Brain-derived neurotrophic factor (BDNF) has been shown to influence monoamine transmitter synthesis, metabolism and release. We investigated possible relationships between four BDNF gene polymorphisms and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 132). All BDNF polymorphisms (270 C/T, -633 T/A, Val66Met, and 11757 G/C) were associated with MHPG (P < 0.02), but not with 5-HIAA and HVA concentrations. At a second clinical investigation 8-20 years after CSF sampling 30% of the subjects had experienced various psychiatric disorders. Development of a psychiatric disorder was predicted by low 5-HIAA concentrations (P = 0.01). The results suggest that BDNF gene variation participates in regulation of norepinephrine turnover rates in the central nervous system of human subjects.