The Relationship Between Two Endophenotypes of Psychosis in Volunteers with Schizophrenia and Bipolar Disorder

Background: Deficits in smooth pursuit eye movements are an established endophenotype for schizophrenia (SZ) and are being investigated as a potential biomarker for psychotic bipolar disorder (BDP). While the molecular determinant of the physiological deficit is still unclear, considerable research has shown deficits in the predictive mechanism of eye movements in SZ using target-masking techniques, as well as with a more recent novel prediction eye movement task. The questions of whether this deficit is related to working memory alterations in SZ and extends to other psychotic disorders like BDP were a focus of this investigation. Methods: Volunteers with schizophrenia (SZ, n = 38), bipolar I disorder with psychotic features (BDP, n = 31), and healthy controls (HC, n = 17) performed a novel eye movement task to assess the predictive mechanism of smooth pursuit. Subjects also completed a battery of neuropsychological tasks that included measures of working memory. Results: Individuals with SZ and BDP performed similarly on both neuropsychological and eye tracking tasks. Both groups evidenced reduced predictive pursuit velocity and worse performance on the Wechsler Spatial Span task compared with healthy controls. Further, a small but significant correlation (r = .27, p = .03) between predictive pursuit gain and working memory performance on Spatial Span was obtained, without statistically significant correlations in other cognitive domains. Conclusions: Individuals with SZ and BDP showed similar deficits on the predictive pursuit eye movement task, suggesting that this alteration could be a characteristic of the psychosis domain. The a priori prediction that the predictive pursuit task is associated with working memory mechanisms was supported in part by its significant and selective correlation with a measure of working memory.