Cellular mechanisms in the vulnerability to depression and response to antidepressants.
As a testable heuristic, the concept of stress response and adaptation is highly appealing, and the support for the concept is strong. This explanatory model of depression may account for hitherto apparently discordant facts--contradictory symptoms, antidepressant drugs that act on differing systems, facilitation of antidepressant response by augmentation, and response to psychotherapy and pharmacotherapy. This article has focused narrowly on specific cellular elements of the stress-adaptational mechanisms, including the AC-PKA and PLC-PKC transductional cascades, together with specific response elements, such as the HPA axis, BDNF, and NMDA receptors; however, other important mechanisms, including specific receptor subtypes (e.g., 5-HT1A and NE alpha 2), transmitter systems (e.g., acetylcholine and depamine), and hormones (e.g., thyroid and growth hormones and prolactin), which may be important, have not been discussed. As the complex interactions of these systems gradually yield to investigation, not only will new treatments be developed, but better matching of treatment to patient may become an achievable goal.
Shelton
R C
RC
Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. richard.shelton@mcmail.vanderbilt.edu
D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000928:Antidepressive Agents