OCD? Your Immune System Could Be to Blame ~ ScienceMag.org

[mzmolly]

Some people just can’t help themselves. They wash their hands over and over, scrubbing their skin raw. Or they lock and relock doors, pull out their own hair, or obsessively rearrange the contents of their closet. Now, a study of mice suggests that faulty immune cells prompt such compulsive behaviors. The results raise the possibility of treating obsessive-compulsive disorder by targeting the immune system rather than the brain.

Mice are fastidious, regularly cleansing their bodies from nose to tail. But animals with a defective version of the gene Hoxb8 groom themselves so much that they tear out patches of fur and develop skin sores. The behavior resembles a type of obsessive-compulsive disorder called trichotillomania, in which people tug out their own hair.

The http://en.wikipedia.org/wiki/Hox_gene">Hox family of genes is best known for helping to organize the embryo’s body, but Hoxb8 has several effects. The protein encoded by the gene functions in neural development, so mice lacking it have abnormal spinal cords and sensory ability, including pain sensitivity. This defect could in theory provoke the rodents to wash excessively, although molecular geneticist Mario Capecchi of the University of Utah School of Medicine in Salt Lake City and colleagues note that Hoxb8-lacking mice also obsessively groom other mice. That suggests that over-cleaning is not a sensory problem but a behavioral one originating in the brain.

When Capecchi and colleagues began looking for the Hoxb8-making cells in the mouse brain, they expected to find that the source was neurons that control grooming. To their surprise, the only cells producing Hoxb8 were microglia, immune cells that guard against pathogens. Although some microglia start out in the brain, others are born in the bone marrow and move in. Overall, adult mice with faulty Hoxb8 harbored about 15% fewer microglia in the brain than normal.

To test whether defective microglia provoke mice to feats of extreme cleanliness, the researchers performed bone marrow transplants. Transferring marrow from Hoxb8-lacking mice into healthy rodents provoked compulsive grooming, the researchers report in the 28 May issue of Cell. And when mice deficient in Hoxb8 received marrow from healthy animals, they cut back on their ablutions. Before this finding, “nobody would say you can cure a behavior with a bone marrow transplant,” Capecchi says.

...

“This is important work,” says developmental biologist Jacqueline Deschamps of the Hubrecht Institute in Utrecht, the Netherlands. “The localization of a bone marrow origin of such a behavioral disturbance is a landmark.”

More at http://news.sciencemag.org/sciencenow/2010/05/ocd-your-immune-system-could-be-.html?sms_ss=email">NEWS.SCIENCEMAG.ORG

[BrklynLiberal]

1. Marking for later perusal. thanks.

[mzmolly]

4. Here is the full text of the original

study if you're interested. http://www.cell.com/fulltext/S0092-8674%2810%2900374-0

I'm off to read before we BBQ. ;)

[aquart]

2. WOW.

[mzmolly]

3. Fascinating isn't it?

:freak: I hope the discovery will lead to new, effective therapies.

[EvolveOrConvolve]

5. This could a nice breakthrough, but...

How feasible is it to provide bone marrow transplants to all the people with OCD? From what I understand, bone marrow transplants are expense operations.

Hopefully, other treatments can be found that do the same thing. I'm only slightly OCD, and it's a horrible thing, so this has the potential to be a life changing finding.

[mzmolly]

6. The study points out that it's not financially feasible and it's too risky, medically speaking.

But as you suggest, the hope is that the discovery will lead to new therapies for mental illness, that target the immune system.

http://www.cell.com/fulltext/S0092-8674%2810%2900374-0#Introduction

The above experiments strongly support the hypothesis that the excessive pathological grooming behavior observed in Hoxb8 mutant mice originates from defective microglia, thus directly connecting hematopoietic function to mouse behavior. The extensive role of microglia, as the brain's monitor and responder of immune activity, in the normal function of our brain is becoming increasingly apparent. As examples, immunological dysfunctions have been widely linked to many psychiatric disorders including OCD, major depression, bipolar disorder, autism, schizophrenia, and Alzheimer's disease (Ashwood et al., 2006,da Rocha et al., 2008,Kronfol and Remick, 2000,Lang et al., 2007,Leonard and Myint, 2009,Strous and Shoenfeld, 2006). In addition, results from genome-wide association studies suggest that genes whose dysfunction have been implicated in immune dysfunction and/or signaling contribute to increased susceptibility to the above mentioned mental disorders (Hounie et al., 2008,Purcell et al., 2009,Shi et al., 2009,Stefansson et al., 2009).

:hi:

[mzmolly]

7. PS

This section from the http://www.cell.com/fulltext/S0092-8674%2810%2900374-0#Discussion">discussion section of the study is very interesting -

Microglia could affect neuronal activity and behavior by a number of mechanisms, including the secretion of cytokines that stimulate or inhibit neuronal activity, and work in parallel with neurotransmitters. Microglia have also been reported to function in regulating neuronal cell death during embryogenesis (Frade and Barde, 1998,Marin-Teva et al., 2004). Absence of appropriate cell death during neurogenesis could manifest itself later as aberrant behavior. Finally, the experiments of Wake et al., 2009 illustrating that microglia processes are very dynamic and engage in intimate contacts with synapses are particularly intriguing. They observed that the duration of contact at synapses is dependent on neuronal activity. From the above, it is becoming apparent that due to their mobility and dynamic contacts with synapses, microglia could represent an additional system for stabilizing and managing neural networks. By virtue of their high abundance in the cortex, including the frontal orbital regions and basal ganglia, the microglia of Hoxb8 lineage are positioned in close proximity to the pathways controlling repetitive behavior.

I can't help but wonder about future stem cell therapy?

[EvolveOrConvolve]

8. Stem cell therapy has definite potential

I would love to see the government push $100 billion or so at the research, but the anti-science nuts would freak out. Heck, if we can spend almost a trillion dollars bailing out huge corporations, $100 billion would be pocket change. I read an interesting article in Newsweek (http://www.newsweek.com/2010/05/15/desperately-seeking-cures.html) about the problems with taking studies like the one you posted and taking the findings to the next level by creating usable and marketable treatments. Right now, there is little incentive to do so.

[mzmolly]

9. Very discouraging article.

It's no wonder people turn to alternative medicine. I hope the Specter bill will merit some fruit. Regardless, it seems we need to better share information and research, and find ways to cooperate internationally in regard to funding etc. We also need to stop relying on a profit driven system for every advancement.

[EvolveOrConvolve]

10. Bingo, you hit the nail on the head

As soon as profit is introduced, real, long-term solutions become very, very difficult to come by. The shareholders and their quarterly profit are, at that point, more important than the customer. The goal of medical care should be to cure disease and help the sick - there isn't a way to reconcile that with a profit-based system.

[tiptoe]

11. microglia

System and Tissue Distribution of Vitamin D Receptors (VDR)