From juvenile stress to adult depressive-like behavior: A systematic review of biomarkers, developmental timing, and sex differences

Abstract

Early adversity during the peripubertal period is a well-established risk factor for the emergence of adult psychopathology, particularly depression. Notably, depression arising from early stress often presents with greater symptomatic complexity and reduced responsiveness to conventional treatments, underscoring the need to identify biomarkers that can predict long-term vulnerability. Despite this, a major research gap persists regarding the effects of juvenile stress in females, even though clinical evidence indicates that women show heightened susceptibility to stress-related depression. To address these issues, we conducted a systematic review of the literature examining the behavioral and biological consequences of juvenile stress and the biomarkers associated with depression-like outcomes in adulthood. Across studies, juvenile stress rarely left brain or behavior unaffected; instead, it biased developmental trajectories toward a range of maladaptive outcomes, with depression being common but not exclusive. The resulting phenotype was strongly shaped by sex, developmental timing, stressor type and duration, and genetic background. Among biological markers, only two domains showed partial convergence. Functional changes, which were consistently linked to anxiety-related behaviors, and neuroplasticity impairments, which were associated with classical depressive-like outcomes. Overall, biomarker profiles were highly context-dependent, supporting the notion that juvenile stress gives rise to multiple neurobiological pathways rather than a single depressive mechanism. A deeper understanding of these divergent trajectories may improve preventive strategies and guide more personalized therapeutic interventions for depression rooted in early-life stress.