The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder

International Journal of Bipolar Disorders

Research

Xinyue Jiang¹  Mikaela K. Dimick¹  Alysha A. Sultan¹  Benjamin I. Goldstein²  Bradley J. MacIntosh³  Clement C. Zai⁴  James L. Kennedy⁴ 

[1] Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada;Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada;Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada;Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, Canada;Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, ON, Canada;Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada;Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada;Tanenbaum Centre for Pharmacogenetics, Psychiatric Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, Canada;

关键词: Bipolar disorder;    Youth;    fMRI;    Resting-state functional connectivity;    CACNA1C;    Seed-to-voxel analysis;    Anterior cingulate cortex;    Orbitofrontal Cortex;    Amygdala;   

DOI  :  10.1186/s40345-022-00281-5

 received in 2022-05-24, accepted in 2022-12-13,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundCACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD.MethodsParticipants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13–20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race.ResultsWe observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01).ConclusionThis study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD.

【 授权许可】

CC BY   
© The Author(s) 2022

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