Relationship Between Muscarinic M Receptor Binding and Cognition in Medication-free Subjects with Psychosis

Overview

Journal Neuroimage Clin

Publisher Elsevier

Specialties Neurology
Radiology

Date 2018 Mar 22

PMID 29560312

Citations 18

Authors

Geor Bakker

Claudia Vingerhoets

Daphne Boucherie

Matthan Caan

Oswald Bloemen

Jos Eersels

Jan Booij

Therese van Amelsvoort

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The potential of muscarinic M and M receptor activators for the treatment of cognitive impairment associated with schizophrenia.

Yohn S, Harvey P, Brannan S, Horan W Front Psychiatry. 2024; 15:1421554.

PMID: 39483736 PMC: 11525114. DOI: 10.3389/fpsyt.2024.1421554.

Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain.

Chang C, Dai W, Hu S Psychopharmacology (Berl). 2024; 242(2):247-269.

PMID: 39158618 DOI: 10.1007/s00213-024-06670-1.

The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis-The Case of the Xanomeline-Trospium Combination: A Systematic Review.

Vasiliu O, Budeanu B, Catanescu M Pharmaceuticals (Basel). 2024; 17(5).

PMID: 38794180 PMC: 11124398. DOI: 10.3390/ph17050610.

PsyCog: A computerised mini battery for assessing cognition in psychosis.

Gifford G, Cullen A, Vieira S, Searle A, McCutcheon R, Modinos G Schizophr Res Cogn. 2024; 37:100310.

PMID: 38572271 PMC: 10987298. DOI: 10.1016/j.scog.2024.100310.

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia.

Kidambi N, Elsayed O, El-Mallakh R Neuropsychiatr Dis Treat. 2023; 19:1145-1151.

PMID: 37193547 PMC: 10183173. DOI: 10.2147/NDT.S406371.

References

Salah-Uddin H, Scarr E, Pavey G, Harris K, Hagan J, Dean B . Altered M(1) muscarinic acetylcholine receptor (CHRM1)-Galpha(q/11) coupling in a schizophrenia endophenotype. Neuropsychopharmacology. 2009; 34(9):2156-66. DOI: 10.1038/npp.2009.41. View

Raedler T, Knable M, Jones D, Lafargue T, Urbina R, Egan M . In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. Neuropsychopharmacology. 2000; 23(1):56-68. DOI: 10.1016/S0893-133X(99)00162-1. View

Motulsky H, Brown R . Detecting outliers when fitting data with nonlinear regression - a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinformatics. 2006; 7:123. PMC: 1472692. DOI: 10.1186/1471-2105-7-123. View

Boundy K, Barnden L, Rowe C, Reid M, Kassiou M, Katsifis A . Human dosimetry and biodistribution of iodine-123-iododexetimide: a SPECT imaging agent for cholinergic muscarinic neuroreceptors. J Nucl Med. 1995; 36(7):1332-8. View

Kapur S, Phillips A, Insel T . Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?. Mol Psychiatry. 2012; 17(12):1174-9. DOI: 10.1038/mp.2012.105. View

Hietala J, Syvalahti E, Vuorio K, Rakkolainen V, Bergman J, Haaparanta M . Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients. Lancet. 1995; 346(8983):1130-1. DOI: 10.1016/s0140-6736(95)91801-9. View

Klauschen F, Goldman A, Barra V, Meyer-Lindenberg A, Lundervold A . Evaluation of automated brain MR image segmentation and volumetry methods. Hum Brain Mapp. 2008; 30(4):1310-27. PMC: 6870639. DOI: 10.1002/hbm.20599. View

Woodberry K, Giuliano A, Seidman L . Premorbid IQ in schizophrenia: a meta-analytic review. Am J Psychiatry. 2008; 165(5):579-87. DOI: 10.1176/appi.ajp.2008.07081242. View

Scarr E, Sundram S, Keriakous D, Dean B . Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia. Biol Psychiatry. 2007; 61(10):1161-70. DOI: 10.1016/j.biopsych.2006.08.050. View

10.

Nathan P, Watson J, Lund J, Davies C, Peters G, Dodds C . The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int J Neuropsychopharmacol. 2012; 16(4):721-31. DOI: 10.1017/S1461145712000752. View

11.

Rodriguez-Jimenez R, Bagney A, Moreno-Ortega M, Garcia-Navarro C, Aparicio A, Lopez-Anton R . [Cognitive deficit in schizophrenia: MATRICS Consensus Cognitive Battery]. Rev Neurol. 2012; 55(9):549-55. View

12.

Fischl B, Salat D, Busa E, Albert M, Dieterich M, Haselgrove C . Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002; 33(3):341-55. DOI: 10.1016/s0896-6273(02)00569-x. View

13.

Fischl B . FreeSurfer. Neuroimage. 2012; 62(2):774-81. PMC: 3685476. DOI: 10.1016/j.neuroimage.2012.01.021. View

14.

Green M, Kern R, Heaton R . Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res. 2004; 72(1):41-51. DOI: 10.1016/j.schres.2004.09.009. View

15.

Beck A, Ward C, Mendelson M, Mock J, ERBAUGH J . An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4:561-71. DOI: 10.1001/archpsyc.1961.01710120031004. View

16.

Dudai Y, Karni A, Born J . The Consolidation and Transformation of Memory. Neuron. 2015; 88(1):20-32. DOI: 10.1016/j.neuron.2015.09.004. View

17.

Bymaster F, Calligaro D, Falcone J, Marsh R, Moore N, Tye N . Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996; 14(2):87-96. DOI: 10.1016/0893-133X(94)00129-N. View

18.

Hasselmo M . The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006; 16(6):710-5. PMC: 2659740. DOI: 10.1016/j.conb.2006.09.002. View

19.

Dean B, Crook J, Pavey G, Opeskin K, Copolov D . Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia. Mol Psychiatry. 2000; 5(2):203-7. DOI: 10.1038/sj.mp.4000684. View

20.

Scarr E, Millan M, Bahn S, Bertolino A, Turck C, Kapur S . Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank. Int J Neuropsychopharmacol. 2015; 18(10):pyv042. PMC: 4648162. DOI: 10.1093/ijnp/pyv042. View