Infant maltreatment is a major risk factor for the development of affective disorders. Using the Scarcity-Adversity Model (SAM), which limits nesting resources (PND 8–12), we previously showed that SAM-exposed dams display violent caregiving. In adulthood, male SAM offspring exhibit passive stress-coping and a blunted corticosterone response, while females show a more resilient phenotype. In this study, we explored the molecular underpinnings of these differences in the Prefrontal Cortex (PFC) and Amygdala (Amy). In male SAM adults, we observed a significant downregulation of Crh and Ppid, coupled with an upregulation of Nr3c1 in the PFC. Conversely, SAM females showed a specific increase in Bag1 expression, suggesting a potential compensatory mechanism. The most striking differences emerged in epigenetic regulators: male SAM rats showed decreased expression of Dnmt3a, Dnmt3b, and Tet1, while SAM females exhibited a coordinated upregulation of these three markers. Finally, functional connectivity analysis (c−Fos correlations) showed a strong negative correlation between the PFC and Amy in Control females that was lost in SAM females, potentially underlying the behavioral disinhibition observed in the Light-Dark Box. Together, our results suggest that infant maltreatment triggers divergent, sex-specific molecular programs, where females recruit epigenetic pathways that may confer resilience against early life adversity.
