Evidence for association between familial bipolar risk and ventral striatal volume

Background: Recent genome-wide association studies (GWAS) of striatal volumes and bipolar disorder (BD) indicate these traits are heritable and share common genetic architecture, however little independent work has been conducted to help establish this relationship. Methods: Subcortical volumes (mm(3)) of young, healthy offspring of BD (N=32) and major depressive disorder (MDD) patients (N=158) were compared to larger healthy control sample (NRANGE=925-1052) adjusting for potential confounds, using data from the latest release (S1200) of the Human Connectome Project. Based on recent GWAS findings, it was hypothesised that the accumbens and caudate would be smaller in offspring of BD, but not MDD patients. Results: After multiple comparison correction, there was a regional and BD specific relationship in the direction expected (Accumbens: F2,1067=6.244, PFDR-CORRECTED=0.014). Discussion: In line with recent GWAS, there was evidence supporting the hypothesis that reduced striatal volume may be part of the genetic risk for BD, but not MDD. Limitations: It cannot be concluded whether this association was specific to BD or consistent with a broader psychosis phenotype, due to a small sample size for offspring of schizophrenia patients. Furthermore, one cannot rule out potential shared environmental influences of parental BD. Conclusions: The common genetic architecture of BD may confer susceptibility via inherited genetic factors that affect striatal volume. Future work should establish how this relationship relates to specific BD symptomology. This work may also help to dissect clinical heterogeneity and improve diagnosis nosology.