McLean Hospital 115 Mill Street Belmont, MA 02478
Kerry J. Ressler, MD, PhD, is chief scientific officer and James and Patricia Poitras Chair in Psychiatry at McLean Hospital, after serving at Emory University for 18 years. He is also a professor in psychiatry at Harvard Medical School and current president of the Society for Biological Psychiatry. Dr. Ressler was previously an investigator of the Howard Hughes Medical Institute and is a member of the National Academy of Medicine (formerly the Institute of Medicine) and the National Academy of Medicine.
Dr. Ressler’s lab focuses on translational research bridging molecular neurobiology in animal models with human genetic research on emotion, particularly fear and anxiety disorders. He has published over 225 manuscripts ranging from basic molecular mechanisms of fear processing to understanding how emotion is encoded in a region of the brain called the amygdala, in both animal models and human patients.
Dr. Ressler’s Neurobiology of Fear Laboratory, founded in 2001 at Emory University and relocated to McLean Hospital in 2015, investigates the molecular, genetic, epigenetic, and neural circuit mechanisms underlying fear processes through an integration of animal models and human genetic research. The hope is that gaining a better understanding of how fear works in the brain will contribute to the development of new treatments, and possibly even prevention, of fear-based psychiatric illnesses.
To truly understand and treat complex neuropsychiatric disorders, we need to know what behaviors are affected, which brain regions are involved, which genes, molecules, and cell types in these regions might be involved, and how the environment affects the propensity to develop these disorders. Dr. Ressler’s research encompasses these questions, with focus on fear and post-traumatic stress disorder (PTSD).
Dr. Ressler’s group uses well-established mouse models to examine different aspects of fear learning and investigate the role of different brain regions, in particular the amygdala, in fear processing. Furthermore, the lab examines how these mechanisms may be involved in the development of fear-based disorders, such as PTSD, phobic disorders, and panic disorder. Utilizing data collected from human clinical populations, Dr. Ressler and his team identify genetic traits and neural processes that may contribute to the underlying causes of these illnesses and provide novel targets for animal models research.
An important observation in recent years is that there are a number of different learning components involved in the fear response following trauma exposure and recovery. Evidence suggests that trauma exposure in the past (in particular, child abuse), prior to the current ‘index trauma’ is associated with increased risk for PTSD onset. Furthermore, twin studies suggest approximately 30-40% genetic heritability. Together these components constitute differential pre-existing sensitivity.
During the minutes to hours to days following trauma exposure, trauma memory remains in a labile state, called the consolidation period. There are many exciting areas of inquiry suggesting that new pharmacotherapeutic and psychotherapeutic approaches can be initiated that may inhibit the emotional component of fear memory consolidation, without affecting the explicit memory formation. Such an approach could prevent the severe emotional reactions that underlie later development of PTSD. There are several additional cognitive mechanisms that are associated with pathological reactions such as generalization and sensitization of trauma memory reminders. In contrast, the mechanisms of discrimination and extinction of memory serve to counter these processes. By understanding multiple different components of fear memory formation and modulation in humans and mice, a number of novel, powerful, and targeted treatment and intervention approaches may become possible.
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers A, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 2011;470(7335):492-7.
Andero R, Dias BG, Ressler KJ. A role for Tac2, NkB and Nk3 receptor in normal and dysregulated fear memory consolidation. Neuron 2014;83(2):444-54.
Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience 2014;17(1):89-96.
Ressler KJ, Pine DP, and Rothbaum BO, eds. Anxiety disorders: translational perspectives on diagnosis and treatment. New York: Oxford University Press, 2015.
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