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Nancy C. Andreasen, MD, PhD; Laura Flashman, PhD; Michael Flaum, MD; Stephan Arndt, PhD; Victor Swayze II, MD; Daniel S. O'Leary, PhD; James C. Ehrhardt, PhD; William T. C. Yuh, MD, MS EE

JAMA. 1994;272(22):1763-1769.

Abstract
Objective.
—To determine general and regional indices of structural brain abnormality in schizophrenia.

Design.
—Case-control comparison study.

Subjects.
—Fifty-two patients diagnosed as having schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, were compared with 90 healthy volunteers recruited from the community.

Measurements.
—Structural brain images were acquired using magnetic resonance; measurements were obtained using three-dimensional visualization of volume-rendered brains and an automated atlas-based dissection of specific regions. General measures included the volume of total brain tissue, total cerebrospinal fluid (CSF), and CSF within the ventricular system. Regional measures included the volume of tissue and CSF in the frontal, temporal, parietal, and occipital lobes and the cerebellum.

Results.
—Compared with the controls, the patients had a smaller average volume of total brain tissue and a greater average volume of total and ventricular CSF. A specific relative decrease in brain tissue was found only in the frontal lobes, although the volume of CSF was greater in patients than in controls in all brain regions.

Conclusion.
—In addition to the generalized brain abnormalities observed in schizophrenia, a regional abnormality may be present in frontal regions. Since the frontal lobes integrate multimodality information and perform a variety of "higher" cognitive and emotional functions that are impaired in schizophrenia, the frontal abnormality noted is consistent with the clinical presentation of the illness. Impaired frontal function and a disruption in its complex circuitry (including thalamocortical projections) may explain why patients with schizophrenia often have significant deficits in formulating concepts and organizing their thinking and behavior.

(JAMA. 1994;272:1763-1769)

Author Affiliations
From the Mental Health Clinical Research Center (Drs Andreasen, Flashman, and Arndt), the Department of Psychiatry (Drs Andreasen, Flaum, and O'Leary), and the Department of Radiology (Drs Ehrhardt and Yuh), The University of Iowa Hospitals and Clinics, Iowa City; and the Veterans Affairs Medical Center, Iowa City (Dr Swayze).

Footnotes
Reprint requests to Department of Psychiatry, Mental Health Clinical Research Center, The University of Iowa Hospitals and Clinics, 200 Hawkins Dr, 2911 JPP, Iowa City, IA 52242-1057 (Dr Andreasen).

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