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Anxiety Disorders Research: Impact of BDNF

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BDNF stands for brain derived neurotrophic factor. This molecule, found in the brain's fear hub could have a significant impact on the study of anxiety disorders including Post Traumatic Stress Disorder. Dr. Francis Lee of Weill-Cornell Medical College is a leading BDNF investigator and was a recent guest lecturer at the National Institute of Mental Health.

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Dr. Francis Lee: I’m very excited about this new paradigm about mental health in the sense that it’s being spearheaded by people that are studying neurodevelopment.

Announcer: Dr. Francis Lee is with Weill-Cornell Medical College and was a recent guest lecturer at the National Institute of Mental Health in Bethesda. Dr. Lee’s primary research is in basic molecular and neural mechanisms and how they relate to brain disorders. His primary focus is on a molecule found in the brain’s fear hub that may influence anxiety disorders. That molecule, BDNF, stands for brain derived neurotrophic factor…

Dr. Francis Lee: It was actually discovered not that long ago… only about three decades ago. It turns out to be one of the major growth factors of the brain so it actually keeps… sort of like… keeps the nerves alive and healthy as one of its main functions. Its other main function is that as you learn or do something new, the neurons have to actually change their electrical capacity or change their shape in order to adjust to the new situations. And brain derived neurotrophic factor seems to be required for all these plastic changes. The way my work fits into this is that we have one of the first mouse models of a human polymorphism that seems to confer some difficulties in dealing with anxieties or stressful situations. And we’re able to actually quantitate in a very rigorous manner in a mouse model and also try to do parallel studies with our collaborators on human models- with human subjects who have this polymorphism in a way we were able to root certain hypothesis about these genetic alternations in mouse models and test them also in biologically relevant way in humans.

Announcer: Dr. Lee’s mouse model research could have a direct impact on the effectiveness of treatment on patients suffering from disorders such as Post Traumatic Stress Disorder…

Dr. Francis Lee: I think what we’re really excited about recently was this finding that the mice- when they have to learn that a previously dangerous signal, in this case a tone, is no longer dangerous. So it actually is a form of learning- that they have difficulty with it. So, that everything in their environment stays dangerous. It’s very akin to what happens in this disorder called Post Traumatic Stress Disorder or PTSD. And actually one of the main treatments for it is, other than standard pharmacological agents like Zoloft which we had mentioned, is a form of behavioral therapy that requires the patient to learn something new. They have to learn that a previously dangerous condition such as being near tall buildings, if they had been a victim of 9-11, is no longer dangerous. And what we’re finding is that is… suggests mice or possibly people with this polymorphism will have greater difficulty with this. This really gives us insight into possible treatment because there are many cognitive enhancers that are currently being developed to try to help people accelerate this extinction process in Iraqi war veterans as well as World Trade Center victims. And this is a perfect example of how you would have personalized medicine.

Announcer: Perhaps the most exciting part of Dr. Lee’s research involves the possibility of identifying people who may be susceptible to future anxiety issues…

Dr. Francis Lee: Ultimately, the best use of this type of information is it suggests that humans and mice that have this polymorphism might not be as resilient to stress and that you might want to-probably- do everything possible if they’re going to be in a stressful situation. A perfect example would be where we’re currently doing various behavioral therapies to prepare West Point cadets before they go off to Iraqi Freedom stints and that it would be great that if in some future we could get people before they actually develop PTSD and say they - identify people that might be at greater risk and essentially, provide appropriate resilience training even before. We actually want to call it something we call stress inoculation.

Announcer: While his research is promising, Dr. Lee knows the study of BDNF could be one step in a much longer journey….

Dr. Francis Lee: One caveat I would say is that if BDNF was the answer for all these treatments, all these diseases, than we would have solved in by now. So, I’m fully aware there are many other molecules and other genes that are probably also affecting this process and we might just be looking at a tip of an iceberg.