed patients who are unresponsive to, or unable to tolerate, more conventional antidepressants.

Formal studies would be needed to determine the potential usefulness of opiates in the treatment of subgroups of MDD patients. Interestingly, there are no reports of addiction when opiates are used in depression, but even if there were a small risk this may be justifiable on the grounds of relieving suffering and improving social functioning. However, it is generally believed that when used appropriately as analgesics, opiate dependence is very unlikely to become a problem.

Conversely, if antidepressants are analgesic for malaise, perhaps the usage of tricyclics could be expanded more widely into other physical illnesses typified by malaise. For instance tricyclics might be effective agents for the symptomatic treatment of acute infections, inflammatory, neoplastic or other types of immune activation. Perhaps tricyclics may even have a role in the management of colds and flu?


Action of SSRIs - emotion buffering?

The class of drugs known as SSRIs - or selective serotonin reuptake inhibitors, such as fluoxetine (Prozac) and paroxetine (Seroxat) - constitute the major class of ‘antidepressants’ other than the tricyclics. Yet these are probably not analgesic - or at least their effect as analgesics appears to be much weaker than the tricyclics. However, they are very effective psychotropic drugs, in the sense that they have transformed the lives of many patients for the better.

David Healy has suggested that SSRIs function mainly as anxiolytics. This certainly fits the fact that in clinical practice SSRIs have largely replaced the benzodiazepines in the treatment of anxiety symptoms and anxiety-dominated syndromes. But their psychological action seems very different from the benzodiazepines. The most striking therapeutic effect of SSRIs could be described as emotion-buffering.

Emotion-buffering (when it happens, and it does not happen in all patients) is usually experienced as a pleasant feeling of a ‘safety net’ under one’s emotions, preventing large and unpleasant downswings. Bad things happen, and people still feel bad about them - but not as bad as they do when not taking SSRIs. Moment to moment emotions probably do not change at all - most of the time people feel the same taking SSRIs as they do when they are not taking the drug. But although everyday emotions may be unaffected the drug gives people a feeling of confidence that they will not be overwhelmed by negative feelings.

The flip side is that emotion-buffering seems to work on upswings as well - people often report that they are not so able to feel ‘high’ or ecstatic in the way they used to. Some people find this unpleasant and cannot tolerate the drug, others do not seem to mind, or think that the effect is more than compensated by the prevention of down swings. A lot depends on personal constitution.

If it is agreed that emotion-buffering is the primary useful action of SSRIs then it may be worth speculating how this might work. Since moods are averaged emotional states, and emotions are the brain’s registration of body states, my suggestion is that SSRIs work on the body. Rapid changes in body states are mainly controlled by the autonomic (sympathetic and parasympathetic) nervous system - this controls the blood vessels and internal organs. Perhaps SSRIs act by stabilizing the autonomic nervous system in order to damp down the powerful and sometimes ‘overwhelming’ activation of the nervous system.

For instance, if you get involved in an unpleasant row, this activates the sympathetic nervous system and may provoke a rapid and massive release of adrenaline and noradrenaline; if something happens that disgusts you it may provoke a similar surge in acetylcholine that stimulates the gut. My suggestion is that SSRIs act upon the autonomic system to damp down these large scale activations of the autonomic nervous system - to avoid extremes of emotion but without affecting everyday fluctuations. SSRIs are not so much anti-malaise analgesics as anti-extreme-emotion agents.



Summary - The nature of depression

It has been argued that major depressive disorder is inappropriate sickness behavior, that the syndrome of MDD is generated by abnormalities in cytokines, and that antidepressants exert their specifically beneficial effects through analgesic action on the core dysphoric emotion of malaise.

The malaise theory does not, of course, simply replace the current ideas about the nature of depression and mode of action of antidepressants. There is a considerable measure of re-definition as well as re-description. Not everybody diagnosed as suffering from MDD would have sickness behavior or be characterized by malaise and not everyone with malaise would be diagnosable as having MDD. In particular, I would expect that many patients with milder forms of MDD are mainly suffering from anxiety and mood swings, which is why SSRIs are so often useful. Not all current ‘antidepressants’ will be analgesics, and not all analgesics will be anti-malaise antidepressants.

So, what I am doing is carving out a new and coherent diagnostic syndrome from the heterogeneous mass that is 'depression', and suggesting the target symptoms against which drug effectiveness can be evaluated.

It will also be noticed that I have not compared the malaise theory with existing theories about depression and antidepressant action. This is mainly because the malaise theory operates at a quite different level of explanation from the dominant group of theories which are more-or-less based on the ‘catecholamine hypothesis’. The malaise theory describes psychological abnormalities associated with a pathological somatic immune state, and the effects of drugs in terms of their action on symptoms. By contrast, the catecholamine hypothesis describes neurotransmitter abnormalities and neurotransmitter-level pharmacological effects, as they apply to syndromal diagnoses. Whether or not these two types of theory can ultimately be synthesized, it is too early to say - but if they are both true, then ultimately they can be integrated.


Mood management and self-help

As well as being - I hope - true, the malaise theory of depression seems to be a clearer, more comprehensible and clinically useful model of depression than the current mainstream model. And given that depression is so common, the management of depression cannot be wholly a matter for professionals and experts. There is an important role for self-diagnosis, self-treatment and the self-evaluation of this treatment.

When a person complains of ‘sadness’ or perceives that they are sad, the first thing is to establish the nature of this sadness, since there are innumerable ways of feeling sad. If the sadness seems to be based upon malaise then the symptoms of malaise - not the sadness - becomes the focus of physical treatment. Whatever treatments are tried, from simple analgesics through to the formal ‘antidepressants’, then it makes sense to monitor treatment by the effect on malaise.

This style of self-monitoring is a skill which requires practice - and some people seem to lack the ability altogether. What is needed is the ability to look behind the ‘I feel awful’, and locate as exactly as possible what it is that feels awful and how. This allows a more helpful focus than is sometimes taken. For instance, many people respond to the I feel awful feeling of malaise (‘like a black cloud pressing on my head’) by getting intoxicated - by obliterating consciousness to a greater or lesser degree. So people get drunk or drugged, or take anxiolytics so that they feel ‘doped’ but suffer less. A better strategy may be to leave consciousness intact, but remove the feeling of malaise (disperse the black cloud).

But even if effective, removal of malaise does not produce feelings of happiness or gratification (except for the short term sense of relief at gaining ease from suffering - the nice thing about hitting your head against a brick wall is that it is lovely when you stop). Removal of malaise allows people to enjoy themselves, it allows the body to enact gratifying emotions once again - but this does not ensure that gratifying emotions will in fact be enacted. Sometimes people are disappointed that antidepressants have not made them happy, and interpret this as meaning that the drugs have not worked. That is expecting too much.

If you have flu and are miserable, exhausted and have a ‘black cloud’ pressing on your head; then when you eventually recover from the flu (or take effective symptomatic treatment) this does not mean that you will automatically become happy. In fact it may be difficult to become happy if you have been living in a gloomy state for some weeks, you may have developed habits of gloomy interpretation and stocked your memory with gloomy thoughts. It still requires the usual effort of life to seek gratification - seldom an easier matter, especially when debilitated by illness. But it should certainly be easier to experience pleasure if you are rid of that black cloud.

And that  - more or less - is the modest, yet extremely worthwhile, contribution of antidepressants to the human condition.



Chapter 10



Mania is the least well-known of the serious psychiatric illnesses. The nearest common equivalent is the word ‘maniac’ when used to describe someone who is violently out of control. The nearest a normal person gets to experiencing mania is probably after certain kinds of jet lag or after stayed-up all night - that buoyed-up feeling of being full of energy, immune to tiredness with no need to relax or sleep (and getting very irritable with anyone who tries to suggests that you need to take a break). Mania is one of the most difficult illnesses to explain - not least because the patient usually denies that they are ill, and may indeed feel abnormally healthy.

Under traditional diagnostic schemes, mania is seen as an affective disorder - an illness of the mood and the opposite of depression. Whereas depression is a low, miserable mood, mania is often a high, elated, grandiose mood. There are two kinds of mania: hypomania, which is milder and non-psychotic; and mania, which is the full blown syndrome including hallucinations, delusions, and rapid speech characterized by frequent changes of subject.

Manic people are overactive, rushing around continually without break; talk fast, too much and too loudly, hardly sleep; are short-tempered and often aggressive. Full-blown mania is usually characterized by a wild over-confidence and over-estimation of one’s ability, often combined with a paranoid belief that these abilities are being thwarted by other people who happen to be around.  

Energy, confidence and activity in the absence of hypomania are valuable attributes, which probably explains why the tendency to mania persists in the population and why genes associated with mania have not been eliminated from the population. So long as actual mania does not emerge, then a somewhat ‘manic’ (ie. energetic, confident and fatigue-resistant) temperament is often an asset - at least in some jobs such as sales and politics. The question is - what pushes such a person over into the damaging and maladaptive state of mania?


Problems with current concepts

Being manic or ‘high’ does not seem to be a illness in the same way as depression. Of course, when mania is psychotic, and so severe as to result in jumbled speech, bizarre delusions (that the manic is Napoleon, Jesus Christ or God himself) and hallucinations, then there is no problem in any objective observer conceiving it as an illness - the patient is ‘raving mad’. But the more common state of hypo-mania can be very difficult to diagnose.

Yet hypomania is potentially a very serious condition - exactly because neither the sufferers nor their family and friends recognize that it is an illness. Someone who is ‘high’ undergoes a change in personality which may destroy their life. They may quarrel with their spouse and break up a marriage; quarrel with their boss, get the sack and become unemployed; spend themselves deep into debt; and behave with dangerous irresponsibility - driving recklessly, getting into fights, having promiscuous and unprotected sex. Despite the high self confidence this mood is brittle and impulsive, and  there is a considerable risk of suicide. The social devastation wreaked by mania may be at least as great as any other psychiatric illness. 

The nature of mania remains obscure. The idea that it is a mood disorder stems from Kraepelin some hundred years ago. But as I have argued for depression, mood is not a primary biological variable, and instead we should regard mood as the outcome of other biological variables. Mood is merely a shorthand summary for certain characteristic modes of behavior.

Anyway, the mood in mania is not very specific - being extremely variable and changeable. There is even a ‘dysphoric’ mania recognized which is characterized by a low and unhappy mood (ie. a ‘depressed’ mood) but combined with a typical manic pattern of over-activity, over-talkativeness and a therapeutic responsivity to anti-manic treatments.  

So, if mania is not a mood disorder - then what is it?


Arousal and analgesia

I suggest that there are two core components to the syndrome of hypomania: excessive arousal and analgesia. Full blown mania arises when chronic, severe sleep deprivation is added to the picture of hypomania - sleep deprivation creates a delirious, functionally brain-impaired state which leads to psychotic symptoms such as jumbled speech, hallucination and delusions.

First, excessive arousal. Arousal is a very general psychological term, which refers to the continuum of alertness, a continuum that ranges between lack of environmental awareness, coma and sleep at one end - to states of high vigilance, energy and activity at the other end.

Most people are familiar with periods of time in which they feel highly aroused: wide-awake, driven, unable to stop working or stop talking, overbearing in manner. Sometimes, paradoxically, hyper arousal can come when we are in fact over-tired - for example after a sleepless night, or a long journey. These are times when we are paradoxically flooded by energy and unable (or unwilling) to switch-off and relax. For example, I recently missed a nights sleep when flying back to England from the USA - when I got home I felt utterly drained, but found it hard to sit down and rest, and impossible to sleep.

Habitual levels of arousal vary widely between individuals, and this is one of the most obvious and important aspects of temperament. Some people have more energy than others - get tired less easily, need less sleep. They may live in a state close to hypomania for long periods of time. Perhaps more common is to experience periods of energy alternating with periods of passivity, withdrawal and rest - this is the so-called cyclothymic temperament.  

The aroused state in its most extreme form is, I suggest, one component of mania, and is about as close as most of us get to mania. What stops this going further and ending up as pathological mania is the negative feedback of fatigue. When we are overactive, eventually fatigue catches up with us and we stop, rest, and sleep. The biochemical basis of fatigue is probably related to that complex group of immune chemicals which we encountered in the chapter on depression - the cytokines. A build-up of cytokines and other similar substances is probably what slows us down and forces us to rest. Fatigue is an example of ‘negative feedback’ in which biological systems balance themselves. Too much activity leads to fatigue, which allows us to recharge our energy supplies to enable more activity.

So although fatigue is a subjectively unpleasant feeling, like pain; fatigue is also a vital biological adaptation, also like pain. Without fatigue we might carry on-and-on charging around and doing things until we collapsed and died of exhaustion.  And this is exactly what used to happen to some manic patients in the days before powerful sedative and tranquillizing drugs were available. ‘Raging maniacs’ would charge around the locked wards for day after day, never resting, never sleeping, until they collapsed and died - usually of heart failure. Acute, severe mania was a fatal illness.

It can be seen that removal of the subjectively aversive sensation that is fatigue can be dangerous because it allows activity to continue when it ought to stop. Since fatigue is an aversive, unpleasant sensation it seems reasonable to suggest that fatigue can, in fact, be considered a form of pain. Substances that remove aversive sensations of pain are called analgesics, and I suggest that these same substances may also remove the aversive sensations we term fatigue - fatigue sensations which are akin to pain and may share similar biochemical causes.

The reason why some people become overactive in the first place may be a matter of temperament, or personality - it is well known that people who suffer from the illness of mania are also usually people who tend to be energetic, confident and highly active even when they are not ill. Energy, confidence and activity are valuable attributes so long as actual mania does not emerge. But such a person may have been forced to ignore fatigue and remain active for some reason beyond their control (demands of work, travel or family life, perhaps). They may stay up late, or stay up all night. In a susceptible person this stress could act to initiate the self-sustaining state that we call hypomania or mania.

My hypothesis is that the factor which probably switches temperamentally hyper-active people over into hypomania is the production of some endogenous, internally-produced anti-fatigue analgesic substance. (Or alternatively perhaps taking some drug with anti-fatigue analgesic properties.)

The suggestion is that mania is characterized by the inappropriate production of  some kind of endogenous analgesic that prevents fatigue, and allows the manic patient to continue with hyperactivity without experiencing the negative feedback of fatigue. When an over-aroused state is combined with an analgesic that removes fatigue then we have hypomania - a state in which over-activity is no longer held in check by fatigue.


Endogenous opiates as anti-fatigue analgesics in mania

For over-arousal to tip over into hypomania, the normal sensation of fatigue needs to be suppressed or over-ridden by an analgesic agent. The human body produces its won analgesics, of various kinds. The ‘high’ mood of mania is a secondary consequence of the ability to remain active without fatigue. Such an ability usually this makes people feel good, feel powerful, they are impressed with themselves. The analgesic activity means that there is a loss of perception of many of the negative feelings that accompany normal life, a blunting of the sense of shame, shyness, fear.

If mania is caused the inappropriate activity of some kind of endogenous analgesic that prevents fatigue, the question arises as to what this analgesic might be. An analgesic drug could be responsible, for example amphetamine which produces a state very similar to mania. However since many patients with manic symptoms are not taking any drugs, this strongly suggests that there is an endogenous or internally-produced analgesic substance which abolishes fatigue in the manic patient.

The nature of this endogenous, anti-fatigue analgesic is not known, but it is reasonable to speculate. Perhaps the most obvious candidates for an endogenous analgesic that could allow hyperactivity to blow-up into hypomania are the endogenous opiates - such as the endorphins and enkephalins. The best understood of the endorphins is beta-endorphin, which is a peptide hormone (ie. a short protein molecule) circulating in the blood. Beta-endorphin is secreted from the anterior pituitary gland and derives from the same precursor molecule as the ‘stress hormone’ ACTH (which causes the secretion of the steroid hormone cortisol), and beta-endorphin is also released under conditions of stress, pain, physical activity, and probably fatigue. Beta-endorphin is termed an ‘endogenous opiate because it has the same kind of pharmacological effect as the opiates such as morphine, heroin, pethidine, and codeine: these all act at the same general class of hormone receptors.

If there was an excessive secretion of endogenous opiates such as beta-endorphin, then this could be at least partly responsible for precipitating mania. That this is plausible is suggested by the observation that ‘exogenous’ opiates given as drugs would have the same capability to induce mania. There are numerous papers in the literature which suggest that opiate drugs may precipitate mania in susceptible individuals. This effect may be surprising, given that opiates are sedative, and it adds support to the theory that the analgesic effect is a vital component part of mania.


The arousal-analgesia model for hypomania leading on to full mania

We can now suggest a plausible sequence of events leading to hypomania. In the first place, there must be a hyper-aroused, driven state leading to over-activity. Perhaps a young businessman is trying to achieve an almost impossible deadline and stays up night after night on paper work. At first he feels exhausted, but keeps pushing himself and finds that the more he does, the less tired he gets.

Normally, over activity would be stopped by negative-feedback from fatigue. But if hyper-secretion of endogenous opiates is present, these may have an analgesic effect that removes the negative feedback of fatigue. In the businessman’s body great floods of endorphins lead to immunity form tiredness, and a feeling of invulnerability. The businessman starts to feel that he is breaking though to a new level of ability - after all, he can work twice the number of hours as anyone else, he feels great, his mind is sharp, and the work he produces is great! He has no time for the slow dull plodders (such as his wife) who tell him he needs a break, a rest a sleep: they may need it, but he does not. He is clearly superior. He asks her to run a bath, this seems to take forever, and then when he gets in the water is too cold!

The businessman turns on his wife, and sees that she and the children are cowering in the corner as if he was some kind of wild beast. Disgusted at their feebleness he storms out of the house slamming the door. Perhaps he should go and find a prostitute instead of his wife - after all a man of his energy cannot expect to be satisfied by just one woman…


Chronic, severe sleep deprivation as the cause of manic psychotic symptoms

Hyperactivity continues, which provides the ‘stress’ necessary to stimulate further endorphin secretion. Overactivity is accompanied by diminished sleep. If over activity is so severe as to reduce sleep below the minimum necessary for human health (usually about four hours a night) and for several days in a row - then the patient might become delirious due to sleep deprivation. The delirium will then lead to classic ‘psychotic’ symptoms such as hallucinations, bizarre delusions, and jumbled speech (‘thought disorder’) superimposed on top of un-fatiguing hypomanic over activity.

So the full state of mania might emerge - over activity, lack of fatigue and psychotic symptoms. The businessman leaves his desk, roams the streets trying to enlist people for his new project, telephones colleagues all through the night, takes a plane to the central office (no time to waste!), harangues the chief executive for his failure to allocate resources to the new project and gets kicked out of headquarters. He realizes that the company are all in a conspiracy to hold back these new ideas. He has stopped sleeping, although he isn’t really fully awake - but in a fluctuating twilight state, finding it difficult to concentrate or frame thoughts.

He begins to hear voices, probably mobile telephone messages in which the chief executive is instructing a gang to find and kill him (although nobody else seems to hear these voices). He tries to inform the police about the whole thing but they just look blank and too stupid to understand; even when he shouts and shakes the desk Sergeant to try and get some sense into him. Next thing he knows, the hard working businessman finds himself on a psychiatric ward - probably (as he imagines) on the orders of the chief executive…


Recovery - mania terminated by deep sleep

At a certain point mania can become self-sustaining. Sleep deprivation, once established, might itself be sufficient ‘stress’ to maintain to hyper-secretion of endogenous analgesics, which would sustain the sleep deprivation. Even if the initial provoking incident was removed, the manic state might then continue until the positive-feedback cycle of sleep deprivation and endogenous anti-fatigue analgesia was broken. The cycle might be broken by sleep, as fatigue eventually took hold.

After the businessman arrives on the ward he is given a tablet ‘to help you sleep’. Reluctantly he takes it and blacks out for hours. When he awakes his head is much clearer, although he can’t really remember how he ended up in a psychiatric hospital. Over the next few days he beings to feel calmer, and the incredible self-confidence is invaded by doubts, embarrassment and despair as he discovers that he has been given the sack

There is a self-sustaining cycle of overactivity causing endorphin hyper-secretion, which abolishes fatigue, which allows more overactivity. Once this positive feedback cycle is terminated by deep sleep, then manic symptoms may resolve rapidly and completely. If the cycle is not broken, the mania can persist for weeks or months. But quick and total recovery from even very severe and prolonged mania is quite usual, although even fully recovered people seldom fully acknowledge that they were ill at the time of mania. After all they felt so well, so confident, so full of energy…

This arousal-analgesia model predicts that full-blown mania is a delirious state. If so, the symptoms of delirium would be present, and an electroencephalogram (EEG) would be abnormal  (if it proves possible to record one on a manic patient). EEG abnormality would be defined as abnormal compared with the patients own non-manic EEG - so that later, post-recovery, EEGs are required for comparison with the ‘while-manic’ EEG. There are many similarities between mania and ‘agitated delirium’ - poor concentration and distractibility being particularly prominent in both conditions. I suggest that the two conditions cannot clearly be distinguished and are indeed different aspects of the same spectrum. The difference between agitated delirium and mania is probably in the cause and long term prognosis rather than the cross-sectional psychopathology.

Full blown mania with psychotic symptoms caused by delirium is therefore, I suggest, properly treated by sleep - deep restorative sleep which can usually be induced by neurolpetic drugs and sedatives such as lorazepam. Alternatively, mania can be rapidly resolved by one or two treatments with ECT - which (as previously argued) may serve as a sleep surrogate or to induce a deep sleep in the post-ictal period. 


The traditional interpretation

The above sequence of events is pretty much an uncontroversial account of the events of a manic episode - but my interpretation of causes is highly unconventional. In the first place, sleep deprivation is conventionally seen as a symptom of mania - not as a cause of mania. Manic patients are assumed to be sleepless because of the elevated mood - and the sleeplessness is not given an important role in generating symptoms such as hallucinations and delusions.

And the effective treatment of mania by neuroleptic drugs is not seen as being directed at causing sleep. Rather neuroleptics are seen as either general purpose ‘behaviour control’ drugs, which reduce physical and psychological over-activity. Or they are seen as ‘anti-psychotic’ agents which specifically remove symptoms such as delusions and hallucinations. The neuroleptic drugs used to treat mania may not be of the sedative kind, and they are often given at regular intervals throughout the day. By contrast I would advocate that specifically sedative drugs are used to treat mania, and these sedative agents would be given (if possible) only at night in order to promote the natural sleep-waking cycle, and to avoid daytime somnolence (which may also make it harder to sleep at the proper time).

Also, ECT is very seldom given for mania except as a last resort - despite abundance evidence as to its effectiveness. Without ECT patients may not respond to drugs, and may remain manic for many weeks or months. But people are reluctant to use ECT in mania, probably since it is seen as an antidepressant treatment ,and there seems no rationale for using ECT to treat an illness that is perceived to be ‘the opposite’ of depression.

Altogether, the field of mania is an extremely confused one. And the fundamental problem stems from the classification of mania as a mood disorder. Once the syndrome is considered in terms of its symptom profile, then everything becomes much clearer.


Other anti-fatigue endogenous analgesics in mania?

Endogenous opiates may not be the only analgesics responsible for mania. There may exist other endogenous molecules with anti-fatigue analgesic properties  - for example the glucocorticoid hormones such as cortisol.

Glucocorticoids, such as cortisol secreted from the adrenal gland, are analgesic, anti-inflammatory hormones that act upon most cells in the body. Compared with endorphins which acts minutes of secretion, cortisol has a slow onset of action over a period of many hours and several days. (Cortisol has its action by diffusing into the cell nucleus affecting DNA transcription - while endorphin binds to a cell surface receptor to induce rapid changes in messenger molecules within the cell.) ACTH is the hormone that stimulates cortisol secretion from the adrenal gland, and ACTH is co-secreted along with beta-endorphin in response to stresses such as pain, fear or anger. So there is a tendency for cortisol levels to increase along with endorphins; hyper-secretion of one might well be accompanied by hyper-secretion of the other. Cortisol might provide a slower acting, but more powerful and sustained, form of anti-fatigue analgesia.

Under normal, adaptive conditions glucocorticoids may work together with the endorphins to provide useful analgesia which allows a more effective ‘fight or flight’ behavior. It is well known that under conditions of excitement or danger (such as during a battle or a sports contest), there is a temporary insensibility to pain which may be useful in allowing escape. However, the combined analgesia of endorphins and cortisol would be maladaptive when it removes the necessary negative feedback of fatigue.

