Association of muscarinic m1 receptor genetic polymorphisms with psychiatric symptoms and cognitive function in schizophrenic patients

Objective: The cholinergic system is important in the search for the pathophysiology of schizophrenia due to its role in cognitive function, interaction with the dopamine system in brain regions relevant to schizophrenia, side effects of antipsychotic medication and potential antipsychotic effect of muscarinic receptor antagonists. This study investigated the association of type I muscarinic receptor (CHRM1) genetic polymorphisms with the clinical characteristics of chronic schizophrenic inpatients.

Methods: We determined the genotype of CHRM1 genetic polymorphisms in 243 schizophrenic patients hospitalized in chronic care wards. Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Folstein Mini-Mental Status Examination (MMSE) test. Sixty of the 243 subjects also completed the Wisconsin Card Sorting Test (WCST).

Results: There was a significant difference in the number of correct responses and the percentage of perseverative errors in the WCST in the CHRM1 C267A genotype group of schizophrenia patients. There was no significant association between age at onset, chlorpromazine equivalents, BPRS scores, MMSE or schizophrenia per se in patients with the CHRM1 C267A genotype. The full exon of the CHRM1 gene was screened out with single-strand conformation polymorphism, and 2 single nucleotide polymorphisms (C267A and C1353T) were identified in our patients and control subjects. These 2 single nucleotide polymorphisms were linked together without exception.

Conclusion: This study demonstrated that in schizophrenic patients, the heterozygote group of CHRM1 C267A polymorphism (267C/A) had more correct responses and less perseverative errors on the WCST performance than the 267C/C homozygote group, implicating that this polymorphism may be related to prefrontal cortical function. Our results also suggested that the C267A polymorphism plays no major role in the susceptibility to and clinical manifestations of schizophrenia.