title: Muscarinic M1 receptor sequence: preliminary studies on its effects on cognition and expression.
abstract: It has been reported that people with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism of the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test than those who are heterozygous. We investigated whether CHRM1 sequence is associated with impaired executive function, a common problem in schizophrenia. We sequenced the CHRM1 using peripheral DNA from 97 people with schizophrenia who completed the Wisconsin Card Sorting Test, a verbal fluency test and the National Adult Reading Test. Clinical severity was assessed using the Positive and Negative Syndrome Scale. To determine whether CHRM1 sequence affected receptor expression, we used post-mortem data, from another cohort, to investigate associations between CHRM1 sequence and mRNA levels. On the Wisconsin Card Sorting Test, 267C/C participants with schizophrenia made more perseverative errors (p<0.05) and perseverative responses (p<0.05) than 267C/A participants. Genotype had no effect on verbal fluency (p=0.8) or National Adult Reading test (p=0.62). Cortical CHRM1 mRNA levels did not vary with gene sequence (p=0.409). The clinical study supports the proposal that CHRM1 sequence is associated with alterations in some aspects of executive function. However, the post-mortem study indicates this is not simply due to altered expression at the level of mRNA, suggesting this sequence alteration may affect the functionality of the CHRM1.
authors.affiliation: Rebecca L. Cooper Research Laboratories, Mental Health Research Institute, Parkville, Victoria 3052, Australia. elscarr@unimelb.edu.au
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
authors.forename: Suresh
authors.initials: S
authors.lastname: Sundram
authors.forename: Azita
authors.initials: A
authors.lastname: Deljo
authors.forename: Tiffany Francis
authors.initials: TF
authors.lastname: Cowie
authors.forename: Andrew Stuart
authors.initials: AS
authors.lastname: Gibbons
authors.forename: Susan
authors.initials: S
authors.lastname: Juzva
authors.forename: Andrew
authors.initials: A
authors.lastname: Mackinnon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.forename: Renee
authors.initials: R
authors.lastname: Testa
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics*; D015331:Cohort Studies; D056344:Executive Function; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*
chemical_list: C086088:CHRM1 protein, human; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic