CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease

Bhat, Shambhu; Dao, David T.; Terrillion, Chantelle E.; Arad, Michal; Smith, Robert J.; Soldatov, Nikolai M.; Gould, Todd D.

doi:10.1016/j.pneurobio.2012.06.001

Cited by 271Bipolar Disorder and TreatmentSchizophrenia research and treatmentIon channel regulation and function

CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease

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Bhat, Shambhu, Dao, David T., Terrillion, Chantelle E., Arad, Michal, Smith, Robert J., Soldatov, Nikolai M., Gould, Todd D.·2012·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2012.06.001PMC PMC3459072

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Abstract

One of the most consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the α(1C) subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC). Genetic variation in CACNA1C have also been associated with depression, schizophrenia, autism spectrum disorders, as well as changes in brain function and structure in control subjects who have no diagnosable psychiatric illness. These data are consistent with a continuum of shared neurobiological vulnerability between diverse-Diagnostic and Statistical Manual (DSM) defined-neuropsychiatric diseases. While involved in numerous cellular functions, Ca(v)1.2 is most frequently implicated in coupling of cell membrane depolarization to transient increase of the membrane permeability for calcium, leading to activation and, potentially, changes in intracellular signaling pathway activity, gene transcription, and synaptic plasticity. Ca(v)1.2 is involved in the proper function of numerous neurological circuits including those involving the hippocampus, amygdala, and mesolimbic reward system, which are strongly implicated in psychiatric disease pathophysiology. A number of behavioral effects of LTCC inhibitors have been described including antidepressant-like behavioral actions in rodent models. Clinical studies suggest possible treatment effects in a subset of patients with mood disorders. We review the genetic structure and variation of CACNA1C, discussing relevant human genetic and clinical findings, as well as the biological actions of Ca(v)1.2 that are most relevant to psychiatric illness.

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Mutations in CACNA1C, which encodes the α1 pore-forming subunit of the L-type calcium channel Cav1.2, are associated with multiple neuropsychiatric disorders including ASD.
“Mutations in CACNA1C, which encodes the α1 pore-forming subunit of the L-type calcium channel Cav1.2, has been associated with multiple neuropsychiatric disorders, including ASD76.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [76]

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Authors: Bhat, S., Dao, D. T., Terrillion, C. E., Arad, M., Smith, R. J., Soldatov, N. M., & Gould, T. D.
Affiliations: University of Maryland, Baltimore (US)
Quanterix (United States) (US)
Corresponding author: Gould, Todd D.
ORCID: Terrillion, Chantelle E.
Soldatov, Nikolai M.
Gould, Todd D.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2012-10
Volume: 99
Issue: 1
Pages: 1-14
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2012.06.001
PMC: PMC3459072
OpenAlex: W2057932313
Cited by: 271
References: 178
Citations by year: 2026: 14 · 2025: 14 · 2024: 15 · 2023: 18 · 2022: 22 · 2021: 15 · 2020: 14 · 2019: 16 · 2018: 22 · 2017: 27 · 2016: 18 · 2015: 34 · 2014: 28 · 2013: 7 · 2012: 7
FWCI: 3.27
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (R21MH093967, MH093967, L30 MH091729)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords: CACNA1C, Cav1.2, L-type calcium channels, bipolar disorder, depression, schizophrenia, autism spectrum disorder, synaptic plasticity, hippocampus, amygdala, mesolimbic reward system, antidepressant-like effects, mood disorders
MeSH terms: Mental Disorders, Humans, Genetic Variation, Calcium Channels, L-Type

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CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease

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