An Overactive Stress Gene Increases Anxiety and Alters Brain Activity
Madison, Wisconsin - A new study shows that overactivity of a gene that mediates the stress response can increase anxiety in young rhesus monkeys, leading to long-lasting changes in the brain. This study, directly altering the activity of a key gene in the amygdala of young primates, suggests that similar alterations in children and adolescents may markedly increase their risk for a lifetime of anxiety and depression.
The new study is from the laboratory of Dr. Ned Kalin, whose work with young primates and children has sought to explain the genetic underpinnings of anxiety and depressive disorders.
In this study, researchers used an intraoperative magnetic resonance imaging (MRI) method to have real-time brain images guide them as they introduced an experimental virus into the brains of five young rhesus monkeys. Similar to gene therapy strategies, the virus was infused into the dorsal amygdala, part of the brain’s fear circuit, and was designed to spur the cells of the amygdala to make more corticotropin-releasing hormone, which drives the body’s stress response.
Dr. Jonathan Oler, one of the lead scientists on the project, said that this new finding was an important step for the field of psychiatry. By combining experimental gene-based treatments with modern neurosurgical techniques, “this study provides a ‘proof-of-concept’ for the further use of gene transfer studies as a means to model psychiatric illnesses in primates,” he said.
The team used behavioral assessments, and different types of brain imaging to compare the five monkeys with the overactive CRH gene to their cage mates, both before and after treatment. They found that the monkeys who received the gene containing virus showed significantly more anxious behavior. Images from functional MRI and diffusion tensor imaging two months after the injection showed changes in the connectivity of the neural circuits associated with anxious temperament. Positron emission tomography (PET) scans showed that the brain circuits associated with anxiety had higher glucose metabolism, and were more active than in the brains of the control monkeys.
“This study provides important insights into why some people may develop stress-related psychopathology and new ideas about how to direct the development of much needed new treatments early in life for reducing anxiety and depression,” says Kalin, who is chair of psychiatry at the University of Wisconsin School of Medicine and Public Health.
“In addition, the results begin to suggest a mechanism underlying the changes in brain function and structure that have been identified to occur in individuals suffering with long-term, recurrent anxiety and depressive disorders.”
This work was supported by the National Institutes of Health grants R01-MH046729, R01-MH63291, R24-OD019803, R43-CA177205, and P51-OD011106.
Date Published: 02/18/2016