The role of glucocorticoids in mania is also supported in the psychiatric literature. Many papers describe elevated cortisol levels found in mania, and cortisol resistance to dexamethasone suppression (which is also indicative of excess cortisol secretion). Mania is itself a well established (although uncommon) side-effect of treatment with glucocorticoid drugs such as prednisone or hydrocortisone. For example, I have seen grandiose manic delusions developing in a man given steroids for multiple sclerosis, and the rapidly symptoms subsided when the steroids were reduced. Mania is also sometimes found among patients with ‘Cushing’s disease who have excess ACTH production (although Cushing’s patients more often feel ill and depressed). 


Psychopharmacological analgesia increases susceptibility to mania

Further evidence for mania being a consequence of arousal and analgesia comes from psychopharmacology. The best example of a drug that produces a manic syndrome is the psycho-stimulant drug amphetamine and its analogues.

Amphetamine is well known to increase arousal, but it is less well known that amphetamine is also an extremely powerful analgesic - almost as powerful as morphine. The fact is abundantly documented in the literature, although - probably due to fear of addiction - amphetamine is very seldom used as an analgesic in clinical practice. My suggestion is that the analgesic effect is a major element in the effect that amphetamine has in reducing fatigue (and amphetamine is probably the most effective known agent at reducing fatigue). This combination of increased arousal and analgesia makes amphetamine a potent agent for inducing manic states.

Indeed, any agent that produces arousal and analgesia should be able to cause (or increase the likelihood of developing) a state resembling hypomania. Caffeine, for instance, is a much weaker drug than amphetamine but shares the ability to produce increased arousal with a significant analgesic effect. The alerting effects of caffeine are well known, the analgesic effect less well known, although caffeine is included in many proprietary pain killers. But according to a recent estimate, caffeine is probably about equivalent in its analgesic effect to paracetamol.

The ‘wired’ state resulting from large scale ingestion of caffeine could therefore be considered a reasonable model for a mild state hypomania - although the unpleasant side effects of excess caffeine, and its rather weak analgesia, mean that caffeine over-use is not exactly equivalent to hypomania.


Induced fatigue as therapy for mania?

The role of anti-fatigue analgesia in causing mania suggests a potential therapeutic avenue in relation to deliberately induced fatigue as a treatment for mania. If hypomania is necessarily accompanied by analgesia for fatigue then any ‘anti-analgesic’ intervention which restored the proper feeling of fatigue might act to restore negative feedback, and potentially be effective in terminating mania.

There is little evidence on this matter, but to speculate we might make a few suggestions how this could be done. The best known anti-analgesic is naloxone, which is an antagonist to morphine and some other opiates including endorphins. There is suggestive (although inconclusive) evidence in the literature that naloxone, when given in sufficient doses, has anti-manic properties. The therapeutic effectiveness of naloxone in mania would certainly make sense in those patients whose mania was considered to have been induced by the anti-fatigue analgesic effects of endogenous opiates. 

The main class of substances that cause fatigue include the cytokines. It has already been argued that cytokines cause the syndrome of major depressive disorder in which fatigue and other painful and dysphoric feelings are so prominent. Some cytokines are ‘hyper-algesic’ - that is they lower the threshold for pain and also for fatigue. This implies that an infusion of cytokines (such as interferon) might be a very effective way of terminating a manic attack. The side effects of cytokine infusion would undoubtedly be unpleasant - just as they are when interferon is used to treat cancer or viral illnesses. Nonetheless cytokine treatment of mania may be a viable option in extreme or resistant cases. 

One way of testing this prediction of the efficacy of cytokine therapy would be to find out whether mania can be ‘spontaneously’ terminated by a cytokine-inducing illness, such as influenza (which typically produces profound fatigue and exhaustion of a kind which is incompatible with mania). Observational studies might be able to answer such a question.

But for the present, the main treatment for acute mania is the class of drugs known as the neuroleptics. And it is the action of this class of drugs that we now turn.



Chapter 11



The current first-line treatment of an acute episode of hypomania or mania, or indeed an acute psychosis of any kind - are the neuroleptic class of drugs. Neuroleptics are also called ‘anti-psychotics’ and ‘major tranquillizers’; and they include drugs such as chlorpromazine (Largactil), haloperidol (Haldol), long-acting injections such as Modecate and Depixol, and more recent ‘atypical neuroleptic’ agents such clozepine (Clozaril).

Chlorpromazine is regarded one of the most successful drugs in the history of medicine - and it broke upon psychiatry with such force that the subject was transformed utterly. Neuroleptics drugs revolutionized the treatment of schizophrenia and other severe psychiatric illnesses. Indeed chlorpromazine is sometimes credited with having ‘emptied the mental hospitals’ in the nineteen fifties and sixties, by enabling many chronically psychotic patients to live in the community.

But like most of the other classes of psychiatric drugs, there is no generally accepted understanding about what neuroleptics actually do. It is known that they shorten episodes of illness, reduce relapse rate, but how they do this remains obscure. In my view, neuroleptics are essentially drugs that blunt emotion, in the sense that they blunt the enactment of emotions. In other words neuroleptics block the ability to produce body states that correspond to emotions. So that neuroleptics diminish anxiety rendering the viscera unresponsive, in a sense by 'fixing' the muscles,  rather than by relaxing the muscles (as diazepam does). The name ‘neuroleptic’ actually means something that ‘seizes’ the nervous system, and this term communicates well the idea that neuroleptics ‘hold’ the body, make the body less responsive to the autonomic nervous system and hormones, and thereby prevent the physical enactment of large emotional changes - whether pleasurable or aversive.

In high doses, some neuroleptics act as ‘chemical strait-jackets’, having a tendency to immobilize patients. This is not the case for all neuroleptics, and the dose at which this becomes apparent varies between individuals (perhaps at a dose roughly ten times that for the neuroleptic effect). This ‘strait-jacketing’ may be a short-term necessity with severely violent patients (or, at least, it may be the best option among a variety of unpleasant alternatives such as physical restraint).


Mode of action of neuroleptics

Although their chemistry and molecular pharmacology have been the subject of vast amounts of investigation, the mode of action of neuroleptics is not known. Many people regard them as ‘anti-psychotic’ agents, and assume that their therapeutic effect is simply to remove abnormal psychological events such as hallucinations and delusions while leaving the rest of cognition intact and unaffected.

However, closer study has revealed that neuroleptics probably do not remove psychotic symptoms (at least, not in chronically psychotic patients), rather they reduce the unpleasant emotional impact of hallucinations or delusions, so that patients become ‘indifferent’ to them, ignore them, cease to act upon them. As one patient said: 'Oh yes, the voices are still there, I just don't listen to them anymore.'

However, it seems more plausible that neuroleptics are drugs that act primarily upon movement - and that the therapeutic effect is actually a milder version of the ‘immobilization’ or chemical strait jacket produced by high dose neuroleptics. Immobilization of muscles prevents emotional expression, and blunted expression actually blunts emotional perception.


Side effects or therapeutic effects?

The most notorious side effect of the neurolpetic drugs are their effects on muscles - the 'motor' side effects. I suggest that the motor effects of neuroleptics are in fact also the cause of the therapeutic effect of emotional blunting.

neuroleptics produce a wide range of movement disorders, some short lasting others perhaps permanent. The most typical effects are Parkinsonian (ie. like Parkinson's disease). So that the triad of muscular rigidity, tremor and bradykinesia (difficulty in initiating movement) are all common. A more difficult to describe motor side effect is 'akathisia' which is a very unpleasant sense of motor restlessness, an inability to get comfortable. Neuroleptics can produce contortions and twisting, for example a forced upward gaze of the eyes (oculogyric crisis). Some effects may be long lasting or even permanent, a syndrome termed tardive dyskinesia. This usually comprises facial movements such as chewing of the jaw, pouting of the lips, and protrusion of the tongue. And even without such obvious changes, people taking neuroleptics often look subtly different, having a somewhat blank and staring and ‘expressionless’ facial expression.

These motor effects are generally considered to be 'side effects' and distinct from the therapeutic neurolpetic effect. The recent development of 'atypical' neuroleptics with far fewer and milder motor effects is evidence of this - since atypicals are supposed to produce the same therapeutic benefits as the old drugs but without the motor side effects.

But in terms of the specifically neuroleptic effect, its ability to control disturbed behavior, the potency of a neuroleptic drug is correlated with its tendency to produce motor side effects. So that the most potent drugs used in psychiatric emergencies to control violent patients, drugs such as haloperidol and droperidol, are also the drugs most likely to produce motor side effects. And the 'atypicals' and other neuroleptics that are largely free of motor effects such as olanzepine or thioridazine, are seldom used for controlling acutely disturbed behaviour (except insofar as their sedative effects may have an independent and useful value).


Action on the basal ganglia

My suggestion is that the specifically neurolpetic effect is a direct consequence of action on the basal ganglia. The basal ganglia are brain centres that fine-tune movement, and neuroleptics probably act to reversibly (usually reversibly) impair the action of these centres. Given the current understanding of emotion as being the brain representation of body changes, it seems plausible to suggest that the emotional blunting which may be therapeutic in some patients on neuroleptics is a consequence of muscle rigidity and other forms of impaired muscle responsivity.

So, the emotional blunting which is the core psychological effect of neuroleptics is caused by increased muscle rigidity and reduced responsivity of muscles to the autonomic nervous system (such rigidity might be expected to be detectable with electromyelogram). This implies that that the blank face characteristic of a person on neuroleptics is itself partly responsible for a blunting of emotion since the brain monitors facial expression as part of its monitoring of emotion. Feedback from the muscles of facial expression is known to be a factor in perceived emotion - for example, manipulating the face into the shape of a smile actually makes people happier! Similarly, the diminution of facial expression reduces the changes in feedback to the brain and produces a feeling of emotional un-responsivity. Emotional blunting may be unpleasant for someone who is not ill, but blunting may be very welcome to somebody tormented by delusions and hallucinations.

Since emotions depend on feedback from physical changes in the body, any drug which stiffens (or paralyses) muscles would be expected to reduce or abolish the intensity of emotions dependent on enactment in those muscles. Anything which diminishes the physical expression of emotion will also diminish the perception of that emotion in the brain. For instance, patients with spinal cord transection have diminished feedback from lower body muscles and viscera, and these patients also have diminished intensity of emotions.

So emotions are blunted by neuroleptics, and the greater the motor ‘side effects’ of a drug, the more powerful the neurolpetic effect. By this account, the chemical strait jacket effect of high doses of high potency neuroleptics is merely a more extreme version of the calming effect of low doses of lower potency neuroleptic drugs. It is not so much a matter of neuroleptic drugs having therapeutic neuroleptic effects and ‘Parkinsonian’ side effects, but that these are points on a continuum of action on the basal ganglia. Crudely speaking, the greater the dose, the greater the immobilization.


Neuroleptics and the somatic marker mechanism

The way in which neuroleptics produce 'indifference' and demotivation can be interpreted in terms of the somatic marker mechanism. For example, motor stiffness would reduce the body's response to a frightening stimulus, and would also reduce the enactment of fear in response to thinking about (internally modeling) a frightening stimulus. This might be regarded as beneficial in  states where emotions are pathologically debilitating.

But this emotional blunting would also apply to pleasurable and gratifying stimuli, so that actually getting a prestigious job might fail to provoke the usual gratifying feelings, and certainly the prospect of achieving a prestigious job would fail to induce happiness. Failure to feel gratification in response to anticipated events is a plausible cause of demotivation, which is another recognized unwanted effect of neuroleptics.  would be a consequence of being unable to pleasurably anticipate events.

Usually, thinking about (ie. internally modeling) events leading up to personal success will lead to the enactment of a physical sensation of happiness (eg. the glow of pleasure as we imagine receiving a Nobel Prize...). This here and now pleasure helps to keep us working towards remote goals. By contrast motivation is less powerful if the prospect of success does not bring with it any here and now reward of pleasurable sensation.

Testing this theory would depend upon distinguishing and measuring the different clinical effects of drugs, for example discriminating between motor effects of old-style neuroleptics, and the therapeutic effects of sedation caused by the newer ‘atypical’ drugs. In so far as the atypicals do not have motor side effects, they are probably not really neuroleptics. Instead their activity probably depends upon their excellent hypnotic properties - as argued in previous chapters, deep and restorative sleep can produce considerable benefit in many psychotic illnesses. 

The conclusion is that neurolpetic drugs are a double-edged sword. In a nutshell, they seem to operate by immobilizing muscles, and thereby blunting emotion. This effect is almost always regarded as unpleasant by healthy people, since pleasant emotions are blunted along with unpleasant ones. This may explain why neuroleptic drugs are virtually never abused - they are very unpleasant to take. But when a person is dominated by unpleasant emotions, ideas, sensations - then this emotional blunting is very welcome.

But unfortunately, the positive effect of dulling the angst of unpleasant emotions with neuroleptics can seldom obtained without the negative effect of blunting pleasant emotions. This emphasizes that the dosage is absolutely critical, and should be carefully individually adjusted to balance the benefits and harms in the most favourable direction possible.


Sedatives as a treatment for mania - the ‘atypical neuroleptics’

Most neuroleptics are sedatives as well as specifically neuroleptic - in other words they reduce arousal and make patients sleepy. The hypnotic effect may be particularly useful in full-blown mania, since it has been argued above that delirium is an important aspect of the psychopathology. When chronic and severe sleep deprivation is a critical factor in pathogenesis induction of sleep may be curative.

Interestingly, sedatives were used to control mania before the invention of neuroleptics. Examples would include such nineteenth century drugs such as bromide and paraldehyde, and later on the barbiturates. However sedatives were probably used in divided daily doses to make manic patients so drowsy that they could not move - a crude and undesirable method of controlling behavior.

But it is possible that sedation and reduction in arousal has a genuine therapeutic effect of its own. The value of non-neuroleptic sedatives is currently recognized in that a combination of low dose neuroleptic and a benzodiazepine (such as lorazepam) is currently a standard treatment for acute manic episodes. This practice implicitly recognizes that the neuroleptic and sedative effects are potentially dissociable, and both desirable.

If sleep deprivation is recognized as a major factor in full-blown, psychotic mania - then the induction of sustained sleep becomes a major priority. This would imply that sedative drugs should be given in a single large dose at night - rather than spread evenly in divided doses throughout the day. As noted above, a ‘good night’s sleep’ sometimes has an immediate effect in terminating psychotic symptoms in mania.

Another alternative is ECT which is immediately beneficial in many cases of mania - producing an instant resolution or substantial improvement in psychotic symptoms such as jumbled speech, hearing voices or grandiose delusions. I have argued elsewhere in this book that ECT is an anti-delirium intervention, which has its therapeutic effect by inducing a state equivalent to deep sleep (the important factor is probably the post-ictal sleep, rather than the epileptic fit itself).


The wheel turns? Anti-epileptic sedatives and mania

Recently, the anti-epileptic drugs carbamazepine (Tegretol) and sodium valproate (Epilim) have been used as ‘mood stabilizers’ to prevent manic episodes. These seem to be effective in some patients, but again the mode of action is not known. It may be that the anti-epileptics are working merely as sedatives and hypnotics; to reduce arousal, reduce anxiety and promote sleep. In other words, antiepileptic drugs may work in a fashion that is very little different from benzodiazepines, or indeed the older tranquillizing drugs such as barbiturates, paraldehyde or bromide - drugs which are also anti-epileptic.

Perhaps the treatment of mania is turning full circle, with an increased understanding of how to use sedatives in treatment - the next step is prevention. Since sleep deprivation has such an important role in causing mania, it could be speculated that mania may be preventable by hypnotics alone - ensuring a good nights sleep, especially when arousal is high and fatigue is low.

Neuroleptics and lithium can both have dangerous side effects, and their emotionally blunting action may be demotivating in some individuals. The possibility of replacing lithium and neuroleptics by sedatives, either for the treatment of acute manic episode, or for the prevention of recurrent episodes, would certainly count as progress - even if (as is probable) this therapeutic option proved effective in only a proportion of patients.


Lithium - a different kind of ‘neuroleptic’

One of the most mysterious drugs in modern psychiatry is lithium. Lithium is simply a metal ion, and it is given as a simple salt such as lithium carbonate. Initially lithium was given to manic patients as a treatment for acute mania, where it seemed to have calming and sedating effects somewhat like the neuroleptics. Nowadays it is more often given (in lower doses) to prevent attacks of mania and depression in patients diagnosed as suffering from ‘bipolar affective disorder’ (more often termed ‘manic depressive’ illness) who are prone to frequent and severe attacks of mania and depression.

At present it seems uncertain what lithium does therapeutically - either in a pharmacological or a psychological sense. Taken prophylactically,  lithium reduces the frequency and severity of manic attacks - but how it does this is a mystery. The usual perception is that apart from its side effects (tremor, thirst etc.) lithium has no effect on a persons state of mind, cognition or emotion.

But on specific questioning most lithium users are insistent that lithium irons out the usual ups and downs of mood, so that they feel both less sad and less happy. So that lithium affects ‘normal’ emotions as well as the extreme emotions of mania and depression. In other words, the ‘mood stabilizing’ effect of lithium sounds very like a mild neuroleptic-like blunting of emotions.

Neuroleptics can be used to treat acute depression as well as mania and are also often effective preventive drugs both for recurrent mania and for depression - the similarities between neuroleptics and lithium are indeed striking. Both produce similar EEG changes, and both classes act on the basal ganglia that control precise movements - although lithium produces a rapid tremor in distinction to the Parkinsonian side effects of neuroleptics. 

My suggestion is that we should conceptualize lithium as a mild quasi-neuroleptic - neuroleptic in terms of its clinical action in blunting emotion, although not chemically a neuroleptic. Like neuroleptics, lithium probably prevents the enactment of emotional body states by means of affecting the basal ganglia, but unlike the neuroleptics it does this in a way that holds the musculature in a way that produces a tremor rather than tonic contraction and stiffness. And lithium has the further advantage of avoiding the long term, probably neurotoxic toxic side effect of tardive dyskinesia.

So lithium probably prevents mania by preventing or damping the ‘high’ state of arousal that initiates the manic sequence. Which means that when given chronically, lithium is not really a prophylactic, at least not in the way it is usually considered to be prophylactic. Rather lithium is a continuously-given acute treatment. And the clinical effect of lithium in mania is to ‘calm’ excited states by means akin to (but not identical with) neuroleptics, as was recognized when the drug was first introduced and used for treating acute manic episodes.

Given chronically to prevent mania, lithium is actually being used in a manner closely analogous to the use of chronic low dose neuroleptics in the prevention of schizophrenic breakdowns - for example when neuroleptics are given as a ‘depot’ injection. Like neuroleptics, lithium probably has the therapeutic action of blunting emotions, and this blunting is not an accidental or unwanted ‘side effect’ of the drug, but is intrinsic to its ability to reduce the frequency and severity of episodes of mania (and depression). People who are prone to wide emotional swings may be grateful for having these confined within narrower boundaries - and lithium can achieve this. Whether or not to take lithium should not be a question of whether people have a formal diagnosis of ‘bipolar affective disorder’; it should be whether people have a better quality of life on the drug than without it. 

If blunting of emotion is the primary therapeutic effect of lithium, then would make sense to titrate the dose of lithium against its effects on emotion. At present lithium dose is not titrated against clinical effect, but is kept within a safe ‘window’ by repeated blood sampling. This black box, all-or-nothing, approach to lithium dosage was inevitable, given that people had no theory of how lithium worked. The dose of lithium was seen as having only three possibilities (based on blood levels): too low and ineffective, too high and toxic - or acceptably within the effective and non-toxic range. But it may be possible (and safer) to give lower doses than those usually considered to be the minimum effective dose in patients whose clinical response of mood-blunting is apparent, even when the blood level below the usual ‘effective’ window.

The aim of lithium prophylaxis should be to achieve an optimal degree of emotional blunting that provides the maximum of therapeutic benefit compared with the minimum of demotivation at the minimum risk of other unwanted effects (tremor, thirst, renal toxicity). People ought to feel better overall when taking lithium than they do without it. They ought to feel that the benefits of blunting aversive emotions and preventing extreme emotions more than compensates them for the cost of ‘taking the top off’ gratifying emotions.

Again temperament and individual disposition is important. But for many people lithium prophylactic therapy will inevitably be a trade off between good and bad psychological effects - and they will not be able to have the one without the other.


Chapter 12



Schizophrenia is the term given to patients suffering psychiatric illnesses that the general public would consider to be the classic form of ‘madness’: - a person roaming the streets conversing with imaginary voices, shouting strange ideas, talking nonsense, adopting bizarre postures. Delusions are prominent and often constitute ‘paranoid’ ideas of self-reference in which the patients sees themselves at the centre of some large scheme or conspiracy which is often hostile with regular references to them in the newspapers and broadcast media.

The diagnosis of schizophrenia dates back a hundred years to the work of Emil Kraepelin, who coined the term ‘dementia praecox’ and drew attention to the long-term and progressive decline in function. The name ‘schizophrenia’ was introduced by Manfred Bleuler to refer to the ‘splitting’ of affect from other psychological functions leading to a dissociation between a social situation and the emotion expressed. Nowadays, schizophrenia is a syndromal diagnosis, made on the basis of long term psychotic symptoms occurring in clear consciousness.

People who are diagnosed as schizophrenic (in the UK) probably include some of the most severe and chronic of psychiatric patients, in the sense that the diagnosis of schizophrenia is associated with a profound disintegration of personality. Schizophrenics include many experience a chronic and usually incurable illness, and whose personality and lifestyle undergo a qualitative, permanent and tragic decline. The diagnostic category of schizophrenia is, in a sense, the most important of all psychiatric diagnoses, because it represents the classic form of functional psychosis, constitutes a major element of the workload of traditional asylum psychiatrists, and stands at the very heart of the dominant nosology.

But whether this group of patients can reasonably be considered as constituting a single, coherent biological category is extremely doubtful.


The nature of schizophrenia

It is part of the argument of this book that acute schizophrenia is essentially indistinguishable from acute mania and agitated delirium. The three cannot be split apart on the basis of examination of acute state of a patient over a few days. Instead, the diagnosis of schizophrenia is made on the basis the long term events and outcome of the illness. A person is only given the diagnosis of schizophrenia if they have been psychotic for a period of several months without recovering. By the time they have attracted the diagnosis of schizophrenia a patient has become part of a group with a generally bad prognosis. By contrast manic patients are those with a relapsing and remitting course (with complete recovery between episodes), and the diagnosis of delirium is made when a physical cause (such as drug intoxication) is made, and there is a swift and complete recovery following removal of this cause. (There is a further, slightly unrespectable, diagnostic category of ‘psychogenic’ psychosis which is made when a person breaks down following extreme ‘stress’ - and which I would suggest is usually an acute delirium caused by sleep deprivation.)

So, schizophrenia is a diagnosis that refers to a group of patients with long term hallucinations, delusions, and thought disorder. In addition patients frequently suffer from a progressive ‘dementing’ process which affects personality, social behavior and cognitive function ( ‘dementia praecox’ means precocious dementia). Broadly speaking, schizophrenia emerges in young adult life with a gradual accumulation of dementing ‘negative’ symptoms such as social withdrawal, lack of emotional reactivity, lack of drive and decline in intellectual ability. The idea is that schizophrenia is a disease in which there is progressive brain damage (with causes perhaps genetic, infective or traumatic) - and this brain damage renders the patient more susceptible to acute psychotic episodes. 

I have described a caricature of a person with schizophrenia, but it is much harder to provide any unitary account of the nature of schizophrenia. It is not possible to answer the question: ‘What is schizophrenia?’ on the basis of a purely syndromal diagnosis. The symptoms and signs are neither causally related to one another, nor to an underlying pathology. Most of the current would-be unifying theories are at the level of suggesting neurotransmitter abnormalities. But neurotransmitter changes are not diagnosable in living humans, and anyway neurotransmitter changes do not explain what is going on at the psychological level, since the intervening links of the causal chain are unspecified.

