Charlton BG. Dialog on depression.
Science. 2000; 288: 975.

In her News Focus article "Global survey examines impact of depression" (7 Apr., p. 39), Constance Holden describes a 25-nation study by the World Health Organization to examine the social and economic effects of depression. From the survey being used for the study, researchers will be able to look for correlations of psychiatric depression with chronic physical problems. Ronald Kessler, an epidemiologist at Harvard Medical School who designed the study, is quoted as saying, "We don't know how many people with headache or fatigue are really suffering from depression in disguise."

But some research suggests almost the opposite--that the diagnostic syndrome of major depressive disorder may be chronic physical illness in disguise (1). It is many years since Kurt Schneider suggested that the core symptoms of depression might be the "vital" symptoms of depression, and that low mood was a secondary consequence of these physical changes (2). This view has received support from modern immunology and pharmacology (3).

The primary symptom cluster of classic depression is the malaise state known as "sickness behavior," which is also the behavioral component of the mammalian immune response to infection or inflammation (4). Malaise is an energy-conserving behavioral pattern designed to mount an acute and all-out attack on invading microbes. Physical malaise includes symptoms such as aches, pains, heaviness, fatigue, somnolence, slowing of thought and action (retardation), and the demotivating inability to feel pleasurable or rewarding emotions. These symptoms are probably produced by circulating immune active cytokines such as the interferons and interleukins (3). Low mood is a consequence of sustained malaise.

By this account, antidepressant drugs do not act on mood directly, but instead have analgesic properties to alleviate the malaise state. For example, tricyclic antidepressants are long-acting and powerful pain killers, used widely in internal medicine (1). So, the effect of antidepressants on mood may be akin to the effect of aspirin in treating a headache--aspirin does not "make" you happy, but by relieving pain and malaise, makes it much "easier" to be happy (5).


1. B. G. Charlton, Med. Hypotheses 54, 126 (2000).

2. K. Schneider, Clinical Psychopathology, M. W. Hamilton and E. W. Anderson, Transl. (Grune and Stratton, New York, 1959), pp.135-137.

3. I. Hickie and A. Lloyd, Int. J. Immunopharmacol. 17, 677 (1995).

4. B. L. Hart, Neurosci. Biobehav. Rev. 12, 123 (1988).

5. B. Charlton, Psychiatry and the Human Condition (Radcliffe, Oxford), in press

* * *


Selected Journalism