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. 2019 Feb 11;19(1):62.
doi: 10.1186/s12888-019-2040-8.

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

Fang Liu  1   2 , Xiaohong Gong  3 , Xudong Yao  1   2 , Lingling Cui  4 , Zhiyang Yin  1 , Chao Li  4 , Yanqing Tang  5   6 , Fei Wang  7   8   9
Affiliations

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

Fang Liu et al. BMC Psychiatry. .

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: Our study demonstrates that BD patients with the CACNB2 rs11013860 AA/CA genotype may exhibit altered hippocampal-cortical connectivity.

Keywords: 11,013,860; Bipolar disorder; CACNB2; Resting-state functional connectivity (rs-FC).

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Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in accordance with the latest version of the Declaration of Helsinki and approved by the Institutional Review Board of the China Medical University. Each participant provided written informed consent prior to commencement of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Main effect of genotype on the rs-FC between AA/CA group and CC group. Clusters presenting lower (blue) or higher (red) rs-FC, p < 0.01 GRF-corrected
Fig. 2
Fig. 2
Interaction between rs11013860 genotype and diagnosis in BD and HC. Clusters presenting lower (blue) or higher (red) rs-FC, p < 0.01 GRF-corrected
Fig. 3
Fig. 3
a Main effect of genotype showing that carriers of high-risk A-allele exhibited higher rs-FC than carriers of C- between the hippocampus and the regions of right inferior temporal, fusiform, and left inferior occipital gyri (independent t-test, p <0 .001). b Interaction graph showing that in BD patients rs-FC was decreased between the hippocampus and right pars triangularis in A-allele carrying individuals compared to that of C-allele carrying individuals, in HC the AA/CA group showed higher rs-FC than CC group, and in carrying C-allele groups the patients with BD had significantly increased rs-FC compared to that of HC
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