There is some evidence that major depression may be caused in part by an overactive hypothalamic-pituitary-adrenal axis (HPA axis) that results in an effect similar to the neuro-endocrine response to stress.
Čeprav je znižane ravni BDNF v plazmi najti pri številnih drugih bolezni, obstajajo dokazi za to, da je BDNF vpletena v nastanek depresije in v mehanizem delovanja antidepresivov.