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

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)...

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Bibliographic Details
Published in:Biological psychiatry (1969) 1996-11, Vol.40 (10), p.1032-1043
Main Authors: Jönsson, Erik, Sedvall, Göran, Brené, Stefan, Petter Gustavsson, J., Geijer, Thomas, Terenius, Lars, Crocq, Marc-Antoine, Lannfelt, Lars, Tylec, Alexandra, Sokoloff, Pierre, Schwartz, Jean Charles, Wiesel, Frits-Axel
Format: Article
Language:English
Subjects:
Adult
Biogenic Monoamines - cerebrospinal fluid
Biogenic Monoamines - metabolism
cerebrospinal fluid
Cerebrospinal Fluid - metabolism
Dopamine - genetics
Dopamine receptor genes
Female
Genotype
Homovanillic Acid - cerebrospinal fluid
Humans
Hydroxyindoleacetic Acid - cerebrospinal fluid
Male
Medicin och hälsovetenskap
Mental Disorders - genetics
Methoxyhydroxyphenylglycol - cerebrospinal fluid
Middle Aged
monoamine metabolites
Polymorphism, Genetic
Receptors, Dopamine - genetics
Seasons
Tyrosine 3-Monooxygenase - genetics
tyrosine hydroxylase gene
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Summary: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.
ISSN:0006-3223
1873-2402
DOI:10.1016/0006-3223(95)00581-1