Abstract
Stress is a fundamental adaptive response mediated by the amygdala and Hypothalamus-Pituitary-Adrenal (HPA) axis. Extreme or chronic stress, however, can result in a multitude of neuropsychiatric disorders, including anxiety, paranoia, bipolar disorder (BP), major depressive disorder (MDD), and Post-Traumatic Stress Disorder (PTSD). Despite widespread exposure to trauma (70.4%), the incidence of PTSD is relatively low (6.8%), suggesting that either individual susceptibility or adaptability driven by epigenetic and genetic mechanisms are likely at play. PTSD takes hold from exposure to traumatic events, such as death threats or severe abuse, with its severity being impacted by the magnitude of trauma, it's frequency, and the nature. This comprehensive review examines how traumatic experiences and epigenetic modifications in hypothalamic pituitary axis (HPA), such as DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling, are transmitted across generations, and impact genes like FKBP5, NR3C1, BDNF, and SLC6A4. It also provides a comprehensive overview on trauma reversal, resilience mechanisms, and pro-resilience factors such as HATs/HDACs ratio, DHEA/Cortisol ratio, testosterone levels, and neuropeptide Y, thus highlighting potential therapeutic approaches for trauma-related disorders. The studies highlighted here underscore the narrative, for the first time, that the examination and treatment of PTSD and other depressive disorders must invoke a multitude of approaches to seek out the most effective and personalized strategies. We also hope that the discussion emanating from this review will also inform government policies directed towards intergenerational trauma and PTSD.
Published Version
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