Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia
- Garry D. Honey†,
- Edward T. Bullmore‡,§,
- William Soni†,
- Malini Varatheesan†,
- Steve C. R. Williams¶, and
- Tonmoy Sharma†,‖
- †Section of Cognitive Psychopharmacology, ‡Department of Psychological Medicine, and ¶Department of Clinical Neurosciences, Institute of Psychiatry (King’s College), De Crespigny Park, London SE5 8AF, United Kingdom; and §Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom
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Communicated by P. S. Goldman-Rakic, Yale University School of Medicine, New Haven, CT (received for review February 15, 1999)
Abstract
Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology.
Footnotes
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↵ ‖ To whom reprint requests should be addressed at: Section of Cognitive Psychopharmacology, Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, United Kingdom. E-mail: t.sharma{at}iop.kcl.ac.uk.
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↵ ** Preliminary results were presented at the XXIst Congress of the Collegium Internationalle Neuro-Psychopharmacologium, July 12–16, 1998, Glasgow, U.K.
- Abbreviations:
- PFC,
- prefrontal cortex;
- fMRI,
- functional magnetic resonance imaging;
- ANCOVA,
- analysis of covariance;
- SMA,
- supplementary motor area;
- BA,
- Brodmann area
- Copyright © 1999, The National Academy of Sciences
