Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics

Trauma can contribute to lasting psychological, behavioral, and physiological effects that extend across generations. Intergenerational trauma refers to trauma-related effects observed in children of exposed parents, while transgenerational trauma describes effects observed in later generations without direct exposure. Proposed mechanisms involve interacting biological and psychosocial processes, including stress-responsive regulatory systems, epigenetic variation, and caregiving environments. This review synthesizes evidence on epigenetic changes associated with acute, chronic, and complex traumatic exposures and their relevance to multi-generational outcomes. Studies published between 1990 and 2025 were identified through PubMed and Google Scholar and evaluated for reported epigenetic findings, caregiving patterns, and offspring health outcomes. Across trauma contexts, reported epigenetic variation most consistently involves pathways related to stress-response regulation, immune-inflammatory signaling, neurodevelopment, metabolic processes, and developmental programming. Patterns across exposure types suggest that acute events are most often associated with stress-related and inflammatory signaling that may influence developmental programming, whereas chronic and complex trauma reflect cumulative physiological adaptation involving broader alterations in stress-regulatory, metabolic, and neurodevelopmental systems. Offspring outcomes most consistently include increased vulnerability to anxiety, depressive symptoms, stress-related disorders, and certain chronic medical conditions, often described alongside shifts in caregiving behaviors and psychosocial environments that may shape developmental vulnerability. Interpretation of the current literature is limited by small sample sizes, varying definitions of trauma, and limited multi-generational cohorts. Overall, current evidence supports a model in which trauma-related outcomes across generations reflect interacting biological and caregiving processes, highlighting the importance of integrated molecular and psychosocial frameworks for prevention and intervention.