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Implications for Regional Brain Dysfunction in Schizophrenia

David Pickar, MD; Alan Breier, MD; John K. Hsiao, MD; Allen R. Doran, MD; Owen M. Wolkowitz, MD; Carlos N. Pato, MD; P. Eric Konicki, MD; William Z. Potter, MD, PhD

Arch Gen Psychiatry. 1990;47(7):641-648.

Abstract
• The relationship between central (cerebrospinal fluid [CSF]) and peripheral (plasma) monoaminergic metabolites and psychotic symptoms was examined in 22 drug-free schizophrenic inpatients. The CSF homovanillic acid levels did not differ significantly between patients and normal controls (n = 33). The CSF homovanillic acid levels, however, were negatively correlated with ratings of psychosis and positive symptoms, and the CSF homovanillic acid and 5-hydroxyindoleacetic acid levels correlated negatively with individual deficit symptoms. Stepwise and hierarchical multiple-regression analysis revealed that among monoaminergic measures, only the CSF and plasma homovanillic acid levels contributed significantly to the total Brief Psychiatric Rating Scale and positive symptom variance with negative and positive partial correlations, respectively. Levels of CSF 3-methoxy-4-hydroxyphenylglycol, but not of CSF norepinephrine, were significantly elevated in the schizophrenic patients compared with controls, and plasma 3-methoxy-4-hydroxyphenylglycol levels were positively correlated with negative symptoms. We discuss the potential implications of these findings for a model of dopaminergic dysfunction in schizophrenia involving distinct cortical and subcortical contributions.

Author Affiliations
From the Section on Clinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Md. Dr Breier is now with the Maryland Psychiatric Research Center, Baltimore. Dr Hsiao is now with the Section on Analytic Biochemistry, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md. Dr Doran is now with the Department of Psychiatry, University of California-Davis, Sacramento. Dr Wolkowitz is now with the Langley-Porter Psychiatric Institute and University of California, San Francisco. Dr Pato is now with the Schizophrenia Research Branch, Division of Clinical Research, National Institute of Mental Health, Rockville, Md.

Footnotes
Accepted for publication December 7, 1989.

Reprint requests to Section on Clinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bldg 10, Room 4N212, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Pickar).

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