An Epigenetic Approach to Rapidly Treat Depression with Comorbid Anxiety: Implications for Suicide Prevention
Carla Nasca, Ph.D., The Rockefeller University
Mentor: Bruce McEwen, Ph.D., The Rockefeller University
2013 Postdoctoral Fellowship
Inside the Research
Bio: Dr. Nasca received her doctorate from Erspamer University in Rome Italy in 2012. She is currently a Postdoctoral Researcher in the Department of Neuroendocrinology at The Rockefeller University.
Research Categories: Neurobiological studies; animal studies; brain functioning studies
Abstract: Although persons with anxiety and depression are shown to be at higher risk of suicide, individuals may also have a genetic predisposition or tendency towards suicidal ideation, which is aggravated further by stressors such as poverty, social isolation, and childhood abuse. This demonstrates the need to uncover both medications that will ameliorate mood (reducing the probability of suicidal behavior), as well as more efficient antidepressants with faster onset of action. The rapid and long-lasting action of the acetylating agent L-acetylcarnitine, a well-tolerated drug, acts by enhancing the levels of the histone H3H27ac bound to the Grm2 gene. Its use strongly suggests a novel approach to examine the epigenetic mechanisms that control the proper expression of multiple genes that are involved in the pathophysiology of psychiatric disorders. The researchers will conduct a stress/postmortem study with mice to examine whether an acetyl-L-carnitine treatment, which directly resets the chromatin assembly, may correct the pathological epigenetic programming associated with stress-related depression and anxiety, improving or restoring normal brain activity. This will inform us whether a novel epigenetic approach to the treatment of stress related disorders can improve or restore normal brain activity and, ultimately, ameliorate the associated deficits in cognitive processing, perception and memory function associated with suicide attempters.
Impact: Understanding how epigenetic mechanisms modulate stress-sensitive endpoints affords the opportunity to explore the molecular mechanisms of current antidepressants and to develop novel pharmacological approaches to rapidly treat and prevent psychiatric disorders, as well as providing insight into how individuals sharing similar genes might show large difference in disease susceptibility.