Cheng Xiaofei, Yang Qian, Zhang Yamin, Zhang Mengmeng, Yu Hua, Ni Peiyan, Li Xiaojing, Li Mingli, Li Tao
Mental Health Center, West China Hospital, Sichuan University, Chengdu, China.
The Fourth People's Hospital of Haining, Jiaxing, China.
BMC Psychiatry. 2025 Feb 27;25(1):183. doi: 10.1186/s12888-025-06611-y.
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.
近期全基因组关联研究已将电压门控钙通道基因与双相情感障碍（BD）联系起来，其中分别报道了CACNB2基因的rs11013860。然而，关于其多态性如何精确影响大脑的结构和功能，人们了解较少。
对173例BD患者和207名健康对照者（HCs）进行了结构和功能磁共振成像扫描，并对CACNB2 rs11013860进行基因分型。采用灰质体积（GMV）、局部一致性（ReHo）和中心度（DC）来检查这些参与者的脑结构、功能活动和连通性。
BD患者的情感回路，如小脑、岛叶、扣带回、梭状回、额上回、颞上/中回、枕中回、舌回、楔前叶、壳核、海马和海马旁回，是GMV、ReHo和DC与HCs存在差异的主要区域。右侧小脑前后叶、海马旁回以及舌回在GMV方面显示出CACNB2 rs11013860基因型与诊断之间的相互作用。此外，在HCs中，随着A风险等位基因剂量的降低，GMV有显著的逐步增加，但BD患者中不存在这种关系模式。在ReHo和DC方面未发现BD与CACNB2 rs11013860之间的相互作用。
这些结果表明，BD患者中CACNB2 rs11013860的多态性可能与小脑、边缘系统和其他脑区的脑结构异常有关，这可能是导致该疾病的原因。