Even more fundamental, it is not at all clear that schizophrenia is ‘one thing’, has one cause or represents a useful delineation. It has long been a truism in some circles that schizophrenia is a collection of separate pathological processes leading to a uniform type of illness. I was taught this twenty years ago, so the idea is hardly novel. On this view, rather like ‘heart failure’, schizophrenia can be taken to describe a pathological end-state of several diseases, rather than a disease in itself. Certainly, ‘schizophrenic’ patients differ widely in their clinical features, in their response to treatment, and in their long-term natural history. Unfortunately, so do the ends-state pathological findings. For instance there is no characteristic brain abnormality from which schizophrenia could be diagnosed. Contrary to what was hoped twenty years ago, schizophrenia does not seem to be characterized by any specific pathological end state - brain abnormalities are non-specific and are do not clearly discriminate schizophrenic patients from those with other psychiatric illnesses or from normal control subjects.

Despite widespread tacit acknowledgment in the heterogeneity of the diagnostic category, most schizophrenia research (and clinical practice) continues to talk of the syndrome as if it were a unitary disease that might have a single cause, single pathology, and a single treatment. There has been little attempt to subdivide schizophrenia into its proper biological and psychological categories.

The most fruitful strategy to approach schizophrenia would be to discover the its pathological processes which are at work in the kind of patients who currently attract a diagnosis of schizophrenia, and link these to the psychological abnormalities that are observed. This turns out to be much easier than might be anticipated. When this happens, schizophrenia becomes a different proposition, and quite novel strategies for treatment become plausible.


Schizophrenic delusions - theory of mind delusions

Firstly consider schizophrenic delusions. It has already been argued that delusions fall into at least two classes. There is a class of false, unshakable, dominating beliefs about the dispositions, motivations and intentions of others that form the category which I have termed ‘theory of mind’ delusions - for example persecutory, jealous and erotomaniac delusions. These delusions can be found in people with no cognitive abnormalities, where these ‘pure cases’ are termed delusional disorder.

Some schizophrenic delusional beliefs fit this ‘theory of mind’ category - for example long term delusions of persecution based upon the belief that a person or group are hostile. Since they are not associated with pathological cognition, we would expect such beliefs to be resistant to persuasion, resistant to drug treatment, and to be present even during remissions of the long term psychotic illness. Probably, these theory of mind delusions are a consequence of the affective abnormalities found in some patients diagnosed as schizophrenic.

For example, I have seen persecutory delusions develop before my eyes, as a patient became more and more fearful following a reduction in the dose of neuroleptic medication. This patient had a pre-existing belief in the ill will of social workers; this belief was present at all times, but when he was well the belief was neither dominant nor distressing. But after reduction of the neuroleptic, the patient’s level of fear gradually escalated (as the emotionally blunting effects began to wear-off). At first the patient became perplexed - fearful and suspicious but uncertain of the reason why. Increasing perplexity was apparently a result of trying to understand what was going on, perhaps exacerbated by a mild degree of cognitive impairment which made it hard to think things through.

At a certain point this patient crossed a line and became convinced that the cause of this increasing fear was increasing persecution by the team social workers, people whose motives he had long suspected. Suddenly everything made sense; and the belief that the social workers were persecuting him came to dominate waking life, and was used to explain all manner of problems and frustrations. When a social worker called around at his flat, or was spotted nearby, this was taken as evidence that they were spying, and collecting data.  In a sense, of course, all this was true and the social workers were observing, collecting and pooling data. But what was misunderstood was the motivation of the social workers - the patient though they were engaged in establishing enough evidence to lock him up permanently (an interpretation which was, of course, not true).

When the dose of neuroleptic was increased, the patient’s arousal and fear diminished, intense but unpleasant emotions were blunted, and the intensity of the belief in persecution also waned until it ceased to dominate. Eventually the patient was left with the long-standing suspicion of social workers, but no overtly false beliefs.

The lesson that this example is intended to reinforce is that the false beliefs that characterize ToM delusions are not wholly treatable by medication; and indeed the false beliefs themselves should not be the focus of treatment. It would have been a serious mistake to keep raising the dose of neurolpetic in an attempt to eradicate all suspicions and false beliefs about social workers, since these were not based on pathological cognition. Rather, what was treatable, and served as the focus of treatment, was to ameliorate the fearful emotional state that both caused and was a consequence of the false beliefs.

Once established, a ToM delusion cannot usually be eradicated, although medication may be effective at diminishing the emotional drive to act upon that belief. But at a cost. The emotion-blunting action of neuroleptics means that this class of drugs has the potential to operate in a generally demotivating fashion When a patients is dominated by unpleasant emotions this can benefit their overall clinical state. In normal controls demotivation is unpleasant and may be debilitating. So that a patient's overall clinical state, their happiness and social adjustment are the appropriate outcome measures against which drug dosage should be titrated - not the presence of a specific false belief.  


Schizophrenic delusions - bizarre delusions

But as well as Theory of Mind delusions, based upon mistaken inferences concerning other people’s intentions, motivations and dispositions, and fueled by affective changes - schizophrenic patients more characteristically also suffer what have been termed ‘bizarre’ delusions. Bizarre delusions can be defined as delusions which are based upon illogical, incoherent or incomprehensible reasoning processes. Since the chain of inference leading up to them is illogical, the beliefs which emerge at as a consequence of this type of reasoning are often impossible propositions - bizarre delusions.

For example I once spoke with a patient who believed she was under surveillance from some kind of laser beams, and these were used to project up large television pictures of herself. She told me that as we were speaking together, her neighbors several miles distant were also sitting around watching a gigantic TV picture of the two of us speaking. Other patients have complained that their minds were being read, or that their thoughts were being somehow extracted, or alien thoughts inserted - again by some vaguely defined technology such as radar or lasers.

Such beliefs are usually a consequence of a sequence of inference which is similar to dream-logic, and the beliefs are never properly worked-out or argued. As argued previously, the reason is that bizarre delusions are a consequence of delirium - they proceed by dream logic because they are almost literally dreams. Bizarre delusions are remembered dreams breaking though into consciousness as a consequence of fluctuating levels of consciousness.

Patients suffering from bizarre delusions are - it is suggested - in an abnormal state of consciousness, fluctuating between delirium and waking, and therefore functionally brain impaired. This ought to be apparent from serial EEGs as well a from observing the clinical signs and symptoms of delirium.

Since bizarre delusions are a consequence of delirium, they are potentially completely curable - if the delirium can be treated. If a remission is attained, then patients should completely lose their bizarre delusions - unlike their ToM delusions.


Schizophrenic hallucinations

Hearing voices is one of the classic symptoms of madness. Specifically, hallucinations in clear consciousness are said to be a sign of psychotic illnesses such as schizophrenia, mania and severe depression. But the definition of ‘clear consciousness is contestable in schizophrenia, and I have suggested that acute schizophrenia is a delirious state.

The pathological mechanism by which hallucinations might arise in clear consciousness have never satisfactorily been elucidated. Various ingenious hypotheses have been devised for explaining why it is that schizophrenic patients are unable to distinguish the ‘inner voices’ of auditory hallucinations from the external voices of other people. None of these seem convincing from a biological perspective.

I suggest that hallucinations do not occur in clear consciousness, they occur only in a delirious state of impaired consciousness. And ‘schizophrenic’ patients with delusions will - I suggest - be found to have impaired consciousness. It is the diagnosis of clear consciousness that is at fault in schizophrenia.

After all hallucinations are not unusual - many normal people have experienced them, but only in states of impaired consciousness. Especially people have experienced hypnagogic or hypnapompic hallucinations which occur when people are drowsily falling to sleep or waking-up. These can be auditory: voices speaking short phrases, shouting, thumps and other noises, or visual: shapes or movements. Such hallucinations therefore happen when people have ‘clouded consciousness’ and not quite awake nor alert. Probably, these are fragments of dreams, breaking through into normal waking awareness as consciousness fluctuates.

Other people have experienced hallucinations, or visual hallucinations, when delirious with a high fever, sunstroke, or similar. And many people deliberately induce visions, voices and hallucinations in other sensory modalities by taking drugs such as LSD. There are many types of hallucinatory state which depend on the drug taken: the common feature to all these hallucinations is functional brain impairment - ie. delirium.

It seems overwhelmingly likely that hallucinations - auditory, visual, somatic - that occur in patients diagnosed as suffering from ‘schizophrenia’ are also the consequence of delirium. In other words hallucinations in schizophrenics are not occurring ‘in clear consciousness’. The idea that hallucinations can occur in clear consciousness is again an artifact of too insensitive a diagnosis of delirium - which fails to use the most accurate test (serial EEGs).

And hallucinations also lead to bizarre delusions as people try to explain their imagined physical experiences. For example, delusions such as that in which a persons thoughts are being ‘withdrawn’ from their head, or in which alien thoughts are inserted, or in which their body is controlled, are possible consequences of physical hallucinations of the sense of touch. Similarly the sense of smell and taste can be subject to hallucinations. 


Acute schizophrenia is a delirious state

If a more valid clinical diagnosis of delirium were to be adopted, it would be predicted that any schizophrenic patient exhibiting bizarre delusions, hallucinations, or the kind of jumbled or nonsensical speech which is taken to characterize ‘thought disorder’ would all be diagnosed as delirious.

The cause of the delirium in such a patient might be any insult to the brain - infective, inflammatory, toxic, or (like psychosis in mania or depression) sleep deprivation. So any probable cause of delirium should be searched for and treated if possible - with chronic, severe sleep deprivation being a likely candidate in many instances. Induction of sleep, either with drugs or ECT, may provide rapid benefit.

But patients attracting a diagnosis of schizophrenia are, by definition, those in a poor prognosis group. And it is known that the effect of any potential cause of delirium is exacerbated when acting upon an abnormal brain. For example delirium is commonest in patients at the extremes of the lifespan with either immature or senile brains, and in patients with Alzheimer’s dementia or multi-infarct dementia. It is very likely that a proportion of patients with schizophrenia have abnormal brains of various types, probably due to a variety of progressive dementing processes that have not yet been identified and classified. More needs to be said about this. 



Negative symptoms

Negative symptoms get their name because they are reductions in normal behavior, absences of behavior - while hallucinations, thought-disorder and delusions are considered positive symptoms in the sense that they add to normal behavior.  The negative symptoms of schizophrenia include lack of emotion and ‘flat’ mood (‘affective blunting’), lack of motivation (‘avolia’), ‘asocial’ behavior in which the patient avoids other people, and ‘alogia’ or ‘poverty of thought (which means that the person speaks very little, and so far as anyone can tell thinks very little).

The negative symptoms of schizophrenia are cognitive and behavioral abnormalities that are probably the consequence of a progressive brain abnormality or dementia - dementia being a generalized intellectual and behavioral decline, usually due to structural brain abnormalities. But there is a potentially very worrying overlap between deterioration due to presumed dementing processes, and an almost identical deterioration due to the neurolpetic drugs used to treat patients prone to acute psychotic breakdowns.

The picture of a patient with prominent negative symptoms is of a strangely-behaving man (usually a man) who leads an isolated life, talking to few people and showing little desire to talk, perhaps nocturnally awake and wandering and sleeping by day, but doing very little and without any ambition. There will usually be hallucinations such that the patient can be seen to react to voices by muttering or shouting back at them. There may be a strange way of walking or strange postures adopted. Acute episodes with agitated behavior and exacerbations of hallucinations and delusions may happen from time to time. Little information can be obtained at interview but there may be evidence of delusions, strange beliefs, and reports of strange perceptions of influenced thinking and body sensations. A considerable range of structural brain abnormalities (usually quantitatively abnormal, rather than qualitatively) may be seen either on a brain scan or when the brain is examined after death.

Such a picture may get progressively worse over time and be essentially permanent and irreversible - at any rate negative symptoms are not responsive to the same treatment as positive symptoms. Indeed negative symptoms demotivation and emotional blunting are usually made worse by neuroleptics, and it is possible that in some patients negative symptoms may be substantially caused by neuroleptics. As discussed previously, neuroleptics blunt emotions probably by an action on the basal ganglia. This blunting is beneficial in the case of pathological aversive emotions such as fear; but unfortunately neuroleptics also blunt pleasurable emotions. And it is plausible that a blunting of pleasurable emotions could cause all of the negative symptoms of schizophrenia. 

A patient unable to experience normal pleasure from social interactions will tend to avoid them. In particular, when pleasurable emotions cannot be enacted in response to anticipation, then motivation may be severely damaged - thoughts of the future do not lead to gratifying feelings in the here and now, so it is hard to make yourself embark on any long term projects. Without the inbuilt system to generate rewarding emotions then thinking becomes an activity without reward, reality seems abstract and distant, an negative, inert and placid life dedicated to avoiding unpleasant emotions offers the greatest satisfaction. This may be exacerbated if patients on neuroleptics are also suffering the extremely unpleasant side effect of akathisia, a state of psychological and physical restlessness which may itself tend to provoke a reaction of social withdrawal.

Therefore it seems likely that patients diagnosed as schizophrenic and suffering from ‘negative symptoms’ contain at least two groups - those who are suffering some kind of dementia which some sorts may be progressive and permanent, and those whose negative symptoms are a side effect of neuroleptics. The important thing is not to misdiagnose patients whose negative symptoms are drug-induced, since these are potentially reversible.

Patients vary widely in their sensitivity to neurolpetic drugs, there are considerable differences in which drugs suit which people, and different doses are required for acute and long term use. Individual tailoring of treatment and dose is almost certainly going to be required. The aim of long term treatment should be to suppress positive symptoms with the minimum of negative symptoms. When the dose is right, the patient should overall feel better - the benefits of treatment should outweigh the disadvantages. 

So, negative symptoms often can be treated. A minimum dose can be sought. Or one of the ‘atypical’ neuroleptics can be tried - and these are probably only very weakly neuroleptic at recommended doses but act mainly as hypnotics. It seems very likely that the schizophrenic patients whose negative symptoms were apparently cured by clozepine were actually benefiting from withdrawal of neuroleptics and loss of their drug-induced negative symptoms. Even with chronic schizophrenics, who had not had a remission for decades, there are sometimes remarkable recoveries.


Schizophrenia is not a unified biological entity

The  clinical picture of schizophrenia is therefore a variable mixture of delirium superimposed on dementia with the possible complication of neurolpetic side effects. There is really no good scientific reason to assume that the many and varied symptoms of schizophrenia can be put down to a single cause.

Neither is the diagnosis of schizophrenia a good guide to prognosis - except in the crude sense that if people have suffered symptoms without recovery for several months, then it is probable (although not certain) that they will continue to suffer similar symptoms in the long term and will not make a full recovery. Similarly patients with a gradual (insidious) onset of symptoms without obvious cause have a worse outlook that patients with an acute onset caused by some obvious and unusual ‘stress’.

The diagnosis of schizophrenia is not a good guide to treatment. Some psychiatrists, encouraged by neurotransmitter theories, see schizophrenia as a specific cerebral pathology (such as some kind of dopamine over-activity), and neuroleptics as having a specific benefit on this perturbed system. However the dopamine hypothesis of schizophrenia has never been strong and has become weaker and weaker over the years. At present the dopamine hypothesis of schizophrenia serves only to reinforce a false unitary concept of schizophrenia, and a categorical mode of treatment with neuroleptics (even in circumstances when drugs are only dubiously neurolpetic and are probably having quite different therapeutic actions). 

It has often been shown that schizophrenia is best treated symptomatically. In other words, the best approach to an illness as heterogeneous as schizophrenia is probably to treat the symptoms that are causing the patient most concern or causing the greatest behavioral disruption. The diagnosis tells you less than the symptoms about the best focus for therapeutic intervention. So that moderate agitation and preoccupation with distressing delusions or hallucinations might be treated by neuroleptics, acute agitation and dominating delusions or hallucinations might be treated by ECT, depression by antidepressants, sleeplessness by hypnotics, anxiety and fear by anxiolytics and so on.

This symptom-focused treatment strategy is not really controversial although it is seldom so explicit; and it strongly implies that schizophrenia is a collection of more-or-less coincident pathologies and symptoms. To me this suggest that ‘schizophrenia’ is a term which is not doing any useful work. Indeed, it is probably doing more harm than good. 


A new psychiatric nosology needed

Time to discard the diagnostic category of schizophrenia

Schizophrenia occupies a central place in the current nosology, a place which it has occupied for the past hundred years since the syndrome was delineated by Kraepelin. Yet schizophrenia is neither biologically valid nor clinically useful as a diagnostic category. When classification is mistaken, then research based upon it is bound to be wrong since the information has been gathered concerning groups of dissimilar patients. Reform of nosology is therefore a pre-requisite for valid psychiatric research.

Schizophrenia is a very old diagnosis - and most hundred year old diagnoses in other more highly developed branches of medicine have long ago been superseded. We no longer talk about an ‘ague’ or a ‘fever’ - we talk about the infective agent, the nature of the pathological process, the specific organ affected, and the processes upon which therapeutic interventions are intended to operate. Where this kind of information is not known, then people are looking for it. It is at least implicitly recognized that where there is no existing satisfactory nosology, then clinical research should be focused upon devising a proper diagnostic classification.

Schizophrenia illustrates perhaps more powerfully than any other example the way in which psychiatric research and clinical progress is being thwarted by the non-biological nature of some of the diagnostic categories. So long as the categories of disease are wrong, and so long as these categories dominate research, psychiatry will be stuck at more-or less its present level. Considering the vast input of research funding over several decades, the clinical progress in schizophrenia has been very modest indeed, amounting to little more than a gradual process of learning how not to poison patients with neuroleptics. At any rate, there seems little doubt that the term schizophrenia is now hampering effective clinical evaluation and treatment.


Factors blocking change

Unfortunately researchers are locked into the present system by a vast infrastructure of journals, conferences and books wholly or partially devoted to schizophrenia research; societies of sufferers and professionals that are organized around the diagnosis; drugs marketed for specifically for schizophrenia, and funding earmarked for research into this area. To reject the validity of the diagnosis of schizophrenia is to reject these sources of position, status and money. Schizophrenia is at the very heart of psychiatry as a profession and as a research enterprise because it is the classic form of madness. If psychiatrists turned out to have been wrong about schizophrenia then what else might they be wrong about?

Psychiatrists are also sensitive to the legacy of 1960’s counter-culture claims that mental illness is not real, but is an arbitrary method of social control. Such views are still actively propagated in the social sciences, and are influential in some of the para-medical health care professions. To admit that schizophrenia is neither a valid nor useful diagnostic category would be to open the psychiatric profession to accusations of carelessness, abuse, dishonesty, incompetence - who knows what? The position of psychiatry has never been so secure that this was felt to be a justifiable risk. Despite the existence of many eminent schizophrenia researchers who are willing, privately and off-the-record, to admit that schizophrenia is neither real nor useful - hardly anybody has ‘broken ranks’. Official and public discourse is solidly unified in its usage of the term schizophrenia.

Perhaps the hope is that schizophrenia can be discarded by stealth, without anybody really noticing. Unfortunately there seems no sign of this. Instead the diagnosis carries an ever greater freight of expectation in terms of research and therapy. Articles on ‘progress’ in schizophrenia are regularly published in the most prestigious journals; scientific, clinical and for a lay audience. The nonsense seems invincible and immortal. And the boundary between ‘normal’ and ‘schizophrenic’ is ever more carefully patrolled - reinforcing the impression that there are schizophrenics, and there are us normal folk. And the two categories neither mesh nor merge.

This has to stop, and the sooner the better. The risks must be taken. Such is its rigidity of inertial misconception, progress in psychiatry depends on the utter demolition of the diagnosis of schizophrenia, and its extirpation from clinical and research discourse. From the rubble of schizophrenia we may construct a new nosology to replace the obsolete conceptions of Kraepelin. 


Schizophrenia and the human condition

What is the relevance of schizophrenia to the human condition? On the face of it, schizophrenia represents something alien from the experience of normal life. What, indeed, is the relevance of delusional disorder, depression and mania and why have I re-explained these disorders using concepts derived from evolutionary psychology and cognitive neuroscience?

The reason is to pave way for a new system of classification of psychiatric illness, a new nosology based upon biologically-valid psychological variables applied both to diseases and to drug effects. And the reason for this is quite simple - it is to unstick psychiatry from its current conceptual stasis and force the subject to emerge from the intellectual ghetto it has occupied for several decades.

Whilst occupying this Kraeplinian prison psychiatry has learned virtually nothing from biology, and has made no substantive contribution to the rest of science at all. It is a pitiful record of misplaced activity, the failure of which has been blurred, but not obscured, by vast efforts at public relations and hype. We should have no regrets in leaving all this behind, breaking down the walls, and refreshing the subject of psychiatry by contact with the scientific disciplines outside the ghetto.  There is a great deal of ground to make up.

The advantages of a properly biological approach to psychiatric classification might be expected produce three major classes of benefit:


1. Research

Firstly, it would enable research to proceed on the basis of potentially valid biological categories. This would not guarantee progress - would at least remove the major obstacle to progress that the present nosology represents.


2. Treatment

Secondly a psychological description would in principle allow symptomatic treatment, tailored to the individual requirements of each patient. At present each patient is categorized, and their treatment determined, by a psychiatric ghetto diagnoses, cut off from any roots in the knowledge base of contemporary biological science. Instead I propose that biologically valid psychological variables derived from evolutionary theory, neuroscience and other disciplines. I have suggested categories such as theory of mind delusions as distinguished from bizarre delusions, delirium measured on the basis of degrees of impaired brain function, sickness behaviour as the basis of major depressive disorder, hypomania as a combination of increased arousal and analgesia, schizophrenia as various combinations of delirium and dementia…

Such a scheme allows a symptomatic profile of each individual patient to be built up on the basis of the presence and relative severity of these variables. A symptom focused treatment can be tailored on an individual basis, based upon knowledge of the effects of individual drugs on these symptoms - the drug effect can be individually titrated against target symptoms.


3. Links to normal behavior

Thirdly, a new nosology based on psychological categories demonstrates the links between psychiatry and everyday life. To this extent, it demystifies and de-stigmatizes psychiatric illness. Psychiatric symptoms are seen as universal aspects of the human condition, varying in their distribution and severity, but which everybody has experienced and from which nobody is immune.

The world of formal psychiatric disorder and the everyday world of ‘the human condition’ are not separate categories, but one in which individuals occupy a moving trajectory on a constellation of biological and psychological variables. There are few aspects of formal psychiatric disorders that are utterly alien to normal experience (when they are considered one at a time in their proper categories) - although the combined and sustained effect is often very strange, very disturbing, and very tragic.

Similarly, psychiatric drugs are seen as members of a much broader category of agents that affect psychology, a category which includes pain killers, mild stimulants such as coffee and tea, relaxants such as alcohol - indeed drugs taken for the reason of making life pleasanter or at least more bearable. The drugs used to treat major psychiatric illnesses such as depression, mania and schizophrenia should, in principle, be no different. Psychotropic drugs should make patients lives pleasanter or at least more bearable. And if they are not doing this, then hard questions must be asked about the role of psychiatric treatment and who is supposed to benefit from it.

In this sense, formal psychiatric disorder has much to teach us about hope to cope with the human condition - how to make the best of our lives.

And it is this topic of how to make the best of our lives that I will turn to in the final section of this book.



Chapter 13

Psychopharmacology and the human condition


A world of artificial gratification is upon us. The human condition is increasingly characterized by the prevalence of technological gratifications of which psychotropic drugs are only one instance. And this should be welcomed - despite the very real hazards - in the sense that life without these alternatives would be diminished for nearly everyone. And for those people to whom technology provides not just alternatives but surrogates, life might be hardly worth living.

What, then, is the role of psychopharmacology in such a world - a world which increasingly we inhabit? What can psychopharmacology do to improve the human condition?

Psychopharmacological agents can help cure illness, relieve symptoms and enhance function; allowing people to get on with life. It is difficult to lead a rich social life and difficult to take a positive view of the future when one is plagued by symptoms of malaise, exhaustion, aches and pains, or gnawed at by anxiety. Insofar as psychopharmacology can remove these obstacles, then it should count as a boon to humankind - one of the greatest.

Analgesia - for instance - is probably the most under-recognized benefit of psychopharmacology. The diminution of pain has immediate gratifying effects - but more importantly it enables people to attain greater fulfillment in life. The availability of effective analgesia has significantly increased the number of days in which people such as myself (a migraine sufferer) can lead a normal life rather than lying in bed suffering pain.

Many people use drugs to fit themselves to the unavoidable rhythms and demands of industrial society. Without pharmacological assistance, many people would probably have to settle for lower paid jobs, or maybe would not be able to work at all. Drugs may provide energy or alertness on demand by the use of stimulants such as caffeine. This may be necessary in coping with long hours of work, when we feel ill or tired, and when high efficiency is expected. Similar benefits may arise from the occasional use of sleeping tablets in people whose lives disrupt normal sleep rhythms. These are not ideal solutions to the problems of contemporary living, but they may be the best available.

