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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Bob on July 31, 2008, at 22:17:25
Study Identifies Changes To DNA In Major Depression And Suicide
31 Jul 2008Autopsies usually point to a cause of death but now a study of brain tissue collected during these procedures, may explain an underlying cause of major depression and suicide. The international research group, led by Dr. Michael O. Poulter of Robarts Research Institute at The University of Western Ontario and Dr. Hymie Anisman of the Neuroscience Research Institute at Carleton University, is the first to show that proteins that modify DNA directly are more highly expressed in the brains of people who commit suicide. These proteins are involved in chemically modifying DNA in a process called epigenomic regulation. The paper is published in Biological Psychiatry.
The researchers compared the brains of people who committed suicide with those of a control group who died suddenly, from heart attacks and other causes. They found that the genome in depressed people who had committed suicide was chemically modified by a process that is normally involved in regulating the essential characteristics of all cells in the body. As Poulter explains, "We have about 40,000 genes in every cell and the main reason a brain cell is a brain cell is because only a small fraction of the genes are turned on. The remaining genes that are not expressed are shut down by an epigenetic process called DNA methylation."
The rate of methylation in the suicide brains was found to be much greater than that of the control group. Importantly, one of the genes they studied was shown to be heavily chemically modified and its expression was reduced. This particular gene plays a major role in regulating brain activity. "Interestingly, the nature of this chemical modification is long term and hard to reverse, and this fits with depression," says Poulter.
"The whole idea that the genome is so malleable in the brain is surprising. Finding that epigenetic mechanisms continue to influence gene expression is pretty unusual," says Poulter, who is also a professor in the Department of Physiology and Pharmacology at Western's Schulich School of Medicine & Dentistry. "These observations open an entirely new avenue of research and potential therapeutic interventions." The research was funded through the Canadian Institutes of Health Research.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------Source: Kathy Wallis
University of Western Ontario
Posted by Chris O on July 31, 2008, at 23:01:28
In reply to Let's try that again... food for thought., posted by Bob on July 31, 2008, at 22:17:25
Well, not to state the obvious, but that is sincerely...depressing!
But it seems to fit with my experience. I can't shake my GAD and depression, no matter how hard I try.
Posted by Bob on July 31, 2008, at 23:37:15
In reply to Re: Let's try that again... food for thought. » Bob, posted by Chris O on July 31, 2008, at 23:01:28
> Well, not to state the obvious, but that is sincerely...depressing!
>
> But it seems to fit with my experience. I can't shake my GAD and depression, no matter how hard I try.Yes, it is quite depressing (no puns intended of course) and these problems are very difficult to solve. Sometimes it seems to me like we all have our individual genetic fates and there's really little we can currently do to change it, unless we somehow go to the source and change our genetic expressions. I still hold out hope though.
Posted by satsumas on August 1, 2008, at 1:31:33
In reply to Re: Let's try that again... food for thought. » Chris O, posted by Bob on July 31, 2008, at 23:37:15
but don't forget that that's what strong medicine and ECT are designed to do in some respects. all these downstream modifications are designed to change the expression of genes, probably via some sort of epigenetic pathway. and remember, he's looking at completed suicides -- obviously let's hope ( or perhaps not hope, I don't know what the correct sentiment is for these sad cases) that those who are being treated with effective doses of the right medications do not have the similar level of epigenetic changes.
although definitely food for thought.
anyone know which psychotropic meds or substances, of any class, do the most action (positive or negative) at the genome itself? solid doses of lithium seem to do something, right?
any other meds remodel the genome or affect its expression thereof?
Posted by Bob on August 1, 2008, at 12:13:45
In reply to Re: Let's try that again... food for thought., posted by satsumas on August 1, 2008, at 1:31:33
> but don't forget that that's what strong medicine and ECT are designed to do in some respects. all these downstream modifications are designed to change the expression of genes, probably via some sort of epigenetic pathway. and remember, he's looking at completed suicides -- obviously let's hope ( or perhaps not hope, I don't know what the correct sentiment is for these sad cases) that those who are being treated with effective doses of the right medications do not have the similar level of epigenetic changes.
>
> although definitely food for thought.
>
> anyone know which psychotropic meds or substances, of any class, do the most action (positive or negative) at the genome itself? solid doses of lithium seem to do something, right?
>
> any other meds remodel the genome or affect its expression thereof?
Yes, agreed, but I was kind of referring to a method which would more directly manipulate the genes I guess. A point at which we could cleanly affect individual genes without requiring a cascade of changes which eventually leads to a modification of gene expression way down the line.
Posted by linkadge on August 1, 2008, at 18:38:33
In reply to Re: Let's try that again... food for thought. » satsumas, posted by Bob on August 1, 2008, at 12:13:45
There is no evidence that current treatments actually do alter the hypermethylation of DNA seen in depression. I remember reading that hypermethylation of hippocampal DNA was associated with low hippocampal serotonin but that agents like imipramine correced the low hippocampal serotonin but not altered DNA methylation.
What you need are agents that are capable of unmethylating DNA. I think inhibition of certain isoforms of HDAC are able to do this.
What about valproate, it is an HDAC inhibitor and appears to be able to reduce abbarent DNA methylation (at least in an animal model of schizophrenia).
Garlic and quercetin are also HDAC inhibitors I believe.
By correting this, one might be able to reduce the chemical fingerprint of stress, depression, or perhaps childhood abuse, bullying etc that often never completely resolves with AD treatment.
Of course, my knoweldge on the topic is very shallow.
Linkadge
Posted by rotem on August 2, 2008, at 9:47:49
In reply to Re: Let's try that again... food for thought., posted by linkadge on August 1, 2008, at 18:38:33
I heard butyric acid (also called butyrate or sodium butyrate) is also a HDAC.
but from butter it doesn't cross the intestine.
the problem it is a two-edged sword : it can cause proliferaiotn, but also apoptosis- which is not good for neurons.
here is a citation from wikipedia
http://en.wikipedia.org/wiki/Butyric_acid
cellular proliferation, apoptosis and differentiation that may be either pro-neoplastic or anti-neoplastic, depending upon factors such as the level of exposure, availability of other metabolic substrate, and the intracellular milieu. Butanoate is thought by some to be protective against colon cancer. However, not all studies support a chemopreventive effect, and the lack of agreement (particularly between in vivo and in vitro studies) on butyrate and colon cancer has been termed the "butyrate paradox." There are many reasons for this discrepant effect, including differences between the in vitro and in vivo environments, the timing of butanoate administration, the amount administered, the source (usually dietary fiber) as a potential confounder, and an interaction with dietary fat. Together, the studies suggest that the chemopreventive benefits of butanoate depend in part on amount, time of exposure with respect to the tumorigenic process, and the type of fat in the diet.[3] Low carbohydrate diets like the Atkins diet are known to reduce the amount of butanoate produced in the colon.
[end of citation]Do you know of a way to consume butyric acid ?
Also, what about folic acid and B12 , that increase methylation. Maybe, therefore, there are shouldn't be consumed by depressed people?
Posted by linkadge on August 2, 2008, at 20:16:07
In reply to Re: Let's try that again... food for thought., posted by rotem on August 2, 2008, at 9:47:49
>Also, what about folic acid and B12 , that >increase methylation. Maybe, therefore, there >are shouldn't be consumed by depressed people?
Yes thats what I was wondering myself. Methylating agents have clear antidepressant effects in some people. Thats probably why DNA overmethylation is probably not a class effect in depression.
But again, I know so little. Do methylating agents like SAMe affect the kind of DNA methylation mentioned in this article?
Linkadge
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