Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia
- 4 March 2008
- journal article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 14 (11), 1017-1023
- https://doi.org/10.1038/mp.2008.28
Abstract
Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [3H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [3H]pirenzepine binding in BA9 divided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [3H]pirenzepine binding compared to controls. We suggest that these individuals make up ‘muscarinic receptor-deficit schizophrenia’ (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging.Keywords
This publication has 33 references indexed in Scilit:
- Histopathologic Diagnosis of Celiac Disease in Children Without Clinical Evidence of MalabsorptionInternational Journal of Surgical Pathology, 2007
- Subtyping schizophrenia: implications for genetic researchMolecular Psychiatry, 2006
- No change in cortical muscarinic M2, M3 receptors or [35S]GTPγS binding in schizophreniaLife Sciences, 2006
- Genetic Evidence for a Distinct Subtype of Schizophrenia Characterized by Pervasive Cognitive DeficitAmerican Journal of Human Genetics, 2005
- M1 Receptor Agonism, a Possible Treatment for Cognitive Deficits in SchizophreniaNeuropsychopharmacology, 2004
- The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapinePsychopharmacology, 2004
- In Vivo Determination of Muscarinic Acetylcholine Receptor Availability in SchizophreniaAmerican Journal of Psychiatry, 2003
- Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophreniaMolecular Psychiatry, 2002
- Low Muscarinic Receptor Binding in Prefrontal Cortex From Subjects With Schizophrenia: A Study of Brodmann’s Areas 8, 9, 10, and 46 and the Effects of Neuroleptic Drug TreatmentAmerican Journal of Psychiatry, 2001
- Collagen genes and proteins in osteogenesis imperfecta.Journal of Medical Genetics, 1985