And at the other end of the emotional scale, people use recreational drugs such as alcohol for unwinding and assisting social intercourse. This anxiolytic effect is quite distinct from seeking obliterative intoxication. The contrast can be seen in Southern Mediterranean countries such as Spain where alcohol is used to lubricate personal  interactions (even being taken at breakfast), yet very seldom consume enough alcohol to become drunk. Indeed, anxiolysis is probably the most sought-after psychotropic drug effect, and alcohol the most popular of the powerful psychopharmacological agents.

So in discussing the role of psychopharmacology in the human condition, the most significant point is not the drugs that make you ‘high’ or intoxicated. These are a more-or-less a sideshow - sometimes diverting and at other times destructive. The real importance lies with those drugs with the potential to remove obstacles to fulfillment, to give life more meaning. When they work, these agent are true ‘happy pills’ - in the sense of being pills that clear the path to human satisfaction.

What of the disadvantages to psychopharmacology? Effective drugs always have side effects, there is the expense, and there is the possibility of addiction. Yet in a world where we have lost hope of political answers, there could be few things more important than technological agents which offer at least some people the possibility of a genuine enhancement in the human condition.

And the proper question about psychotropic agents should surely be the questions of control and access. Regulation, safety and costs naturally require consideration, but we should not lose sight of the principle that individual people who wish to avail themselves of psychopharmacological agents should have access to these agents: the person who stands to receive benefit or suffer harm should be the person who take primary responsibility for control of these agents. The question is not whether to use psychopharmacology in pursuit of the good life - but how. …



Evolution and the cognitive neuroscience of awareness, consciousness and language


What follows is the most conceptually difficult section of this book, and readers without some scientific background may have to skip it, perhaps returning to grapple with it later. They should not feel guilty. But this section contains the fundamental theory of organization of the human mind which underpins much of the argument in this book. It describes what is distinctive about human intelligence, including the evolutionary basis, nature, function and neurological mechanisms of human consciousness and language.

Consciousness is sometimes regarded as intrinsically mysterious - something probably beyond human comprehension, maybe even impossible to define. On the other hand consciousness is an ordinary fact of life - babies are born without it and develop it over the first few years of life. And whatever it is, it presumably evolved - like other complex biological phenomena. Even if we regard consciousness as a curse, then that makes it even more plausible that it has a biological benefit to counterbalance its obvious disadvantages - or else natural selection would have gotten rid of it long ago (saving a lot of hungry brain tissue in the process). We experience the dawn of consciousness every morning when we awaken.

So consciousness cannot be any more biologically mysterious than any of the other extremely hard to understand and explain abilities we and many other animals enjoy. Indeed, consciousness is almost certainly a great deal simpler than human vision - which requires enormous amounts of brain tissue and hundreds of millions of years of evolution to perfect. Consciousness seems to have taken only tens of millions of years to develop, and involves only a relatively small amount of the cerebral cortex.


Evolution of ‘awareness’

People often find ‘consciousness’ mysterious, but the real mystery is awareness - and many other animals are aware, so this is not a specifically human mystery.

The question of consciousness can therefore be approached by considering the general phenomenon of awareness, of which consciousness is one particular example. The mystery usually consists in puzzlement over why humans are apparently ‘conscious’ (ie. aware) of at least some of their own 'thinking' (ie. cognitive processing), rather than cognitive processing simply generating behavior without awareness. Why do we know that we know, instead of just knowing it? Since most of mental life (including some of the most computationally difficult tasks, such as those concerned with vision) proceeds perfectly well without awareness of processing, the question arises: why should awareness exist at all?


Function of awareness

But this question is badly framed. The proper questions should be as follows. Firstly, is awareness an evolved adaptation? In other words did awareness evolve to solve a problem with reproductive consequences for the animal, or is awareness it perhaps an epiphenomenon? And if we assume that awareness is an adaptation with a biologically useful function, the second question concerns the biological nature of this adaptation - what is the mechanism by which awareness solves the problem it evolved to solve?

So, the first difficulty with the 'mystery' of consciousness is that the question as commonly stated bundles together several questions that require separate consideration. There is the general phenomenon of awareness, and consciousness is ‘merely’ a specific type of awareness. In fact, consciousness is awareness of inner body states, as will be described later.

Awareness is not distinctive to humans, many animals display the characteristics of awareness, it is something that seems to have evolved many times in many lineages. And awareness has a quite exact definition: it is the ability selectively to direct attention to specific aspects of the environment, and to be able cognitively to manipulate these aspects over a more prolonged timescale than usual cognitive processing will allow. To hold in mind selected aspects of the perceptual landscape.

Technically, awareness is attention plus working memory - ie. the ability to attend selectively among a range of perceived stimuli and a short term memory store into which several of these attended items can be ‘loaded’, held simultaneously, and combined. Awareness is a standard variable in psychological research, unproblematically measured in, for example, animal vision. It is studied by means such as measuring performance at memory tasks while monitoring gaze direction, delaying responses, and recording brain activity. When brain activity correlates exactly with performance of tasks then it can be assumed that that bit of brain is involved in that particular task. And the length of time which brain activity is sustained corresponds to an animals ability to ‘hold in mind’ information for immediate use. Researchers are therefore recording the operation of a temporary store.

Awareness is not therefore an aspect of social intelligence. Instead, awareness is a mechanism of integration. Awareness is a way of converging and combining information, and it is a functional ability that is found in complex animals living in complex environments.  Awareness therefore relates to the ability to cope with complexity or perception and behavior, and it is found not only in social animals, but also in solitary animals. While awareness is found in animals right across the animal kingdom; consciousness is of much more limited distribution. I suggest that consciousness is probably confined to a small number of recently-evolved social animals such as the great ape lineage - especially common chimpanzees and bonobos - and perhaps a few other recently-evolved social mammals such as elephants and dolphins.


Awareness is in located in working memory

Awareness comprises attention and working memory (WM). To be aware of an perception it must be selectively attended to, and the representation of that entity must be kept active and held in the brain for a length of time adequate to allow other cognitive representations to interact with it and in a place where other cognitive representations can be projected. Working memory is such a place, a place where information converges and is kept active for longer than usual periods. Hence working memory is the anatomical site of awareness.

The nature of working memory can be understood using concepts derived from cognitive neuroscience. Working memory is a three-dimensional space filled with neurons that can activate in patterns. Cognition is conceptualized as the processing of information in the form of topographically-organized (3-dimensional) patterns of neural activity called representations - because each specific pattern ‘represents’ a perceptual input. So that seeing a particular shape produces a pattern of cell activation on the retina, and this shape is reproduced, summarized, transformed, combined etc in patterns of cell activation in the visual system of the brain - and each pattern of brain cell activation in each visual region retains a formal relationship to the original retinal activation.

Representations are the units of thinking. In the visual system there may be representations of the colour, movement and shading of an object, each of these having been constructed from information extracted from the original pattern of cell activation in the retina (using many built-in and learned assumptions about the nature of the visual world). The propagation and combination of representations is the process of cognition.

Cognitive representations in most parts of the brain typically stay active and persist for a time scale of the order of several tens of milliseconds. But in working memory cognitive representations may be maintained over a much longer time scale - perhaps hundreds or thousands of milliseconds - and probably by the action of specialized ‘delay’ neurons which maintain firing over longer periods. So WM is a 3-D space which contains patterns of nerve firing that are sustained long enough that they can interact with other 'incoming' patterns. This sustaining of cognitive representations means that working memory is also a ‘convergence’ region which brings together and integrates highly processed data from several separate information streams.

Any animal that is able selectively to attend-to and sustain cognitive representations could be said to possess a WM and to be 'aware' - although the content of that awareness and the length of time it can be sustained may be simple and short. The capacity of WM will certainly vary between species, and the structures that perform the function of WM will vary substantially according to the design of the central nervous system. In other words working memory is a function which is performed by structures that have arisen by convergent evolution, WM is not homologous between all animals that possess it - presumably the large and effective WM of an octopus is performed by quite different brain structures from WM in a sheep dog, structure that have no common ancestor and evolved down a quite a different path. The mechanism and connectivity of the human WM allows cognitive representations from different perceptual modalities or from different attended parts of the environment to be kept active simultaneously, to interact, and to undergo integration in order that appropriate whole-organism behavioral responses may be produced.

Working memory is reciprocally-linked to long term memory (LTM), such that representations formed in WM can be stored in LTM as patterns of enhanced or impaired transmission between nerve cells (the mechanism by which this occurs is uncertain but probably involves a structure called the hippocampus). So temporary patterns of active nerves are converted to much more lasting patterns of easier or harder transmission between nerves. The patterns in LTM may be later recalled and re-evoked in WM for further cycles of processing and elaboration.

This is how complex thinking gets done - a certain ,maximum number of representations can interact in WM in the time available (maybe a couple of seconds). So there is a limit to what can be done in WM during the span of activation of its representations. To do more requires storing the intermediate steps in reasoning. The products of an interaction in WM can be summarized (‘chunked’) and ‘posted’ to LTM where they wait until they are need again. When recalled and reactivated these complex packaged representations from LTM can undergo further cycles of interaction and modification, each building up the complexity of representations and of conceptual thought.

WM is therefore conceptualized as a site for integration of attended perceptual information deriving from a range of sensory inputs. Awareness seems to be used to select and integrate relevant inputs from a complex environment to enable animals to choose between a large repertoire of behavioral responses. There is a selective pressure to evolve WM in any animal capable of complex behavioural responses to a complexly variable environment. So the cognitive representations in WM in non-conscious animals are derived from external sensory inputs (eg. vision, hearing, smell, taste and touch).

The critical point for this current argument is that non-conscious animals may be aware of their surroundings, but they lack the capacity to be aware of their own body states. Awareness of outer environment is common, but awareness of inner body states is unique to conscious animals.


Evolution of ‘consciousness’


Awareness of body states

So the starting point for evolution of consciousness is an aware animal with an integration centre called working memory which is able to maintain the activity of attended perceptual representations. The evolutionary breakthrough to consciousness occurs when working memory receives not just external perceptual information from senses, but also projections of inner body states. In other words, in a conscious animal WM memory contains body state representations as well as perceptions of the external environment.

Consciousness arises when body state information becomes accessible to awareness. And consciousness depends upon the animal evolving the ability to feed information on its internal physiological state into WM, so that it can be integrated with sensory perceptual information.

First, some terminology. The physiological state of the body states constitutes what is more commonly called an emotion. To put it another way, emotions are body states as they are represented in the brain. Damasio points out that although we think of the brain as being concerned mainly with processing information derived from inputs by the five senses, in fact controlling internal body states is the primary evolutionary process of the brain. The primitive brain in lower animals is mainly a devices for monitoring what is going on in the body - brains (or rather a central nervous system) evolved when bodies got too large to allow communication to occur purely by diffusion of chemicals. So the main business of the brain is to monitor and interpret body states (including emotions), and to modulates these states.

Feelings is the term for emotions of which we are aware. For instance, 'fear' is activation of the sympathetic nervous system and preparation of the body for ‘fight or flight’ - so fear is the effects of the sympathetic nervous system on the disposition of internal organs ('viscera') such as muscle tension, heart rate, sweat glands and so on. When these body states register in the brain and affect behavior without awareness this can be termed the emotion of fear, when we become aware that we are frightened then this is termed the feeling of fear.

By this account emotions may be non-conscious, while feelings are conscious. And emotions are found in many animals, most of which are not conscious and not aware of their emotions. A cow can experience the emotion of fear (and react appropriately) but it will not have the feeling of fear - it will not know it is frightened, it will just be frightened. In other words, fear does not have a representation in the WM of a cow. By contrast a person can experience fear without or with awareness. Fear is present when the body state of fear is present, but humans may or may not have awareness of this - a person can be frightened without knowing, just as a cow can. For example when watching a horror film and absorbed in the action a person might experience the physiological state of fear (thumping heart, hair standing on end - a preparation for action). But the person may lack the awareness that they are frightened until such a point as they are interrupted and asked whether we are frightened - at which point an awareness of fear is produced, an awareness of tense posture, creeping skin, hair on end….

So that fear can be an emotion, leading to an adaptive behaviour such as fight or flight - and the behavior may occur without a person having any awareness of their inner state. But in conscious animals such as humans there may also be awareness of an inner state: the person may know that they are scared. The question is, what is the use of knowing that one is frightened, what is the adaptive function of consciousness - especially given that most animals function perfectly well without such knowledge? What function did consciousness evolve to perform?

The answer is that consciousness is an aspect of social intelligence, and the adaptive function of consciousness is to enable the cognitive modeling of social situations. Animals evolved the ability to project body state representations into working memory in order that emotions could interact with perceptions. And awareness of inner body states is an accidental by-product of bringing together cognitive representations of emotions and cognitive representations of social perceptions in working memory.


Working memory as a convergence zone for emotions and perceptions

Consciousness therefore exists because WM is the location - the only location - where the streams of internal and external information converge, where information on the environment is juxtaposed with information on the body, where emotional representations can interact with, modify and evaluate representations of social perceptions.

The point is critical: once consciousness had evolved, representations of socially-relevant perceptions (eg. a particular person) could be ‘evaluated’ by correlating a perception with subsequent changes in body state (eg. fear after seeing that particular person). So that a particular person would be evaluated as ‘fear-provoking’. Social events often lead to emotional responses and adaptive behavior - and fear of a particular person may lead to avoidance without awareness of the process. But in a conscious animal, cognitive representations of both the social event and the resulting emotion can interact in working memory, and we can become aware that we fear a particular person because the juxtaposition has occurred in working memory.

This perceptual-emotional interaction creates the possibility for new kinds of cognitive representation: representations comprising information from both the senses and the body. It is an accidental by product of convergence in working memory that these new kinds of perceptual-emotional representation are able to become the subject of awareness. Awareness of inner body states is not the primary role of consciousness, rather it is an epiphenomenon of the fact that convergence is attained in working memory - that is just the way that things happened to evolve. If, in an alternative history, internal and external information converged in another part of he brain than MW, then presumably we would not be aware of body states - and we would not therefore be ‘conscious’

It is probable that consciousness is crucially dependent upon neural circuits located in the pre-frontal cerebral cortex of humans - this is the most recently evolved part of the human brain. The dorso-lateral (DL) prefrontal cortex - the upper-outer lobes of the front of the brain - are probably the site of working memory in humans. Indeed, it is perhaps specifically the DL frontal cortex of the dominant (language-containing) hemisphere. And working memory probably functions by having arrays of ‘delay neurons’ capable of remaining active for longer than most neurons, and by arranging these in an hierarchical pattern. Information from different perceptual inputs which is fed into working memory at the posterior part of the DL prefrontal cortex can become integrated as it converges towards the upper levels of the hierarchy. So, in most people, working memory is probably located in the large dome of brain above the left eye and extending about one third of the way back - and the further forward one goes, the more integrated the information becomes and the ‘higher’ the level of processing.

I am suggesting that body state representations are constructed in the parietal lobe of the non-dominant (usually right) cortex - so that information on the state of the body converges on the non-dominant parietal lobe, is interpreted for its emotional importance, and behaviours are initiated that are appropriate to this information - the whole process happening with out any need for conscious awareness. The parietal region seems to be necessary to interpret the biological meaning of body state feedback in terms of relevance to behavior.

In other words, the parietal region seems to conceptualize feedback in terms of a continuously updated body image, and the continual updating of this image is necessary to the experience of emotions. Without the relevant parietal region body states would not be interpretable. Destruction of the right sided parietal (for example in a stroke or a traumatic brain injury) will destroy the body image representation and the ability to determine what is body and what is not will be lost. In the common phenomenon of ‘neglect’ or anosognosia,  a person with a non-dominant parietal lesion may lose their awareness of the opposite side of their body. While they are actually looking at the left hand, they may be able to comprehend that it is indeed a part of their body. But when they are not observing the hand and rely on internal information this awareness is lost - presumably the hand is omitted from their body image, and they may neglect to move or care for the left hand, may even deny that the hand belongs to them, or feel it is an alien hand. This emphasizes the extent to which we depend upon an internal representation of our body state I order to monitor and control the body

Continually-updated body state representations are projected from the right parietal lobe, across the fibres of the corpus callosum that link the two sides of the brain, and to the left dorsolateral prefrontal lobe. Just as destruction to the non-dominant parietal prevents the body state information from being constructed into a body image, so any lesion to the fibres as the cross the corpus callosum or penetrate the prefrontal lobe will prevent body image representations reaching WM. Since the SMM loses emotional input, and perceptions cannot be evaluated by reference to the body states (emotions) that they evoke, lesions to the non-dominant parietal or to the corpus callosum are associated with impaired social intelligence (eg. severing the corpus callosum as a treatment for epilepsy or severing the horizontal connections between the prefrontal region of the cortex and the rest of the brain (as in certain types of ‘leucotomy’) will both severely impair social intelligence - consistent with the assumption that social intelligence needs emotional information (ie. body states) in order to perform its function. A patient with a right sided stroke will often deny they have any disability, and their social judgment is very poor. Similarly ‘split brain’ patients with a surgically severed corpus callosum apparently cannot cope with employment that requires the exercise of planning and judgment, and their social interactions are impaired.


Why can we be aware of body states?

Why should animals such as humans have evolved to become aware of body states? One answer is that awareness of body states was adaptive, it enabled evaluation of social information by emotions, and this gave the conscious animal competitive advantages in the social arena by enabling strategic social intelligence. But it is not the awareness of body states that is adaptive in itself - rather we are aware of our body states an accidental by product of the fact that they are juxtaposed with perceptions in working memory. The ability to ‘introspect’ and become aware of our internal milieu (heart beat, abdominal sensations, tiredness etc.) does not itself have an adaptive function.

It is often stated that the things that consciousness does could not be done equally well or better without consciousness - for example by a 'zombie'. Theorists arguing along this line either suggest that consciousness is non-adaptive, an accidental by product of something else. Or they argue that consciousness is a mechanism necessary to the solution of some particular adaptive problem that can only be solved by consciousness, or at least a problem for which consciousness provides the simplest or most efficient, engineering solution.

However, this is a non-biological and potentially misleading approach to understanding adaptive function. There are many theoretically potential solutions to any specific behavioral problem. The actual solution reached by natural selection is seldom the simplest or most efficient engineering solution. this arises because contingent historical factors constrain the possible directions natural selection can take, each evolutionary step must be an incremental improvement on what went before, and furthermore the genetic mutations upon which adaptations are built are random and undirected. In the case of consciousness, constraints such as the previously existing structure of the brain are critical in determining the range of possibilities for subsequent evolution.


Consciousness is sufficient to perform its adaptive function, but not necessary

The fact that a cognitive task could in principle be performed without consciousness is irrelevant to the adaptive argument. Even if the task could be performed more simply and efficiently by other methods the only thing that matters is what, as a matter of historical fact, actually was the solution arrived at by natural selection.

Consciousness is therefore required to be sufficient to, but not necessary for, the performance of the task which it is evoked to explain - just as legs are sufficient to, but not necessary for, locomotion. Wheels would also do the job. The ‘ultimate’ reason why humans locomote by legs rather than wheels is a matter of contingent historical constraints rather than, say, mechanical effectiveness or engineering simplicity. Whatever the relative functional pros and cons of wheels versus legs, humans just happened to have evolved from ancestors with legs - wheels were not an option. Similarly consciousness working by awareness of body states was not the only way of integrating emotions and social perceptions - the task could in principle (ie. under different constraints) have been does without awareness.

To recapitulate. In principle, humans would not need to be aware of body states in order to integrate body state information with perceptual information. If our evolutionary history had taken a different path, then integration might have been achieved in brain regions where cognitive processing did not reach awareness. But, by the ‘accidents’ of evolutionary history, WM happened to be the place in which emotions and perceptions were brought together. Hence, human awareness of emotions is a consequence of contingent evolutionary factors, it is not a formally necessary aspect of strategic social intelligence and in this sense its mechanism is accidental. And at the same time the awareness of emotions does not in its own right confer an adaptive advantage - it is only the convergence of emotions with social perceptions in working memory that is adaptive. Its mechanism will now be explored.



The somatic marker mechanism


Emotions and feelings

According to Damasio the primary evolutionary function of the animal brain was to serve as an integrative centre to monitor, coordinate and regulate the ‘inner world’ of a complex organism. Therefore the human brain, like the brains of other complex animals, receives on-line, continuously updated representations of the state of the body. These representations are mostly derived from sensory autonomic nerves from the inner organs and somatic nerves from muscles and skin, modified by hormonal chemical messages. They comprise the afferent or feedback arm of a feedback and control mechanism for monitoring, integrating and modulating the current ‘state of the organism’: internal viscera, skin, muscle, connective tissue, joints, blood chemistry and so on.

It seems likely that there is a region of the parietal lobe in the ‘non-dominant’ hemisphere of the cerebral cortex (ie. the side that does not have the language specialization - usually the right hand side) that is responsible for integrating information from body state feedback to create a continually updated representation of the body state. If this region is destroyed (for example when someone has a stroke affecting the right parietal lobe) they exhibit a phenomenon termed ‘neglect’ or anosognosia. The person becomes unaware of all or part of the left side of the body and visual field - that part controlled by the right cerebral hemisphere.

‘Feelings’ occur when body state representations in working memory indicate a change in body state in response to change in the environment. Hence, consciousness uses feedback concerning body states in order to evaluate perceptual inputs, by juxtaposing feelings with the perceptions that have preceded them. In other words, changes in the soma (body) are used to mark perceptions in WM. What is formed are perceptual-emotional representations - representations which encode information on both perceptual information and the body state that occurred in response. We might imagine a visual perception of an aggressive male as one representation and the emotion of terror as another representation - both active in WM at the same time. The SMM will combine these two representations to create a single representation (aggressive male-fear) that when it is activated in WM will elicit both recognition of the perception, and replaying of the emotion. 

Perceptual-emotional representations evolved in order to deal particularly with social situations:  consciousness is adapted to function as an aspect of social intelligence. In summery, the Somatic Marker Mechanism (SMM) evolved in order to evaluate social information and enable strategic social intelligence.


Theory of mind and the somatic marker mechanism

The somatic marker mechanism is a vital aspect of the so-called Theory of Mind Mechanism (ToMM) - although the full theory of mind ability requires (I will argue) language, as well as the SMM.

Theory of mind has been proposed as a cognitive mechanism by which overt behaviour is interpreted in the light of inferred mental attributes. In other words, an animal with the ToMM is able to make a ‘theory’ about the contents of another animal’s mind - this is the ability that Baron-Cohen has termed ‘mind reading’. The ability is termed a ‘theory’ of mind mechanism, because the attribution of mental contents of another animal is based on inference - obviously animals do not have direct access to the contents of each other’s minds and every inference is in this sense a ‘theory’. From observation of behavior and context I may draw the conclusion that someone is angry, I don’t know for sure that the person feels anger -  this is a theory designed to account for the situation and predict the future outcomes, and humans are good enough at this mind-reading that loss of the ability (as in autism) is a severe handicap.

In an animal with ToM, the primary interpretative inference is ‘mentalistic’, and overt behaviour is understood in the context of ascribed motivations, dispositions and intentions. For example, we infer the meaning of a smile by reference to a person's state of mind - the smile could be understood as one of sympathy, of shared delight, of ingratiating deception, or maybe a superior sneer - according to our understanding of the smiler's state of mind. By contrast, it is assumed that most animals - lacking a ToM - infer the meaning of behaviour directly from overt behavioral cues - to such an animal a smile is unambiguously a smile, an expression having a single meaning.

The selection pressure which led to the evolution of ToM was probably the potential ambiguity of social cues when overt behavior is ambiguous (eg. when behavior is complex, rapidly-changing, or deceptive). When behavioral cues are ambiguous, interpretation of a given cue becomes dependent upon inferences concerning intentions, dispositions and relationships.

For example, the approach of another human is ambiguous - it may have several meanings, some hostile some friendly. In the interpretative sequence ‘That man is angry, and approaching me - therefore I must get ready to fight’; the mentalistic ascription of anger is logically prior to the interpretation of overt behavioral cues. If the ascription of disposition were to be changed from ‘angry’ to ‘happy’, then - even when the immediately perceived cues are identical - the inferred meaning of the overt behaviour ‘approaching me’ (and the implications for an adaptive response) would also change.

