Relationship between muscarinic M 1 receptor binding and cognition in medication-free subjects with psychosis

• Published in: NeuroImage clinical Vol. 18; pp. 713 - 719
• Main Authors: Bakker, Geor, Vingerhoets, Claudia, Boucherie, Daphne, Caan, Matthan, Bloemen, Oswald, Eersels, Jos, Booij, Jan, van Amelsvoort, Thérèse
• Format: Journal Article
• Language: English
• Published: Netherlands 2018
• Subjects: Adult; Cognition - physiology; Female; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Humans; Male; Neuropsychological Tests; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - metabolism; Psychotic Disorders - psychology; Radiology; Receptor, Muscarinic M1 - metabolism; Tomography, Emission-Computed, Single-Photon; Young Adult
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2018.02.030

AbstractBackgroundIt is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M 1 receptor agonists suggest alterations in M 1 receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M 1 receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M 1 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 1 receptor binding in the DLPFC and hippocampus in relation to cognitive functioning. MethodsMuscarinic M 1 receptor binding potential (BP ND) was measured using 123I-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. ResultsAssessment of cognitive domains showed that lower M 1 BP ND in the DLPFC was related to overall lower performance in verbal learning and memory. In addition, lower M 1 BP ND in the DLPFC was related to greater negative symptom severity. Lastly, lower M 1 BP ND in the hippocampus was related to worse delayed recognition of verbal memory. ConclusionThis is the first study to show that variation in M 1 receptors in the DLPFC is related to cognitive and negative symptom outcome in psychotic disorders. The M 1 receptor may be an important biomarker in biological stratification of patients with psychotic disorders.