Can adult neurogenesis buffer stress responses and depressive behaviour?

As all novel theories, the neurogenesis model of depression has triggered reactions ranging from messianic conviction to total scepticism. The recent paper by Snyder et al.1 helps us refine this model, by introducing a crucial link with a major biological system consistently disrupted in depression, the hypothalamic–pituitary–adrenal (HPA) axis.2 The main finding is that inhibition of neurogenesis induces the classical neuroendocrine phenotype described in major depression: increased HPA axis activity and glucocorticoid resistance, that is, impaired suppression of HPA axis activity by dexamethasone. As stress and high levels of glucocorticoid hormones are well known to inhibit neurogenesis, the authors suggest that stress, by inhibiting neurogenesis, may lead to enhanced HPA axis responsiveness to future stressors, and thus establish a potentially vicious circle leading to the development of depressive behaviour.1