Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins

Abstract

Objective: The authors previously reported that in monozygotic twins discordant for schizo-phrenia 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 dorsolateralprefrontal cortex duringperformance ofthe Wisconsin Card Sorting Test. The present study was an investigation ofthe relationship between hippocampalpathol-ogy and prefrontal hypofunction in the same twin pairs. Method: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampalvolume andxenon-inhalation rCBF testingfor determination of prefrontal physi-ological 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 ofunaffected twins. Conclusions: This finding is consistent with the notion that schizophreni