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

Abstract

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.

Eye movement as a biomarker of schizophrenia: Using an integrated eye movement score

“…There have been many studies on the effect of antipsychotics on smooth pursuit, and the results vary. A recently published multisite study reported no significant association between smooth pursuit measures and antipsychotic use . Studies on antipsychotic‐naïve patients with schizophrenia have also shown smooth pursuit abnormalities before treatment initiation as well .…”

“…Previous studies of eye movement abnormalities in schizophrenia have shown a significant decline in saccade control and smooth pursuit eye movement, and studies integrating genetics and brain function add knowledge to the underlying cause of these abnormalities . Studies using single eye movement measures as neurophysiological biomarkers have been conducted, showing specific findings in schizophrenia compared to mood disorders . There are also studies that use multiple eye movement measures to classify patients with schizophrenia and healthy controls, resulting in a discriminative accuracy of 80–90% .…”

Eye movement characteristics in schizophrenia: A recent update with clinical implications

“…In example plots of the eye positions during smooth pursuit, healthy participants smoothly follow the visual target (Figure A). However, in the participants with schizophrenia, the position of the eye often lags behind the target (especially in the horizontal direction) because the speed of eye movements tends not to keep up with the speed of the moving visual target, and catch‐up saccades are seen immediately afterward (Figure B). Studies have also shown the possibility that genetic factors are associated with smooth pursuit eye movement characteristics in schizophrenia …”

“…The Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIPS) Consortium was formed to examine intermediate phenotypes involving smooth pursuit eye movement measures and saccade control measures across psychotic disorders including schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic symptoms . Their study included more than 1000 participants and showed that impairments of smooth pursuit were larger in participants with schizophrenia than participants with the other disorders . In Japan, the Cognitive Genetics Collaborative Research Organization (COCORO) consortium (Figure ) has recently been organized, and multicenter eye movement research is currently running within this framework.…”

“…The pioneer 66 Their study included more than 1000 participants and showed that impairments of smooth pursuit were larger in participants with schizophrenia than participants with the other disorders. 27 In Japan, the Cognitive Genetics Collaborative…”