Stress is a fundamental adaptive response that invokes amygdala and hypothalamus-pituitary-adrenal (HPA) axis along with other brain regions. Extreme or chronic stress, however, can result in a multitude of neuropsychiatric disorders, including anxiety, paranoia, bipolar disorder (BP), major depressive disorder (MDD), and posttraumatic 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, its 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, noncoding RNAs, and chromatin remodeling, are transmitted across generations, and impact genes such as FKBP prolyl isomerase 5 (