Posted by Shawn. T. on May 29, 2003, at 19:32:06
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
"As for cortisol replacement therapy, I would agree with davpet in that this is really only a short-term solution. I once emailed Charles Nemeroff himself on this issue, and he responded that a low dose of prednisone might be beneficial. However, I really don't think that such a therapy is getting to the root of the problem and the side effects of this drug might be more trouble than it is worth."
Agreed.
"Levels of cortisol have been inconclusive when measured in atypicals (some find them normal, some too high, some too low). Also, cortisol acts as a negative feedback mechanism for CRF, so more cortisol isn't necessarily a good thing. Some experts believe that a potentiator of CRH might be beneficial for atypical depressives, while others disagree."
Good article. Note that they mention that it would not be surprising to note normal cortisol levels in people with CRF deficiency. Multiple feedback systems exist to keep cortisol levels within a certain range; decreased CRF excretion would likely be compensated for in many cases. I've gathered the following observations on atypical depressive patients from four different articles: {high ACTH, low cortisol}; {low ACTH, normal cortisol, low CRF}; {low ACTH, normal cortisol}; {normal ACTH, normal cortisol}. Assuming that the most important factor involved in atypical depression is hypofunction of CRF neurons, all of this data does not nullify that hypothesis. I've also read that some people with atypical depression exhibit exaggerated suppresion of cortisol in response to dexamethasone (Levitan et al., 2002). I'm not sure how CRF deficiency might lead to such responses, but there may be some connection.
"But this just begins to tell only part of the story of atypical depression. The question remains, why are some depressed people not able to sleep, eat, etc., and why do some react oppositely? There are two hypothesis to answer this question: 1) Atypical depressives are those individuals whose stress system have crashed, meaning that high levels of HPA output have desensitized the receptors and made them less able to respond in normal day-to-day life situations; 2) Atypical depressives are really an offshoot of bipolar depression and the symptoms atypical depressives exhibit are manifestations of larger cortical dysregulation found to be typical of the bipolar illness as whole. Considering that there have been genetic differences seen between the two different unipolar conditions (melancholic vs atypical), then this theory might hold some water."See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12658618&dopt=Abstract for some recent information on the link between early onset unipolar and bipolar II. I haven't yet seen enough evidence to lump all early onset atypicals into the bipolar II category; I'm sure we'll see a lot more on this in the next few years. I think it's also important to note that not all bipolars experience atypical depression; I haven't seen any exact figures on the prevalence of atypical depression in bipolar disorder, but a very significant percentage of bipolars do not experience atypical symptoms. With regard to genetic differences, the availability of genetic research on atypical depression is extremely scarce. I'm still baffled by the situation. In the long term, the optimal treatment options for people with any psychiatric disorder will be determined from genetic evidence. Unfortunately, atypical depression genetic research lags far behind every other disorder. Perhaps research that further identifies exactly which groups of people do experience atypical depression will fuel genetic studies involving those groups. Until then, I do believe that progress in other areas is being made. More studies involving CRF/NE deficiency should do much to clarify the biological aspects of atypical depression.
Shawn
poster:Shawn. T.
thread:228381
URL: http://www.dr-bob.org/babble/20030525/msgs/230047.html