The association of genetic variation in CACNA1C with structure and function of a frontotemporal system

Objectives: A single nucleotide polymorphism at the CACNA1C gene (rs1006737) has been reported in genome-wide association studies to be associated with bipolar disorder (BD) with genome-wide significance. However, the neural system effects of CACNA1C that mediate the association are not known. In this study, we assessed associations between rs1006737 variation and both morphology and functional connectivity within a corticolimbic frontotemporal neural system implicated in BD. Methods: A total of 55 European Americans were divided into two groups: a GG group homozygous for the ' G ' allele (n = 30) and carriers of the high risk A allele (' A-carrier ' group, AA / AG genotypes; n = 25). The subjects participated in both high-resolution structural magnetic resonance imaging (MRI) scans and functional MRI scans during emotional face-processing. Voxel-based morphometry and functional connectivity analyses were performed. Results: Compared to the GG group, the A-carrier group showed significantly increased gray matter volume and reduced functional connectivity within a corticolimbic frontotemporal neural system (p < 0.05, corrected). Conclusion: The findings support effects of the rs1006737 variation on the frontotemporal neural system implicated in BD, both in gray matter morphology and in functional connectivity. This suggests that influence of CACNA1C variation on corticolimbic structure and function may be a mechanism contributing to the neural circuitry of BD.