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  Vol. 60 No. 3, March 2003 TABLE OF CONTENTS
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Compounded Brain Volume Deficits in Schizophrenia-Alcoholism Comorbidity

Daniel H. Mathalon, PhD, MD; Adolf Pfefferbaum, MD; Kelvin O. Lim, MD; Margaret J. Rosenbloom, MA; Edith V. Sullivan, PhD

Arch Gen Psychiatry. 2003;60:245-252.

Background  Schizophrenia and alcoholism are characterized by brain volume abnormalities. Despite the frequent comorbidity of these conditions, the potentially compounded effects of comorbidity on brain structure have seldom been rigorously assessed.

Methods  To determine the compounding effect of schizophrenia and alcoholism on regional brain volumes, we performed retrospective quantitative analysis of magnetic resonance images from men who participated in research protocols at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. Participants were selected on the basis of diagnostic criteria, yielding 4 comparison groups: 35 men comorbid for DSM-III-R schizophrenia or schizoaffective disorder and lifetime alcohol abuse or dependence; 64 men with DSM-III-R schizophrenia or schizoaffective disorder; 62 men with Research Diagnostic Criteria alcoholism; and 62 healthy men screened to exclude any Axis I diagnosis or heavy alcohol use. The comorbid group matched the schizophrenia group on age and illness severity but was younger and drank 5 times less alcohol in their lifetimes than the alcoholism group. Gray and white matter volumes from 6 cortical regions were expressed as age- and head size–corrected z scores and were subjected to multivariate profile analyses.

Results  Gray matter volume deficits were present in all 3 patient groups but were greatest in the comorbid group. In the comorbid group, the most prominent volume deficits were in the prefrontal and anterior superior temporal regions.

Conclusions  Despite lower alcohol exposure than in pure alcoholism, the comorbidity of schizophrenia with alcoholism has a particularly profound effect on prefrontal gray matter volume, compounding the prominent prefrontal deficits present independently in schizophrenia and alcoholism.


From the Department of Psychiatry, Yale University School of Medicine/Veterans Affairs Connecticut Healthcare System, West Haven (Dr Mathalon); the Neuroscience Program, SRI International, Menlo Park, Calif (Dr Pfefferbaum); the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif (Drs Pfefferbaum and Sullivan and Ms Rosenbloom); and the Department of Psychiatry, University of Minnesota School of Medicine, Minneapolis (Dr Lim).



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