title: REM sleep alteration and depression.
abstract: Alterations in sleep patterns are often recognized as a premorbid symptom accompanied by affective disorders, particularly by major depression. However, the mechanism is rather complex, and differentiating its causalities from those of depression undergoes hardships. Indeed, depression is a complex disease. It has been clearly demonstrated that depressed patients display very characteristic changes in sleep architecture. Previous animal studies also demonstrated that several depression models, which had targeted elevated hypothalamic-pituitary-adrenocortical (HPA) axis, showed increased rapid eye movement (REM) sleep while insomniac sleep phenotype did not evidently appear. However, all stress hormones seem to be elevated in those models. Therefore, it has been difficult to determine which particular hormone in the HPA axis is primarily responsible for altered sleep in depression. In recent years, we have widely analyzed sleep characteristics of conditional transgenic mouse lines focusing on corticotropin-releasing hormone (CRH), the initial mediator of the HPA system, in which the levels of peripheral stress hormones are normal. Conditional CRH-overexpressing (COE) mice, especially those overexpress CRH limitedly within the forebrain including limbic structures (CRH-COE-Cam), dis- play enhanced REM sleep. Further, the higher occurrence of REM sleep in CRH-COE-Cam mice could be due to their hyper-cholinergic activity. REM sleep disinhibition observed in depressed patients similarly appears in animals which are genetically stress-vulnerable strain or chronically stressed, possibly due to enhanced action of limbic CRH. Indeed, REM sleep is a fragile vigilance state and closely connected with emotional control. Thus, depressive episodes may affect REM sleep earlier than nonREM sleep, and such altered REM sleep can be a state marker of depression.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Email:kimura@psych.mpg.de.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Email:kimura@psych.mpg.de.
authors.forename: M L
authors.initials: ML
authors.lastname: Curzi
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Email:kimura@psych.mpg.de.
authors.forename: C P N
authors.initials: CP
authors.lastname: Romanowsi
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology; D012895:Sleep, REM
chemical_list: D003346:Corticotropin-Releasing Hormone