BDNF and melancholia: Atypical depression may be a result of reduced function in the hypothalamic–pituitary–adrenal (HPA) axis, in contrast to melancholic depression, which has been linked with overactivity of the HPA axis.43, 44 This overactivity of the HPA axis in melancholic depression has been linked to reductions in BDNF expression.45 As a result, normalization of symptoms in atypical depression would result in increased HPA activity and decreased BDNF production.