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James L. Reilly, PhD; Margret S. H. Harris, MA; Matcheri S. Keshavan, MD; John A. Sweeney, PhD

Arch Gen Psychiatry. 2006;63:1189-1197.

Context  Working memory impairments are a central neurocognitive feature of schizophrenia. The nature of these impairments early in the course of illness and the impact of antipsychotic drug treatment on these deficits are not well understood. The oculomotor delayed response task is a translational spatial working memory paradigm used to characterize the neurophysiologic and neurochemical aspects of working memory in the primate brain.

Objective  To examine oculomotor delayed response task performance in patients with first-episode schizophrenia before and after antipsychotic drug treatment.

Design, Setting, and Participants  Twenty-five antipsychotic drug–naive, acutely ill patients with first-episode schizophrenia performed an oculomotor delayed response task at baseline before any drug treatment and again after 6 weeks of risperidone treatment. Twenty-five matched healthy controls were studied in parallel.

Main Outcome Measure  Accuracy for remembered spatial locations on an oculomotor delayed response task.

Results  Before treatment, patients demonstrated baseline impairment in the ability to maintain spatial location information in working memory at longer delay-period durations (8 seconds), when maintenance demands on working memory were greatest. After 6 weeks of risperidone treatment and significant clinical improvement, this pretreatment impairment worsened such that patients were uniformly impaired across all delay period durations (1-8 seconds). This occurred in the absence of any generalized adverse effect on oculomotor systems or significant extrapyramidal adverse effects.

Conclusions  Deficits in the maintenance of spatial information in working memory are present early in the course of illness. Risperidone treatment exacerbated these deficits, perhaps by impairing the encoding of information into working memory. Studies with nonhuman primates performing oculomotor delayed response tasks suggest that the apparent adverse effect of risperidone might result from treatment-related changes in modulatory functions of prefrontal D₁ receptor systems.

Author Affiliations: Center for Cognitive Medicine, Department of Psychiatry, University of Illinois at Chicago (Drs Reilly and Sweeney and Ms Harris); Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pa (Drs Keshavan and Sweeney); and Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Mich (Dr Keshavan).

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