CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes and cardiovascular comorbidity

Xiao Ou; David E Crane; Bradley J MacIntosh; L Trevor Young; Paul Arnold; Stephanie Ameis; Benjamin I Goldstein

doi:10.1016/j.neubiorev.2015.04.022

CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes and cardiovascular comorbidity

Neurosci Biobehav Rev. 2015 Aug:55:198-210. doi: 10.1016/j.neubiorev.2015.04.022. Epub 2015 May 11.

Authors

Xiao Ou¹, David E Crane², Bradley J MacIntosh², L Trevor Young³, Paul Arnold⁴, Stephanie Ameis⁴, Benjamin I Goldstein⁵

Affiliations

¹ Department of Psychiatry, Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada; Department of Pharmacology, University of Toronto, Medicine, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: xiao.ou@utoronto.ca.
² Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada.
³ Department of Psychiatry, Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada; Department of Psychiatry, University of Toronto, Medicine, 250 College Street, Room 835, Toronto, ON, M5T 1R8, Canada.
⁴ Department of Psychiatry, University of Toronto, Medicine, 250 College Street, Room 835, Toronto, ON, M5T 1R8, Canada; Department of Psychiatry, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
⁵ Department of Psychiatry, Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada; Department of Pharmacology, University of Toronto, Medicine, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Department of Psychiatry, University of Toronto, Medicine, 250 College Street, Room 835, Toronto, ON, M5T 1R8, Canada. Electronic address: benjamin.goldstein@sunnybrook.ca.

PMID: 25976633
DOI: 10.1016/j.neubiorev.2015.04.022

Abstract

Recently, multiple genome-wide association studies have identified a genetic polymorphism (CACNA1C rs1006737) that appears to confer susceptibility for BD. This article aims to summarize the existing literature regarding the impact of rs1006737 on functional and structural neuroimaging intermediate phenotypes. Twenty eight articles, representing 2486 healthy participants, 369 patients with BD and 104 healthy first-degree relatives of patients with BD, are incorporated. Multiple studies have demonstrated structural differences, functional differences associated with emotion-related and frontal-executive tasks, and/or differences in behavioral task performance in risk allele carriers (AA or AG). Results comparing participants with BD to health controls are generally less pronounced than within-group genetic comparisons. The review concludes with an integration of how cardiovascular comorbidity may be a relevant mediator of the observed findings, and proposes future directions toward optimized therapeutic use of calcium channel blockers in BD.

Keywords: Bipolar disorder; CACNA1C; Calcium channel blockers; Cognition; Magnetic resonance imaging.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Bipolar Disorder / epidemiology*
Bipolar Disorder / genetics*
Brain / pathology
Calcium Channels, L-Type / genetics*
Cardiovascular Diseases / epidemiology*
Cardiovascular Diseases / genetics*
Comorbidity
Genotype
Humans
Phenotype
Polymorphism, Single Nucleotide / genetics*

Substances

CACNA1C protein, human
Calcium Channels, L-Type