Neuropsychopharmacology. 2025 Jun 25. doi: 10.1038/s41386-025-02158-4. Online ahead of print.
ABSTRACT
The early years of life are a critical period for brain development, encompassing high sensitivity to adverse experiences. Early life stress (ELS) is known to “scar” the brain and shape mental health trajectories later in life. Still, a great percentage of children faced with ELS develop adaptive competencies that maintain normal physiological and behavioral function across the lifespan, a process referred to as resilience. Work in humans and rodent models has demonstrated that resilience is an active process mediated largely by the induction of unique molecular, cellular, and circuit adaptations. In this review, we highlight evidence from rodent studies exploring the behavioral, circuit, cellular, and molecular effects of ELS and discuss resilient phenotypes that emerge from specific ELS paradigms. To this end, we focus on models comprising ELS exposure within pre-weening and adolescence. We next address critical factors that influence the effects of ELS, such as behavioral readouts, environmental conditions, or sex differences, and we compare these findings in light of human studies. Finally, we advocate for the use of novel and more sophisticated behavioral tasks for rodents that capture, at least in part, resilient phenotypes observed in humans and that can be directly linked to specific brain circuits.
PMID:40562842 | DOI:10.1038/s41386-025-02158-4