As a plausible example in chimpanzees, the approach of a male stranger might evoke fear - the physiological state of arousal in preparedness for ‘fight or flight’. This response comprises a characteristic physiological state. Cognitive representations of changing body state are continually constructed in the brain from feedback from the afferent nerves, chemo-receptors and other inputs converging and being integrated probably in the right sided parietal lobe. So emotions are created in this way - using feedback from the body.

In an animal lacking an SMM, such cognitive representations of the changing body state may affect behaviour - so that the emotion of fear might provoke involuntary flight. But in an animal with an SSM, a cognitive representation of this changing body state may be projected forward into the prefrontal cortex and the region which performs the working memory (WM) function. In WM the body state representation that is the emotion of fear becomes accessible to awareness as a conscious feeling of fear. The cognitive representation of ‘fear’ may then be used as a somatic marker when sustained in WM in temporal juxtaposition to the perceptual representation of the male stranger’s identity.

The juxtaposition of the somatic marker for fear with the stranger’s identity that evoked it, creates a novel cognitive representation incorporating what is, in effect, the disposition of that individual - this stranger is disposed to be violent. Although it does not specifically make reference to the mind - this is a theory of mind inference, an inference that the stranger is of aggressive intent. The combined perceptual-emotional representation is implicitly one of ‘that fear-evoking stranger’: ie. aggression and hostility are attributed as a ‘theory’ of the stranger’s mental contents. The combined representation can be stored in long term memory, and when recalled to WM it will be capable of re-evoking individual identity (perception) and simultaneously re-enacting the linked body state of fear (emotion) as a change in body state.

The ventro-medial (lower middle) prefrontal cortex appears to be necessary for the interaction of body state-representations with WM that enables consciousness. What possibly happens is that working memory in the upper-outer (DL) frontal lobe sends a message down through the inner-middle (VM) frontal lobe to deeper structures called the basal ganglia which then evoke the appropriate emotional state in the rest of the body. In patients who have suffered damage to either the ventro-medial prefrontal cortex or the basal ganglia, this damage can prevent the expression of secondary emotional states in response to cognitive modeling - the assumption is that upper-outer frontal, inner-middle frontal and basal ganglia form links in a chain that produce emotion in response to cognitive representations in working memory. If this chain is broken, then we would no longer be able to experience fear as a result of imagining frightening events although we would still experience fear in response to actual frightening events. We would no longer enact the emotion of fear when thinking about a tiger attack - although a real life tiger attack would still produce arousal and flight.


Internal-modeling of behavior by the SMM

The somatic marker mechanism is a system for internally modeling social behavior, and its emotional consequences. The possibility of creating a combined perceptual-emotional representations means that social relationships can be variously combined and sequenced in working memory, and the consequences of this deployment can be evaluated by re-experiencing the enacted emotional body state as gratifying or aversive.

For instance, in an ancestral situation perhaps the representation of my aggressive and lustful male cousin recalled from long term memory along with a representation of my beautiful but gullible daughter, and these two representations are juxtaposed  in working memory. Their interaction will. perhaps, lead to the enactment of an aversive emotion of anxiety which would suggest that bringing these two people together in real life should only be done with caution. Or, modeling the possible outcome of my having a fight with this male cousin might lead to the enactment of a pleasurable sensation, which would encourage me to challenge to this potentially dangerous character.

These examples are simplified, but perhaps communicate the idea that because of the SMM, secondary emotions will accompany the interaction of representations in working memory, and these emotions serve as a guide to interpreting the past and planning future social behaviors. These emotions enacted in response to imagined scenarios are presumed to influence our choice of future action. At the simplest level we are more likely to pursue a course of action which, when played-out by the SMM, leads to a gratifying outcome than we are to pursue a course of action that leads to an aversive outcome. And this is what I mean by strategic social intelligence: it involves the ability to decide between which alternative strategies to pursue on the basis of modeling social interactions and evaluating them by the brain sensing how the predicted outcome feels to us as emotions are enacted in our bodies.

Somatic marking is therefore the actual mechanism of ToM, and in this sense the SMM is the basis of ‘mind-reading’: the SSM is a mechanism for inferring what are de facto intentions, motivations and dispositions. Nonetheless the SMM could be considered almost the reciprocal of the common cognitive conceptualization of the ToMM. For example, hostility would not be represented directly as the hostile contents of another’s mind, but instead as the reciprocal attribution of the feeling of ‘fear’. A ‘hostile’ male stranger would actually be represented by the SMM as a ‘fear-evoking’ male stranger - an identity ‘marked’ by an emotion - with the inference that if we feel fear, then he is probably hostile.


Tactical and strategic social intelligence

The behavior of Damasio’s patients with damage to the system that enacts secondary emotions is characterized by exactly this kind of poor judgment in interpreting and planning social behaviours, and other complex behaviors such as business decisions and gambling. The concept of strategic social intelligence requires further elucidation, both here and elsewhere. Strategy can be contrasted with tactics - strategy being long-term and tactics concerned with the here-and-now, strategy to do with general plans and tactics a matter of immediate responses.

It is presumed that the somatic marker mechanism is not used in tactical social interactions; since the demand for high speed responsivity dictates that behaviours are elicited by directly reading-off the meaning of overt behavioral cues. Modeling in working memory occurs over a timescale of hundreds or thousands of milliseconds, and deploying emotions in the body by the autonomic nervous system and hormonal regulation occurs over an even slower timescale of seconds or minutes. When engaged in face to face argument or flirtation, facial expression, gesture and language must all be minutely and rapidly responsive to the situation (over a timescale that is tens or hundreds of times more rapid than working memory) - and this kind of tactical social intelligence occurs by ‘instinctive’ and unconscious mechanisms. But planned and reflective social interactions, strategic social intelligence, depends upon mental modeling.

Of course strategic and tactical social intelligence will interact. In conscious animals, mentalistic ascriptions of the ToM type form a ‘mind-set; in-place in advance of tactical interactions. Each mind set establishes a tendency for interpretation of cues. So that if we fear an individual on the basis of strategic modeling of their intentions, then we will tend to interpret tactical behavioral cues in the light of them being hostile. If, for instance, you have decided that our lustful cousin has designs to seduce your daughter, then his ‘tactical’ here and now behavior will be interpreted in the light of that assumption - we will interact in a suspicious and cautious manner, and perhaps with a greater tendency to aggression.

Many behaviors are intrinsically ambiguous, having a variety of possible meanings or being capable of being deployed in a dishonestly manipulative fashion. A gift from the lustful male cousin may be generosity or seduction, and which is decided on the basis of strategic modeling of his motivations, intentions and dispositions.  This is one plausible interpretation of the chain of events leading to persecutory delusions - strategic social intelligence creates a mind set in which we falsely assume hostile intentions in a person, then ambiguous behavioral cues associated with that person are consistently misinterpreted during tactical interactions, and these misinterpretations serve to reinforce the false belief in hostility.

The evolution of consciousness probably occurred some time before the divergence of the human and chimpanzee lineages, so that modern humans and chimpanzees are both conscious; although human consciousness differs from chimpanzee consciousness due (mainly) to the addition of abstract symbolic language in humans. Whether consciousness and strategic social intelligence extend further throughout primate species, or to other social mammals (eg. elephants, dolphins), is a question which would need to be explored in the light of an understanding of the SMM. My hunch is that elephants and dolphins are both conscious, and capable of strategic social intelligence. Time will tell.


Humans are essentially social creatures

The nature of the SMM and the functioning of consciousness means that the conscious human world is essentially social. This is a matter of common observation. We are aware of people rather than things, most of our conversation is gossip about the doings of other people, our aspirations are usually related to love and lust while our worst fears usually take the form of threats from other humans. Aside from the times when problems of ecological survival are immediate and urgent - extreme hunger, discomfort or danger - we see the world through social lenses and pursue social goals.

Kummer has commented on the fact that high status, power and wealth are usually achieved for success in the social realm of human versus human competition; and a person’s performance at ecological survival tasks is given much less prestige except insofar as it impinges on this social realm. So that many of the lowest status, poorest and most powerless individuals are those doing the ‘most important’ work of growing and preparing food, sanitation, rearing children, building and so on. At the same time the rich and famous are often people like politicians, managers, entertainers or (in other societies) soldiers - people whose relationship to the world of survival is at best indirect.

This is a consequence of the success of social animals in solving problems of survival. When group living animals have succeeded in developing effective strategies for obtaining food and shelter and repelling predators, then their main source of competition becomes the other members of the group. So, although human cooperation is what made us such as successful social animal, at the same time intra-species, between-person competition characterizes the human condition. To use the biological jargon, ee are both intrinsically altruistic and agonistic.





In considering the human condition there is much that humans share with other animals, many causes of pleasure and pain, survival or death. But there is also much human that is unique, and of these feature probably the most obvious is language.

It is clear that in some sense, ‘language’ is indeed unique to humans - although exactly what it is about language that is unique requires further definition. Many other animals communicate, a few have extremely sophisticated systems of communication. It seems that only humans have evolved a complex, abstract symbolic language which also has that feature that is biologically crucial about human communication - human communication is both complex, and capable of displacement.


Defining ‘language’ as displacement-communication

Displacement refers to the capacity of language to refer to entities and events that are ‘displaced’ in time or space - ie. not you or me, not here, or not now. This is the subject matter of much human language - we do not just talk of the here and now, but conversation ranges widely over reminiscence of the past, hope and fears for the future. But although necessary to allow this, displacement is not necessarily a part of complex communications systems. For example the bee dance is an abstract symbolic communication of spatially displaced information but occurring in an extremely simple and specific communications system. The dance is capable of transmitting information about where to find nectar in relation to the place of the dance (ie. displacement to another place) but that is  pretty much all the dance can do. 

But displacement in human language is built on top of an already extremely sophisticated social communication system we inherited from our ape and primate ancestors - a system based on facial expression, gesture, and a range of sounds. For example, even without language we could talk about ‘my brother’ and what he is doing at the waterhole. So long as my brother and the waterhole are both present they can be indicated by gesture, and so long as we restrict ourselves to what is actually happening her and now then the subject matter can be indicated by further gestures and body language, and our feelings about them indicated by facial expressions and vocalization. So if he was swimming, this could be indicated by pointing at him and the waterhole and miming the swimming. This is how many social animals communicate, and how humans may communicate with other animals such as dogs and with people who do not have language (such as children), or people with whom we do not share language. But without some system of displacement we cannot refer to my brother and waterhole in relation to another time or place, and we could not refer to any person who was not present here and now.

Displacement would inevitably involve some way of symbolizing my brother and the waterhole by creating an abstract referent (eg. this stone is my brother and the leaf is the waterhole; or this gesture, or this word), and by indicating the nature of the relationship between bother and waterhole (ie. swimming - which might be done by facial expression, gesture and vocalization for simple concepts). Brother, waterhole and swimming are a scenario. The act of displacement involves indicating that the brother and waterhole and the relationship are to be understood as being at another time or place - probably by linking the described scenario with indicators of another time or place.

Using displacement we might talk of my brother (even though my brother is not here at present), we might talk of my brother at the waterhole (although the waterhole is not in sight), and the fact that he is swimming. The scenario is one of my brother swimming at the waterhole, and to perform the displacement we might talk of my brother swimming at the waterhole last full moon (past), or the conjecture that he may swim at the waterhole next full moon (future). The scenario is displaced by associating the scenario (brother-waterhole-swimming) with an indicator of different time or place. Displacement requires merely that we can symbolize the full moon and indicate whether we are referring to the last one or the next one, and that this can be linked to the scenario. My suggestion is that displacement works by establishing such linkages to displace scenarios to other times, or places.


Displacement is necessary, but not sufficient, for the definition of language

Displacement is here taken to be the defining feature of language as contrasted with communication. Displacement is defining since displacement is an aspect of communication that could not - even in principle - be replaced by gesture, grunts, facial expression, body language and other non-linguistic communications. Displacement requires symbols, and symbolic communication must already have existed before displacement could have evolved. This implies that symbols can occur without displacement, and that we have inherited a symbolizing ability from our primate ancestors. Common chimpanzees and bonobos who have been trained to use large vocabularies of symbols in communicating with humans seem to have considerable abstract symbolic ability. So human ancestors already had an ability to symbolize and ‘only’ required to evolve the ability to perform displacement .

Displacement is therefore proposed as necessary, although not sufficient, for a communication system to be termed a language. In other words, there is a great deal more to language than just displacement; but without displacement, communication does not count as language. Broadly speaking, chimpanzee ability communication plus the capability of displacement equals what most people would term a full language - human-type language.

There should be a clear distinction between speech as a system of communication, and the existence of and displacement to constitute language. The highly restrictive definition of only displacement-communication as language proper means that most of verbal communication (even in humans) is not language, since most communication is potentially, in principle, replaceable by non-language communication. By this account, most of ‘linguistics’ is not about language, but about speech. And chimpanzee communication - although it may be very sophisticated, capable of complex instructions, and perhaps even have its own ‘grammar’ - would only be considered a full language if turns-out to be true that chimpanzee communication of social information is indeed displaceable. And the speech of children, or adults with mental handicap, however subtle a form of here and now speech-based communication, would only be considered to constitute a full language if the individuals were able to make functional use of displacement.

But it is important to point out that the forms of displacement by themselves, such as the use of words indicative of past and future tense, are not by themselves evidence of displacement. For example it is possible to ‘parrot’ grammatical forms such as past or future tense without any understanding of how to use them in practice. A demented person may use phrases indicative of false memories or imagined fears for the future - but these are socially (and biologically) non-functional. The test is that full language uses the forms of displacement in a functional way with real world applicability.

The idea that displacement is a distinctive and defining quality of human language is certainly not currently accepted. For instance, at present, many of the formal 'tests' of language ability (e.g. the test ‘batteries’ used by speech and language researchers) do not function as tests of displacement. For example, when a doctor asks a patient who has had a stroke to name a watch or a pen being presented to them, this does not count as a test of language. Indeed, there are currently no language tests designed specifically to measure the ability to perform displacement. Displacement is not a recognized key variable in language function.

Furthermore, current ‘linguistic analysis’ is essentially the study of speech or written communication. The discipline of linguistics does not make a distinction between the displacement functions that are unique to language and the use of speech that could, in principle, be replaced by expression and gesture. This emphasizes the distance that the discipline of linguistics need to develop in order to become properly integrated as a biological science.


Why displacement evolved - role and adaptive benefits

The benefits of displacement may seem obvious, since it gives access to knowledge of social events that are remote in space of time, but since displacement does not seem to have evolved in other social primate species such as common chimpanzees, bonobos, gorillas, orang utans and baboons - it needs further explanation. If displacement is useful for humans, why has it not (or not obviously) arisen in other primate species? 

The assumption that there is an adaptive reason why displacement evolved, and that language is not an accidental by product of some other adaptation, must be justified. The adaptive role of displacement is strongly suggested by the social intelligence perspective which sees language as primarily concerned with the communication of information about human beings and their doings. It should also be borne on mind that human brain is difficult to grow and develop, and is metabolically very expensive to maintain, in other words brain is a very costly tissue. This implies that there must be considerable benefits to offset the costs of substantial neural construction such as was required to support the advanced functions of language.

Almost any level of brain damage to the more recently evolved parts of the cerebral cortex will impair language function. Even when the actual production of grammatical speech is apparently unimpaired (as in non-dominant lobe lesions or frontal lobe lesions) so that the brain damaged subject can perform purely linguistic tests at a normal level; the actual applicability of language to social situations is almost always impaired. Close study of most patients with any significant degree of brain damage will usually reveal that factors such as appropriateness, prosody (ie. the rise and fall of intonation), or use of metaphors are impaired - in other words the social function of language is impaired. Language function certainly appears to depend on brain function, and indeed on sustained function of most of the brain.

The first assumption is that whatever the reason for the evolution of displacement - it is social. This is in line with the social intelligence assumption that recent human evolution has been driven by social selection pressures. The social assumption reshapes the question about displacement into asking what is was about ancestral human social organization that made displacement so useful, and how these features differed from other related ape species which did not evolve displacement as part of their communication systems. This argument is, of course, based upon only a few species of primates, and (like almost all scientific theorizing) contains some elements of post hoc circularity, but this does not mean that the theory is untestable.

Even when methods of testability are not immediately obvious, once a scientific theory has been described in a clear and explicit fashion, ways can usually be found by which its novel consequences may be put to the test of observation and experiment. 


Constraints on the evolution of displacement-language

In a conscious social animal without language (such as a chimpanzee) the SMM enables the modeling of differential social identity together with somatic markers to represent disposition, motivation and intention. The SSM can form combined perceptual-emotional representations (implicitly symbolic) such as ‘that angry, aggressive male who hates me’. The SMM therefore allows abstract, symbolic thought - thought in which representations can interact and be manipulated. The addition of language to consciousness augments this combined social-emotional representation with further displacement-markers indicative of other times, other places, other persons.

The specifically socially-adaptive nature of language is supported by evidence from spontaneous language usage (most of which constitutes ‘gossip’ concerning the doings of other people), neuroanatomical correlations between regions concerned with language and social intelligence, and by temporal and genetic informational constraints on human evolution. Conservatively estimated, there has been only around 5-6 million years since divergence of the human lineage from that of chimpanzees, and less than 2000 genes (ie. under 2% of the genome) differ between humans and chimpanzees. This amount of DNA has been estimated to contain  c.35 000 (35K) bits of useful design information - which is not much: certainly not enough to code for something as complex as the whole of the human communication systems.

And although the frontal lobe of the brain has expanded substantially since our lineage diverged from that of chimpanzees, the brain substance itself does not appear to changed qualitatively in its structure. There is no obviously different new cortical region which has been added to the chimpanzee brain in order to perform the function of language - the human brain just looks like more of the same. It seems as if humans have merely evolved more of the same kind of brain stuff as was already present in the ancestors we share with chimpanzees - a relatively quick and easy thing to evolve, since it merely requires a few genetic mutations to instruct the body to ‘make more of this’, and to ‘wire-it -up’ in such a fashion.

These constraints make it likely that the evolution of human linguistic capacity was largely dependent upon pre-established neuroanatomical circuitry, and the evidence on the specifically socially-adaptive nature of language means that the neuroanatomical circuitry of language is very probably the systems which evolved to subserve social intelligence - in other words, working memory and the somatic marker mechanism. The constraints of limited evolutionary time also imply that the extra computations required for language processing were relatively simple - the computations are probably of the same kind as those performed in the primate frontal cortex of other species - the difference is in the connectivity between the computational areas, particularly the addition of extra levels to the hierarchy of convergence and integration.

The extra power of the human brain may be a matter of greater integration. For example the visual system seems to have evolved by new brain regions sampling more different aspects of the visual information generated by the retina, and bringing together these different aspects in new syntheses to extract more and more information from the same initial signal. In other words the human brain is pretty much a bigger chimpanzee brain, with most of the extra brain at the front.


Displacement, group size, and the sexual division of labour

So why did displacement evolve? If the common chimpanzee is taken to be closely similar to the human ancestor of five million years ago, and if we assume that the bonobo also evolved from something very like a common chimpanzee, then a plausible scenario can be constructed. Both chimpanzee species exhibit extremely sophisticated ‘here and now’ tactical social communication by facial expression, gesture and verbal signaling - but apparently this communication relates only to individuals and circumstances that are currently present. The question is: under what ecological circumstances might a great ape benefit substantially from an extra ability, the ability to do something more than this and to communicate about individuals not present and events not now?

My suggestion is that displacement-language evolved for two reasons. The first reason is that social groups became sufficiently large that unique identities were required to keep track of and refer to individuals. Humans inhabit large social groups, compared with chimpanzees, and perhaps this led to an enhanced ability to use abstract symbols to refer to individuals since it would not always be possible to indicate individuals by gesture. Bonobos seem to have abstract symbolic ability to a higher degree than chimpanzees - which fits with the fact that their social groups are much larger. As well as the symbolic ability of chimpanzees and bonobos trained to use abstract geometric shapes to communicate with humans, examples of symbol use have been recorded in natural conditions - for example the young bonobo that used a log of wood as a ‘doll’ to play with exactly as if it were a baby; or the way in which bonobos communicate the need to move on to a new camp by dragging a large branch around the troop and showing it to each member - the branch seems to serve as a symbol (presumably learned) of the need to move. 

But for displacement to be useful, as well as a large group size it may also be necessary that the group splits up for significant periods before being reunited. So the second selection pressure favoring displacement would be division of labour - tasks dividing the group for significant but temporary periods. Given that language (it is assumed) evolved for the communication of information on other people, splitting of the larger group into smaller groups for significant periods would mean that communication of information about other members of the group who were not present would require displacement. The advantages of this are that individuals and their behaviors can be evaluated in their absence - for example information could be gathered concerning the suitability of a potential mate, or rival. 

Humans under ancestral conditions exhibited exactly such a sex-based division of labour. Ancestral groups were nomadic foragers, and these groups would have split-up frequently and for hours or even days at a time, due to the sexual division of labour - men going off to hunt while women remained near the camp, gathering vegetable food and looking after the children. My idea is that this splitting up of the troop would have provided a strong selection pressure to favour those people who could talk about others even while they were not present; to ‘gossip’ in order to understand their personality, interpret their past behaviors and predict their next moves. 

For instance, one plausible scenario is that displacement-language may have evolved initially among women for exchanging information about the absent men, in order to evaluate potential mates and discover more about the behavior of the males of the family.  Females could exchange knowledge (knowledge which might, of course, be biased or deceptive) concerning the absent males. Men are often the topic of conversation among women under such circumstances today. By contrast while displacement would certainly enhance the planning of hunting in principle, such planning is clearly not essential to the activity of hunting. Many, many animals including common chimpanzees hunt effectively in groups without the need for displacement-language, and hunting does not appear to be a selection pressure for displacement ability. And men who are hunting often speak little with one another.

So this scenario suggest that displacement-language evolved initially primarily to benefit women in exchanging information about men who were away hunting, but this language ability was also inherited by men since most inherited traits are shared and displacement would also have benefited men albeit is a secondary fashion. This speculation fits contemporary evidence of higher level linguistic ability (‘verbal intelligence’) in women, a high frequency of spontaneous language use among groups of women, and the observation that the subject matter of private women-to-women conversations if often focused on the subject of men.

I find the story both plausible and attractive, but inconclusive. It could be tested by further study of communication and language use in chimpanzees, and especially bonobos. Although bonobos do not have sexual division of labour, their groups are large (many dozens of individuals) and since bonobos live in jungle they would not be able to keep all group members under observation. This would be a selection pressure for some degree of displacement, and might explain the greater linguistic ability of bonobos relative to common chimpanzees.


Displacement in WM depends on sufficient spatial capacity for complex representations

The radical view put forward here is that there are no recently evolved specialized ‘language centres’ in the brain, but that instead displacement-language has been made possible by a quantitative expansion of the functional capability of working memory, on top of the already-evolved and pre-existing somatic marker mechanism.

This view is in contradiction to a vast amount of linguistic, neurological and evolutionary speculation which is based on a different conceptualization of language (a conceptualization which does not, for example, define displacement as the crux of language, and which does not clearly differentiate language from speech). But when the concept of language is built up in this step-wise and evolutionary fashion, by considering the somatic marker mechanism assumed to be present in chimpanzees and bonobos and adding the capacity of displacement, then it becomes plausible that the evolution of language may be a much simpler and straightforward matter than usually believed.

The basic, underlying principle of displacement of social relevant information could be the interaction of representations created by the somatic marker mechanism with further markers for displacement. What is envisaged is that - for example - a representation such as ‘aggressive-male cousin’ is a combined perceptual-emotional representation, comprising (at least) two representations that have been combined in WM. There is a representation of the perception of a specific person (the male cousin) and a representation of the associated emotional state from which infer that the male cousin is aggressive. To displace the representation of aggressive-male cousin requires nothing more than to create an association with a further symbolic marker which represents another time or another place. 

So, this entity of aggressive-male cousin contains both perceptual information on individual identity and the information to trigger a specific emotional response. This perceptual-emotional representation may be associated with a symbolic marker that represents (for example) a temporal displacement such as ‘tomorrow morning’, or a spatial displacement such as ‘water hole’, or a symbol for another person (including the emotional response) such as ‘my younger sister’. The process is one of incremental expansion and association of information in working memory, whereby representations are ‘superimposed’ and loaded with more and more information  - both perceptual and emotional.

