Posted by jrbecker on March 11, 2003, at 17:23:12
In reply to Re: CRF and depression, posted by Shawn. T. on March 11, 2003, at 16:34:28
Good point, regarding the limited utility of the CRH anatagonists. I've actually been in contact with George Chrousos of NIMH as well as Charles Nemeroff at Emory. Both agree that there is a need for CRH partial agonists for atypical depression. However, they also see a possible utility of using CRH antagonists in some forms of atypical depression as well. This is evident because many sufferers do not fit exclusively in either category of melancholic or atypical type, and thus, cannot be suffering from consistent hypo- or hyper-active states, respectively, all of the time. There is a study I used to have cited that shows that the breakdown of sufferers who actually meet the criteria for both subtypes, and who falls somewhere in the middle, but it eludes me now. Anyway, the point is that, for many, a complete desensitization of the stress system has not fully occurred, and that their features are not wholely atypical all of the time. Thus, in these individuals, there might also be some benefits to just modulating the stress system somehow, either through slight deregulation of the CRH pathway, or even through the means of a low-affinity antagonist itself.
On another note, there seems to be some preliminiary work being done to study regulation of the glucocorticoid receptor (GR). One compound in early development is Organon's Org-34517. It is hoped that this will increase the sensitivity of GR and reinstate normal control of the HPA axis. This would make theoretical sense for treating atypical sufferers.
poster:jrbecker
thread:207835
URL: http://www.dr-bob.org/babble/20030310/msgs/208173.html