DOPAMINE-RELATED GENES AND THEIR RELATIONSHIPS TO MONOAMINE METABOLITES IN CSF

Monoamine metabolite (MM) levels in lumbar cerebrospinal fluid (CSF) a re 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 tyros ine hydroxylase (TH) genes and their relationships to CSF MM in health y volunteers (n = 66), Concentrations of homovanillic acid (HVA), 3-me thoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5- HIAA) were corrected for back length, a confounding variable. Correcte d MM levels were not related to age, gender height, weight heredity, s eason or atmospheric pressure at sampling. Individuals with specific D RD2 and TH allele and genotype configurations significantly differed i n 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 tur nover in the central nervous system. Accordingly monoamine receptors a nd synthesizing enzyme genotypes appear to be variance factors influen cing Mil concentrations in CSF, The relationships found in this study support MM concentrations as markers for monoamine transmission in the human brain. (C) 1996 Society of Biological Psychiatry