title: Sleep architecture variation: a mediator of metabolic disturbance in individuals with major depressive disorder.
abstract: Remarkable proportions of individuals diagnosed with major depressive disorder (MDD) have comorbid metabolic disturbances (i.e., obesity, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia), and vice versa. Accumulating evidence suggests that common pathophysiologic pathways such as a chronic, low-grade, proinflammatory state mediate this frequent co-occurrence. However, it remains unclear what traits precede the onset and increase the risk for these pathologic states. The aim of our review was to evaluate the evidentiary base supporting the hypothesis that the increased hazard for metabolic disturbance in MDD subpopulations (and vice versa) is mediated in part by endophenotypic variations in sleep architecture. We conducted a PubMed search of all English-language literature with the following search terms: sleep disturbance, circadian rhythm, inflammation, metabolic syndrome, obesity, MDD, mood disorder, prodrome, T2DM, cytokine, interleukin, hypertension, dyslipidemia, and hypercholesterolemia. Longitudinal and meta-analysis data indicate that specific variations in sleep architecture (i.e., decreased slow-wave sleep [SWS], increased rapid eye movement [REM] density) precede the onset of depressive symptomatology for a subpopulation of individuals. The same sleep architecture variations also are associated with obesity, T2DM, and hypertension. Decreased SWS and increased REM density is correlated with an increase in proinflammatory cytokines (e.g., IL-6, tumor necrosis factor, etc.). This proinflammatory state has been independently shown to be associated with MDD and metabolic disturbances. Taken together, our review suggests that sleep architecture variation of increased REM density and decreased SWS may be an endophenotypic trait, which serves to identify a subpopulation at increased risk for depressive symptoms and metabolic disturbances. Future research is needed to discern the predictive value, sensitivity, and specificity of using sleep architecture variation as a biomarker for MDD and metabolic disturbances. Validation of this marker would have broad clinical implications, such as primary, secondary, and tertiary preventative health strategies.
authors.affiliation: Department of Psychiatry, University of Toronto, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. Electronic address: paul.kudlow@gmail.com.
authors.forename: P A
authors.initials: PA
authors.lastname: Kudlow
authors.forename: D S
authors.initials: DS
authors.lastname: Cha
authors.forename: R W
authors.initials: RW
authors.lastname: Lam
authors.forename: R S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D003865:Major Depressive Disorder / Q000378:metabolism* / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008659:Metabolic Diseases / Q000378:metabolism* / Q000503:physiopathology*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012894:Sleep Stages / Q000502:physiology*
keywords: Biological markers; Hypertension; Inflammation; Major depressive disorder; Obesity; Polysomnography; Sleep; Type 2 diabetes mellitus