Posted on 10/17/2007 1:50:41 PM PDT by crazyshrink
How schizophrenia develops: Major clues discovered Findings may lead to better medications to correct gene-related problem Schizophrenia may occur, in part, because of a problem in an intermittent on/off switch for a gene involved in making a key chemical messenger in the brain, scientists have found in a study of human brain tissue. The researchers found that the gene is turned on at increasingly high rates during normal development of the prefrontal cortex, the part of the brain involved in higher functions like thinking and decision-making – but that this normal increase may not occur in people with schizophrenia.
The study was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH) and National Institute of Child Health and Human Development.
The gene, GAD1, makes an enzyme essential for production of the chemical messenger, called GABA. The more the gene is turned on, the more GABA synthesis can occur, under normal circumstances. GABA helps regulate the flow of electrical traffic that enables brain cells to communicate with each other. It is among the major neurotransmitters in the brain.
Abnormalities in brain development and in GABA synthesis are known to play a role in schizophrenia, but the underlying molecular mechanisms are unknown. In this study, scientists discovered that defects in specific epigenetic actions – biochemical reactions that regulate gene activity, such as turning genes on and off so that they can make substances like the GAD1 enzyme – are involved.
Results of the research were published in the October 17 issue of the Journal of Neuroscience, by Schahram Akbarian, MD, PhD, Hsien-Sung Huang, PhD student, and colleagues at the University of Massachusetts Medical School and Baylor College of Medicine.
“This discovery opens a new area for exploration of schizophrenia,” said NIMH Director Thomas R. Insel, MD. “Studies have yielded very strong evidence that schizophrenia involves a decrease in the enzymes, like GAD1, that help make the neurotransmitter GABA. Now we’re starting to identify the mechanisms involved, and our discoveries are pointing to potential new targets for medications.”
Another enzyme, Mll1, may play a role in the epigenetic actions. For genes to be turned on, temporary structural changes in certain proteins - histones - must take place to expose the genes' blueprints in DNA. The researchers found evidence that, in schizophrenia, changes in Mll1 activity may interfere with this process in histones whose alterations enable the GAD1 blueprint to be exposed.
The researchers also showed, in mice, that antipsychotic medications like clozapine appear to correct this epigenetic flaw. This raises the possibility of developing new medications aimed at correcting defects in the mechanisms involved.
Finding more precise molecular targets for development of new schizophrenia medications is a key effort, because it can lead to more effective treatments with fewer side effects. Clozapine and other current antipsychotic medications are effective for many patients, but not all, and they can cause side effects severe enough that some people choose to stop treatment.
The researchers also found that people with three different variations of the GAD1 gene – variations previously associated with schizophrenia – also were more likely to have indicators of a malfunction in brain development. Among them were indicators of altered epigenetic actions related to GABA synthesis.
“We’ve known that schizophrenia is a developmental disease, and that something happens in the maturation of the prefrontal cortex during this vulnerable period of life. Now we’re beginning to find out what it is, and that sets the stage for better ways of preventing and treating it,” Akbarian said.
### For more information, visit the NIMH web site at http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website: http://www.nimh.nih.gov/.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Reference: Huang H-S, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S. Prefrontal Dysfunction in Schizophrenia Involves Mixed Lineage Leukemia 1-Regulated Histone Methylation at GABAergic Gene Promoters. Journal of Neuroscience, October 17, 2007.
Now if only Scientists could discover how Liberalism develops ...
The voices in my head agree......
Roses are red, violets are blue. I’m schizophrenic & so am I.
Wow, this is really exciting.
I agree.
Me, too.
So much for talk therapy.
I had the highly educational good fortune to be involved in a very peripheral way with this sort of study with respect to the immune system, and the exquisite delicacy of the machine is mind-boggling. My hat's off to the researchers.
Your dissociative disorders are confused with your schizophrenia.
Beat me to it. BMTI.
Bump To The Top. BTTT.
The voices in my head are ROFLTAO!.........
Link between schizophrenia and MoRon.org, dailycuss, Huff'n Puff Post, mediasmatters university studies claim.
Too much dependence on feeeeeeeeelings, said one researcher.
This really is an exciting development — if we could find a way to develop new antipsychotic medications, or perhaps work to somehow improve the existing ones like Clozapine to reduce the side effects, the results could be tremendous.
We now know that Clozapine corrects the changes in Mll1 activity...hopefully, we will see new studies about the effects on GAD1.
I can see the day when nonoprobes can be sent to the defective gene(s) and cause the gene to correct itself. It would be the near end of so many of today’s medical anomalies (ADHD, diabetes, thyroid, etc.)
Plus, no more worrying about low compliance rates brought on by the various side effects.
Agreed. We could rid ourselves of the use of many drugs even.
Just off the top of one of my heads, someone who has suffered from schziphrenia for a couple of decades and then is cured by whatever cure comes from this research (please God) could maybe use some company in putting his life back together and dealing with the stresses that normal peple deal with.
If we imagine somebody who was struck with some kind of infantile paralysis before he learned to walk, and then imagine the paralysis is cured, we can see that curing the paralysis hasn't cured the patient. It's just gotten him to where he can be cured, by learning to walk and to run.
Also, just 'cause you have measles doesn't mean you don't also have a cold or a sprained ankle, and curing the measles won't address those problems.
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LOL! You may be right. :)
GABA is interesting stuff, thought by some to be in short supply in brains of alcoholics and by others to assist in transmitting signals between eye and brain in aging people—at least in aging lab chimps. Article in The New Scientist a couple of years ago. At about $5 per bottle and available at health food stores, it’s worth a try. Yes, it seems to work for my eyes.
http://www.freerepublic.com/focus/f-news/904174/posts
The 2003 thread on GABA, aging and vision. Pretty amazing stuff. Available online for about $5 from a little outfit called BeyondACentury.com.
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