Adolescents and young adults in residential youth care (RYC) face cumulated adversity and high emotional and behavioral problems yet face structural barriers that limit access to evidence-based mental health care. While digital tools promise scalability and flexibility, real-world implementation and effectiveness in vulnerable youth in institutional care remain understudied. This study aimed to evaluate the implementation and effectiveness of a newly developed web-based self-help or group-facilitated version of the START NOW intervention in a three-arm cluster-randomized control trial for youth in RYC in Switzerland. 164 adolescents and young adults (M = 16.6 years, SD = 1.5; 43.8

Childhood maltreatment (CM) increases the risk of lifelong mental illness, yet the underlying biochemical mechanisms remain unclear. Oxidative stress (OS), alongside inflammation, may contribute to this link. This study examined whether OS mediates the link between CM and mental health in a highly vulnerable group of formerly out-of-home placed young adults and explored associations between OS and inflammatory markers. Data were collected from 131 participants (31

Objectives:Adolescent mental distress has increased in recent decades. It is unclear whether this is associated with changes in health-risk behaviors. Methods:We analyzed five waves (2002-2018) of the repeated cross-sectional Swiss Health Behavior in School-aged Children study (ages 11-15; N = 30,122). Latent Profile Analyses identified health-risk behavior profiles in each wave using five indicators (physical inactivity, poor sleep, unhealthy diet, smoking, alcohol use). Associations with sociodemographic variables and mental distress (internalizing and somatic symptoms, life satisfaction) were tested using multinomial and linear regressions, including profile*sex interactions. Results:A consistent four-profile solution (low-risk; high alcohol use/slightly elevated substance use; moderate substance use; highest risk) fit best across waves. The low-risk profile was most prevalent and increased in later cohorts (2014-2018), while elevated-risk profiles declined. Older adolescents were more likely to belong to elevated-risk groups, which were associated with greater mental distress, especially in earlier cohorts. No significant sex interactions were found. Conclusion:Health-risk behavior profiles remained stable, but their associations with mental distress weakened over time. Prevention efforts should adapt to evolving adolescent contexts.

Childhood maltreatment (CM) has long-lasting effects on physical and mental health with CM type specific effects being reported. Epigenetic processes, like deoxyribonucleic acid methylation (DNAm), might mediate this link, and CM types might be linked to differential alterations in DNAm. While a study by Cecil et al. (2016) suggests that different forms of CM share common but also exhibit distinct epigenetic signatures, it is unclear whether these results are generalizable to other high-risk samples. The aim of this preregistered study was to replicate the study of Cecil and colleagues (2016) in a sample of N = 116 previously out-of-home placed young adults (32% women, age mean = 26.38, SD = 3.49). Participants completed the Childhood Trauma Questionnaire - Short Form (CTQ-SF), DNA was extracted from whole blood and DNAm was assayed using the Illumina Infinium MethylationEPIC BeadChip Microarray. Using state-of the-art processing pipelines, we failed to replicate the original finding of common and shared epigenetic signatures by CM type. When using a pipeline that was closely matched to the original study, we could replicate that DNAm of cg07032930 was linked to emotional neglect, but in the reverse direction as in the original report. Overall, replication rates per CM subtype were only modest. These findings highlight challenges in independently replicating reported epigenetic associations in high-risk samples and underscore the importance of replication attempts in the field of behavioral epigenetics. Further research is needed to clarify the robustness and specificity of DNAm signatures linked to distinct CM types.

BACKGROUND:Large-scale population-based studies of risk and protective factors for youth mental health rarely assess youths' first-hand experiences in their own words. This longitudinal study analyzed young people's self-reported most important life events and examined how the key topics changed from midadolescence to young adulthood and are associated with internalizing symptoms. METHODS:N = 1,442 participants from an urban, multiethnic cohort reported their most important life events at ages 15, 17, 20, and 24 in open-text segments. Themes in N = 5,670 descriptions were analyzed using topic modeling with the Python library BERTopic. RESULTS:Most reported events were positive in valence (83.1%), and were often 'normative', commonly occurring experiences spanning diverse life domains (education and career development, social relationships, leisure activities and successes, mental health and well-being, and other life transitions and independence). Event topics displayed systematic developmental shifts from midadolescence to adulthood. Higher internalizing symptoms were associated with a greater likelihood of reporting interpersonal and stressful events rather than positive or achievement-related ones. CONCLUSIONS:Longitudinal population-based research can draw on open-text data and employ NLP techniques to assess young people's lived experiences. The predominance of positive events and their associations with internalizing symptoms suggest that an increased focus on promoting beneficial experiences, next to reducing stressful events, may promote youth mental health.

