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Re: Is depression damaging my brain? » catmint

Posted by Pfinstegg on November 26, 2002, at 22:44:18

In reply to Is depression damaging my brain?, posted by catmint on November 26, 2002, at 0:54:02

Under "normal" circumstances- i.e. optimal challenge and stress to your brain, but not continued or excessive stress, the hippocampus is thought to add several thousand new neurons each day- this is the substrate of learning. However, during periods of continued, excessive stress, the hippocampus stops creating new neurons. The neurons which remain become somewhat smaller in volume due to unfavorable changes in their metabolism, and to the shortening of their dendrites- the structures with which they communicate neurochemically with other neurons. These changes are what underlie the common findings seen on MRI's and SPECT scans during depression- a loss of volume (up to 20%) in the hippocampus- in particular the left side of it, and a decrease in the volume of bloodflow to it. The left pre-frontal region is also affected in the same manner, but to a lesser degree. It is generally thought that cell death is NOT INCREASED during depression, although of course it does occur in various types of ischemic brain injury, which is different. The changes in brain volume and blood flow seen in depression can be shown to be reversed, by natural remissions, by a number of drugs (the tricyclics seem to do it best, but SSRI's may also do it- as to the newer atypicals, I haven't been able to find out yet), and also by ECT and TMS.

So, there is much to be hopeful about-depression is a potentially reversible disorder, physically. As treatments become more focussed on regulating the abnormalities in stress hormones, it is going to be much easier for people to attain really good remissions. Specifically, these would be cortisol-lowering drugs such as mifepristone, and a bit more in the future, CRH (corticotrophin-releasing hormone) antagonists. There are others, too, but they all have in common the goal of restoring HPA (hypo-pituitary-adrenal) axis regulation, and, by doing so, preventing various hormone excesses (in chronic fatigue syndrome and atypical depression, there may be brief bursts of excess hormones, followed by too little, but in bipolar and unipolar depression, there is chronic overproduction). Regulating these various hormones will, in turn, allow the hippocampal and pre-frontal neurons to regain normal volumes and dendrites, which should allow the various neurotransmitters- serotonin, dopamine and nor-epinephrine, plus others-to be released and taken up in a normal fashion.

That being said, we are all faced with the realities of our present situation. I think it is true that the longer a depression goes on, and the more severe it is, the more difficult it is to recover by the means we presently have. The medications we have now just attempt to treat one of the end-stage manifestations of the disease- the neurotransmitter levels, and I think it is quite uncommon for someone to feel that they have been cured of their symptoms completely by any of the drugs we have now.

I think that someone with either bipolar or unipolar depression, which is severe, long-lasting, and resistant to a range of drug trials, should consider either ECT, TMS or one of the mifepristone trials. Mifepristone is the first drug ever to have been "fast-tracked" for depression by the FDA (it did that in August, '02). Because it has been used so often as an abortifacient, a lot is already known about its safety, which is very good for short-term use. The trials going on at present are of 7 to 10 days in length, with investigation of "booster" doses- a lot like ECT, and apparently at least as effective.

It's really encouraging to know that the hippocampus can renew itself if the stress hormones can be regulated- the only thing is- it's so hard to wait for the new treatments!

Pfinstegg


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poster:Pfinstegg thread:129341
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