A large capacity working memory can therefore create very complex representations, and these representations can enable displacement  - or indeed some other extra complexity of information. Incremental expansion of working memory over an evolutionary timescale is biologically plausible, and would enable progressively more and more of these iterative associations to be accumulated within the capacity of WM.


Limits of working memory

What are the limits of working memory, what defines how much it can carry? As working memory is essentially an anatomical space where representations (in the form of three dimensional patterns of neural activity) are sustained, then the major constraints on the capacity of WM are set by the complexity of representations that may be sustained, and by the duration that representations may be sustained. In other words, working memory size is defined by the capacity of WM (how complex a representation it can accommodate) and by the timespan of WM (how long the representations can be sustained).

Capacity is probably constrained by the size of the brain devoted to WM (the more neurons in WM, the greater the complexity of representation it can enact). Timespan probably constrains the number of representations that may be kept active simultaneously - along the lines of ‘Miller’s magic number’ (known to all Psychology undergraduates) which suggests that a maximum of from 5-9 items can be sequentially loaded and retained in working memory at one time. The exact number is less important than the fact that there is some such temporal limit on the timepan an item can be kept active in WM.

In evolutionary history the capacity and timespan of WM would presumably have varied between species, according to evolutionary constraints - some species being able to retain items over a greater timespan, and other to enact larger and more complex representations than others. Some evidence from maze tasks suggests that humans and rats do not differ substantially in the timespan of working memory - and it is likely that the very great size of the dorsolateral prefrontal cortex implies that the special thing about human working memory is the size and complexity of representations that it is capable of sustaining (rather than a particularly large capacity for sequential loading with items). This is speculative, but it seems plausible that the large volume of the anatomical substrate of human memory evolved I order to allow complex (hence large volume) cognitive representations to be enacted. 

 According to current evidence, it seems that the WM of a common chimpanzee is insufficient to support the displacement of social information; although it is possible that specific individual chimpanzees with exceptionally large WM capacity may be able to perform displacement. It might also be that chimpanzees can perform displacement on tasks which are computationally simpler than social intelligence. As suggested from the work of Sue Savage Rumbaugh, bonobos may be much nearer to possessing a human-like language ability - which implies that they should have a larger capacity WM than the common chimpanzee. Clearly these questions would require specific exploration.

But the assumption here is that the chimpanzee working memory has the same nature and functional capacity as the human WM - the only important structural difference relates to size. The idea is that the evolution of the very large human prefrontal cortex was driven by the advantages of expanding working memory, and the primary function that was served by the expansion of WM was displacement-language - the ability to form complex associations not just of social identity and emotion, but also markers of other times and places. Such representations containing information on persons, emotional reactions to these persons and also markers of other places and/ or times would, presumably, be highly complex and large, requiring a greater capacity from WM.

It should also be emphasized that the neural substrate for displacement is not specific to displacement. The expansion of WM over human evolutionary history has a very wide range of other consequences, since it enables greatly increased complexity of all types of cognitive modeling - an increase in what many people would consider to be ‘general intelligence’. Expanded WM also enables other types of complex grammatical construction such as representing contingency, and performing many layers of embedding of clauses.

In summary, the assertion is that the selection pressure for the expansion of WM capacity occured in order to enable displacement of language - that was its selective driving force - and therefore that enabling displacement is the adaptive consequence of expanded WM. The other consequences of expanded WM capacity such as many aspects of ‘general intelligence’, although perhaps more obvious under modern conditions, are epiphenomenal by-products when viewed from the evolutionary perspective.


Some consequences and predictions

To put it crudely but reasonably accurately, a human brain may be pretty much a chimpanzee brain with a larger working memory - (plus some motor and auditory specializations to enable speech). The larger size of human working memory means that bigger and more complex patterns of nerve activation (cognitive representations) can be accommodated, and these representations can become so complex as to include information on social identity, emotion and displacement.

General-purpose human intelligence, as applied to the vast range of cultural activity, is an accidental consequence of the adaptive benefits of social intelligence - especially the somatic marker mechanism and the need to displace social information. The enhanced human ability to symbolize may also be a consequence of expanded WM - so that very complex representations can then be further linked to abstract perceptual entities (such as words).

Presumably symbolization is made possible by association of representations occurring in working memory . A perceptual representation interacts with an emotional representation to form a bridging representation that links both. So the bonobo links the perceptual representation of a baby with a particular baby-sized piece of wood, or the need to move camp with the dragging of a branch. The symbol also links the relevant emotions (evoked by a real baby, or a need to move) to the symbolic use of a particular shape and size of wood. With the doll, a specific piece of wood acts to trigger a mental representation which both recalls a baby, and also evokes the emotions appropriate to a baby. The wood is an effective symbol of the baby because it stands both for identity and emotion.


1. Enhancing chimpanzee working memory

This relatively simple scheme seems to include - in outline - many of the features a biological description of language would require. One way to test it would be somehow to increase the working memory of a chimpanzee, and see if this brought its communication ability towards that of humans. It is possible that this amplification of working memory is exactly what has been achieved by teaching chimpanzees the use of visual symbols on a board - each symbol is a convenient ‘chunk’ of the perceptual features of that to which it refers. Each symbol is ‘stored’ on a board for reference which leaves more of the chimpanzee working memory free to manipulate and integrate other representations. Symbol boards can be seen as an indirect method for amplifying chimpanzees working memory rather as humans do by writing or using counters to calculate.

Certainly it seems that the better a common chimpanzee or bonobo can master a symbol board the more  human-like their language becomes, and it does not look too unlikely that Doctor Dolittle’s desire to ‘talk to the animals’ may have been achieved by Sue Savage Rumbaugh and her bonobos.


2. Humans with low capacity WM may lack language (ie. lack displacement)

If displacement-language depends on WM in a quantitative fashion, then this has several other testable consequences. Humans who have WM capacity below a critical threshold, perhaps due to brain trauma, disease, congenital brain damage or other forms of intellectual handicap, would be expected to display redued WM capacity and also lack displacement language - even when they have speech and the ability to communicate theory of mind information. Once again it is important to emphasize the difference between speech and language.

So that - for example - the prediction is that mentally handicapped individuals with Williams Syndrome, who are supposed to have remarkable social and ‘linguistic’ abilities, would be found on specific examination to lack the ability to perform functionally efrfective displacement with language. Displacement is not - of course - merely a matter of being able to use the appropriate grammatical forms such as ‘tense’ - that could be achieved by merely ‘parroting’ (ie. repeating without understanding forms heard elsewhere). But the displacement-language must also be adaptive, must be appropriate to the social situation, and refer to real world events.


3. The social structure of language

The somatic marker mechanism is not restricted to social information, because working memory is not restricted to social information (which is not a distinct module - but is composed of projections from a wide variety of processed perceptual data as well as information on body states). This means that these associations are not confined to social, temporal and spatial information; but may be used to relate any kind of associations. Hence although the adaptive function of consciousness is specific to social intelligence, the mechanisms are general-purpose; and non-social information can use the SMM processes as an accidental by-product of brain connectivity.

Language, by its location in working memory, serves as a ‘translation’ device by which non-social domains of knowledge can gain access to the cognitive apparatus that evolved to deal with social intelligence. Working memory is an association mechanism, and any entities that can be deployed in WM can be associated with one onether. Presumably this is why humans can use their social intelligence to reason about non-social matters such as technology and natural history, by using the SMM in an expanded-capacity working memory.

In effect humans use social intelligence as a system for generating analogies, so that different classes of proposition are processed as if they were social problems. Much of high level human intelligence can be considered as analogical; a system in which SMM works by ‘anthropomorphizing’ non-social topics as if they were stories about intentional agents. I discuss this further in the chapter on creativity.

This capacity to ‘over-learn’ new topics onto the somatic marker evaluation-system of social intelligence has proved to be the crucial factor in the development of ‘symbolic’ human culture.


Language and the human condition

This book is only about language insofar as language is a major element in human nature - language is an aspect of what Bronowski called ‘human specificity’. Language is a big part of what makes humans distinctive.

The current prevailing view of the nature and structure of language is dominated by the assumption that language is a general purpose specialization, by contrast the social theory of language assumes that language evolved for the purpose of communicating social information (‘gossiping’ as Dunbar terms it). The concept of displacement-communication is an incomplete evolutionary and neuroscientific account of full language. In particular, the above scheme distinguishes language from speech, and says nothing of the anatomical, motor and perceptual specializations necessary for verbal communication of language. However, the above view assumes that most of what linguists call ‘language’ is not biologically distinct from ,other forms of verbal and gestural communication. Only displacement-language is biologically distinct from other forms of here and now communication.

This view also overturns the idea of traditionally defined ‘language areas’. Brain areas such as Broca’s and Wernicke’s areas are actually concerned with speech - with verbal communication rather than language. For example Broca’s area is concerned with fine control of motor systems (including those involved in the articulation of speech), while Wernicke’s are is probably concerned with specializations to the sense of hearing and verbal monitoring that evolved along with the evolution of verbal communication.

The remarkable sureness and rapidity of human language acquisition is seen as a consequence of the human drive to communicate combined with the gradual maturation of the central nervous system. There is no evolved ‘language acquisition device’ which makes us learn language. The drive to communicate is based upon our fundamental nature as social animals, and the immediate advantages a child gets from its ability to communicate social information. Normal children communicate as soon as the maturity of the nervous system allows them to do so - and it is the maturation of the nervous system which times the stages of linguistic development.  Common observation shows that in a social milieu a child wants to communicate social information, and tries to talk because it is so useful to the social environment. Learning to talk happens when the physical apparatus of speech is mature, and when the working memory capacity has grown to a sufficient size. Displacement is the last major attribute of language to occur in a normal developing child (at about the time when myelinisation of the central nervous system is complete)  and displacement presumably happens when working memory is large enough to deploy the complex representations which displacement requires.

The social theory of consciousness and language also makes some predictions about the structure of language - its grammar. It predicts that much of the structure of language derive from social intelligence, in other words from the structure and operation of the somatic marker mechanism. It is possible that social entities (intentional agents such as persons) and the nature of social interactions (as represented by the SMM) might constitute some of the fundamental categories of language. These speculations lie beyond the scope of this book, but will be pursued elsewhere.

The crucial point about the dependence of distinctively human intelligence upon the somatic marker mechanism is that, because it is based upon social categories and driven by social motivations, even our abstract thought world is saturated with emotions, preferences and aversions, pleasures and pain. At a deep level, this is why humans are able to care about that accidental and artificial product of human invention that we call culture.




Human creativity and the Col-oh-nell Flastratus phenomenon


Creativity and culture

Creativity at first sight appears to be distinctive to humans, although the more we discover about chimpanzees the more creative they seem. Both common chimpanzees and bonobos are able to innovate and transmit innovations to such an extent that each group they could be described as possessing a ‘culture’. Wrangham and Peterson have listed the contents of such a culture, which include the use of tools (termite probes, sponges etc.) and protective ‘clothing’ (eg. ‘slippers’ and ‘umbrellas’ made of leaves). 

If this is culture at its simplest, the following section focuses upon the opposite extreme - creativity at the highest levels, and the special human satisfactions from creative activity.


A dream

Some months ago I had a bizarre dream in which I was vouchsafed a secret which would ensure my wealth and success. I will share the secret. It was the title for a comic novel - a title so loaded with humorous potential, so funny even in its own right, that it would (I was assured) guarantee classic status for any book to which it was attached. The title was Oh Colonel Flastratus! The important factors about this title were twofold. Firstly that the word ‘Colonel’ should be spelled conventionally but pronounced in three syllables - Col-oh-nell. Somehow this had to be communicated to the potential audience through advertising. And secondly the exclamation mark at the end was vital in order to demonstrate the correct tone of exasperation.

The distinctive feature about my dream was not its silliness but that for several minutes, at least, the event possessed a quality of profound significance. On awakening I wrote down the title and puzzled over its meaning and consequences. Quite abruptly it dawned on me that, whatever its numinous quality, the objective content of my experience was nil. The only ‘funny’ thing about Oh Colonel Flastratus! was the surrealist absurdity of my having attached significance to it.  

But if it hadn’t been for this absurdity, my dream had all the subjective hallmarks of a transcendental or mystical episode. Perhaps if the title had possessed more conventionally spiritual connotations, or if my own sense of the ridiculous had been less acute, or if I had lived in a different society - I would indeed have placed a religious interpretation on the dream: the experience might have seemed like a message from the gods, or enlightenment. If it caught-on, we might have had a Colonel Flastratus cult on our hands.


Peak experiences

Such experiences are not uncommon - the psychologist Abraham Maslow wrote extensively on the subject in the middle of this century. He labeled the phenomena ‘peak experiences’ (PEs). Peak experiences are those moments, lasting from seconds to minutes, during which we feel the highest levels of happiness, harmony and possibility. They range in degree from intensifications of everyday pleasure, to apparently ‘supernatural’ episodes of enhanced consciousness which feel qualitatively distinct from, and superior to, normal experience.

Some people regard PEs as pointing the way to what ought to be the norm in a truly healthy, ideal human life. By this account, normal everyday life is a disease state during which we function at a lower level - firing on three cylinders, as it were. Everyday life is semi-human, and only during peak experiences are we fully awake, alert, aware, conscious, alive. According to this line, PEs are to be valued as providing a privileged insight into ‘reality’. Because they represent a higher state of consciousness, knowledge obtained in this state has greater validity than the insights of the normal, sub-optimal level of consciousness associated with mundane life. Certainly peak experiences constitute some of the most memorable and subjectively significant events in life. 

I do not go along with the idea that peak experiences are a window onto a transcendental reality (because I do not believe there is such a thing), neither do I consider them to constitute a pathway to a higher ‘evolutionary’ state (because I do not recognize any other significant creative evolutionary process than the very slow workings of natural selection). Nevertheless there seems to be something worth pursuing in the idea that PEs are of special significance. Certainly, they do not strike at random, they are associated with particular circumstances. Furthermore, their occurrence may be associated with a transformation in personal behaviour or goals. The potentially profound subjective significance of a peak experience is not open to serious doubt - but the objective validity of the content of that experience is another matter.


Peak experiences in science

The objective significance of a peak experience is a complex matter.  The best test of  is found in a consideration of PEs as they occur in science. Since scientific propositions generated as PEs are susceptible to external validation, they may tell us whether PEs are no more than the Colonel Flastratus phenomenon writ large, or whether they might perhaps be indicative of something rather more interesting.

A recent memorable example of a peak experience was reported in an interview on BBC televisions Horizon program in which the mathematician Andrew Wiles described the moment when he solved ‘Fermat’s Last Theorem’- a problem that has exercised the minds of the greatest mathematicians for three centuries. After working on the problem for seven years in solitude and secrecy, Wiles announced success - only to find a flaw in the reasoning. Another year of tense and desperate work ensued. Then: ‘Suddenly, totally unexpectedly, I had this incredible revelation… It was so indescribably beautiful; it was so simple an so elegant. I just stared in disbelief for twenty minutes’. As Wiles recounted his peak experience, he became overwhelmed with emotion at the recollection.

This was only a recent instance of overpowering subjective sensations accompanying creative insight. Leo Szilard, the discoverer of the principle of the nuclear ‘chain reaction’ wrote: ‘I remember that I stopped for a red light… As the light changed to green it suddenly occurred to me that if we could find an element… which would emit two neutrons when it absorbed one neutron [this] could sustain a nuclear chain reaction’. Thus was discovered the concept which led directly to the atom bomb.

From the original ‘eureka’ moment of Archimedes in the bath, right through to the other intellectual giant’s of the twentieth century, the phenomena of scientific creativity display striking similarities. And peak experiences occur at all levels of achievement, not only the most elevated. There is a special quality attached to the best scientific insights - a sense of crystallization.


A personal example

In my own experience I have experienced these moments. For example, one evening I had stayed behind to examine some new microscope slides of the human adrenal gland which had been stained to show both the cholinergic and adrenergic nerves. The cholinergic nerves were dark brown, while the adrenergic nerves glowed green under a fluorescent lamp. When I flipped the microscope back and forth between natural light and fluorescent light I suddenly realized that the slender, knobbly green nerves were winding over and around the thick trunks of brown nerves. The two systems were entwined, but the cholinergic nerves were passing through the gland while the adrenergic nerves were releasing their noradrenaline into the substance of the cortex. It suddenly dawned that nobody had ever seen this before. It was a moment of apparently mystical significance, in that twighlit room: I knew something for the first time in human history. 

Scientific theories are even more mysterious than experimental discoveries, in that a breakthrough dawns without any insight into the steps by which it was reached. Only afterwards comes an attempt to assemble a rational pathway by which this insight can be justified and defended. In order for the idea potentially to become a part of the body of science - ‘reliable’ knowledge to be placed before the peer group for debate and critique - propositions must be expressed in a form that will be widely understandable, check-able and useable. This kind of expression may not be an easy task to achieve. It took me more than six months to write the malaise theory of depression as a paper, grappling with expression, constructing a plausible chain of inference to back up my intuition. It will take even longer to get the idea across to the scientific peer group, constructing convincing rationale, an enlightening example, a memorable name and an appealing analogy to assist understanding. And even longer to test its scope and validity.

Darwin spent twenty years musing and gathering evidence of evolution by natural selection before he was stampeded into publication by Alfred Wallace independently having the same idea (he was also deterred from publication by worry over the controversy which he, accurately, guessed would follow publication). And it took approximately another 100 years before the theory of Natural Selection was completed by its synthesis with genetics. Einstein had key insights into relativity as a very young man (eg. when he imagined what it would be like to ride a beam of light) but several years of work were necessary to turn that insight into published science. And Richard Feynman was using his diagrams to solve problems of quantum electrodynamic theory for several years without being able to explain what he was doing, or why it worked. It required an intervention from his friend Freeman Dyson to indicate to the broader community of physicists just what Feynman was up to. Clearly the insight and its ‘translation’ into a comprehensible form are two different phenomena - sometime requiring two different people. WD Hamilton and GC Williams published breakthroughs in evolutionary theory in the early 1960s, but these proved largely incomprehensible until Richard Dawkins re-expressed them and provided the necessary metaphor a decade later in his famous book The Selfish Gene.

This is the nature of peak experiences concerned with scientific theory. They are emphatically not self-validating. Even when the insights are of matchless brilliance their implications must be spelled out and checked. For instance, there was the moment when Francis Crick and his co-workers realized that they had been thinking along the wrong lines about how genes were made into proteins. On the one hand there was ‘the sudden flash of inspiration.. that cleared away so many of our difficulties… When I went to bed… the shining answers stood clearly before us.’ On the other hand Crick knew that ‘it would take months and years of work to establish these new ideas’. However, ‘We were no longer lost in the jungle. We could survey the open plain and clearly see the mountains in the distance’.


The nature of the scientific peak experience

The typical insight associated with a PE is integrative in nature, with the sense of meaningfulness that comes from assembling the right things in the right order to make some kind of sense from them. Jacob Bronowski emphasized that creation exists in finding unity - the likeness and pattern that underlies variety; and that this applies equally to the sciences and the arts: he quotes Samuel Taylor Coleridge: ‘beauty is unity in variety’. The moment during which superficial differences crystallize into comprehensible order is the peak experience - it is the ‘moment of creation’.

The crystallization metaphor is, in some respects, misleading. A theory is much more than a summary and re-ordering of the facts; a theory postulates that which lies behind the facts and generates them. A good theory selects from the facts and points beyond them. Science is structured knowledge, not merely a loose-leaf folder of ‘facts’. It is the structure that enables scientific knowledge to be testable

The peak experience of scientific creativity does not merely constitute a simple elegant and compelling arrangement of data that is already in the mind; the PE involves an insight into which of facts are the important ones, and how they are related to one another by causal processes. A scientific theory involves carving nature into new shapes, and saying it is this that matters rather than that; and these processes rather than those.

So as well as integration of previous knowledge, the PE is typified by a sense of possibility. The PE can be conceptualized as a point of stillness, where an understanding of the past and the potential of the future intersect. So that the PE is a reaching of conclusions which have implications. The PE is therefore a kind of symbolic narrative - a story with roots and branches. It is not simply a pleasant event in a life; it is an experience with the potential to lead onto other things. And in this inheres its subjective significance to a life. But the fascinating and distinguishing aspect of scientific creativity is the further constraint that the content of scientific PEs should be ‘objectively’ valid and accepted by the community of co-scientists. Scientific knowledge must not merely be compelling to the scientist who thought of it, but should also fit with the best of current information and have the potential for future testability, peer group consensus and reliability in practice.


Limitations of the PE

It is perhaps tempting to assume that the PE is some kind of guarantee of the truth of a scientific insight. But this cannot be the case; science is not underwritten by a subjective sense of conviction, it should be useable by anyone competent. Delusions are all too common, and people can believe almost any proposition with absolute, unshakable confidence. Furthermore, almost all scientific insights - however valuable in the short term - will turn out to be mistaken or only approximate in the longer term. Yet the PE is not wholly irrelevant to the concept of truth at the individual level.

Peak experiences may be associated with insights that are wrong but for the right reasons. In other words, the scientist has done the best possible job of making sense of things at that particular stage in history - but later developments will overthrow their insight. Indeed, this is the usual fate of scientific knowledge. Equally, PEs may also be associated with insights that are right, but for the wrong reasons: the scientist happens to have hit upon the right answer, but using a non-valid method of getting there. Some of the early astronomers such as Kepler were number mystics, leading to them seek new planets in order to make them up to reach a magical figure of seven. They found the extra planet they sought, but were wrong about why it was there - as became apparent even more planets turned up to spoil the mystic symmetry.

On the other hand, there are scientific PEs where - despite a strong and subjectively profound sense of personal conviction - the scientist is wrong and for the wrong reasons. Mathematicians, in particular, are prone to assume that their peak-experience-inducing insights, which may be valid in the axiomatic world of mathematics, will inevitably be reflected in the real world where their assumption s have not been confirmed. This kind of thinking is currently widespread in the speculations of ‘chaos’ and ‘complexity’ theorists in theoretical biology; as well as in the field of consciousness studies. You can’t get peanuts out of oranges, as my old chemistry teacher used to say - likewise you cannot get biology out of mathematics: the relevant knowledge of causes and entities must be present before crystallization can occur.



The meaning of the PE

If peak experiences are not a guarantee of objective truth; what do they signify? My hunch is that a scientific PE is some kind of personal guarantee of the subjective truth of an insight. In other words, scientific PEs are a marker which the mind attaches to those of its insights the mind considers most profound - albeit having made that decision largely as a result of subconscious, inaccessible processing. The PE is therefore a signal that states: ‘This is good stuff, by your standards - maybe the best you are capable of, under current circumstances. Don’t ignore it, don’t forget it, and try to understand it’. 

The PE seems to function as a means of focusing attention - the characteristic emotion asserts that the marked insight is something we should dwell upon, puzzle over, sort out - do something about. It seems to me that a vital component of the PE is exactly this sense of a call to action in the sense of making a decision, changing our lives. The PE is not - or should not be - simply a passive feeling of happiness and insight. Indeed, episodes of quiescent bliss and idiosyncratically personal insight are easily confused with PEs.

The crucial variables relate to knowledge base and brain state. A peak experience cannot generate valid new theories unless the person has sufficient knowledge of the field. There has to be something dissolved in the solution before crystallization can occur. There are an infinite number of wrong theories - and only a few right ones. There is a negligible probability that the right ones will crystallize out unless the right ingredients are somewhere in the solution.


Delirious delights

Cerebral pathology, intoxication with pharmaceutical agents, the clouding of consciousness on the borders of sleep, or the reduced consciousness of sleep itself are all associated with the production of pseudo-peak experiences. Any PE that occurs when the brain is functionally impaired (ie. delirious) is automatically suspect.

Clouding may induce strange outcomes. William James described the effects of alcohol in promoting the ‘mystical’ faculty, and documented the ‘transcendental’ experiences of people under the influence of anesthetic agents such as nitrous oxide (laughing gas) and chloroform. Such agents were able to elicit the sense of direct access to God led to an embryonic anaesthetic-based ‘psychedelic’ religious cult during the nineteenth century. More recently, during the nineteen sixties, there were similar claims made for special insights to be obtained as a result of using ‘mind-expanding’ hallucinogens such as LSD, mescaline or peyote. Contemporary New Age pharmacological mystics advocate the drug ‘Ecstasy’ (MDMA) combined with prolonged dancing to pulsating electronic music and flashing lights.

