James L Reilly1, Kyle Frankovich2, Scot Hill3, Elliot S Gershon4, Richard S E Keefe5, Matcheri S Keshavan6, Godfrey D Pearlson7, Carol A Tamminga8, John A Sweeney8. 1. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL; james.reilly@northwestern.edu. 2. Center for Mind and Brain and Department of Psychology, University of California at Davis, Davis, CA; 3. Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago, IL; 4. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL; 5. Department of Psychiatry, Duke University, Durham, NC; 6. Beth Israel Deaconess Hospital and Massachusetts Mental Health Center, Harvard Medical School, Boston, MA; 7. Olin Neuropsychiatry Research Center, Yale School of Medicine, New Haven, CT; Department of Psychiatry, Institute of Living/Hartford Hospital, Hartford, CT; 8. Department of Psychiatry, UT Southwestern Medical School, Dallas, TX.
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.
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.
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