Adverse childhood experiences in relation to mental health outcomes: a systematic review and meta-analysis of dose response and population attributable risk
Creators: name: Sison, Erica J.
Publisher: name: No Publisher Supplied
Year: 2025

description: Adverse childhood experiences (ACEs) are common in the United States population1-3. The relationships between ACEs and various health outcomes in adolescence and adulthood are well documented2-5. ACEs are linked to the five leading causes of death in the United States including coronary heart disease, respiratory diseases, diabetes, and suicide 2,3,6. ACEs are not only linked to chronic disease but also increase the risk of socioeconomic challenges and health conditions such as depression, anxiety, and drug or alcohol abuse 2,3,7. In the last decade or so, deeming ACEs a public health issue is widely acknowledged and has reached national attention2,8,99. This growing acknowledgement aligns with the increasing recognition of mental health as a critical component of public health, given the significant contribution of mental and behavioral disorders to the global burden of disease10,11. Further exploration of the relationship between ACEs and mental health is warranted. Several studies have shown that the risk of adverse outcomes, such as depression and suicidality, increases with the cumulative number of ACEs to which one is exposed 2,7. However, the assumption that ACE related outcomes are attributable primarily to those with highest exposure of ACEs may or may not be accurate. The Prevention (Rose) Paradox states “A large number of people exposed to a low risk is likely to produce more cases than a small number of people exposed to a high risk.”12 Population attributable risk (PAR) can determine the proportion of cases of an outcome that potentially could be reduced if the exposure were prevented. Research on PAR of ACEs within US population remains limited. Notable contributions include studies by Merrick et al3 and Dube et al13 that estimated the population of adult health problems, including depression and attempted suicide, attributed to ACES across multiple states. Swedo et al14 also explored PARS of ACES for specific outcomes including mental health among US adolescents. Bellis et al1 was the first to conduct a meta-analysis on PAR on ACEs and health outcomes however examined a broader North America population that extends beyond the US. No studies have explicitly applied the Prevention paradox in examining the relationship between ACEs and health outcomes.This dissertation includes a systematic review and meta-analysis of observational studies that explore the relationship between ACEs and mental health outcomes and a discussion of risk management. The first aim of the dissertation was to summarize the dose-response relationship of ACEs and two mental health outcomes. The health outcomes examined include depression in adulthood, and lifetime suicidality. The second aim assessed the distribution of mental health outcomes associated with ACEs to identify the extent to which the Prevention paradox applies in the relationship between ACEs and negative mental health outcomes. The third aim evaluated the findings from aim 1 and aim 2 to explore the public health implications of Prevention paradox for development of targeted policy interventions and preventive strategies aimed at reducing ACEs and mitigate their impact on mental health outcomes. The results demonstrate a strong, graded association between ACE exposure and increased risks of adult depression and lifetime suicidality. Individuals with any exposure to ACEs bear a significant burden of adult depression and suicidality. For depression, those with at least one ACE is attributable to 29% of cases. Similarly, ACE exposure is strongly associated with lifetime suicidality, with nearly 70% of cases attributable to individuals with one or more ACEs. The findings provide evidence for the Prevention paradox in adult depression, where lower and moderate ACE levels collectively contribute more to the population burden than high ACE exposure alone. Although this pattern was not observed for suicidality, the cumulative impact of lower and moderate ACE levels remains substantial, reinforcing the importance of a balanced approach that combines population-based strategies for preventing ACEs with targeted interventions to mitigate their negative effects on mental health.