The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia.
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.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria 3053, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3052, Australia. Electronic address: vcropley@unimelb.edu.au.
Vanessa L
VL
Cropley
Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3052, Australia; Molecular Psychiatry Laboratory, Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia.
Elizabeth
E
Scarr
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria 3053, Australia; Brain and Mental Health Laboratory, Institute of Cognitive and Clinical Neuroscience, Monash University, Clayton, Victoria 3168, Australia.
Alex
A
Fornito
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria 3053, Australia; Brain and Mental Health Laboratory, Institute of Cognitive and Clinical Neuroscience, Monash University, Clayton, Victoria 3168, Australia.
Paul
P
Klauser
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria 3053, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3052, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia.
Chad A
CA
Bousman
The School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, New South Wales 3208, Australia; Neurobehavioural Genetics Unit, Hunter Medical Research Institute, New Lambton, New South Wales 2305, Australia.
Rodney
R
Scott
The School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, New South Wales 3208, Australia; Neurobehavioural Genetics Unit, Hunter Medical Research Institute, New Lambton, New South Wales 2305, Australia.
Murray J
MJ
Cairns
The School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, New South Wales 3208, Australia; Neurobehavioural Genetics Unit, Hunter Medical Research Institute, New Lambton, New South Wales 2305, Australia.
Paul A
PA
Tooney
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria 3053, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3052, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia.
Christos
C
Pantelis
Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3052, Australia; Molecular Psychiatry Laboratory, Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia.
Brian
B
Dean
D000328:Adult; D001315:Australia / Q000453:epidemiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043643:Receptor, Muscarinic M1 / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
D043643:Receptor, Muscarinic M1
Imaging; Muscarinic M1 receptor (CHRM1); Schizoaffective disorder; Schizophrenia; Set-shifting; Single nucleotide polymorphism; Voxel-based morphometry