Neurochemistry and neurophysiology of sleep abnormalities associated with depression

Major depressive disorder (MDD) is associated with well characterized sleep abnormalities. The differences in rapid eye movement (REM) sleep that are observed in the depressed patient can be related to an imbalance between monoaminergic and cholinergic systems, a difference that could therefore underlie the neurochemical basis of the disorder. The sleep disruption that is typically present in MDD has recently been identified as a possible causative factor for the cellular and synaptic changes in brain morphology that are seen in depression, so providing additional insight and potential new treatments. Bodyweight dysregulation also occurs in MDD in conjunction and correlated with the differences in sleep, implying fundamental changes in the control of energy balance. This has led to revised hypotheses about the etiology of depression to implicate two hypothalamic neuropeptides, orexin (i.e., hypocretin) and melanin-concentrating hormone (MCH). These neuropeptides are important for the regulation of metabolic status and also are now known to influence sleep, especially REM sleep. Although speculative, data from rodent sleep and behavioral studies, anatomy, molecular genetics, and initial clinical trials of an MCH receptor antagonist converge to link differences in MCH activity with depression. Sleep abnormalities in depression Mood disorders and disorders of sleep are seemingly inextricably linked; indeed it has been known since antiquity that depression is often accompanied by insomnia [1]. Not only is the overlap in the patient populations with these disorders considerable, since about 90% of patients with major depressive disorder show some sleep abnormality [2], but there is also evidence that sleep is most affected in the severest cases of depression [3]. This relationship between sleep and depression may eventually prove to be important for an understanding of the neuropathology of MDD.