Hypothalamo-pituitary-adrenal axis abnormalities in depression: a review and a model

A wide range of abnormalities of the hypothalamo-pituitary-adrenal (HPA) axis has been described in depression. This paper reviews recent advances in the understanding of this system, and draws them together to construct a model for the purposes of further research and discussion. It is proposed that there are two fundamental changes which both originate in the hypothalamus: an increased secretion of corticotropin-releasing hormone, and a neurally mediated adrenal hyper-responsivity to ACTH. The resulting changes in hormone regulation would be expected to produce all the characteristic HPA axis abnormalities commonly seen in depression. The model makes several predictions which could be tested by future experiment.