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

Abstract

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.

Keywords: bipolar disorder; depression; meta-analysis; offspring; schizophrenia.

Fig. 1.

Literature search results and study eligibility for meta-analysis of rates of mental disorders in offspring of individuals with severe mental illness (SMI).

Fig. 2.

Risk ratio (RR) of severe mental illness (SMI; schizophrenia, bipolar disorder, or depression) in offspring of parents with SMI compared with control offspring of parents with no SMI. Results of random-effect meta-analysis are presented as RR with 95% CI, stratified by mean offspring age at last diagnostic assessment and overall. hrn, number of high-risk offspring; ccn, number of control offspring. For each comparison, the small black diamond symbol in the middle represents the RR of high-risk offspring compared with controls. The horizontal line is the 95% CI. The empty diamonds represent the overall weighted RR for (1) studies of offspring with mean age under of 20 (top), (2) studies of offspring with mean age 20 or older (middle), and (3) overall weighted RR across all studies. The width of the empty diamonds represents their 95% CI.