The genetics of early-onset bipolar disorder: A systematic review

Background Early-onset bipolar disorder has been associated with a significantly worse prognosis than late-onset BD and has been hypothesized to be a genetically homogenous subset of BD. A sizeable number of studies have investigated early-onset BD through linkage-analyses, candidate-gene association studies, genome-wide association studies (GWAS), and analyses of copy number variants (CNVs), but this literature has not yet been reviewed. Methods A systematic review was conducted using the PubMed database on articles published online before January 15, 2015 and after 1990. Separate searches were made for linkage studies, candidate gene-association studies, GWAS, and studies on CNVs. Results Seventy-three studies were included in our review. There is a lack of robust positive findings on the genetics of early-onset BD in any major molecular genetics method. Limitations Early-onset populations were quite small in some studies. Variance in study methods hindered efforts to interpret results or conduct meta-analysis. Conclusions The field is still at an early phase for research on early-onset BD. The largely null findings mirror the results of most genetics research on BD. Although most studies were underpowered, the null findings could mean that early-onset BD may not be as genetically homogenous as has been hypothesized or even that early-onset BD does not differ genetically from adult-onset BD. Nevertheless, clinically the probabilistic developmental risk trajectories associated with early-onset that may not be primarily genetically determined continued to warrant scrutiny. Future research should dramatically expand sample sizes, use atheoretical research methods like GWAS, and standardize methods.