Abstract
It is currently unclear whether early life stress (ELS) affects males and females differently. However, a growing body of work has shown that sex moderates responses to stress and injury, with important insights into sex-specific mechanisms provided by work in rodents. Unfortunately, most of the ELS studies in rodents were conducted only in males, a bias that is particularly notable in translational work that has used human imaging. Here we examine the effects of unpredictable postnatal stress (UPS), a mouse model of complex ELS, using high resolution diffusion magnetic resonance imaging. We show that UPS induces several neuroanatomical alterations that were seen in both sexes and resemble those reported in humans. In contrast, exposure to UPS induced fronto-limbic hyper-connectivity in males, but either no change or hypoconnectivity in females. Moderated-mediation analysis found that these sex-specific changes are likely to alter contextual freezing behavior in males but not in females.
Highlights
Childhood maltreatment (CM) is a broad term used to define a heterogenous group of early adversities that range from severe bullying to physical, emotional, and/or sexual abuse (White and Kaffman, 2019a; Teicher and Samson, 2016)
Given that 30–40% of the adult population have experienced some form of CM (Agorastos et al, 2019), clarifying these issues is necessary in order to effectively diagnose and treat the enormous clinical and economic burden associated with CM (White and Kaffman, 2019a)
A main effect of rearing on body weight was consistently found at P14 (F (1, 106)=36.66, p
Summary
Childhood maltreatment (CM) is a broad term used to define a heterogenous group of early adversities that range from severe bullying to physical, emotional, and/or sexual abuse (White and Kaffman, 2019a; Teicher and Samson, 2016). Newer models have expanded this framework to highlight that different forms of CM fall along multiple dimensions, and this in turn more directly impacts later outcomes than number of CM instances per se (McLaughlin et al, 2014; McLaughlin and Sheridan, 2016). Neither of these models has addressed the potential role that sex plays in moderating CM-associated outcomes
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