Studying animals in behavioral experiments has been a cornerstone of psychological research, but whether the observations are relevant for human behavior has been unclear. Now, Weill Cornell Medical College (WCMC) researchers have identified an alteration to the DNA of a gene that imparts similar anxiety-related behavior in both humans and mice, demonstrating that laboratory animals can be accurately used to study these human behaviors.
The research, published in the Jan. 14 issue of the journal Science, found that people with a certain altered gene have a harder time recovering from a highly stressful experience. The finding may help researchers develop new clinical strategies to treat humans with such anxiety disorders as phobias and post-traumatic stress disorder (PTSD).
"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," said B.J. Casey, co-senior author of the study and professor of psychology in psychiatry at the Sackler Institute for Developmental Psychobiology at WCMC.
The researchers observed common behavioral responses between humans and mice that possess an alteration in the brain-derived neurotrophic factor (BDNF) gene. The mice were genetically altered -- meaning that they had a human genetic variation inserted into their genome.
To make their comparison, the researchers paired a harmless stimulus with an aversive one to elicit an anxious-like response, known as conditioned fear. However, after the fear learning, when people are exposed numerous times to the harmless stimulus (without the aversive stimulus), they usually eventually stop responding anxiously.
"But 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 Fatima Soliman, lead author of the study, who is currently a Tri-Institutional M.D.-Ph.D. student who has completed her Ph.D.
In addition to observational testing, the researchers also performed brain scans on the human participants to see if brain function differed between people with the normal and abnormal BDNF gene.
They found that a circuit in the brain involving the frontal cortex and amygdala -- responsible for learning about cues that signal safety and danger -- was altered in people with the abnormality, compared with participants who did not have the abnormality.
"Testing for this gene may one day help doctors make more informed decisions for treatment of anxiety disorders," explains Dr. Francis S. Lee, co-senior author of the study and associate professor of psychiatry and pharmacology at WCMC.
Therapists use exposure therapy -- a type of behavior therapy in which the patient confronts a feared situation, object, thought or memory -- to treat people who experience stress and anxiety in certain situations. Sometimes, exposure therapy involves reliving a traumatic experience in a controlled, therapeutic environment. The goal is to reduce the distress, physical or emotional, felt in situations that trigger negative emotion. Exposure therapy is often used for the treatment of anxiety, phobias and PTSD.
"Exposure therapy may still work for patients with this gene abnormality, but a positive test for the BDNF genetic variant may let doctors know that exposure therapy may take longer, and that the use of newer drugs may be necessary to accelerate extinction learning," explains Soliman.