The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder

Recent genome-wide association studies have linked voltage-gated calcium channel genes to bipolar disorder (BD), in which CACNB2 gene rs11013860 is respectively reported. Less is known, though, about how precisely its polymorphism affects both the structure and function of the brain.

173 BD patients and 207 healthy controls (HCs) were underwent structural and functional magnetic resonance imaging scan and genotyped for CACNB2 rs11013860. Grey matter volume (GMV), regional homogeneity (ReHo) and degree centrality (DC) were used to examine the brain structure, functional activity and connectivity of these participants.

The emotional circuits in BD patients, such as cerebellum, insula, cingulate gyrus, fusiform gyrus, superior frontal gyrus, superior / middle temporal gyrus, middle occipital gyrus, lingual gyrus, precuneus, putamen, hippocampus and parahippocampal gyrus, were the main areas where GMV, ReHo, and DC differed from HCs. And the right anterior and posterior cerebellar lobes, parahippocampal gyrus as well as lingual gyrus showed an interaction between CACNB2 rs11013860 genotypes and diagnoses in GMV. In addition, there was a significant step-wise increase of GMV with decreased dosage of the A risk allele in HCs, but this pattern of relationship was absent in BD patients. No interaction between BD and CACNB2 rs11013860 was found in ReHo and DC.

These results suggest that the polymorphism of CACNB2 rs11013860 in BD patients may be associated with brain structural abnormalities in cerebellar, limbic system and other brain regions, perhaps contributing to the disease.