Elsevier

Progress in Neurobiology

Volume 134, November 2015, Pages 36-54
Progress in Neurobiology

Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders

https://doi.org/10.1016/j.pneurobio.2015.09.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • Voltage-gated calcium channel classification—genes and proteins.

  • Genetic analysis of neuropsychiatric syndromes.

  • Calcium channel genes identified from GWA studies of psychiatric disorders.

  • Rare mutations in calcium channel genes in psychiatric disorders.

  • Pathophysiological sequelae of CACNA1C mutations and polymorphisms.

  • Monogenic disorders resulting from harmful mutations in other voltage-gated calcium channel genes.

  • Changes in calcium channel gene expression in disease.

  • Involvement of voltage-gated calcium channels in early brain development.

Abstract

This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients.

Keywords

Calcium channel
Neuropsychiatric disorder
Polygenic disorder
Mutation
Single nucleotide polymorphism

Abbreviations

DISC1
Disrupted in Schizophrenia 1
fMRI
functional magnetic resonance imaging
FMRP
Fragile X mental retardation protein
GWAS
genome wide association study
SNP
single nucleotide polymorphism

Cited by (0)

1

Equal contribution.