TY - JOUR T1 - Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression JF - Journal of Psychiatry and Neuroscience JO - JPN SP - 185 LP - 193 VL - 29 IS - 3 AU - Nicholas Barden Y1 - 2004/05/01 UR - http://jpn.ca/content/29/3/185.abstract N2 - Major alterations of the hypothalamic–pituitary–adrenocortical (HPA) system that can be reversed by successful antidepressant therapy are often seen in depressed patients. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor (GR) system in these changes. Support for this also comes from studies of transgenic mice that express an antisense RNA, complementary to the GR mRNA, and have numerous neuroendocrine characteristics of human depression as well as altered behaviour. Many of these neuroendocrine and behavioural characteristics of the transgenic mice can be reversed by antidepressants. A possible explanation for this is that the antidepressant-induced increase in GRs renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs. ER -