A meta-analysis of the risk of major affective disorder in relatives of individuals affected by major depressive disorder or bipolar disorder

Background: To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated.

Methods: A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods.

Results: Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72-2.67), increasing to OR=3.23 (95% CI 2.11-4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45-25.61), and OR=6.58 (95% CI 2.64-16.43) for FDRs of two BD probands.

Conclusions: These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates.