Elsevier

Medical Hypotheses

Volume 54, Issue 1, January 2000, Pages 126-130
Medical Hypotheses

Regular Article
The malaise theory of depression: major depressive disorder is sickness behavior and antidepressants are analgesic

https://doi.org/10.1054/mehy.1999.0986Get rights and content

Abstract

The malaise theory of depression constitutes a re-conceptualization and re-definition of major depressive disorder (MDD). It is proposed that the state or emotion of malaise should be considered the core symptom of depression, rather than sadness of mood. The syndrome of MDD is identified as a consequence of inappropriate sickness behavior mediated by immune activation including abnormalities in cytokines. Antidepressants are suggested to exert their specifically beneficial effects through an analgesic effect on the core dysphoric symptoms of malaise. These ideas are consistent with a substantial body of published literature and lead to a wide range of testable predictions.

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