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Karen Faith Berman, MD; E. Fuller Torrey, MD; David G. Daniel, MD; Daniel R. Weinberger, MD

Arch Gen Psychiatry. 1992;49(12):927-934.

Abstract
• We addressed several questions regarding hypofunction of the prefrontal cortex ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow during three different cognitive conditions in monozygotic twins who were discordant or concordant for schizophrenia or who were both normal. These questions included the prevalence of hypofrontality, the importance of genetic predisposition, and the role of long-term neuroleptic treatment. Significant differences between affected and unaffected discordant twins were found only during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test. During this condition, all of the twins with schizophrenia were hypofrontal compared with their unaffected co-twins, suggesting that, if appropriate cognitive conditions and control groups are used, hypofrontality can be demonstrated in the majority of, if not all, patients with schizophrenia. When unaffected cotwins of patients with schizophrenia were compared with twins who were both normal, no differences were observed, suggesting that nongenetic factors are important in the cause of the prefrontal physiologic deficit that appears to characterize schizophrenia. When concordant twins with a high- vs a low-dose lifetime history of neuroleptic treatment were compared, the twin receiving the higher dose was more hyperfrontal in six of eight pairs, suggesting that longterm neuroleptic treatment does not play a major role in hypofrontality.

Author Affiliations
From the Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIMH Neuroscience Center at St Elizabeth's, Washington, DC.

Footnotes
Accepted for publication April 23, 1992.

Reprint requests to Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIMH Neuroscience Center at St Elizabeth's, 2700 Martin Luther King Jr Ave, Washington, DC 20032 (Dr Berman).

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