Serotonin, Sleep and Depression: A Hypothesis

Abstract

For most cases of endogenous depression (major depression), the hypothesis of monoamine deficiency, despite a number of limitations it faces, is still considered the most acceptable explanation. The main difficulty faced by this hypothesis is the reason for the decrease in the level of cerebral monoamines (primarily serotonin) during depression. It is assumed either increased activity of the MAO enzyme, which metabolizes serotonin, or a mutation with the loss of function of the gene of the Tph-2 enzyme, which synthesizes serotonin, as possible causes. In this review, a third cause is proposed, which can explain a number of cases of «spontaneous» onset of depressive symptoms in apparently healthy people, as well as links the hypotheses of “monoamine deficiency” and “disturbances in circadian rhythms.” It is assumed that the formation of endogenous depression is due to a combination of two factors: a reduced “basal” level of cerebral serotonin and excessively long pre-morning periods of REM sleep, during which the release of cerebral monoamines stops altogether. As a possible way to of non-drug treatment of depression, not deprivation, but fragmentation of this phase of sleep is suggested, that is much easier for patients to tolerate.

A Narrative Review on REM Sleep Deprivation: A Promising Non-Pharmaceutical Alternative for Treating Endogenous Depression

“…The development of endogenous depression was recently described as a combination of two key factors: reduced levels of cerebral monoamines (particularly norepinephrine and serotonin) and prolonged periods of REM sleep. Thus, REM-D started to be explored as a non-drug treatment for endogenous depression [ 25 , 26 ].…”