Neuroanatomical correlates of genetic risk for bipolar disorder: A voxel-based morphometry study in bipolar type I patients and healthy first degree relatives.

Background: Bipolar disorder (BD) is a highly heritable mental illness which is associated with neuroanatomical abnormalities. Investigating healthy individuals at high genetic risk for bipolar disorder may help to identify neuroanatomical markers of risk and resilience without the confounding effects of burden of illness or medication.

Methods: Structural magnetic resonance imaging scans were acquired from 30 euthymic patients with BD-I (BP), 28 healthy first degree relatives of BD-I patients (HR), and 30 healthy controls (HC). Data was analyzed using DARTEL for voxel based morphometry in SPM8.

Results: Whole-brain analysis revealed a significant main effect of group in the gray matter volume in bilateral inferior frontal gyrus, left parahippocampal gyrus, left lingual gyrus and cerebellum, posterior cingulate gyrus, and supramarginal gyrus (alphasim corrected (≤0.05 FWE)). Post-hoc t-tests showed that inferior frontal gyrus volumes were bilaterally larger both in BP and HR than in HC. BP and HR also had smaller cerebellar volume compared with HC. In addition, BP had smaller left lingual gyrus volume, whereas HR had larger left parahippocampal and supramarginal gyrus volume compared with HC.

Limitations: This study was cross-sectional and the sample size was not large. All bipolar patients were on medication, therefore we were not able to exclude medication effects in bipolar group in this study.

Conclusions: Our findings suggest that increased inferior frontal gyrus and decreased cerebellar volumes might be associated with genetic predisposition for bipolar disorder. Longitudinal studies are needed to better understand the predictive and prognostic value of structural changes in these regions.