These pharmacological maneuvers are supposed to provide PEs ‘on tap’ - but all of them produce brain impairment. Critical faculties are lowered, euphoric states induced, so that mundane insights take on apparently profound importance. But only those who are equally ‘stoned’ find the results impressive.  

Another argument heard in favour of the benefits of inducing PEs is that intoxication removes sensory barriers and experiential filters - allegedly put in place by a repressive social system - to enable a greater immediacy of perception. On this view, knowledge is ‘out there’ ready formed and awaiting the apprehending mind. Drugs, presumably, are believed to render the mind permeable so as to ‘blot-up’ the truth.

Such notions assume that people are naturally and spontaneously ‘creative’, but have creativity crushed out of them by societal controls, maladaptive learning, capitalism and other nasty things. This kind of analysis leads to advocating the use of consciousness-altering drugs as a self-educational tool, a technique to open the ‘doors of perception’ and un-bottle spontaneous genius. Intoxication is assumed to remove sensory barriers and experiential filters, break up rigid patterns of unnatural thinking and allow the melted mind to recrystallize in conformity with underlying truth. Aldous Huxley expressed this view in perhaps its most extreme form when he suggested that the human mind knew everything in the universe, but had evolved a filtering mechanism (a ‘valve’) in order that we are not overwhelmed with stimuli. The peak experience (induced in his case by mescaline) had the effect of releasing this perceptual valve and allowing more of reality to get through to awareness; giving access to otherwise arcane knowledge concerning events and entities in the universe of which we have no direct experience.

Creativity is here seen as something to be liberated. It is sometimes claimed that by rendering apparently peak experiences more common and controllable, drugs may allow the attainment of a ‘higher’ form of human evolution.


Sorry to be boring, but…

Evolutionary theory takes exactly the opposite view to Huxley - instead of humans ‘naturally’ knowing everything and evolving the ability to experience less; biology sees the starting point in insentient, inert matter and regards the capacity to perceive anything at all as having evolved gradually over many millions of years.

Knowledge is certainly not out there waiting to burst in on our minds as soon as intoxication lets it through. Rather, the capacity to attain knowledge, to perceive, and to be aware of our perceptions, are all adaptations that have been painstakingly constructed over an evolutionary timescale. Neither is scientific creativity spontaneous, natural or pre-formed; it is attained by constructive human striving - something made, not a spontaneous fact of nature.

No scientific breakthroughs have ever come from ignorant and uneducated prodigies who happened to be intoxicated. Neither does creativity in science emerge like a beautiful butterfly breaking from a chrysalis of social convention, rather it is something constructed by efforts and gifts (and luck) - including the efforts and gifts of colleagues. Science requires knowledge and skill as well as the right state of mind.


Consciousness as a storyteller

Human consciousness operates as a storytelling device. The somatic marker mechanism associates perceptions with emotions in working memory, so that thought is accompanied by a flow of emotions. These emotions in turn generate a flow of expectations or predictions, which the story may either confirm, or else contradict in interesting ways that - after they have happened - can retrospectively be seen to flow from what went before by less obvious paths hence are not contradictory after all. What makes a story is essentially this flow of linked emotions, a bodily enactment of physical states that have been associated with those propositions that we use in internal modelling.

Consciousness seems always to ascribe causality - it is not content with recording detached representations, but works by synthesizing events into a linked linear stream which is then projected into the future as a predictive model to guide behaviour. As bodily emotions fluctuate, feedback to the brain will monitor and interpret this flux in terms of the meaning of perceptions - the emotions interpret the perceptions. Since the somatic marker mechanism is a device for using emotions to infer intentions and other states of mind, then sequences of emotions will automatically create inferred narratives of quasi-social relationships - in other words stories.

Consciousness is so compulsive a storyteller as to be a master confabulator - consciousness will always invent a story in terms of cause and effect relations, even when it has no idea what is going on, and available data are inadequate or contradictory. Young children will interpret abstract computer images that ‘pursue’ and ‘flee’ and ‘hit’ one another in terms of exactly these social behaviours - they will give the abstract shapes personalities and intentions even though they are merely shapes moving on a screen. Seeing faces in the fire, or animals in the clouds, is another instance of the same kind of nearly automatic meaning-generation.

Theoretical science works largely by analogy, by modelling. Perhaps nobody can reason in utter abstraction. Scientists build simplified working models of reality, and map these models onto reality to make predictions - seeking a one to one correspondence between the model and the world. Some scientific models are mathematical - where real world entities are mapped onto mathematical symbols and real world causes are summarized in mathematical operations - such as Einstein’s theory of special relativity: e = mc2 where e stands for energy, m stands for mass and c is a very large number. Mathematics predictions can then be tested against observation to see whether the model corresponds to reality.

Other models are much simpler - the ‘ball-and-spring’ models to show atoms and chemical bonds and valencies, and a host of idiosyncratic mental models which are used to make breakthroughs and then discarded, often unacknowledged. The molecular shapes used by Crick and Watson to construct their model of the double helix of DNA are a well known example, the models represented the shape of molecules and some of their ways of bonding to each other - and physically manipulating the shapes was a vital element in solving the structure of DNA. Indeed the ‘eureka moment’ was probably when Watson put together cardboard shapes of the bases and saw that they formed specific complementary pairings. The great physicist Clark Maxwell’s notebook musings about how electro-magnetism works strike modern observers as extraordinarily ‘childish’ - with their peculiar shapes and swirls of how magnetism and electricity might operate - yet they nonetheless led this first-rate genius to the insights that enabled several major breakthroughs in theoretical physics.   


The social nature of scientific models

Stories are perhaps the commonest mode of analogical thought. The link between story-telling and scientific theorizing is instructive. A scientific hypothesis is like a story in the sense that entities and causal processes are analogous to characters and their motivations. I would guess that - at a deep level - the science and the storytelling processes of the conscious mind are identical; what differs are the ingredients. It has even been suggested that theoretical physicists and chemists endow their musings with human like qualities, just as chess masters constantly deploy ‘battle’ metaphors to describe their strategies in what would otherwise appear to be the most objective and mathematical of games.

Certainly, I find that I develop emotions about all aspects of science. For example I must admit to an idiotic preference for adrenergic over cholinergic neurotransmitters, since the adrenergic system was associated with physical action (eg. the ‘adrenalin rush’, while cholinergic activity had connotations of lying around feeling bloated after a meal (acetylcholinergic fibres innervate the gut). Silly, of course, but I couldn’t help anthropomorphizing about entities which were important to me.

I would go so far as to suggest that creative science is constrained anthropomorphism. Learning to do a science involves learning how to tell a particular kind of story: who are the important characters and what are their typical causal motivations - that is the anthropomorphism. Each scientific discipline has a distinctive set of personalities and behaviours - in physics there might be fundamental particles acted on by gravitational, electromagnetic and nuclear forces; in biology there might be cells and organisms acted on by macromolecules such as DNA and proteins under the influence of natural selection.

The constraint comes in because the range of possible stories one is permitted to tell about particular entities is strictly limited by previous relevant science. So that whether the entities in the story are attracted or repelled, counterbalanced or exaggerated, add or multiply their effects… these aspects are controlled strictly by scientific criteria.

But having established a proper set of ‘dispositions, motivations and intentions’ for the entities, we predict what they will do by exactly the kind of ‘story generating’ social intelligence that we have been exploring in the earlier parts of this book. Indeed, I would go so far as to say that most people can only be creative in this quasi-narrative fashion, and scientific creativity involves storytelling of a highly specialized kind - the exception is mathematics, where the outcome of interacting entities is determined not by quasi-social factors but by mathematical functions.

The role of narrative is both to generate theories and to make them useable - because science is a human product it needs to be shaped to the human mind. If a scientific theory cannot be put into a quasi-social shape, then we find it very difficult to think about. Our mind, after all, is bubbling with social meaning even when the world is chaotic: we see pictures random dots, monsters in the shadows. We confabulate causal pathways to explain our emotions and behaviours. Inanimate objects - such as stones, rivers and trees - are imbued with personality and powers of malevolence or benignity. For humans, the world is full of relevance and purpose. Reality comes to us already imprinted with labels of preference. Theories that cannot be subsumed to this world do not have much chance of being remembered or used, they will be forced aside by more ‘interesting’ ideas.

So it is a fusion of constrained reality, trained aesthetic appreciation and emotional preference that makes possible the scientific peak experience. The peak experience is that moment when analogy strikes us - we see underlying unity, similarity in difference, meaning emerging from chaos - a bunch of disconnected facts coalescing into a story. 



Humans view the world through spectacles of social intelligence. And this applies to science as well as the arts, both endeavors are intensely subjective and the difference lies in the social validity of their insights rather than the mode of generation.

The significance of a peak experience is essentially subjective. The apparently self-validating emotion of deep and profound significance which sweeps like a wave across clear consciousness is probably a somatic marker informing us that we have performed cognitions of special importance and significance to our own goals - and to reward us with ecstatic feelings for having done so. It is analogous to the satisfaction of a good story, well-told - a story with the ring of truth to it.

The subjective importance of the PE is considerable. The peak experience has a talismanic function, something remembered as a reward for difficult but desirable behaviour in the immediate past, something pointing toward a fruitful line of behaviour for the longer term future.

The objective validity of the scientific peak experience is determined by its public dimension - whether it stands up to testing by peers. The predictive value to be placed upon an hypothesis attained during a peak experience is not wholly arbitrary, however; it is a product of the quality of the scientist. In the first place a scientist must be competent to assert the hypothesis, he should have a mind that is informed and unclouded. The probable objective validity of a scientific peak experience is affected by the quality of the scientist’s thinking and preparation, and how well he has internalized the processes and constraints of his discipline.

Peak experience insights have the potential to mislead as well as enlighten. The easy induction of pseudo-profound insights by intoxicants serves as a warning of the potential pitfalls. When the mind is deranged by drugs, delirium or drowsiness, then this emotion may short-circuit and ‘spontaneously discharge’ to become attached to almost any event - such as an idiosyncratic pronunciation of the word ‘Coll-oh-nell’ or the importance of an exclamation mark. Then an arbitrary object or stimulus becomes labeled with an obscure sense of delight and personal relevance. When the brain is impaired, the specific object to which the sense of significance attaches itself may be a matter of chance, and the insights may be nonsensical - a process we might call the Colonel Flastratus phenomenon - portentous meaning projected onto an irrelevant stimulus. By making the peak experience easier, and by severing affect from cognition, intoxication also diminishes its meaningfulness.

Peak experiences are the result of a ‘significance alarm’ going off in the brain. When things are working properly, this alarm will only be triggered when something ‘important’ has happened, that is worthy of sustained attention. So we are often right to take peak experiences seriously - yet their ‘significance’ is seldom transparent, and we cannot take the insights of peak experiences at face value. Perhaps the best approach is to regard them as a fascinating enigma, a code which may contain a message of profound import.

On the other hand, after laboriously cracking the cipher, we may not find the secret of life - merely a pointless pun. 




There are two individuals who require primary acknowledgment as the intellectual fathers of this book: David Healy and Antonio R Damasio. This book attempts to synthesize the conceptual breakthroughs of Healy and Damasio and place them within an evolutionary context.

Since reading his first book, The suspended revolution, I have become ever more convinced that David Healy is the most insightful and original British psychiatrist of recent decades. His unparalleled knowledge of phenomenology, psychopharmacology and the history of medical science are unique, and exactly what is required for the present time. Suffice it to say that it was Healy’s work that stimulated my own return to psychiatry as the focus of my work. David Healy has become a friend, but I have never met Antonio Damasio. However, my reading of Damasio’s 1994 volume Descarte’s error was a watershed. Damasio has brought emotions within the perspective of cognitive neuroscience, and has ‘solved’ the ancient problem of the nature of consciousness through his discovery and explication of the somatic marker mechanism.

There are many other colleagues who richly deserve acknowledgment, and this is provided largely by means of the citations and references which follow. But special mention should be given to Jonathan Rees and to my brother Fraser Charlton whose weekly conversations - on and around medicine and science (Jonathan), and on and around everything but medicine and science (Fraser) - have been a major source of intellectual stimulus over the past years.

Drs Alan Kerr and Desmond Dunleavy are consultant psychiatrists with whom I worked in the early 1980s, and who have since made me welcome on their ward rounds. Without the timely stimulus of clinical experience they made possible, the ideas that form this book would not have happened.

Solitary contemplation, reading and conversation are the life blood of my academic life as a theoretician - and the coffee room conversation in my current Department of Psychology is particularly good. Professor Malcolm Young, not only provided the niche necessary for writing this book, but was a source of vital insights concerning brain organization and function. He has also subjected me to steady encouragement (and pressure) to get down and write it, and has reacted with enthusiasm to ideas and enquiries. My editor at Radcliffe, Gillian Nineham, commissioned this book with an excitement, swiftness and confidence that I found immensely heartening.

Considerable support both needed for me to get even a slender a book done, since I am more naturally a sprinter than a long distance runner when it comes to writing. So special thanks must go to Gill Rye, my wife as well as my major sub-editor, sounding board and pragmatic critic.   




Further Reading and References


Chapter 1 - Psychiatry and the Human Condition

The background to this chapter, and to the book as a whole, arises from a conference I attended at University College London during 4-5 March 1998, which was organized by Carl Elliott. I prepared a talk for this conference which was later published in JRSM as Psychopharmacology and the human condition, and had formative discussions form David Healy and Peter Kramer who were also participants. The general idea of psychiatric illness as a common fact of everyday life had previously been provoked by Healy’s The suspended revolution and The antidepressant era, and Kramer’s Listening to Prozac. In particular I was stimulated by grappling with the implications of the fact that ‘antidepressants’ often benefited people who did not fulfill the criteria of Major Depressive Disorder.  

Since 1994 I have been involved in the emerging field of Evolutionary Psychology, and by recent progress in evolutionary biology especially as it applies to humans and human behavior. My interest was first grabbed by Matt Ridley’s The Red Queen which concentrated mainly on sexual selection, and then by the trailblazing edited volume The adapted mind. In a chapter of The adapted mind, and in Darwin, Sex and status, the anthropologist Jerome F Barkow showed how an evolutionary perspective could throw light on human culture. More of this came from Jared Diamond in The rise and fall of the third chimpanzee which drew my attention to the egalitarian and leisured society of our nomadic foraging ancestors, the transition to agriculture, and to the major idea of James Woodburn’s that societies could be divided into ‘immediate-return and delayed-return’ economies (which constitutes one of the most valid and profound categories in the social sciences, in my view). The work of Ernest Gellner on types of human society and the transitions between them confirmed and sharpened these insights.


Barkow JH. (1989). Darwin, sex and status. Toronto: University of Toronto Press.

Barkow JH, Cosmides L, Tooby J (eds) (1992). The adapted mind. New York: Oxford University Press.

Bird-David N. (1992). Beyond ‘The original affluent society’: a culturalist reformulation (and replies). Current Anthropology, 33, 25-47.

Byrne RW, Whiten A. (1988). Machiavellian intelligence: social expertise and the evolution of intellect in monkeys, apes and humans. Oxford: Oxford University Press.

Charlton BG. (1997). The inequity of inequality: egalitarian instincts and evolutionary psychology. Journal of Health Psychology 2: 413-425.

Charlton BG. Psychopharmacology and the human condition. JRSM 1998; 91: 599-601.

Cohen M, Armelagos G (eds). (1984). Paleopathology at the origin of agriculture. Orlando: Academic Press.

Diamond J. (1992). The rise and fall of the third chimpanzee. London: Vintage.

Erdal D, Whiten A. (1996). Egalitarianism and Machiavellian Intelligence in human evolution. In PA Mellars, KR Gibson (eds) Modelling the early human mind. Cambridge: Cambridge McDonald Institute for Archaeological Research.

Gellner E. (1988). Plough, sword and book: the structure of human history. London: Collins.

Healy D. The suspended revolution London: Faber, 1990.

Kramer PD. Listening to Prozac London: Fourth Estate, 1994.

Ridley M. (1993). The red queen: sex and the evolution of human behaviour. London: Viking.

Sahlins M. (1968). Notes on the original affluent society. In (Eds.) RB Lee and I DeVore Man the hunter. Chicago: Aldine, 85-89.

Woodburn J. (1982). Egalitarian societies. Man, 17, 431-451.



Chapter 2 - Social intelligence and the somatic marker mechanism.

The profoundly important concept of social intelligence originates with Nicholas Humphrey, and has been taken-up and extended in the ‘Machiavellian Intelligence’ volumes by Andrew Whiten and Richard Byrne. This work merges into the literature concerning the concept of ‘theory of mind’ which I explored particularly in the work of Simon Baron Cohen and his colleagues interested in autism. But I have introduced a distinction between here-and-now tactical social intelligence (common to many animals) and strategic social intelligence based upon internally-modeling and evaluating social interactions (which is probably confined to a few species of social mammal). It is strategic social intelligence that is distinctive, although possibly not unique, to the primate lineage and probably best deserves the ‘Machiavellian’ sobriquet.

The nature of strategic social intelligence depends upon the nature of the mechanism which performs it, that is the somatic marker mechanism as described in the work of Antonio R Damasio and his colleagues - especially in the book Descartes error. The idea of the somatic marker mechanism is expounded more fully in the Appendix. The crucial fact that emerges from Damasio’s analysis is that emotions are body states, and that the most obvious way to affect emotion is to affect its bodily expression. Since psychiatric illness is often dominated by changes in emotion, this provides a way of understanding psychiatric drug action. Any drug that effects the body will potentially effect emotion. And selectivity of peripheral action is a plausible mode whereby drugs might exert specific emotional effects.

The usual idea is that psychiatric drugs work on the brain in very specific ways. My general view is that most drugs that really do work on the brain do so by having pretty crude and general effects on overall brain activity - producing crude and general behavioral effects such as sedation or arousal - and that tolerance quite rapidly develops to these effects.

So, I will argue that most psychiatric drugs either exert general effects on the brain leading to general effects on behavior, or specific effects on the body leading to specific effects on behavior.

References for this area are provided in the Appendix.


Chapter 3 - Psychiatric classification

My interest in psychiatric classification goes back to my time as a medical student and in clinical practice during the early 1980s. Harrison Pope drew my attention to the fact that diagnostic categories could be misleading as a guide to prognosis and treatment unless account was also taken of the prominent symptoms, Eric Wood told me of the US studies in which psychotic patients randomized to imipramine and chlorpromazine were found to respond by symptoms rather than by diagnosis, and I became sympathetic to Tim Crow’s then concept of a ‘unitary psychosis’. I learned a great deal of neuroendocrinology science from the likes of Nicol Ferrier, Phil Lowry and Alan Leake. I was also aware that the action of psychiatric drugs did not conform to such categories as ‘antidepressant’ or neuroleptic’ and that we needed a different - and probably symptom based - way of understanding these questions.

By 1990 I was persuaded that the existing strategies of psychiatric research were going nowhere, and I argued this in a somewhat notorious paper in Psychological Medicine - but I had little idea of what to do instead - except to adapt the approach of cognitive neuropsychology which I read about in Tim Shallice’s book From neuropsychology to mental structure, and in works by John Marshall, and discussed with my friend Janice Kay who worked on aphasia. In 1992 I read David Healy’s The suspended revolution, which persuaded me of the need for a more ‘phenomenological’ kind of psychiatry, with attention paid to reports of subjective psychological states. Shortly afterwards, Tony David published an exciting editorial in Psychological Medicine about the proposed field of cognitive neuropsychiatry. But since I had no new ideas about clinical practice, therapy or drug development, these criticisms were rendered pretty narrowly ‘academic’ and a matter only for pure research.

The breakthrough in understanding psychiatric drugs was also made through reading David Healy: specifically the series of books comprising Psychiatric drugs explained, The Psychopharmacologists volumes I and II, and The antidepressant era - also by conversations and correspondence with the man himself.

When Healy’s phenomenology and psychopharmacological insights were combined with cognitive neuropsychiatry, cognitive neuroscience (of which I had become aware since joining the Department of Psychology at Newcastle), and my own basis of evolutionary biology - at long last a new way of looking at mental illness and its treatment began to crystallize. I saw that the job of a new and biologically valid approach to clinical psychiatry was to was to describe and classify categories of ‘psychiatric’ symptoms and to ‘match’ this nosology with categories of drug effects. Then each patient’s condition could be treated in an individually-tailored fashion, and the clinician (or the patient themselves) would know what aspect of the illness the drugs was trying to treat - which would potentially enable the minimum effective dose to be established, again on an individual basis. Damasio’s theory of emotions alerted me to look at the body rather than the brain as a basis for the emotional state’s characteristic of psychiatric illness. The final step was to return to clinical work, attending rounds and speaking to patients - and seek to confirm these ideas by observing patient’s experience of symptoms and responses to drugs. This triggered more ideas. Then it was a matter of writing it all down, which takes us up to the present…


Caramazza A. (1986). On drawing inferences about the structure of normal cognitive systems from the analysis of patterns of impaired performance: the cases for single patient studies. Brain and Cognition, 5, 41-66.

Charlton BG, (1990). A critique of Biological Psychiatry. Psychological Medicine, 20, 3-6.

BG Charlton, F Walston (1998). Individual case studies in clinical research. Journal of Evaluation in Clinical Practice  4: 147-155. 

Damasio, AR. Descartes error: emotion, reason and the human brain. New York: Putnam, 1994.

David A. (1993). Cognitive neuropsychiatry? Psychological Medicine, 1992, 23, 1-5.

Healy D. (1992). The suspended revolution, London, Faber.

Healy D. (1996). The psychopharmacologists. London: Altman.

Healy D. (1997). Psychiatric drugs explained. London: Mosby.

Healy D. (1998). The psychopharmacologists II. London: Altman.

Healy D. (1998). The antidepressant era. Cambridge, Massachusetts: Harvard University Press

Marshall JC, Newcombe F. (1984). Putative problems and pure progress in neuropsychological single-case studies. Journal of Clinical Neuropsychology, 6, 65-70.

Shallice T. (1988). From neuropsychology to mental structure. Cambridge, Cambridge University Press.


Chapter 4 - The delusional disorders and Chapter 5 - Bizarre delusions

The original idea for these chapters also came from some comments about the ordinary, everyday nature of paranoia by David Healy, in The suspended revolution. This insight preyed upon my mind for several years, until I saw a way to combine it with an evolutionary perspective and the implications of the somatic marker mechanism. And the whole approach was refined during a year long and extremely detailed phenomenological case study of persecutory delusions I did with Florence Walston, who was at that time a medical student. Conversations with Hamish McClelland were able to draw on his unparalleled clinical experience to confirm and refine these ideas. So we developed the hypothesis of ‘theory of mind’ delusions.

The category of bizarre delusions emerged as a consequence of the need to differentiate the truly ‘mad’ ideas of brain-impaired people from false beliefs that emerge logically from ‘mistaken’ inferences about what other people are thinking or intending. Although consistent with what I have gleaned of clinical experience and from the literature, the section on bizarre delusions section is primarily speculative and theoretical. I hope that someone will soon take the opportunity of testing this formally.


Baron-Cohen S. (1990). Autism: a specific cognitive disorder of ‘mind-blindness’. International Review of Psychiatry, 2, 81-90

Brothers L. (1990). The social brain: a project for integrating primate behavior and neurophysiology in a new domain. Concepts in Neuroscience, 1, 27-51.

Buss DM. (1994). The evolution of desire, New York, BasicBooks.

Byrne R.W. & Whiten A. (ed.). (1988). Machiavellian intelligence social expertise and the evolution of intellect in monkeys, apes and humans. Oxford: Clarendon Press.

Charlton BG. (in the press) Theory of mind and the ‘somatic marker mechanism’ (SMM), Behavioral and Brain Sciences

Charlton BG, McClelland HA. Theory of mind and the delusional disorders. Journal of Nervous and Mental Disease, 1999; 187:380-3.

Charlton BG & Walston F. (1998) Individual case studies in clinical research. Journal of Evaluation in Clinical Practice, 4, 147-155.

Damasio AR. (1994). Descartes error: Emotion, Reason and the Human Brain, New York , Putnam.

Dunbar, R. (1996). Grooming, Gossip and the Evolution of Language. London: Faber.

Garety PA & Hemsley DR. (1994). Delusions: investigations into the psychology of delusional reasoning, Hove, Psychology Press.

