Elsevier

Biological Psychiatry

Volume 40, Issue 10, 15 November 1996, Pages 1032-1043
Biological Psychiatry

Dopamine-related genes and their relationships to monoamine metabolites in CSF

https://doi.org/10.1016/0006-3223(95)00581-1Get rights and content

Monoamine metabolite (MM) levels in lumbar cerebrospinal fluid (CSF) are extensively used as indirect estimates of monoamine turnover in the brain. In this study we investigated genotypes for DNA polymorphisms in the D2 (DRD2), D3 (DRD3), and D4 (DRD4) dopamine receptor and tyrosine hydroxylase (TH) genes and their relationships to CSF MM in healthy volunteers (n = 66). Concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were corrected for back length, a confounding variable. Corrected MM levels were not related to age, gender, heightl, weight heredity, season or atmospheric pressure at sampling. Individuals with specific DRD2 and TH allele and genotype configurations significantly differed in HVA and MHPG concentrations. DRD3 homo- and heterozygotic genotypes had significantly different CSF 5-HIAA levels. DRD4 genotypes were not related to MM concentrations. The results suggest that specific DRD2, DRD3, and TH genotypes participate in the regulation of monoamine turnover in the central nervous system. Accordingly monoamine receptors and synthesizing enzyme genotypes appear to be variance factors influencing MM concentrations in CSF. The relationships found in this study support MM concentrations as markers for monoamine transmission in the human brain.

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    Part of this investigation has been presented at the 3d Umeå Annual Meeting in Psychiatric Genetics in Umeå, Sweden, March 16–18, 1995.

    This study was supported by grants from the Swedish Medical Research Council (03560), the National Institute of Mental Health (44814), the Memory Foundation of Ulf Lundahl, the Ragnar Söderbergs stiftelse, the Memory Foundation of Bror Gadelius, and the Commission of European Communities (Biomed I BMHI-CT92-1086). Stefan Brené was supported by a fellowship from the Swedish Medical Research Council. Lars Lannfelt had a scholarship as a visiting scientist from INSERM, France, and the Swedish Medical Research Council.

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