The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia

Psychiatry Res. 2015 Nov 30;234(2):182-7. doi: 10.1016/j.pscychresns.2015.09.004. Epub 2015 Sep 10.

Abstract

Previous research has demonstrated that individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test (WCST) than those who are heterozygous. This study sought to determine whether variation in the rs2067477 genotype was associated with differential changes in brain structure. Data from 227 patients with established schizophrenia or schizoaffective disorder were obtained from the Australian Schizophrenia Research Bank. Whole-brain voxel-based morphometry was performed to compare regional grey matter volume (GMV) between the 267C/C (N=191) and 267C/A (N=36) groups. Secondary analyses tested for an effect of genotype on cognition (the WCST was not available). Individuals who were homozygous (267C/C) demonstrated significantly reduced GMV in the right precentral gyrus compared to those who were heterozygous (267C/A). These preliminary results suggest that the rs2067477 genotype is associated with brain structure in the right precentral gyrus in individuals with schizophrenia/schizoaffective disorder. Future studies are required to replicate these results and directly link the volumetric reductions with specific cognitive processes.

Keywords: Imaging; Muscarinic M1 receptor (CHRM1); Schizoaffective disorder; Schizophrenia; Set-shifting; Single nucleotide polymorphism; Voxel-based morphometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia / epidemiology
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Cognition Disorders / genetics
  • Female
  • Genetic Variation / genetics*
  • Gray Matter / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Organ Size
  • Polymorphism, Single Nucleotide / genetics
  • Receptor, Muscarinic M1 / genetics*
  • Schizophrenia / diagnosis*
  • Schizophrenia / epidemiology
  • Schizophrenia / genetics*

Substances

  • Receptor, Muscarinic M1