Geary DC, Rumsey M, Bow-Thomas CC & Hoard MK. (1995). Sexual jealousy as a facultative trait: evidence from the pattern of sex differences in adults from China and the United States. Ethology and Sociobiology, 16, 355-383.

Walston F, David AS & Charlton BG. (1998) Sex differences in the content of persecutory delusions: a reflection of hostile threats in the ancestral environment? Evolution and Human Behaviour, 19, 257-260.

Whiten A. & Byrne R.W. (ed.) (1997). Machiavellian intelligence II: extensions and evaluations. Cambridge: Cambridge University Press.

Wiederman MW & Allgeier ER. (1993). Gender differences in sexual jealousy: adationist or social learning explanation? Ethology and Sociobiology, 14, 115-140

Wilson M, Daly M. (1992). The man who mistook his wife for a chattel. In: Barkow JH, Cosmides L, Tooby J. (1992). The adapted mind: evolutionary psychology and the generation of culture New York: Oxford University Press, pp 289- 322.


Chapter 6 - Delirium and brain impairment

The absence of delirium in patients diagnosed as suffering from one of the ‘functional psychoses (syndromes such as schizophrenia, mania and depression) lies at the very heart of the neo-Kraepelinian nosology. My heretical idea that is that - contrary to this doctrine - patients with functional psychoses who have symptoms of hallucinations, bizarre delusions and thought disorder, must instead be functionally brain impaired and therefore suffering from delirium. This view (which will strike many clinicians as absurd or foolish) was more or less forced upon me by trying to understand the cognitive mechanisms behind (in particular) auditory hallucinations in the context of contemporary knowledge about how the brain works.

Paul Janssen’s interview with David Healy in The Psychopharmacologists Volume II was a revelation of the significance of sleep to normal human functioning, and the importance of chronic, severe sleep deprivation in many psychiatric syndromes. Particularly the sentence: ‘What always struck me was that so many chronic schizophrenics not only hallucinate and have delusions and difficulty to establish human contact but they also complain of sleep disturbances and if we actually objectively measure their EEG it is very abnormal’. Janssen also pointed out the effectiveness of Risperidone in producing increased deep sleep (as measured on EEG). The obvious implication (not explicitly made my Janssen) is that it is sleep disturbance which causes the hallucinations and delusions (rather than the reverse), that the ‘abnormal’ EEG is evidence of delirium in these patients (abnormal EEG implies abnormal brain function), and that the ‘anti-psychotic’ effect is (at least partly) produced by the effect of increasing deep sleep.

My own clinical enquiries into the history of the psychiatric patients I was seeing confirmed that true psychotic phenomena seemed always to be accompanied either by severe sleep deprivation or some other cause of delirium (eg. drug intoxication), that the mental state of these patients could plausibly be interpreted as a light state of delirium, and that clinical improvement was often preceded by improvement in sleep. The most obvious conclusion is that chronic severe sleep deprivation causes the delirium, and the delirium causes the psychotic symptoms, and induction of sleep by ‘tranquillizing’ drugs is what alleviates psychotic symptoms. Unfortunately I have not been able to perform the EEG research studies which might confirm or refute this - but the idea appears to be compatible with the literature on EEG in psychotic illnesses, including some excellent but largely forgotten work form the 1950s and 60s.


Charlton BG. Psychiatric implications of surgery and critical care. Chapter in Applied physiology for surgery and critical care. Ed M A Glasby & CL-H Huang. London: Butterworth Heinemann, 1995. pp 739-742.

Janssen P. From haloperidol to risperidone. In Healy D (ed.). (1998). The psychopharmacologists II. London: Altman, pp 39-70.

Lipowski ZJ. Delirium: acute confusional states. New York: Oxford university Press, 1990.

Niedermeyer E, da Silva L. Electroencephalography: basic principles, clinical applications , and related fields. Baltimore: Williams and Williams, 1993.

Sims A. (1995). Symptoms in the mind. London, WB Saunders.

Slater E, Roth M. Clinical Psychiatry 3rd edition. London: Balliere Tindall, 1977.

Stromgren LS. ECT in acute delirium and related clinical states. Convulsive therapy 1997; 13:10-17.

Wehr TA. Effects of wakefulness and sleep on depression and mania. In Sleep and biological rhythms: basic mechanisms and applications. Edited by Montplaisir J, Godbout R. New York: Oxford University Press, 1990. pp 42-86.


Chapter 7 - The ‘anti-delirium’ theory of electro-convulsive therapy (ECT) action

Having made the link between chronic, severe sleep deprivation and the kind of psychotic phenomena seen in the most severe instances of depression, then the probable nature of ECT action became much clearer. The idea that ECT might work primarily in those depressed patients who were delirious (by the definitions of the previous chapter, and usually as a consequence of sleep deprivation) seems to fit with early research into ECT action; and also explains how ECT often benefits patients with acute mania (which many people consider to be the ‘opposite’ of depression). This was strikingly confirmed by observing the immediate resolution of chronic, intractable, non-neuroleptic responsive mania following a single ECT treatment and sound sleep. The exact nature of ECT action - in particular whether it is the epileptic fit itself or the ‘post-ictal’ sleep which follows the seizure that produces benefit, is not yet clear; but this would be a relatively straightforward matter to research.



Abrams R. Electroconvulsive therapy 3rd edition. New York: Oxford University Press, 1997.

Carney MWP, Roth M, Garside RF. The diagnosis of depressive symptoms and the prediction of ECT response. British Journal of Psychiatry 1965; 111: 659-674.

Charlton BG. Psychiatric implications of surgery and critical care. Chapter in Applied physiology for surgery and critical care. Ed M A Glasby & CL-H Huang. London: Butterworth Heinemann, 1995. pp 739-742.

Fink M, Sackeim S. Convulsive therapy in schizophrenia? Schizophrenia Bulletin 1996; 22: 27-39.

Lipowski ZJ. Delirium: acute confusional states. New York: Oxford university Press, 1990.

Niedermeyer E, da Silva L. Electroencephalography: basic principles, clinical applications , and related fields. Baltimore: Williams and Williams, 1993.

Slater E, Roth M. Clinical Psychiatry 3rd edition. London: Balliere Tindall, 1977.

Small JG, Klapper MH, Kellams JJ, Miller MJ, Milstein V, Sharpley PH, Small IF. ECT compared with lithium in the management of manic states. Archives of General Psychiatry 1988; 45: 727-732.

Stromgren LS. ECT in acute delirium and related clinical states. Convulsive therapy 1997; 13:10-17.

Wehr TA. Effects of wakefulness and sleep on depression and mania. In Sleep and biological rhythms: basic mechanisms and applications. Edited by Montplaisir J, Godbout R. New York: Oxford University Press, 1990. pp 42-86.


Chapter 8 - The malaise theory of depression

For me, this is the most exciting idea in the book - since it is the culmination of a nearly two decades of (albeit intermittently) intensive research, reading and thinking about the nature of depression. Given this, perhaps I may be forgiven the hubris of suggesting that this theoretical framework offers considerable potential for improving the lives of large numbers of people; although naturally this cannot be known for sure unless or until formal studies to test the ideas begin to emerge.

Once again the germ of the idea comes from a remark of David Healy’s in The suspended revolution which stuck in my mind. The penny finally dropped during a ward round when I asked a ‘depressed’ inpatient AK whether she felt ill - and she turned to look hard at me and said vehemently ‘Yes! And that it the first time anyone has asked me that’. This insight was further explored in a series of in-depth phenomenological interviews for which I am extremely grateful to AK. The immunological side of this theory was very usefully checked over by presenting a paper to the immunologists club at Newcastle General Hospital and by the convenor of that club, Consultant clinical immunologist Dr Gavin Spickett.




Charlton BG. Psychopharmacology and the human condition. JRSM 1998; 91: 599-601.

Charlton BG. (in the press). The malaise theory of depression: Major depressive disorder is sickness behavior and antidepressants are analgesic. Medical Hypotheses

Connor TJ, Leonard BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sciences 1998; 62: 583-606.

Damasio, AR. Descartes error: emotion, reason and the human brain. New York: Putnam, 1994.

Hart BL. Biological basis of the behavior of sick animals. Neuroscience and Biobehavioral Reviews 1988; 12: 123-137.

Healy D. The suspended revolution London: Faber, 1990.

Healy D. Psychiatric drugs explained London: Mosby-Wolfe 1996.

Hickie I, Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? International Journal of Immunopharmacology 1995; 17: 677-683.

Maes M, Bosmans E, Suy E Vandervost C, Dejonckheere C, Minner B, Raus J. (1991). Depression-related disturbances in mitogen-induced lymphocyte responses, interleukin 1-beta, and soluble interleukin-2-receptor production. Acta Psychiatrica Scandinavica 84: 379-386.

Maes M. A review on the acute phase response in major depression. Reviews in the Neurosciences 1993; 4: 407-416.

Maier SF, Watkins LR. Bidirectional communication between the brain and the immune system: implications for behavior. Animal Behavior 1999; 57: 741-751.

Joyce PR, Hawes CR, Mulder RT, Sellman JD, Wilson DA, Boswell DR. Elevated levels of acute phase plasma proteins in depression. Biological Psychiatry 1992; 32: 1035-1041.

Kent S, Bluthe R-M, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. Trends in Pharmacological Sciences 1992; 12: 24-28.

Schneider K (translated by Hamilton MW and Anderson EW). Clinical psychopathology New York: Grune and Stratton, 1959: pp135-7.

Sims A. Symptoms in the mind 2nd edition. London: WB Saunders.1995.

Smith A, Tyrrell D, Coyle K, Higgins P. Effects of interferon alpha on performance in man. Psychopharmacology 1988; 96: 414-416.

Yirmiya R. Behavioral and psychological effects of immune activation: implications for ‘depression due to a general medical condition’. Current Opinion in Psychiatry 1997; 10: 470-476.


Chapter 9 - Antidepressant drug action

There is, it turns out, a tremendous amount of supportive evidence in the literature for the idea that depression is sickness behaviour - so the nature of MDD seemed reasonably clear once that link had been made. But the mode of action of ‘antidepressants’ remained obscure until I realized that the link between MDD and influenza implied that an effective antidepressant would need to be an analgesic or pain killer, of the same general type that provides symptomatic relief in influenza.

I already knew that tricyclic ‘antidepressants’ were used in pain clinics, but had not realized that their analgesic properties were so well established, nor that they were so widely used in the symptomatic and palliative care of cancer and other malaise-related conditions. The complementary implication is that analgesics - especially opiates - should have clinically valuable ‘antidepressant’ (ie. anti-malaise) properties, and this is massively, (although inconsistently) supported in the psychiatric literature going back more than a hundred years.

I am still unsure how SSRIs fit into this scheme. They certainly differ from tricyclics in their primary mode of therapeutic action, and I am convinced that they are very valuable drugs for some people, and have transformed lives for the better. Direct enquiry from patients and a detailed reading of the literature has led to the idea that the special action may be one of ‘emotion-buffering’ - probably through some kind of stabilizing effect on the autonomic nervous system. Certainly SSRIs are more effective in the population of anxiously miserable outpatients than in the populations of ‘melancholic, psychotic’ inpatients - and their analgesic activity is not striking (with perhaps the exception of fluoxetine), and their benefits to people with labile emotions (including post-stroke patients) seems to be accumulating. The nature of emotion-buffering requires further exploration, and would seem a fruitful area for research.

Charlton BG. (in the press). The malaise theory of depression: Major depressive disorder is sickness behavior and antidepressants are analgesic. Medical Hypotheses

Holland JC, Romano SJ, Heiligenstein JH, Tepner RG, Wilson MG. A controlled trial of fluoxetine and desipramnine in depressed women with advanced cancer. Psychooncology 1998; 7: 291-300.

Lee R, Spencer PSJ. Antidepressants and pain: a review of the pharmacological data supporting the use of certain tricyclics in chronic pain. Journal of International Medical Research 1977; 5, supplement 1: 146-156.

McDaniel JS, Musselman DL, Porter MR, Reed DA, Nemeroff CB. Depression in patients with cancer: diagnosis, biology and treatment. Archives of General Psychiatry 1995; 52: 89-99.

Panerai AE, Bianchi M, Sacerdote P, Ripamonti C, Ventafridda V, De Conno F. Antidepressants in cancer pain. Journal of Palliative Care 1991; 7: 42-44.

Portnoy RK, Kanner RM. Pain management: theory and practice. FA Davis: Philadelphia, 1996: pp226-229. Muller H, Moller HJ. Methodological problems in the estimation of the onset of the antidepressant effect. Journal of Affective Disorder

Xia Y, DePierre JW, Nassberger L. Tricyclic antidepressants inhibit IL-6, IL-1beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 1996; 34: 27-37.

Vereby K. editor (1982). Opioids in mental illness: theories, clinical observations and treatment possibilities. New York: New York Academy of Science.


Chapter 10 - Mania

Mania is at the same time one of the most obvious and ‘real’ of psychiatric illnesses, and one of the hardest to define - in particular the idea that the manic state should be defined by a ‘high’ mood has proved a red herring. The insight presented here, that the essence of mania is freedom from the negative feedback of fatigue, crystallized from a consideration of the importance of fatigue in depression, and the role of analgesia (such as tricyclics) in removing the symptoms of fatigue. This allowed me to distinguish between a state of ‘arousal’ and high energy, which is a part of the spectrum of normal life - and the pathological state of ‘hypomania’ when this arousal is not limited by the negative feedback of fatigue.

So I have come to see fatigue as being an ‘algesic’ state, akin to pain - and treatable by pain-killers. In other words, fatigue is different from sleepiness - fatigue is the dysphoric state that leads us to want to rest, to stop activity - sleepiness is the desire for sleep. The two are dissociable, as when one is ‘exhausted’ with fatigue but cannot sleep. And fatigue can be treated (eg. with analgesics, such as tricyclics) even when the drug is sedative. I have not so far been able to find anyone else who regards fatigue as an ‘algesic state’ in quite this manner - although it certainly seems compatible with much of what is known on the subject of fatigue.

If mania was primarily an absence of fatigue then this implies that chronic amphetamine usage as a pharmacological model of mania might be working less by amphetamine causing arousal (which I had previously assumed was the case) and more by amphetamine causing analgesia. On searching the literature I was astonished to discover that amphetamine is one of the most powerful of known analgesics (a fact presumably kept quiet because of real but exaggerated fears of amphetamine addiction). And caffeine also turns out to be an analgesic as well as mild psychostimulant. The whole picture of causes, treatments and consequences fits together in such a neat way, that one must take seriously the possibility that it is true!

Rather than providing a set of manufactured references, generated post hoc I will indicate how I went about checking the validity of this theory of mania.. In the first place, I already knew - from the seven or so years when I was a full-time neuroendocrinologist and adrenal researcher - quite a lot about endorphins and the other endogenous opiates, and about cortisol and the other glucocorticoids. Predictions about the possibly mania-inducing effects of glucocorticoids and opiates were followed-up by trawling large swathes through the Medline computerized reference system, and by reading through whatever books were available in the library on this topic. My conclusion was that there was a great deal of confirmatory evidence for the proposition that endorphins and glucocorticoids might be anti-fatigue analgesics with a tendency to induce mania, and that the opiate antagonist naloxone probably had an anti-manic effect when given in adequate doses. There were also plenty of published papers that disagreed with this - however, I felt that these were all sufficiently flawed that I could disregard them. I also read about the physiology of sleep generally, and that seemed to fit.

Then there was clinical work. By luck, I was able to see a reasonable number of classic manic patients, maybe a couple of dozen, through their illness and into recovery - and could check whether or not the natural history of their illnesses was consistent with the natural history predicted by the arousal-analgesia theory. It was. In particular the idea that chronic severe sleep deprivation is necessary to flipping a hypomanic person into full blown psychotic mania, and that sleep would terminate the psychotic features of mania, seemed to be exactly right. And if the pharmacological treatments were interpreted as hypnotic rather than ‘anti-psychotic’ then the scheme of understanding still worked perfectly.

So I am quite confident about these ideas in relation to mania. Of course, I have been selective concerning what I believed and disregarded - but not arbitrarily so, since I have an exact and constraining theory against which to test observations. Selectivity in choosing evidence is nothing to be ashamed of - as the greatest living member of my tribe of theoretical biologists (Francis Crick) says in What mad pursuit, this just how theoretical science is done. After all, most observational evidence (like most scientific propositions) will turn out to be wrong - so it would be an error to include all the observational evidence. To generate true theories one must discard most of the observational evidence. And if that sounds like a paradox, then think again!


Chapter 11 - Neuroleptics

In current practice, acute mania is treated by sedation and neuroleptics, while ‘mood stabilizers’ such as lithium are used to prevent its recurrence when people have frequent repeated episodes of mania (or of mania and depression). Despite their central importance to psychiatry, very little is known at present about the therapeutic action of either neuroleptics or lithium - although a lot is known about their ‘side effects’. (Indeed, there is no information at all in most psychiatric textbooks or even monographs concerning the clinical therapeutic actions of these drugs. There are sections on supposed molecular level actions, but nothing whatsoever on psychological or physiological therapeutic effects.) I have come to believe that in both neuroleptic and lithium the therapeutic action is also one of the main so-called ‘side effects’.

The action of both neuroleptics and lithium can both be described in a general way as blunting emotions. Damasio’s insight is that emotions are actually the brain representations of body states - so that if the bodily enactment of emotions is blocked, so will our experience of these emotions. Since neuroleptics (certainly) and lithium (very probably) both block the muscular manifestations of emotion, then this motor action seems an obvious way in which these drugs might produce a blunting of subjective emotion. So, although neuroleptics and lithium differ in several respects, it is suggested that they share a primary therapeutic action of impairing the motor manifestations of emotion. This is probably due to an effect upon the basal ganglia - basal ganglia activity is impaired such that the muscular enactment of emotions is impaired, and since enactment is impaired so is the subjective perception of emotion. My hunch, and it is just a hunch, is that the nature of motor impairment is different in each case - neuroleptics producing a kind of ‘tonic’ impairment, and lithium a ‘clonic’ impairment. This proposition could easily be tested using measuring drug effects in enactment of somatic emotion (such as skin conductance) in  response to emotion-inducing stimuli.

Again, I will refrain from an elaborate bibliography - suffice it to say that a trawl through Medline reveals that there is plenty of literature out there in support of these theories, or at least consistent with them - and little to contradict them. The idea that atypical neuroleptics may be operating primarily as sedative hypnotics comes from Paul Janssen’s interview with David Healy in The Psychopharmacologists II, and seems consistent with the general run of commentary of ‘atypicals’ (reading between the lines, sometimes) and my own recent clinical observations. What is needed now is testing in practice - not more literature reviews.


Chapter 12 - Schizophrenia

For the last twenty years I have consistently heard it said by experts that schizophrenia is not one thing but many things - I first heard the idea from Harrison Pope on my student elective to Harvard and shortly afterwards from Angus Mackay at a journal club in Newcastle, and Tim Crow implied as much with his unitary psychosis ideas. The heterogeneity of schizophrenia (ie. its lack of biological validity as a unitary category) seems mainstream. Nevertheless the category is continuously used in research and clinical practice - presumably because there is no other available way of conceptualizing chronic psychotic patients.

My purpose here is to set out some symptomatic variables which can be used to classify chronic psychotic patients for the purposes of research and communication, and in order to provide a focus for treatment. Broadly speaking, I think that many patients can be classified in clinical practice using the organic categories of delirium (for symptoms of acute schizophrenia), dementia (chronic, negative state schizophrenia), and secondary the drug side-effects from treating primary symptoms.

The extent to which negative symptoms may be a consequence of neuroleptic treatment of positive symptoms comes from David Healy, who has also published a fascinating study of the effects of the neuroleptic droperidol in normal volunteers (Healy D, Farquhar G. (1998). Immediate effects of droperidol Human Psychopharmacology-Clinical and Experimental 13, 113-120.) Some of the chronic psychotic patients who currently attract a diagnosis of schizophrenia may - of course - also suffer from other symptoms such as malaise, anxiety, fatigue etc, and these may have further treatment implications.

It is important to get away from the automatic equation of a schizophrenic diagnosis with neuroleptic (‘antipsychotic’) drug treatment, as if schizophrenia was a disease and neuroleptics had some kind of fundamental anti-disease activity. This is based on the serious error that neuroleptics correct a brain abnormality in schizophrenia in the same kind of way as L-dopa (partly) corrects a brain abnormality in Parkinson’s disease. Instead treatment should be symptomatic and aimed primarily at making patients feel better. Treatment should therefore be tailored to individual patients on the basis of focusing on their dominant symptoms using the safest drugs with the least debilitating side effects. and involving (ideally) a therapeutic partnership with the patient and (at least) serious attempts to understand the patient’s subjective response to treatment. This strategy, which is superbly expounded in Healy’s Psychiatric Drugs Explained, needs evaluating against current practice


Chapter 13 - Psychopharmacology and the human condition

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APPENDIX 1 - Evolution and the cognitive neuroscience of awareness, consciousness and language

This section is just plain difficult! I have done my best to make things clear, particularly by the use of examples, but I found this very hard to grasp (I read Damasio’s book four times before I really got it) - and it is likely that your will find it hard too. However, it is just about as important as science gets…


Evolution of awareness

The nature and role of awareness depends upon Francis Crick’s The astonishing hypotheses - although what Crick terms ‘consciousness’ I would term awareness. I found Zeki’s A vision of the brain extremely useful in understanding the general organization of the brain as revealed by vision researchers. I have also drawn heavily upon the work and conversation of my colleagues in the Psychology Department at Newcastle University who are active in visual research and cortical connectivity - especially Malcolm Young, Jack Scannell, Martin Tovee and Piers Cornelissen.     


Evolution of consciousness

The key to understanding the nature of consciousness is the somatic marker mechanism, as described by Antonio Damasio in Descarte’s Error. But while Damasio describes many of the things that consciousness does and what happens when consciousness is absent (in patients with brain damage), he does not say why consciousness evolved. This is my concern here - to describe what was the social selection pressure for evolving consciousness, and what was the specific nature of the social task performed by this general mechanism. So, the neural nature of the SMM needs to be combined with an understanding of the nature of strategic social intelligence.


The somatic marker mechanism

I would consider Damasio’s concept of the somatic marker mechanism to be one of he most fruitful ideas I have encountered. It is, however, a difficult concept to grasp on paper (although easier to explain verbally) which may explain its otherwise astonishing lack of major impact to date. One difficulty is that the SMM overlaps conceptually with ‘consciousness’ and ‘theory of mind’ - which are also slippery and elusive ideas. I have striven to bring some terminological clarity and precision to these matters, since the concepts themselves are not so difficult as the terminological tangle makes them. I have equated the SMM with consciousness, suggested that the function of consciousness is strategic social intelligence, and that theory of mind is based upon the SMM - but with the addition of abstract symbolic language in humans which introduces a new set of possibilities for what is represented.



Language is another terminological and conceptual minefield. This chapter was immeasurably helped by discussions with Tina Fry over about two years. Tina is trained in linguistics, and we are working together on the evolution of language. Most of the new ideas relating to the concept of displacement - the crucial aspect of displacement, the mechanism of displacement by association in WM, the putative ecological conditions for language evolution and so on - were developed in the course of discussions with Tina, and as a consequence of her knowledge. She has taught me a tremendous amount, and by-and-large eliminated some of my grossest errors - but there are a few points at which I have defied her advice, and for which I take full responsibility.


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Appendix 2 - Human creativity and the Col-oh-nell Flastratus phenomenon

I have enjoyed the work of Abraham Maslow ever since I was introduced to it by Colin Wilson’s book. The moments of subjective delight and insight described as ‘peak experiences’ feel important, and deserve exploration. The form of the peak experience seems biologically explicable in terms of the somatic marker mechanism, and the fact that we impose story-like explanations appears to be an aspect of human social intelligence; but the content of the experience is individually and culturally variable - and the validity of even the most subjectively compelling content is fascinatingly uncertain.   


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also by Bruce Charlton
Peak Experiences
Cargo Cult Science
The Meaning of Life
Delirium and Psychotic Symptoms
Public Health and Personal Freedom
Pharmacology and Personal Fulfillment
Awareness, Consciousness and Language
Injustice, Inequality and Evolutionary Psychology
The Modernization Imperative by Bruce Charlton and Peter Andras