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BACKGROUND Autophagy is central to health, and a decline in autophagy from the youthful, healthy state correlates with disease and aging. Among the diseases in which a decline in autophagy is prominent are neurological and neuroimmune disorders, such as Alzheimer's and Parkinson's. Psychiatric disorders are characterized almost universally by increased inflammation and oxidative stress, which are negatively related to levels of autophagy. Treatments designed to restore or increase autophagy may have efficacy in psychiatric disorders such as depression, bipolar disorder, and schizophrenia. FINDINGS Recent research has found that many psychoactive drugs in several different classes, such as anti-psychotics, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and lithium, strongly promote autophagy in neurons. Other diverse interventions, such as rapamycin, trehalose, and exercise, have been shown to have antidepressant effects in animals and sometimes in humans. Most drugs used in other areas of medicine do not activate autophagy. The case is made in this paper that autophagy may play a central role in the mechanism of action of these drugs and interventions through direct effects on autophagy as well as concomitant lowering of levels of inflammation and oxidative stress. CONCLUSIONS Many drugs used in the treatment of psychiatric illnesses activate autophagy, and this may be their central mechanism of action, which lends new insight into the pathogenesis of mental illness and to potential new therapies for them.

Autophagy activation as a mechanism of action of psychoactive drugs, revised and expanded version