Sex differences in PTSD resilience and susceptibility: Challenges for animal models of fear learning

PTSD occurs in only a small fraction of trauma-exposed individuals, but risk is twice as high in women as in men. The neurobiological basis for this discrepancy is not known, but the identification of biological determinants of resilience and susceptibility in each sex could lead to more targeted preventions and treatments. Animal models are a useful tool for dissecting the circuits and mechanisms that underlie the brain's response to stress, but the vast majority of this work has been developed and conducted in males. The limited work that does incorporate female animals is often inconsistent across labs and does not broadly reflect human populations in terms of female susceptibility to PTSD-like behaviors. In this review, we suggest that interpreting male vs. female comparisons in these models be approached carefully, since common behavioral outcome measures may in fact reflect distinct neural processes. Moreover, since the factors that determine resilience and susceptibility are likely at least in part distinct in men and women, models that take a within-sex approach to response variability may be more useful in identifying critical mechanisms for manipulation.