Monoamine metabolites in cerebrospinal fluid of depressive subgroups

Lumbar punctures were performed on 69 patients who met Research Diagnostic Criteria (RDC) for major affective disorder, while they were drug-free and depressed. None of the patients met RDC for alcoholism. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured by fluorometry and 3-methoxy-4-hydroxyphenylglycol (MHPG) by gas chromatography. Family histories were ascertained by systematic interviews of patients and their relatives, and diagnoses were made by family history diagnostic criteria (Andreasen et al., 1977). Depressed patients with alcoholism in a first degree relative had significantly lower levels of 5-HIAA and MHPG than patients without a family history of alcoholism (p < 0.05). No difference in HVA levels was found. The metabolite differences remained significant when the influence of sex ratio was considered. These results are in agreement with previous work linking alcoholism to abnormal serotonin metabolism. They provide further biochemical evidence of distinct genetic subtypes of affective disorder along lines suggested by Winokur (1979a, 1979b), and illustrate the usefulness of the family history method in defining patient subgroups.