Variation in the CACNB2 gene is associated with functional connectivity of the Hippocampus in bipolar disorder

• Published in: BMC psychiatry Vol. 19; no. 1; p. 62
• Main Authors: Liu, Fang, Gong, Xiaohong, Yao, Xudong, Cui, Lingling, Yin, Zhiyang, Li, Chao, Tang, Yanqing, Wang, Fei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.02.2019; BioMed Central; BMC
• Subjects: 11,013,860; Adolescent; Adult; Alleles; Bipolar disorder; Bipolar Disorder - diagnostic imaging; Bipolar Disorder - genetics; Brain; Brain mapping; CACNB2; Calcium channels; Calcium channels (voltage-gated); Calcium Channels, L-Type - genetics; Cortex; Diagnosis; Diagnostic imaging; Female; Functional magnetic resonance imaging; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genetic research; Genetic screening; Genetic testing; Genome-Wide Association Study; Genomes; Genomics; Genotype; Genotypes; Hippocampus; Hippocampus (Brain); Hippocampus - diagnostic imaging; Humans; Magnetic Resonance Imaging; Male; Medical research; Mental disorders; Nerve Net - diagnostic imaging; Neural networks; Neuroimaging; Neurons; NMR; Nuclear magnetic resonance; Polymorphism, Single Nucleotide; Psychiatry; Pyramidal cells; Resting-state functional connectivity (rs-FC); Single nucleotide polymorphisms; Single-nucleotide polymorphism; Young Adult; China; Shenyang China; CACNB2; Bipolar disorder; Resting-state functional connectivity (rs-FC); 11,013,860
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-019-2040-8

Calcium voltage-gated channel auxiliary subunit β2 is a protein that, in humans, is encoded by the CACNB2 gene. The β2 subunit is an auxiliary protein of voltage-gated calcium channels, which is predominantly expressed in hippocampal pyramidal neurons. A single-nucleotide polymorphism at the CACNB2 gene (rs11013860) has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural effects of rs11013860 expression are unknown. Thus, the current study investigated the mechanisms of how the CACNB2 gene influences hippocampal-cortical limbic circuits in patients with bipolar disorder (BD). A total of 202 subjects were studied [69 BD patients and 133 healthy controls (HC)]. Participants agreed to undergo resting-state functional magnetic resonance imaging (rs-fMRI) and have blood drawn for genetic testing. Participants were found to belong to either a CC group homozygous for the C-allele (17 BD, 41 HC), or an A-carrier group carrying the high risk A-allele (AA/CA genotypes; 52 BD, 92 HC). Brain activity was assessed using resting-state functional connectivity (rs-FC) analyses. A main effect of genotype showed that the rs-FC of the AA/CA group was elevated more than that of the CC-group between the hippocampus and the regions of right-inferior temporal, fusiform, and left-inferior occipital gyri. Additionally, a significant diagnosis × genotype interaction was noted between the hippocampus and right pars triangularis. Furthermore, in BD patients, the AA/CA group showed lower rs-FC when compared to that of the CC group. Additionally, individuals from HC within the AA/CA group showed higher rs-FC than that of the CC group. Finally, within C-allele-carrying groups, individuals with BD showed significantly increased rs-FC compared to that of HC. Our study demonstrates that BD patients with the CACNB2 rs11013860 AA/CA genotype may exhibit altered hippocampal-cortical connectivity.