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