A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?

Abstract

Post-traumatic stress disorder is a prevalent disorder within the USA and worldwide with a yearly diagnosis rate of 2–4% and affecting women more than men. One of the primary methods for study of this stress disorder relies on animal models as there are few noninvasive methods and few replicated peripheral biomarkers for use in humans. One area of active research in psychiatric neuroscience is the field of epigenetics – how the chemical modifications of the genetic code regulate behavior. The dynamic changes in histone acetylation and deacetylation in the brain are not fully reflected by the study of peripheral biomarker. In this review, we aim to examine the role of histone acetylation and deacetylation in memory formation and fear memory learning. The studies discussed here focus largely on the role of histone deacetylases (HDACs) in animal models of trauma and fear response. Many studies used HDAC inhibitors to elucidate the effects after inhibition of these enzymes after trauma or stress. These studies of memory processing and cued fear extinction in animal can often shed light on human disorders of cued fear responses and memory dysregulation after stress or trauma such as in PTSD. These results provide strong evidence for a role of these enzymes in PTSD in humans. The few clinical studies that exist with HDAC inhibitors also suggest a fundamental role of these enzymes in the neurobiology of the stress response. Further study of these enzymes in both clinical and pre-clinical settings may help elucidate the neurobiology of stress-related pathology like PTSD and provide a foundation for novel therapy to treat these disorders.