Effects of second-generation antipsychotic medication on smooth pursuit performance in antipsychotic-naive schizophrenia

Context: Analyses of smooth pursuit eye movement parameters in patients with schizophrenia provide information about the integrity of neural networks mediating motion perception, sensorimotor transformation, and cognitive processes such as prediction. Although pursuit eye tracking deficits have been widely reported in schizophrenia, the integrity of discrete components of pursuit responses and the effect of second- generation antipsychotic medication on them are not well established. Objective: To examine different components of smooth pursuit performance in antipsychotic-naive patients with schizophrenia before and after treatment with second-generation antipsychotic medication. Design, Setting, and Participants: Thirty-three antipsychotic-naive patients with schizophrenia performed 3 different smooth pursuit paradigms designed to evaluate specific components of the pursuit response. All of the patients were retested after 6 weeks of treatment with risperidone or olanzapine. Testing was also performed with 39 matched healthy individuals. Thirteen patients and 21 healthy participants were retested after 26 and 52 weeks. Main Outcome Measures: Pursuit initiation, maintenance gain (ratio of eye velocity over target velocity), and frequency of catch-up saccades during pursuit maintenance. Results: Prior to treatment, pursuit gain when tracking less predictable ramp targets tended to be reduced, latency of pursuit initiation was speeded, and catch-up saccade frequency was increased during predictive pursuit. After antipsychotic treatment initiation, pursuit gain decreased with ramp targets, indicating treatment-emergent impairments in sensorimotor processing. No changes were observed for predictive pursuit. Exploratory analyses in the subgroup with follow-up to 1 year revealed that these effects continued through long-term follow-up with some partial normalization at 1 year. Deficits were unrelated to drug dosage and clinical ratings. Conclusions: Impaired sensorimotor function was observed after initiation of second- generation antipsychotic medications, which may be explained by their serotonergic antagonism of brainstem sensorimotor systems. Predictive mechanisms supported by frontostriatal-cerebellar circuitry were not affected by treatment initiation and appear able to compensate for treatment-emergent sensorimotor impairments during predictive tracking.