Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia.
The involvement of specific pathways mediated through muscarinic receptor activity has been widely implicated in schizophrenia. Extensive pharmacological evidence supports the systems role in mediating antipsychotic drug efficacy, while mounting physiological evidence demonstrates the presence of significant alterations to normal muscarinic receptor integrity in the disorder. The mechanisms that facilitate the systems involvement and their magnitude, however, remain poorly understood. We have proposed that alterations to normal muscarinic receptor expression exist in schizophrenia, and that these significantly influence the physiological changes often reported for the system amongst patients. In this study, we investigate this potential, and have selected to examine the muscarinic 1 receptor, which constitutes a major target for antipsychotic action and plays a conspicuous role in those regions central to the disorders pathophysiology. Using relative gene quantification, we measured post-mortem levels of steady-state cortical muscarinic 1 receptor cDNA in patients (N = 20) and unaffected controls (N = 20), and examined group differences in expression levels. Commensurate with our hypothesis, we observed significant reductions in muscarinic 1 receptor cDNA in our patient sample (F(1,37) = 4.73, P = 0.036) and have estimated this to constitute a 28% decrease compared to the control subjects (95% CI from 2 to 47%). These results provide evidence in support of altered muscarinic 1 receptor expression in schizophrenia, though further work is needed to corroborate these findings.
Mancama
D
D
Section of Clinical Neuropharmacology, Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, England, UK. sphadtm@iop.kcl.ac.uk
Arranz
M J
MJ
Landau
S
S
Kerwin
R
R
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000737:chemistry; D003337:Corpus Callosum / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043643:Receptor, Muscarinic M1 / Q000172:deficiency* / Q000235:genetics; D012559:Schizophrenia / Q000378:metabolism*
D018076:DNA, Complementary; D043643:Receptor, Muscarinic M1