Using Translational Models of Fear Conditioning to Uncover Sex-Linked Factors Related to PTSD Risk

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder that follows exposure to a traumatic event; however, not every person who experiences trauma will develop PTSD. Women are more likely to be diagnosed with PTSD than men even when controlling for type and amount of trauma exposure. Circulating levels of gonadal hormones such as estradiol, progesterone, and testosterone may contribute to differential risk for developing PTSD. In this review, we briefly consider the influence of gonadal hormones on fear conditioning processes including fear acquisition, fear inhibition, extinction learning, and extinction recall within translational neuroscience models. We discuss findings from human studies incorporating samples from both community and traumatized clinical populations to further understand how these hormones might interact with exposure to trauma. Additionally, we propose that special attention should be paid to the specific measure used to examine fear conditioning processes as there is evidence that common psychophysiological indices such as skin conductance response and fear-potentiated startle can reveal quite different results and thus necessitate nuanced interpretations. Continued research to understand the influence of gonadal hormones in fear learning and extinction processes will provide further insight into the increased risk women have of developing PTSD and provide new targets for the treatment and prevention of this disorder.

Keywords: PTSD; extinction; fear conditioning; fear learning; fear-potentiated startle; gonadal hormones; sex differences; skin conductance response.

Figure 1.

Typical estrogen and progesterone fluctuations across the 28-day human menstrual cycle. The solid line represents estrogen levels, which peak at ovulation and remain relatively elevated during the luteal phase. The dashed line represents progesterone level, which peaks after ovulation and is high during the luteal phase (adapted from [16] copyright © CMAJ Group).