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Re: Corticotropin Releasing Factor » elanor roosevelt

Posted by dessbee on December 15, 2006, at 7:42:59

In reply to wsj article on depression, posted by elanor roosevelt on December 14, 2006, at 20:53:58

I think you are referring to corticotropin releasing factor also called CRH - corticotropin releasing hormone.

CRH is a part of the HPA-axis (Hypothalamic-Pituitary-Adrenal Axis). CRH triggers release of ACTH (adrenocorticotropin), which triggers release of cortisol, which inhibits release of CRH.
HPA-axis is a feedback system, like a thermostat for stress. Stress could be anything from a chemical, a bacteria or social environment.

http://www.biology.ucr.edu/people/faculty/Garland/HPA_axis.jpg

http://cti.itc.virginia.edu/~psyc220/kalat/JK367.fig12.6.HPA_axis.jpg

It is interesting that animal models show that low glucocorticoid receptor density in the forebrain produces depression-like changes in adrenal axis regulation and behavior. Cortisol is a Glucocorticoid receptor agonist and act on these receptors to inhibit CRH release. So low glucocorticoid receptor density makes HPA-axis less sensitive and more cortisol is needed for feedback inhibition. Depression is like a thermostat gone haywire initiating a stress cascade.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=544280

In my mind SSRI only alleviates depression, it is not the true cure of depression. It only modulates the HPA-axis indirectly.

CRF1 receptor antagonists will probably be a far better antidepressant since it intervenes the HPA-axis directly, blocking the pathogenesis of a depression.
The most optimal treatment for depression would most likely be a therapy that increases Glucocorticoid receptor expression/density; this would hopefully heal the depression at its core, maybe the true etiology of a depression.



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