Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression.
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.
Barden
Nicholas
N
Neuroscience Research Department, Centre Hospitalier de l'Université Laval Research Centre, Sainte-Foy, QC. barden@crchul.ulaval.ca
D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology*; D020125:Mutation, Missense / Q000235:genetics; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D016372:RNA, Antisense / Q000235:genetics
D000928:Antidepressive Agents; D016372:RNA, Antisense