Association between the hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation in patients with major depression and polymorphisms in the brain derived neurotropic factor (BDNF) and neurotrophic tyrosine kinase receptor 2 (NTRK2) gene

Recent models of major depression propose an involvement of malfunctions of neurotrophic factors. Additionally the dysregulation of the HPA axis system is one of the major neuroendocrine abnormalities in major depression. As BNDF and its receptor (NTRK2) have been shown to be involved in affective disorders we investigated the impact of SNPs in each gene (BDNF: val66met, rs2049045, rs6484320; NTRK2: rs1221, rs993315, rs1387925) on HPA axis dysregulation, determined by the Dex/CRH test in 182 patients with major depression. Homozygous carriers of the met-allele, the C-allele (rs2049045) and the T-allele (rs6484320) in the BDNF gene showed higher cortisol stimulation during the first Dex/CRH test after admission than the other genotypes (ANOVA (AUC): p=0.01 for val66met, p=0.003 for rs2049045, p=0,01 for rs6484320). Also ACTH levels were elevated for CC- (rs2049045) and TT- (rs6484320) genotypes (p=0.002 for rs2049045, p=0,05 for rs6484320). Similar results were obtained for two of the NTRK2 SNPs. Homozygous carriers of the C allele (rs1221, rs993315) had higher cortisol and ACTH levels than the other genotypes (rs1221: p=0.005 (ACTH), ns. (cortisol); rs993315: p=0.004 (cortisol), ns. (ACTH)). Our data suggest that polymorphisms in the BDNF and NTRK2 genes might be crucial factors for the HPA system hyperactivity in major depression. This project is supported by the German Federal Research Ministry within the promotional emphasis "Competence Nets in Medicine".