Muscarinic M1 receptor sequence: Preliminary studies on its effects on cognition and expression

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• 作者：Elizabeth Scarr^a ; ^b ; ^{elscarr@unimelb.edu.au} ; Suresh Sundram^b ; ^c ; ^d ; Azita Deljo^d ; Tiffany Francis Cowie^e ; ^f ; Andrew Stuart Gibbons^a ; ^b ; Susan Juzva^b ; Andrew Mackinnon^g ; Stephen J. Wood^h ; ⁱ ; Renee Testa^h ; ^j ; Christos Pantelis^h ; Brian Dean^a ; ^b
• 关键词：Schizophrenia ; Executive function ; Muscarinic M1 receptor (CHRM1) ; Single nucleotide polymorphism ; Human ; mRNA
• 刊名：Schizophrenia Research
• 出版年：2012
• 期刊代码：240_09209964
• 类别：med
• 出版时间：June, 2012
• 卷：138
• 期：1
• 页码：94-98
• 文件大小：303 K

摘要

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 (m>CHRM1m>) perform less well on the Wisconsin Card Sorting Test than those who are heterozygous. We investigated whether m>CHRM1m> sequence is associated with impaired executive function, a common problem in schizophrenia.

We sequenced the m>CHRM1m> 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 m>CHRM1m> sequence affected receptor expression, we used post-mortem data, from another cohort, to investigate associations between m>CHRM1m> sequence and mRNA levels.

On the Wisconsin Card Sorting Test, 267C/C participants with schizophrenia made more perseverative errors (m>pm> < 0.05) and perseverative responses (m>pm> < 0.05) than 267C/A participants. Genotype had no effect on verbal fluency (m>pm> = 0.8) or National Adult Reading test (m>pm> = 0.62). Cortical m>CHRM1m> mRNA levels did not vary with gene sequence (m>pm> = 0.409).

The clinical study supports the proposal that m>CHRM1m> 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.