Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder

Abstract

Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naïve first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naïve first-episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP.

Keywords: Dorsolateral prefrontal cortex; Psychosis; Risperidone; Saccades; Striatum.