title: CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes and cardiovascular comorbidity.
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.
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ou
authors.affiliation: Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada.
authors.forename: David E
authors.initials: DE
authors.lastname: Crane
authors.affiliation: Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: MacIntosh
authors.affiliation: 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.
authors.forename: L Trevor
authors.initials: LT
authors.lastname: Young
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Arnold
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ameis
authors.affiliation: 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.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D001921:Brain / Q000473:pathology; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type
keywords: Bipolar disorder; CACNA1C; Calcium channel blockers; Cognition; Magnetic resonance imaging