Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

Int J Mol Sci. 2019 Jul 19;20(14):3537. doi: 10.3390/ijms20143537.

Abstract

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however, new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is crucial for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. Finally, we will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

Keywords: anxiety; attention-deficit and hyperactivity disorder; autism spectrum disorder; auxiliary subunits; bipolar disorder; calcium channel modulators; genetic risk variations; major depressive disorder; psychiatric disorders; schizophrenia; voltage-gated calcium channels.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / chemistry
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Clinical Trials as Topic
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Ion Channel Gating / drug effects
  • Mental Disorders / diagnosis
  • Mental Disorders / drug therapy
  • Mental Disorders / genetics*
  • Mental Disorders / metabolism
  • Molecular Targeted Therapy
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Structure-Activity Relationship
  • Treatment Outcome

Substances

  • Biomarkers
  • Calcium Channel Blockers
  • Calcium Channels