Fear, Memory, and Post-Traumatic Stress Disorder

Traumatic events, such as experiencing a war, domestic violence, or a car crash, can have an enduring negative impact on the mental, physical, and emotional health of an individual. Such events could lead to a difficulty in coping and adjusting with life and can possibly trigger anxiety related disorders such as post-traumatic stress disorder (PTSD). PTSD results in severe anxiety, nightmare, and flashbacks of the traumatic even in response to mild stressors. Approximately 5% of Americans have PTSD at a given time. The severity of PTSD often leads to depression and drug abuse and changes in long term behavior and mood in patients. Post-traumatic stress disorder is one of the most common and serious mental disorders, therefore the development of new and effective treatments is necessary.

            In the article, “Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress,” researchers developed a model for acute stress that parallels symptoms of PTSD. Michael Fanselow and his research partners developed stress-enhanced fear learning (SEFL), a model that creates non-associative sensitization of fear in rodents  in order to simulate and describe PTSD. Firstly, the role of corticosterone (CORT) was examined in SEFL. The CORT synthesis blocker, metyrapone, was used to test the necessity of CORT. Metyrapone diminished SEFL  but only when administered at prior to the stressor. Additionally, CORT administered without the stressor did not produce SEFL. The results showed that CORT changes during the presence of stress are necessary for SEFL. The findings of this research reveal the mechanisms that underlie the expression of fear caused by a traumatic stressor. Furthermore, an increase in GluA1 AMPA receptor was correlated with SEFL. GLuA1 is located in AMPAR, and is important in fear expression. The GluA1 could potentially be targeted in order to reverse the increased fear response to a stressor and thus combat PTSD.

            A novel approach that has potential in treating PTSD has been receiving more attention in the past few years. According to the National Geographic article, “Memories Can Be Altered in Mice. Are Humans Next?” ongoing experiment are taking place in testing the ability to alter memories as potential treatment for a variety of mental conditions. MIT researchers  Steve Ramirez and Xu Liu were able to target cells in a rodent brain that make up one engram (brain tissue associated with a particular memory) and implanted a false memory. The final goal is to potentially target the painful memories that cause severe trauma and result in lasting psychological impact. Furthermore, the researchers are also examining whether negative and positive memories are stored in different cells and the possibility of altering them. Another group of researchers from the University of Toronto were successfully able to eliminate a small portion of fear memories in mice and as a result they stopped being afraid of a particular stressor.

            The power to alter memories in humans comes with numerous ethical implications.  Nonetheless, these studies have  a great potential in contributing to PTSD treatment in humans that can help millions of lives.  The study by Michael Fanselow revealed that metyrapone prevents SEFL and the elevation of GluA1 in the basolateral amygdala. A drug targeting the upregulation of GluA1 could possibly reduce the expression of SEFL. These findings can serve as a foundation for future research to broaden the applicability of metyrapone and GluA1 regulation as potential PTSD treatment. This along with the other studies regarding memory alteration are significant breakthroughs in treating PTSD and other anxiety related disorders.

          

References:

Perusini, J. N., Meyer, E. M., Long, V. A., Rau, V., Nocera, N., Avershal, J., … Fanselow, M. S. (2015). Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress. Neuropsychopharmacology, 41(1), 45–57. doi: 10.1038/npp.2015.224

Zaki, J. (2018, July 18). Memories Can Be Altered in Mice. Are Humans Next? Retrieved from https://www.nationalgeographic.com/science/2018/07/news-memory-manipulation-research-neuroscience/.