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Am J Psychiatry 1992; 149:890-897
Copyright © 1992 by American Psychiatric Association
Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins
DR Weinberger, KF Berman, R Suddath and EF Torrey
Clinical Brain Disorders Branch, NIMH, St. Elizabeths Hospital, Washington, DC 20032.
OBJECTIVE: The authors previously reported that in monozygotic twins
discordant for schizophrenia the affected twin almost invariably had a
smaller anterior pes hippocampus, measured with magnetic resonance imaging
(MRI), and invariably had less regional cerebral blood flow (rCBF) in the
dorsolateral prefrontal cortex during performance of the Wisconsin Card
Sorting Test. The present study was an investigation of the relationship
between hippocampal pathology and prefrontal hypofunction in the same twin
pairs. METHOD: Nine pairs of monozygotic twins discordant for schizophrenia
underwent MRI scanning for determination of anterior hippocampal volume and
xenon-inhalation rCBF testing for determination of prefrontal physiological
activation associated with the Wisconsin Card Sorting Test. RESULTS: The
differences within twin pairs on the MRI and rCBF measures were strongly
and selectively correlated. Specifically, the more an affected twin
differed from the unaffected twin in left hippocampal volume, the more they
differed in prefrontal physiological activation during the Wisconsin Card
Sorting Test. In the affected twins as a group, prefrontal activation was
strongly related to both left and right hippocampal volume. These
relationships were not found in the group of unaffected twins. CONCLUSIONS:
This finding is consistent with the notion that schizophrenia involves
pathology of and dysfunction within a widely distributed neocortical-limbic
neural network that has been implicated in, among other activities, the
performance of cognitive tasks requiring working memory.
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