Physical youth-to-parent aggression (PYPA) is among the most understudied forms of family aggression in the general population. This study examined the prevalence and developmental course of PYPA from adolescence into young adulthood and investigated childhood behavioral and interpersonal risk (e.g., ADHD symptoms, low self-control, harsh parenting) as well as protective factors (e.g., conflict coping, parental involvement). Data came from six assessments of the prospective-longitudinal Zurich Project on Social Development from Childhood to Adulthood (z-proso), including N = 1522 participants. Participants reported PYPA at ages 11, 13, 15, 17, 20, and 24. Risk and protective factors were measured at or before age 11. Generalized estimating equations were used to examine the developmental course of PYPA, and logistic regression analyses examined its risk and protective factors. One in three youth (32.5%) reported engaging in PYPA at least once. Prevalence followed a cubic trajectory: increasing from age 11 to 13, then declining at varying rates through age 24. ADHD symptoms (OR (95%CI) = 1.26 (1.10, 1.45)), harsh parenting (OR (95%CI) = 1.24 (1.08, 1.42)), and interparental disagreement (OR (95%CI) = 1.17 (1.01, 1.35)) were associated with higher odds of PYPA; whereas competent conflict coping (OR (95%CI) = 0.83 (0.72, 0.96)) and parental involvement (OR (95%CI) = 0.83 (0.72, 0.95)) were associated with lower odds after accounting for participants' aggressive tendencies during childhood. Reducing children's aggressive tendencies and exposure to aggression and conflict, while fostering competent coping skills and supportive family environments could decrease PYPA and the burden of family aggression.

Background: Childhood maltreatment (CM) is associated with an increased risk of mental disorders, with oxidative stress (OS) being proposed as a potential mediator. However, it remains unclear whether exposure to specific types of CM during distinct developmental periods is associated with altered OS levels.Objective: This study aimed to explore the association between CM type and timing and OS in young adulthood.Methods: We studied 116 adults (30.5% women; mean age = 26.3 years) with previous residential care placements. CM exposure was assessed with the Maltreatment and Abuse Chronology of Exposure (MACE-X) scale, capturing types (parental abuse, neglect, peer violence, sexual abuse), overall severity, multiplicity, and duration. OS was measured via blood-based biomarkers: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRed), and GPx/GRed ratio. Conditional random forest regressions and Spearman correlations were used to test effects of CM types and timing on OS.Results: Abuse and neglect during adolescence showed the highest variable importance (VI) for GRed. Abuse was associated with increased, and neglect with decreased GRed. Neglect at ages 8 and 12 showed the highest VI for GPx/GRed and were positively associated with the biomarker ratio. Furthermore, no significant associations were found between overall CM severity, multiplicity, or duration and any of the OS biomarkers examined.Conclusion: Type- and timing-specific characteristics may be important when examining associations between CM and OS in adulthood. More research is needed to test whether such associations can inform preventive strategies that aim to mitigate mental health impairments following CM.

Abstract Trust in others plays an important role in psychological development. However, longitudinal and developmentally informed research on trust remains limited and fragmented across disciplines. This study aimed to investigate the developmental course of generalized trust from adolescence into young adulthood, and to test sociodemographic, family-level, and peer victimization-related antecedents of trust in an urban cohort. Generalized trust was self-reported at age 13, 15, 17, 20, and 24 in the Zurich Project on Social Development from Childhood to Adulthood (z-proso; n = 1,481). Mean-level and rank-order stability of trust were described. Growth trajectories were modeled using longitudinal linear mixed models (LMMs). Sociodemographic and childhood family-level factors, and longitudinal peer victimization were tested as predictors of trust. Mean-levels of trust followed a curvilinear trajectory characterized by an early decline from age 13 to 17 (Cohen’s d = -.48) and a slight increase from age 17 to 24 (d = .11). Rank-order stability of trust increased throughout adolescence (Spearman’s r = .40 to 0.58). Notably, socioeconomic disadvantage and migration background were each associated with widening trust disparities over time. Individuals from more disadvantaged backgrounds showed lower and more slowly recovering trust trajectories compared to their more advantaged peers. Maternal trust and parental involvement were associated with higher trust, whereas aversive parenting and parental divorce or separation were linked with lower trust. Peer victimization was associated with lower trust, while increases in peer victimization showed the strongest associations with trust at ages 17 and 20. Generalized trust is a malleable yet increasingly stable construct from adolescence into adulthood. Childhood and adolescent risk and protective factors are important contributors to trust development and should be considered when designing developmentally informed policies and interventions.

