Relationship between muscarinic M receptor binding and cognition in medication-free subjects with psychosis.

Background: It is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M receptor agonists suggest alterations in M receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M receptor binding in relation to cognitive impairments have been done. As cognitive deficits have similar course and prognostic relevance across psychotic disorders, the current study assessed M receptor binding in the DLPFC and hippocampus in relation to cognitive functioning.

Methods: Muscarinic M receptor binding potential (BP) was measured using I-IDEX, single photon emission computed tomography (SPECT) in 30 medication-free subjects diagnosed with a psychotic disorder. A computerized neuropsychological test battery was used to assess cognition, and the positive and negative syndrome scale (PANSS) to assess severity of psychotic symptoms.

Results: Assessment of cognitive domains showed that lower M BP in the DLPFC was related to overall lower performance in verbal learning and memory. In addition, lower M BP in the DLPFC was related to greater negative symptom severity. Lastly, lower M BP in the hippocampus was related to worse delayed recognition of verbal memory.

Conclusion: This is the first study to show that variation in M receptors in the DLPFC is related to cognitive and negative symptom outcome in psychotic disorders. The M receptor may be an important biomarker in biological stratification of patients with psychotic disorders.