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III. A New Cohort and Evidence for a Monoaminergic Mechanism

Daniel R. Weinberger, MD; Karen Faith Berman, MD; Barbara P. Illowsky, MD

Arch Gen Psychiatry. 1988;45(7):609-615.

Abstract
• We previously reported that compared with normals, patients with chronic schizophrenia have reduced regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) during performance of the Wisconsin Card Sort Test (WCS), a DLPFC-related cognitive task, but not during nonprefrontal tasks, such as a simple number-matching (NM) test. We also found that unlike normals, patients failed to activate DLPFC during the WCS over their own baseline (NM) level. To explore the reproducibility of these findings, a new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies under the following conditions: at rest, while performing the WCS, and while performing NM. The results confirmed our earlier findings. In addition, the concentrations in cerebrospinal fluid of homovanillic acid and 5-hydroxyindoleacetic acid correlated with prefrontal rCBF during the WCS but not during the NM test or at rest. The results show that behavior-specific hypofunction of DLPFC in schizophrenia is reproducible, and they implicate a monoaminergic mechanism.

Author Affiliations
From the Clinical Brain Disorders Branch, National Institute of Mental Health, Intramural Research Program, St Elizabeths Hospital, Washington, DC.

Footnotes
Accepted for publication Feb 10, 1988.

Reprint requests to Clinical Brain Disorders Branch, National Institute of Mental Health, Intramural Research Program, William A. White Building, St Elizabeths Hospital, Washington, DC 20032 (Dr Weinberger).

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