BACKGROUND:Adults formerly placed out-of-home (care leavers) often accumulate multiple psychosocial adversities that can lead to poor quality of life (QoL) and place them at high risk for developing mental disorders persisting into adulthood. This study examines the development of mental disorders among care leavers and their QoL, differentiating by disorder groups. METHODS:The sample consisted of 119 young adults formerly placed out-of-home (Mage at baseline = 15.0 years; Mage at follow-up = 25.4 years). Mental disorders were assessed at baseline using the Kiddie Schedule for Affective Disorder and Schizophrenia-Present and Lifetime Version and at a 10-year follow-up with the Structured Clinical Interview for DSM-5 Disorders-Clinician Version. Personality disorders were evaluated at both time points using the Structured Clinical Interview for DSM-IV-TR Axis II. QoL was measured at follow-up using the World Health Organization QoL-BREF questionnaire. RESULTS:Four groups based on the presence or absence of mental disorders at baseline and follow-up were identified: resilient (n = 24, 20.2%), persistent (n = 56, 47.0%), remitted (n = 25, 21.0%), and newly occurring (n = 14, 11.8%). Regarding the mental disorder groups, internalizing disorders at baseline (β = -0.44, p < .05, 95% CI [-0.85, -0.04]) and internalizing (β = -0.78, p < .001, 95% CI [-1.14, -0.43]) and externalizing disorders (β = -0.50, p < .01, 95% CI [-0.86, -0.13]) at follow-up were negatively associated with QoL in young adulthood. CONCLUSIONS:Mental disorder trajectories from childhood to young adulthood can negatively impact care leavers' QoL. Prevention and early intervention, as well as addressing mental health during out-of-home placement and transition into young adulthood, are important to reduce the risk of persistent psychopathology and lower QoL.

Background: Young people living in residential youth care (RYC) face heightened mental health risks due to complex life circumstances and histories of adversity. Strengthening resilience and emotion regulation in these settings is essential but challenging. The START NOW WebApp was developed to support adolescents and caregivers in building emotional and behavioral coping skills. This qualitative study aimed to examine the implementation of the START NOW WebApp in RYC and to identify barriers and facilitators to implementing this digital intervention in these settings. Methods: Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, semi-structured interviews were conducted with 27 professionals and managers from 18 RYC institutions across German-and French-speaking Switzerland. Interviews were transcribed verbatim and analyzed using MAXQDA using structured content analysis. A combined deductive-inductive coding process aligned emerging themes with RE-AIM categories to ensure conceptual coherence and contextual sensitivity. Results: Caregivers and institutional managers reported that the intervention might support adolescents' emotional awareness and behavioral regulation and may help establish a shared language around emotions and coping. Implementation success depended on caregiver motivation, digital literacy, and institutional commitment. Challenges included workload constraints, variable staff engagement, and integration into daily routines. Institutional adaptation, peer support, and managerial endorsement facilitated sustainable use across RE-AIM dimensions. Conclusions: Organizational readiness, flexible adaptation, and sustained caregiver engagement are central to embedding digital interventions in RYC. The findings provide actionable insights for designing, implementing, and maintaining digital interventions and underscore the need to embed these within institutional digitalization initiatives, strengthen staff digital literacy, and integrate digital tools into blended formats that complement interpersonal care rather than replace it.

