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

Abstract Background 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 br...

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Main Authors: Xiaofei Cheng, Qian Yang, Yamin Zhang, Mengmeng Zhang, Hua Yu, Peiyan Ni, Xiaojing Li, Mingli Li, Tao Li
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06611-y
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author Xiaofei Cheng
Qian Yang
Yamin Zhang
Mengmeng Zhang
Hua Yu
Peiyan Ni
Xiaojing Li
Mingli Li
Tao Li
author_facet Xiaofei Cheng
Qian Yang
Yamin Zhang
Mengmeng Zhang
Hua Yu
Peiyan Ni
Xiaojing Li
Mingli Li
Tao Li
author_sort Xiaofei Cheng
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions 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.
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spelling doaj-art-dce67da02dce4c1ea2ce18b03e97f08f2025-08-20T02:01:34ZengBMCBMC Psychiatry1471-244X2025-02-0125111210.1186/s12888-025-06611-yThe impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorderXiaofei Cheng0Qian Yang1Yamin Zhang2Mengmeng Zhang3Hua Yu4Peiyan Ni5Xiaojing Li6Mingli Li7Tao Li8Mental Health Center, West China Hospital, Sichuan UniversityThe Fourth People’s Hospital of HainingAffiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineMental Health Center, West China Hospital, Sichuan UniversityAffiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineMental Health Center, West China Hospital, Sichuan UniversityAffiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12888-025-06611-yBipolar disorder (BD)CACNB2 Rs11013860Grey matter volume (GMV)ReHoDegree centrality (DC)
spellingShingle Xiaofei Cheng
Qian Yang
Yamin Zhang
Mengmeng Zhang
Hua Yu
Peiyan Ni
Xiaojing Li
Mingli Li
Tao Li
The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
BMC Psychiatry
Bipolar disorder (BD)
CACNB2 Rs11013860
Grey matter volume (GMV)
ReHo
Degree centrality (DC)
title The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
title_full The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
title_fullStr The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
title_full_unstemmed The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
title_short The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
title_sort impact of the cacnb2 rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder
topic Bipolar disorder (BD)
CACNB2 Rs11013860
Grey matter volume (GMV)
ReHo
Degree centrality (DC)
url https://doi.org/10.1186/s12888-025-06611-y
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