Contribution of genes and unique environment to cross-sectional and longitudinal measures of subcortical volumes in bipolar disorder

Abstract

The influence of genes and environment on the association between bipolar disorder (BD) and volumes of subcortical brain regions involved in emotion processing has rarely been studied. Furthermore, as far as we know, longitudinal twin studies of subcortical brain volume change in BD have not been carried out at all. In this study, we focused on the genetic and environmental contributions to cross-sectional and longitudinal measures of subcortical brain volumes in BD. A total of 99 twins from monozygotic and dizygotic pairs concordant or discordant for BD and 129 twins from monozygotic and dizygotic healthy control pairs underwent magnetic resonance imaging at baseline. Longitudinal assessment was carried out in 48 twins from monozygotic and dizygotic patient pairs and 52 twins from monozygotic and dizygotic control pairs. Subcortical volume measures were obtained with Freesurfer software and analyzed with structural equation modeling software OpenMx. At baseline, BD was phenotypically and genetically associated with smaller volumes of the thalamus, putamen and nucleus accumbens. BD was not associated with subcortical brain volume change over time in any of the examined regions. Heritability of subcortical volumes at baseline was high, whereas subcortical volume change had low heritability. Genes contributing to BD showed overlap with those associated with smaller volumes of the thalamus, putamen and nucleus accumbens at baseline. Further evaluation of genetic contributions to abnormalities in subcortical brain regions assumed to be involved in emotion processing is recommended.