Posted by Cam W. on April 18, 2001, at 11:45:48
In reply to Re: Depression, Antidepressants, Life (ramble) » Cam W., posted by SLS on April 18, 2001, at 9:53:09
Scott - Man, I had an eloquent post formulated and them lost the whole damn thing. Here we go again.
I think that the third-third-third "tenet" is more of a clinical rule of thumb rather than hard science ("mooshy" science?). I first heard about with regard to schizophrenia during one of my first days working at Mental Health (strictly outpatient). Many of my colleagues feel that this "tenet" applies to all of their patients, regardless of diagnosis. I do believe that there have been some retrospective studies done on this subject, but one has to be careful with retrospective studies, as they can creatively say whatever you want them to. Off the top of my head, I know of no prospective studies in this area.
In the 1/3 gets worse category you do have to factor in that in most, if not all, cases that depression is a chronic disorder with relapses and remissions of varying lengths. Also, as you say, you must factor in side effects of treatments, as well as placebo effect, patient/doctor concordance (therapeutic relationship), patient expectations and abilities, causation of the disorder, and a myriad of other variables that would be near impossible to factor out.
As for the NO thing, there was a neat study in (oh, God, I didn't copy the reference, just the abstract). Damn! Good day already! I will post the reference in a follow-up. I'm not going to lose this post.
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
The placebo effect and relaxation response: neural
processes and their coupling to constitutive nitric
oxideGeorge B. Stefano a,b A gstefano@li.net, Gregory L. Fricchione a,c,d , Brian T.
Slingsby b and Herbert Benson a
[a]The Mind/Body Medical Institute, CareGroup, Department of Medicine, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115,
USA[b]Neuroscience Research Institute, State University of New York at Old
Westbury, Old Westbury, NY 11568, USA[c]The Carter Center Mental Health
Program, 1 Copenhill, 453 Freedom Parkway, Atlanta,GA 30307,
USA[d]Department of Psychiatry, Brigham and Women's Hospital, Harvard
Medical Center, 75 Francis Street, Boston, MA 02115, USA
A Corresponding author. Neuroscience Research Institute, State University of
New York at Old Westbury, Old Westbury, NY 11568, USA. Tel.:
+1-516-876-2732; fax: +1-516-876-2727
Manuscript accepted 17 October 2000;Abstract
The placebo effect appears to be a real phenomenon as is the scientifically demonstrated
and examined relaxation response. Given this, we attempt to understand how these
phenomena work in light of our current understanding of central and peripheral nervous
system mechanisms. Central to our hypothesis is the significance of norepinephrine, nitric
oxide and opioid signaling both in the central and peripheral nervous system. In this
regard, we find that nitric oxide controls norepinephrine processes on many levels,
including synthesis, release and actions. In closing, we conclude that enough scientific
information exists to support these phenomena as actual physical processes that can be
harnessed to provide better patient care.© 2001 Elsevier Science B.V. All rights reserved.
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~As for the genome thing. I really have to disagree with you on the genome project doing much more than finding genetic links to diseases. The more I look into this, the greater the role environmental factors play in our development and make-up. Everything we say, do or will do depends on what we have done in the past. You could expand this fatalistic view to environmental factors changing genes or gene expression in your parents, your parent's parents, ad nauseum. I know this philosophic view doesn't hold any scientific water, but it is interesting to ponder.
So, what I am saying is that it is not the genome that is determining how you end up. It is the secondary messengers, acting from receptor stimulation, using the genome as a template to put proteins and enzymes where the second messengers say they need to be placed. Yes, introns and exons of genes play a big role in deciding this, but ultimately it is how the cascade of secondary messengers line-up which determine how the template is to be used. If we modify the cascade, we modify the protein, and these modifications will be different for everyone (although there may be some homogeneity across disorders). The protein or enzyme which is malfunctioning may not necessarily be an aberrant genetic mutation, it may be being placed wrong once it leaves the nucleus.
We may be able to eventually tell which proteins and enzymes regulate neuronal plasticity and be able to better target abnormalities causing (let's say) depressive symptoms, but I doubt we will be able to do this by changing the genome. Many different processes will use that enzyme or protein in different functions. If we target the enzyme or protein in the DNA we may be doing more damage other places. Like sickle cell anemia being preventative for malaria, depression may be preventative for something else (eg perhaps having some protective role in slowing the incidence of full blown psychoses - this is just a fictitious example). It may be better to locally target secondary messenger systems and leave the DNA alone.
I believe that biologic vulnerability is only one of several avenues that need to be explored. Yes, it is interesting to be able to predict who is vulnerable, but it would be better to be able to fix the end point problem (with minimal disruption to other systems and avoid stigmatization in biologically vulnerable people who will never show the disorder). I guess you could say that I like epigenetic solutions rather than genetic ones.
Just my views - Cam
poster:Cam W.
thread:60209
URL: http://www.dr-bob.org/babble/20010417/msgs/60316.html