Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder:a highrisk study in the Chinese population

Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder.Nevertheless,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.Aims To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,China.The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,respectively.Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.Results Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than O-control.Subgroup analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts,confirming the central role of circadian rhythm dysfunction in bipolar disorder.The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.