BACKGROUND:Juveniles in residential care systems have high rates of suicidal ideation (SI). This study aims to expand knowledge of the prevalence and stability of SI, as well its associated factors among young adult care leavers. METHODS:Swiss juveniles in residential care (N = 179; non-Swiss origin: 12,29%; N = 22) were followed up into young adulthood (34% female/66% males; AgeBaseline (16.41, 2.86, 11-16); AgeFollow-Up (26.64, 3.22, 20-38 years)). SI was assessed at baseline and 10-year follow-up. Statistics included descriptives, proportion of enduring cases (categorical mean-level stability), tetrachoric correlation (Rtet; categorical rank-order stability), χ²- and Kruskal-Wallis tests (to test differences between SI pathways), and multinomial logistic regression analyses (RRR; to investigate risk and protective factors for SI pathways). RESULTS:SI prevalence was 45.25% (baseline) and 31.84% (follow-up). Females showed higher rates. SI appeared moderately stable (43.2%) with higher estimates in females. Participants with remitted and persistent SI experienced more NSSI, internalizing/ externalizing symptoms, lower self-directedness, and lower quality of life than those without SI. Higher self-directedness, cooperativeness and quality of life predicted a lower likelihood of persistent SI. CONCLUSIONS:Results suggest a higher risk and moderate stability of SI for young adult care leavers. Residential care practitioners should watch for risk factors, especially among females, and encourage self-directedness and cooperativeness.

ImportanceAssociations between child maltreatment (CM) and health have been studied broadly, but most studies focus on multiplicity (number of experienced subtypes of CM). Studies assessing multiple CM characteristics are scarce, partly due to methodological challenges, and were mostly conducted in patient samples.ObjectiveTo determine the importance of CM characteristics in association with physical multimorbidity in adulthood for women and men in a German representative sample.Design, Setting, and ParticipantsThis survey study used data from a representative sample of the German population between July and October 2021. Households were randomly selected within regional areas by a German demographic consultation company, and the Kish-Grid method was applied to ensure random participation. Reasons for nonparticipation were refusal of the selected household or target person to participate and failure to contact a household after 4 visits. Analyses took place between June 2023 and July 2024.ExposureCharacteristics of CM, including subtypes of CM, multiplicity, age at time of maltreatment (timing), number of years of experienced maltreatment (duration), frequency, and subjective severity (measured with the ISPCAN Child Abuse Screening Tools Retrospective version questionnaire).Main Outcomes and MeasuresThe main outcome was physical multimorbidity, defined as the sum score of lifetime leading morbidity and mortality causes in Western countries (obesity, diabetes, cancer, hypertension, myocardial infarction, chronic obstructive pulmonary disease, and incident stroke). Conditioned random forest regression analyses (a machine learning regression technique) were conducted to examine what characteristics of CM were most importantly associated with physical multimorbidity in adulthood while considering all other variables in the model.ResultsOf 5908 individuals invited, the study sample included 2514 participants (response rate, 42.6%), with 1297 (51.6%) women (mean [SD] age, 50.6 [17.9] years) and 1217 (48.4%) men (mean [SD] age, 49.5 [18.2] years). Duration of CM was the most important factor for physical multimorbidity in adulthood for both women (importance = 0.595; 95% CI, 0.599-0.601) and men (importance = 1.389; 95% CI, 1.386-1.394). Duration and timing variables were more importantly associated with outcomes than multiplicity in women and men. For women, severity and experiencing CM at age 4 years was significantly associated with physical multimorbidity in adulthood. For men, experiencing CM at age 11 years was most importantly associated with physical multimorbidity in adulthood.Conclusions and RelevanceIn this survey study, conditioned random forest regression analyses were applied to provide insights in the importance of duration and timing of CM for physical health in addition to the frequently studied multiplicity. These findings suggest that CM assessments should be considered in diagnostics of individuals with physical health conditions and may also inform strategies to mitigate the risk.

