Lower levels of cortical [3H]pirenzepine binding to postmortem tissue defines a sub-group of older people with schizophrenia with less severe cognitive deficits

Multiple lines of evidence argue for lower levels of cortical muscarinic M1 receptors (CHRM1) in people with schizophrenia which is possibly due to a sub-group within the disorder who have a marked loss of CHRM1 (muscarinic receptor deficit sub-group (MRDS)). In this study we sought to determine if the lower levels of CHRM1 was apparent in older people with schizophrenia and whether the loss of CHRM1 was associated with symptom severity by measuring levels of cortical [3H]pirenzepine binding to CHRM1 from 56 people with schizophrenia and 43 controls. Compared to controls (173 +/- 6.3 fmol / mg protein), there were lower levels of cortical [3H]pirenzepine binding in the people with schizophrenia (mean +/- SEM: 153 +/- 6.0 fmol / mg protein; p = 0.02; Cohen's d = -0.46). [3H]pirenzepine binding in the people with schizophrenia, but not controls, was not normally distributed and best fitted a two-population solution. The nadir of binding separating the two groups of people with schizophrenia was 121 fmol / mg protein and levels of [3H]pirenzepine binding below this value had a 90.7 % specificity for the disorder. Compared to controls, the score from the Clinical Dementia Rating Scale (CDR) did not differ significantly in MRDS but were significantly higher in the sub-group with normal radio-ligand binding. Positive and Negative Syndrome Scale scores did not differ between the two sub-groups with schizophrenia. Our current study replicates and earlier finding showing a MRDS within schizophrenia and, for the first time, suggest this sub-group have less severe cognitive deficits others with schizophrenia.

Automated summary

This study found lower levels of cortical muscarinic M1 receptors (CHRM1) in older people with schizophrenia, and this loss of CHRM1 was associated with symptom severity. Compared to controls, people with schizophrenia showed lower levels of [3H]pirenzepine binding to CHRM1. A cut-off value of 121 fmol/mg protein for [3H]pirenzepine binding had a 90.7% specificity for diagnosing schizophrenia. Cognitive deficits were less severe in the muscarinic receptor deficit sub-group (MRDS) of schizophrenia, while the sub-group with normal radio-ligand binding had higher scores on the Clinical Dementia Rating Scale (CDR).