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

doi:10.1016/j.schres.2018.06.029

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^*

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

8 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 language	English (US)
Pages (from-to)	212-216
Number of pages	5
Journal	Schizophrenia Research
Volume	202
DOIs	https://doi.org/10.1016/j.schres.2018.06.029
State	Published - Dec 2018

Funding

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. 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 . 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).

Keywords

Antipsychotic
COMT
PCET
Psychosis

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

UN SDGs

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10.1016/j.schres.2018.06.029

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Nelson, C. L. M., Amsbaugh, H. M., Reilly, J. L., Rosen, C., Marvin, R. W., Ragozzino, M. E., Bishop, J. R., Sweeney, J. A., & Hill, S. K. (2018). Beneficial and adverse effects of antipsychotic medication on cognitive flexibility are related to COMT genotype in first episode psychosis. Schizophrenia Research, 202, 212-216. https://doi.org/10.1016/j.schres.2018.06.029

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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.",

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

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year = "2018",

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doi = "10.1016/j.schres.2018.06.029",

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AU - Rosen, Cherise

AU - Marvin, Robert W.

AU - Ragozzino, Michael E.

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AU - Sweeney, John A.

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AB - 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.

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ER -

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

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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