Epigenetic mechanisms regulating the acquisition and extinction of conditioned fear: exploring the neurobiology of relapse

A major obstacle in the treatment of fear-related anxiety disorders is their likelihood for relapse. Fear-related behaviour can be inhibited with extinction therapy (repeated exposure to specific fear-inducing cues). This is, however, a temporary fix because fear often returns after exposure to cues associated with the original learning. In the case of post-traumatic stress disorder, fear can also “incubate” or sensitize over time and further exacerbating symptoms of the disorder. These phenomena likely reflect long-term neural adaptation that occurs during learning – changes that may be based on lasting epigenetic modification of genes responsible for maintaining fear memories. Epigenetic modifications influence the way a gene functions without altering the underlying DNA sequence- processes now recognized to participate in the regulation of gene expression in the adult brain. Rapidly emerging evidence suggests that epigenetic mechanisms play an important role in psychiatric disease and in disorders of learning and memory. Dr. Timothy Bredy is employing state-of-the-art technologies to investigate the fundamental epigenetic mechanisms of associative fear memory. He is using a genome-wide approach to examine epigenetic machinery involved in regulating critical gene targets during the acquisition and extinction of conditioned fear. Dr. Bredy hopes his findings will provide insight into the molecular basis of relapse and its prevention and that this research will ultimately contribute to the design of novel pharmacotherapeutic treatment approaches for fear-related anxiety disorders.