REM Sleep and Depression

Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960s polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression presents a disturbed sleep EEG pattern that is characterized by a reduction of slow wave sleep and a disinhibition of REM sleep, with a shortening of REM Latency, a prolongation of the first REM period and increased REM density. These findings have stimulated many sleep studies in depressive patients and patients with other psychiatric disorders by using cholinergic drug modulation. Indeed REM sleep dysregulation has been hypothesized to be sustained by a relative or absolute cholinergic overdrive. Moreover, shortened REM Latency and REM activity have been both considered biological marker depressive episode. Moreover they contribute to cognitive dysfunction of depressive disorders, including negative self-appraisals, altered emotional memory processing. These Rem alterations might also predict relapse and recurrence of depression. Most antidepressants suppress REM sleep and it appears to be a distinct requirement for antidepressant effects. Moreover REM Latency was shown to predict the response to the treatment with a certain antidepressant or even the course of the disorder for several years. Several high risk studies including healthy relatives of patients with depression demonstrate that REM alterations may precede the clinical expression of depression and may be useful in identifying those at highest risk for the illness. REM sleep alterations have recently been considered not only biological scars but true endophenotypes for depression. Indeed REM sleep changes in depression are under genetic control and are mediated by complex neurobiological modifications that involve noradrenergic, serotoninergic and cholinergic systems. It has been hypothesized that one proximate mechanism that does directly yield the pathophysiologic pattern in mood disorders is stressrelated REM hyperactivation or dis-inhibition. Moreover, available data favor the hypothesis that the increase of stress hormones affects adult neurogenesis and it may endanger hippocampal integrity, thereby leading to cognitive dysfunction and contributing to the development of mood disorders (allostatic load). Hosts of genetic, neurochemical and neurobiological factors are implicated in the complex relationship between REM sleep and the production of depressive symptomatology, hence several theoretical models have been developed. This paper thus reviews the hypothesis of this complex relationship from a historical perspective to the modern era of neuroscience that combines psychopathology, molecular biology, psychophysiology and genetics