Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

Lusi Zhang; Scot Kristian Hill; Bin Guo; Baolin Wu; Ney Alliey-Rodriguez; Seenae Eum; Paulo Lizano; Elena I. Ivleva; James L. Reilly; Richard S.E. Keefe; Sarah K. Keedy; Carol A. Tamminga; Godfrey D. Pearlson; Brett A. Clementz; Matcheri S. Keshavan; Elliot S. Gershon; John A. Sweeney; Jeffrey R. Bishop

doi:10.1016/j.pnpbp.2021.110464

Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

Lusi Zhang, Scot Kristian Hill, Bin Guo, Baolin Wu, Ney Alliey-Rodriguez, Seenae Eum, Paulo Lizano, Elena I. Ivleva, James L. Reilly, Richard S.E. Keefe, Sarah K. Keedy, Carol A. Tamminga, Godfrey D. Pearlson, Brett A. Clementz, Matcheri S. Keshavan, Elliot S. Gershon, John A. Sweeney, Jeffrey R. Bishop

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

3 Scopus citations

Abstract

Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRS_CAD) were quantified for each participant across 13 p-value thresholds (P_T 0.5-5e⁻⁸). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRS_CAD was examined in relation to the BACS and the optimized P_T was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRS_CAD-cognition associations. Multiple regression analyses examined PRS_CAD under the optimal P_T and medication burden in relation to the BACS composite and subtest scores. Results: Higher PRS_CAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRS_CAD. After controlling for PRS_CAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). Conclusions: Higher PRS_CAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.

Original language	English (US)
Article number	110464
Journal	Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume	113
DOIs	https://doi.org/10.1016/j.pnpbp.2021.110464
State	Published - Mar 8 2022

Keywords

Cardiovascular medication
Cognition
Coronary artery disease
Polygenic risk score
Psychosis

ASJC Scopus subject areas

Pharmacology
Biological Psychiatry

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10.1016/j.pnpbp.2021.110464

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Zhang, L., Hill, S. K., Guo, B., Wu, B., Alliey-Rodriguez, N., Eum, S., Lizano, P., Ivleva, E. I., Reilly, J. L., Keefe, R. S. E., Keedy, S. K., Tamminga, C. A., Pearlson, G. D., Clementz, B. A., Keshavan, M. S., Gershon, E. S., Sweeney, J. A., & Bishop, J. R. (2022). Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 113, Article 110464. https://doi.org/10.1016/j.pnpbp.2021.110464

Zhang, L, Hill, SK, Guo, B, Wu, B, Alliey-Rodriguez, N, Eum, S, Lizano, P, Ivleva, EI, Reilly, JL, Keefe, RSE, Keedy, SK, Tamminga, CA, Pearlson, GD, Clementz, BA, Keshavan, MS, Gershon, ES, Sweeney, JA & Bishop, JR 2022, 'Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 113, 110464. https://doi.org/10.1016/j.pnpbp.2021.110464

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title = "Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders",

abstract = "Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e−8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. Results: Higher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). Conclusions: Higher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.",

keywords = "Cardiovascular medication, Cognition, Coronary artery disease, Polygenic risk score, Psychosis",

author = "Lusi Zhang and Hill, {Scot Kristian} and Bin Guo and Baolin Wu and Ney Alliey-Rodriguez and Seenae Eum and Paulo Lizano and Ivleva, {Elena I.} and Reilly, {James L.} and Keefe, {Richard S.E.} and Keedy, {Sarah K.} and Tamminga, {Carol A.} and Pearlson, {Godfrey D.} and Clementz, {Brett A.} and Keshavan, {Matcheri S.} and Gershon, {Elliot S.} and Sweeney, {John A.} and Bishop, {Jeffrey R.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2022",

month = mar,

day = "8",

doi = "10.1016/j.pnpbp.2021.110464",

language = "English (US)",

volume = "113",

journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",

issn = "0278-5846",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

AU - Zhang, Lusi

AU - Hill, Scot Kristian

AU - Guo, Bin

AU - Wu, Baolin

AU - Alliey-Rodriguez, Ney

AU - Eum, Seenae

AU - Lizano, Paulo

AU - Ivleva, Elena I.

AU - Reilly, James L.

AU - Keefe, Richard S.E.

AU - Keedy, Sarah K.

AU - Tamminga, Carol A.

AU - Pearlson, Godfrey D.

AU - Clementz, Brett A.

AU - Keshavan, Matcheri S.

AU - Gershon, Elliot S.

AU - Sweeney, John A.

AU - Bishop, Jeffrey R.

PY - 2022/3/8

Y1 - 2022/3/8

N2 - Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e−8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. Results: Higher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). Conclusions: Higher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.

AB - Background: Cognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. Methods: Neuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e−8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. Results: Higher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). Conclusions: Higher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.

KW - Cardiovascular medication

KW - Cognition

KW - Coronary artery disease

KW - Polygenic risk score

KW - Psychosis

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U2 - 10.1016/j.pnpbp.2021.110464

DO - 10.1016/j.pnpbp.2021.110464

M3 - Article

C2 - 34756932

AN - SCOPUS:85118840926

SN - 0278-5846

VL - 113

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

M1 - 110464

ER -

Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

Abstract

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