ABSTRACT
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.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Brain/metabolism , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Norepinephrine/metabolism , Polymorphism, Genetic/genetics , Adult , Brain Chemistry/genetics , DNA Mutational Analysis , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing , Genotype , Homovanillic Acid/analysis , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/analysis , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/analysis , Neurocognitive Disorders/genetics , Neurocognitive Disorders/metabolism , Neurocognitive Disorders/physiopathology , Predictive Value of Tests , Serotonin/metabolism , Young AdultABSTRACT
Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been suggested to be associated with schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n=187) and control subjects (n=275) were assessed for four BDNF gene polymorphisms. There were no significantly different allele, genotype or haplotype frequencies between cases or controls. Neither were there any differences when schizophrenic patients were sub-divided with regard to a number of different clinical variables, although a small group of psychotic patients with prominent affective features displayed higher frequencies of the less common alleles of the Val66Met and 11757 G/C polymorphisms compared to controls. The present Swedish results do not verify previous associations between putative functional BDNF gene polymorphisms and schizophrenia. However, when combined with previous studies meta-analyses indicated that the BDNF 270 T-allele and the Val66Met homozygous state were associated with the disorder. Thus, the BDNF gene may confer susceptibility to schizophrenia. Additional studies are warranted to shed further light on this possibility.