Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms

Circadian desynchronization triggers premature cellular aging in a diurnal rodent

International audienceChronic jet lag or shift work is deleterious tohuman metabolic health, in that such circadian desynchronizationis associated with being overweight and the prevalenceof altered glucose metabolism. Similar metabolic changesare observed with age, suggesting that chronic jet lag andaccelerated cell aging are intimately related, but the associationremains to be determined.We addressed whether jet laginducesmetabolic and cell aging impairments in young grassrats (2–3mo old), using control old grass rats (12–18 mo old)as an aging reference. Desynchronized young and control oldsubjects had impaired glucose tolerance (+60 and +280%)when compared with control young animals. Despite no significantvariation in liver DNA damage, shorter telomereswere characterized, not only in old animal liver cells (218%),but also at an intermediate level in desynchronized young rats(29%). The same pattern was found for deacetylase sirtuin(SIRT)-1 (257 and229%), confirming that jet-lagged youngrats have an intermediate aging profile. Our data indicatethat an experimental circadian desynchronization in younganimals is associated with a precocious aging profile basedon 3 well-knownmarkers, as well as a prediabetic phenotype.Such chronic jet lag–induced alterations observed in a diurnalspecies constitute proof of principle of the need todevelop preventive treatments in jet-lagged persons and shiftworkers