Beneficial and adverse effects of antipsychotic medication on cognitive flexibility are related to COMT genotype in first episode psychosis

Courtney L.M. Nelson, Hayley M. Amsbaugh, James L. Reilly, Cherise Rosen, Robert W. Marvin, Michael E. Ragozzino, Jeffrey R. Bishop, John A. Sweeney, S. Kristian Hill

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

This study evaluated the ability to flexibly shift cognitive set and to consistently maintain a new response preference using the Penn Conditional Exclusion Test (PCET). The relationship of performance errors with catechol-O-methyltransferase (COMT) rs4680 (Val158Met) genotype (Met carriers vs. Val homozygotes) on test performance before and after antipsychotic treatment in 32 first episode psychosis (FEP) patients was examined. After treatment, patients demonstrated a mixture of beneficial and adverse cognitive outcomes that varied in relation to COMT genotype. Met carriers showed decreased perseverative and regressive errors, reflecting improved cognitive flexibility and enhanced stability of behavioral preferences, respectively. In contrast, Val homozygotes exhibited an increase in regressive errors after treatment. These findings suggest that Val homozygotes may be vulnerable to adverse effects of antipsychotic medication on cognitive processes that maintain consistent adaptive response preferences, an ability linked to the striatum in rodent models.

Original languageEnglish (US)
Pages (from-to)212-216
Number of pages5
JournalSchizophrenia Research
Volume202
DOIs
StatePublished - Dec 2018

Bibliographical note

Funding Information:
We thank Drs. Ovidio DeLeon, Margret Harris, Hugo Solari, Peter Weiden, and the clinical core staff of the UIC Center for Cognitive Medicine for their contributions to diagnostic and psychopathological assessments. We also thank Shitalben Patel for her contributions to the genotyping portions of this work. This study was supported in part by NARSAD, NIMH Grants MH077862, MH083888, MH062134, MH080066, and MH072767 and American College of Clinical Pharmacy.

Funding Information:
We thank Drs. Ovidio DeLeon, Margret Harris, Hugo Solari, Peter Weiden, and the clinical core staff of the UIC Center for Cognitive Medicine for their contributions to diagnostic and psychopathological assessments. We also thank Shitalben Patel for her contributions to the genotyping portions of this work. This study was supported in part by NARSAD , NIMH Grants MH077862 , MH083888 , MH062134 , MH080066 , and MH072767 and American College of Clinical Pharmacy .

Funding Information:
This project was supported by the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) and the National Institutes of Health (NIMH: MH077862, MH062134, MH080066, and MH072767).

Publisher Copyright:
© 2018 Elsevier B.V.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • Antipsychotic
  • COMT
  • PCET
  • Psychosis

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