Polymorphisms in the BDNF and BDNFOS genes are associated with hypothalamus-pituitary axis regulation in major depression.

Major depression is a stress-related disorder with robust clinical and preclinical data implicating that both, dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) axis and of the neurotrophin system of the brain are involved in the pathophysiology. Genetic variations within the brain-derived neurotrophic factor (BDNF) gene region, a major representative of the brain neurotrophins, are suggested to influence response to antidepressant treatment. Specifically, we recently identified two BDNF single nucleotide polymorphisms (SNP), rs2049046 and rs11030094, as associated with antidepressant treatment response in a large pharmacogenetic study of hospitalized patients. We now analyzed these two SNPs in a sub-sample for their association with HPA axis dysregulation using the combined dexamethasone suppression/corticotropin releasing hormone challenge (dex/CRH) test at hospital admission (N = 266) and at discharge (N = 190). Rs11030094, located 3′ outside the coding region of BDNF, is also located in an intron of BDNFOS coding for a functional antagonist of BDNF. We further included the non-synonymous Val66Met (rs6265) polymorphism in our analysis, for which - albeit being extensively studied - conflicting results in respect to its role in antidepressant treatment response have been reported.