Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: A meta-analysis of family high-risk studies

Objective: Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method: Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results: We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P <. 001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57-5.02, P <. 001) and of other types of SMI (RR = 1.92; 95% CI: 1.48-2.49, P <. 001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02-2.58; P =. 042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20-18.78, P <. 001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19-15.16, P =. 631). Conclusions: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.