TY - JOUR
T1 - Adverse effects of risperidone on spatial working memory in first-episode schizophrenia
AU - Reilly, James L.
AU - Harris, Margret S H
AU - Keshavan, Matcheri S.
AU - Sweeney, John A.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
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U2 - 10.1001/archpsyc.63.11.1189
DO - 10.1001/archpsyc.63.11.1189
M3 - Article
C2 - 17088499
AN - SCOPUS:33750719948
SN - 0003-990X
VL - 63
SP - 1189
EP - 1197
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 11
ER -