Cumulative adverse childhood experiences and risk of mental disorders: A systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) are consistently linked to poor mental health across the lifespan. However, the cumulative impact of multiple ACEs and the extent to which methodological and population factors shape these associations remain insufficiently synthesized. METHODS: A systematic review and meta-analysis of 56 studies (40 in meta-analysis) was conducted following PRISMA 2020. Random-effects models estimated pooled odds ratios (ORs), dose-response patterns, and subgroup differences. Study quality, heterogeneity, publication bias, and sensitivity were rigorously assessed. RESULTS: Cumulative ACEs were strongly associated with increased risk of mental disorders (pooled OR = 3.18, 95% CI: 2.84-3.56). A clear dose-response gradient emerged: risk rose steadily from 1 ACE to 4+ ACEs. Methodological factors (study design, ACE tools, diagnostic approaches) and population characteristics (age, region, disorder type) significantly moderated associations. Findings were robust across sensitivity tests with minimal publication bias. CONCLUSION: ACEs exert a powerful, graded, and consistent influence on mental disorder risk. Strengthening prevention, trauma-informed care, and global equity in ACE research is essential.