Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories

James L. Reilly, Kyle Frankovich, Scot Hill, Elliot S. Gershon, Richard S E Keefe, Matcheri S. Keshavan, Godfrey D. Pearlson, Carol A. Tamminga, John A. Sweeney

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives' deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.

Original languageEnglish (US)
Pages (from-to)1011-1021
Number of pages11
JournalSchizophrenia Bulletin
Volume40
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Psychotic Disorders
Schizophrenia
Phenotype
Antipsychotic Agents
Personality

Keywords

  • Bipolar disorder
  • Endophenotype
  • Family study
  • Schizoaffective disorder
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Reilly, J. L., Frankovich, K., Hill, S., Gershon, E. S., Keefe, R. S. E., Keshavan, M. S., ... Sweeney, J. A. (2014). Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories. Schizophrenia Bulletin, 40(5), 1011-1021. https://doi.org/10.1093/schbul/sbt132

Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories. / Reilly, James L.; Frankovich, Kyle; Hill, Scot; Gershon, Elliot S.; Keefe, Richard S E; Keshavan, Matcheri S.; Pearlson, Godfrey D.; Tamminga, Carol A.; Sweeney, John A.

In: Schizophrenia Bulletin, Vol. 40, No. 5, 2014, p. 1011-1021.

Research output: Contribution to journalArticle

Reilly, JL, Frankovich, K, Hill, S, Gershon, ES, Keefe, RSE, Keshavan, MS, Pearlson, GD, Tamminga, CA & Sweeney, JA 2014, 'Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories', Schizophrenia Bulletin, vol. 40, no. 5, pp. 1011-1021. https://doi.org/10.1093/schbul/sbt132
Reilly, James L. ; Frankovich, Kyle ; Hill, Scot ; Gershon, Elliot S. ; Keefe, Richard S E ; Keshavan, Matcheri S. ; Pearlson, Godfrey D. ; Tamminga, Carol A. ; Sweeney, John A. / Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories. In: Schizophrenia Bulletin. 2014 ; Vol. 40, No. 5. pp. 1011-1021.
@article{5edd57a9fc6f437485b5236f5948fccb,
title = "Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories",
abstract = "Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives' deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.",
keywords = "Bipolar disorder, Endophenotype, Family study, Schizoaffective disorder, Schizophrenia",
author = "Reilly, {James L.} and Kyle Frankovich and Scot Hill and Gershon, {Elliot S.} and Keefe, {Richard S E} and Keshavan, {Matcheri S.} and Pearlson, {Godfrey D.} and Tamminga, {Carol A.} and Sweeney, {John A.}",
year = "2014",
doi = "10.1093/schbul/sbt132",
language = "English (US)",
volume = "40",
pages = "1011--1021",
journal = "Schizophrenia Bulletin",
issn = "0586-7614",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories

AU - Reilly, James L.

AU - Frankovich, Kyle

AU - Hill, Scot

AU - Gershon, Elliot S.

AU - Keefe, Richard S E

AU - Keshavan, Matcheri S.

AU - Pearlson, Godfrey D.

AU - Tamminga, Carol A.

AU - Sweeney, John A.

PY - 2014

Y1 - 2014

N2 - Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives' deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.

AB - Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives' deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.

KW - Bipolar disorder

KW - Endophenotype

KW - Family study

KW - Schizoaffective disorder

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84907339441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907339441&partnerID=8YFLogxK

U2 - 10.1093/schbul/sbt132

DO - 10.1093/schbul/sbt132

M3 - Article

C2 - 24080895

AN - SCOPUS:84907339441

VL - 40

SP - 1011

EP - 1021

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 5

ER -