February 4, 2010

Researchers Say Mice May Be Crucial To Understanding Human Anxiety

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Researchers at WCMC have successfully pinpointed a DNA alteration that evokes similar anxiety reactions from both humans and mice, indicating the potential for future reciprocal research and the development of new treatment methods.

The research, published in the Jan.14 issue of Science, demonstrated that humans and mice with a particular genetic alteration experience difficulty recovering from high-stress experiences. The correlated results may help researchers formulate new clinical treatments for anxiety disorders, phobias and Post Traumatic Stress Disorder (PTSD) which has seen a 30% rise recently, according to the VA.

Beginning in 2006, research studies led by Francis Lee at WCMC began to demonstrate a connection between the gene for brain-derived neurotrophic factor (BDNF) and heightened anxiety. The most recent study has affirmed this connection.

“We found that humans and mice who had the same human genetic alteration also had greater difficulty in extinguishing an anxious-like response to adverse stimuli,” stated Dr. B.J. Casey, co-senior author of the study and professor of psychology at the Sackler Institute for Developmental Psychobiology at WCMC.

In the study, researchers noted a behavioral commonality between humans and mice that held a BDNF alteration. In the case of the mice, a human genetic variation was inserted into their genome. The researchers coupled innocuous stimuli with aversive stimuli to invoke an anxiety response, or “conditioned fear” in the mice. While this fear reaction normally fades after subsequent innocuous stimulus only, the study’s genetically altered test subjects continued to react anxiously.

“Both the mice and humans found to have the alternation in the BDNF gene took significantly longer to “get over” the innocuous stimuli and stop having a conditioned fear response,” said Dr. Fatima Soliman, lead author of the study. “They continued to show fear responses when they were no longer warranted.”

Ithaca’s Cornell research community reacted to the published study with a view towards future animal/human experimentation.

“It’s good to hear that we are continuing to find links/commonalities between analogous systems in humans and rodents,” said Marc Sackeli ’08, who studies Biomechanics and Sports Medicine at Cornell’s Mechanical Engineering Gao Laboratory, via email. “Being able to work with animals, especially mammals, has given scientists great insight into the inner workings of physiological systems across a variety of species. Rodents in particular have been essential in providing a physiology that is comparable to humans.”

Others saw potential for new treatment methods as a result of the study’s results.

“We know surprisingly little about anxiety disorders, let alone how to treat them,” said Julia Stimac ’10, who assisted research studies in Professor David Smith’s Biopsychology Laboratory. “With regards to non-invasive therapy for psychiatric disorders, these types of studies can do wonders for finding effective approaches to treatment.”

The authors of the study at CWMC predicted that their findings could inform future treatment of anxiety disorder patients through exposure therapy.

“Personalized medicine is still a long way off for psychiatric disorders, but work on BDNF and other genes may eventually enable psychiatrists to use genetic profiles to help choose the best treatment for a given patient,” Soliman said. “The BDNF alteration leads to a deficit in extinction learning. Patients with anxiety disorders who have the BDNF alteration may not be as sensitive to therapy approaches such as exposure therapy, which relies on extinction mechanisms.”

Original Author: Dan Freedman