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

Academic Article
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Overview

authors

  • Jonsson, E.
  • Sedvall, G.
  • Brene, S.
  • Gustavsson, J. P.
  • Geijer, T.
  • Terenius, Lars
  • Crocq, M. A.
  • Lannfelt, L.
  • Tylec, A.
  • Sokoloff, P.
  • Schwartz, J. C.
  • Wiesel, F. A.

publication date

  • November 1996

journal

  • Biological Psychiatry  Journal

abstract

  • 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, height, 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.

subject areas

  • Adult
  • Biogenic Monoamines
  • Cerebrospinal Fluid
  • Dopamine
  • Female
  • Genotype
  • Homovanillic Acid
  • Humans
  • Hydroxyindoleacetic Acid
  • Male
  • Mental Disorders
  • Methoxyhydroxyphenylglycol
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, Dopamine
  • Seasons
  • Tyrosine 3-Monooxygenase
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Research

keywords

  • cerebrospinal fluid
  • dopamine receptor genes
  • monoamine metabolites
  • tyrosine hydroxylase gene
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Identity

International Standard Serial Number (ISSN)

  • 0006-3223

Digital Object Identifier (DOI)

  • 10.1016/0006-3223(95)00581-1

PubMed ID

  • 8915563
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Additional Document Info

start page

  • 1032

end page

  • 1043

volume

  • 40

issue

  • 10

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