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Monoamine Neurotransmitter Interactions and the Prediction of Antidepressant Response
John K. Hsiao, MD;
Hans Agren, MD;
John J. Bartko, PhD;
Matthew V. Rudorfer, MD;
Markku Linnoila, MD, PhD;
William Z. Potter, MD, PhD
Arch Gen Psychiatry. 1987;44(12):1078-1083.
Abstract
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• Clinical studies of monoamine neurotransmitter function in depression have concentrated on individual monoamines without focusing on interactions between monoamine systems. Virtually all modern studies have found significant correlations between monoamine metabolite concentrations in cerebrospinal fluid (CSF). These correlations should in part reflect interactions between central monoamine systems. In the present analysis, CSF had been obtained from depressed patients before (n = 40) and after (n =36) antidepressant treatment. The patients were grouped based on their response to treatment. Absolute concentrations of CSF monoamine metabolites (homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol) did not differ between the two groups before or after treatment. However, when correlations between metabolites were compared, nonresponders to treatment differed considerably from responders. In responders, as in previously described normal populations, all three metabolites correlated with one another before and after treatment, and treatment-induced changes in metabolite concentrations also correlated with one another. In contrast, metabolites in nonresponders did not correlate with one another before treatment, nor did treatment-induced changes correlate with one another in this group. Furthermore, correlations between treatment-induced changes in metabolites differed significantly between responders and nonresponders, and there was a trend for pretreatment correlations to differ as well. The lack of correlation between monoamine metabolites in nonresponders suggests that interactions between monoamine systems may be disrupted in these individuals. Using CSF metabolite correlations to study neurotransmitter interactions may have clinical relevance and yields information not available from examining neurotransmitters in isolation.
Author Affiliations
From the Section on Clinical Pharmacology, Laboratory of Clinical Sciences (Drs Hsiao, Agren, Rudorfer, and Potter), and the Division of Biometry and Applied Sciences (Dr Bartko), National Institute of Mental Health, Bethesda, Md; the Department of Psychiatry, University Hospital, Uppsala, Sweden (Dr Agren); and the Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, Bethesda, Md (Dr Linnoila).
Footnotes
Accepted for publication Aug 4, 1987.
Reprint requests to Section on Clinical Pharmacology, Laboratory of Clinical Science, NIMH, Bldg 10, Room 2D46, Bethesda, MD 20892 (Dr Hsiao).
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