Sex-Related Predisposition to Post-Traumatic Stress Disorder Development-The Role of Neuropeptides

Post-traumatic stress disorder (PTSD) is characterized by re-experiencing a traumatic event, avoidance, negative alterations in cognitions and mood, hyperarousal, and severe functional impairment. Women have a two times higher risk of developing PTSD than men. The neurobiological basis for the sex-specific predisposition to PTSD might be related to differences in the functions of stress-responsive systems due to the interaction between gonadal hormones and stress peptides such as corticotropin-releasing factor (CRF), orexin, oxytocin, and neuropeptide Y. Additionally, in phases where estrogens levels are low, the risk of developing or exacerbating PTSD is higher. Most studies have revealed several essential sex differences in CRF function. They include genetic factors, e.g., the CRF promoter contains estrogen response elements. Importantly, sex-related differences are responsible for different predispositions to PTSD and diverse treatment responses. Fear extinction (the process responsible for the effectiveness of behavioral therapy for PTSD) in women during periods of high endogenous estradiol levels (the primary form of estrogens) is reportedly more effective than in periods of low endogenous estradiol. In this review, we present the roles of selected neuropeptides in the sex-related predisposition to PTSD development.

Automated summary

Post-traumatic stress disorder (PTSD) is a condition that involves repeated experiences of traumatic events, avoidance, negative changes in cognition and mood, hyperarousal, and severe impairment in functioning. Women are twice as likely as men to develop PTSD, and this sex-specific predisposition may be related to differences in the functioning of stress-responsive systems influenced by gonadal hormones and stress peptides. Estrogen levels play a role in the risk of developing or exacerbating PTSD, and there are genetic factors, such as estrogen response elements, that contribute to sex differences in corticotropin-releasing factor (CRF) function. It has been found that fear extinction, which is important for the effectiveness of behavioral therapy for PTSD, is more effective in women during periods of high estrogen levels.