Pursuit eye movements as an intermediate phenotype across psychotic disorders: Evidence from the B-SNIP study.

Smooth pursuit eye tracking deficits are a promising intermediate phenotype for schizophrenia and possibly for psychotic disorders more broadly. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium investigated the severity and familiality of different pursuit parameters across psychotic disorders. Probands with schizophrenia (N=265), schizoaffective disorder (N=178), psychotic bipolar disorder (N=231), their first-degree relatives (N=306, N=217, N=273, respectively) and healthy controls (N=305) performed pursuit tracking tasks designed to evaluate sensorimotor and cognitive/predictive aspects of pursuit. Probands from all diagnostic groups were impaired on all pursuit measures of interest compared to controls (p<0.001). Schizophrenia probands were more impaired than other proband groups on both early pursuit gain and predictive gain. Relatives with and without enhanced psychosis spectrum personality traits were impaired on initial eye acceleration, the most direct sensorimotor pursuit measure, but not on pursuit gain measures. This suggests that alterations in early sensorimotor function may track susceptibility to psychosis even in the absence of psychosis related personality traits. There were no differences in pursuit measures between relatives of the three proband groups. Familiality estimates of pursuit deficits indicate that early pursuit gain was more familial than predictive gain, which has been the most widely used measure in previous family studies of psychotic disorders. Thus, while disease-related factors may induce significant impairments of pursuit gain, especially in schizophrenia, the pattern of deficits in relatives and their familiality estimates suggest that alterations in sensorimotor function at pursuit onset may indicate increased susceptibility across psychotic disorders.