Theoretical background: Children and adolescents in out-of-home care report a wide range of adverse childhood experiences (ACEs) and potentially traumatic life events (PTEs) that significantly shape their life trajectories. However, there is a lack of research on this topic, particularly regarding young adults who were formerly placed in out-of-home care. Objective: This study investigates the prevalence, accumulation, co-occurrence, and sex differences of ACEs and PTEs among young adults who were formerly placed in out-of-home care. Method: We assessed a total of 211 young adults formerly placed in out-of-home care (M-age = 25.9, SD = 3.3; 31.8 % women) from a Swiss cohort study using the Maltreatment and Abuse Chronology of Exposure (MACE-X) Scale, which measures the extent of ACEs across ten types of maltreatment, and the Life Events Checklist-Revised (LEC-R), which captures direct exposure to or witnessing of PTEs. Results: The vast majority (87.3 %) reported having experienced at least one ACE, and a quarter (25.9 %) reported five or more. Additionally, 88.6 % reported at least one PTE, with over a fifth (22.8 %) reporting seven or more. Participants reported an average accumulation of 3.0 ACEs and 4.5 PTEs. The most frequently reported ACEs were emotional neglect (65.8 %), parental verbal abuse (32.0 %), and peer physical abuse (30.0 %). Witnessing or self-experiencing physical assault was the most common PTE (63.0 %), followed by transport accidents (50.2 %) and witnessing the death of a close person (39.3 %). Women reported significantly more cumulative ACEs than men (W = 2,287.50, p < .001), particularly higher rates of parental physical abuse, parental nonverbal emotional abuse, sexual abuse by parents/other adults/peers, physical neglect and peer emotional abuse. We found no significant sex differences in the sum of PTEs, although women reported significantly higher rates of physical maltreatment and sexual victimization in childhood as well as sexual victimization in adulthood, whereas men reported higher rates of being in a fire or explosion and in nontransport accidents. Different ACEs often co-occurred, with patterns showing system-overlapping exposure to violence within the family, outside the family, and in the peer context. For PTEs, we identified various patterns of childhood abuse, accidents, and various forms of physical assault. Discussion and conclusion: Young adults with a history of out-of-home care accumulate a wide range of ACEs and PTEs. This underlines the need for prevention and intervention efforts starting in childhood and continuing throughout the life course. Such efforts should consider sex differences and specific co-exposure patterns of ACEs and PTEs.

Childhood maltreatment (CM) increases the risk of psychopathology. Besides CM types and severity, the timing of exposure is an important modulating factor in this association, as childhood and adolescence comprise sensitive developmental periods for brain maturation and socio-emotional development. Nevertheless, previously reported associations between the severity of subtypes and timing of CM and psychopathology have been heterogeneous and have hardly considered vulnerable groups broadly exposed to CM, such as out-of-home-placed youth. Thus, we investigated the association between CM types and timing and psychopathology in a sample of formerly out-of-home placed young adults (N = 185; 32% women, age mean = 26.38, SD = 3.49 years). CM was assessed using the Maltreatment of Abuse Chronology of Exposure Scale and general, internalizing and, externalizing problems were assessed using the Achenbach System of Empirically Based Assessment. We employed conditional random forest regression to estimate the importance of CM types (abuse, neglect, peer victimization, and sexual abuse), timings (ages 3–18) as well as CM severity, multiplicity, and duration on adult general, internalizing, and externalizing problems. We validated the results using diagnoses of mental disorders assessed in clinical interviews, which were classified under general, internalizing, and externalizing clusters based on the Hierarchical Taxonomy of Psychopathology model. We found that CM severity and multiplicity were stronger predictors of internalizing problems than timing-specific effects of CM types. Abuse in early childhood and peer violence in late adolescence were stronger predictors of externalizing problems compared to global CM measures. Our findings highlight the importance of considering CM type and timing when testing CM-associated risks for psychopathology. This might further be valuable in therapeutic settings to guide maltreatment-informed interventions. Reducing violent caregiving environments in early childhood and preventing peer victimization in adolescence may be especially important in counteracting CM-associated risks of externalizing behaviors.

Adults with a history of residential out-of-home care (care leavers) often experience emotional and behavioral problems, which can negatively impact quality of life (QoL) into adulthood. Social support can improve mental health and reduce psychological symptoms. However, longitudinal studies examining how early emotional and behavioral problems are associated with the QoL of young adult care leavers are lacking. This study investigated the relationship between emotional and behavioral problems in adolescence and QoL in young adulthood, as well as the mediating and/or moderating role of social support. A total of 220 care leavers (Mage at baseline = 15.9 years, SD = 2.1; Mage at follow−up = 26.1 years, SD = 2.8, 32.9

Zusammenfassung: Fragestellung: Ehemalig fremdplatzierte junge Erwachsene (Care Leaver) waren in ihrer Kindheit einer Vielzahl psychosozialer Belastungsfaktoren ausgesetzt. Im deutschsprachigen Raum ist bisher wenig darüber bekannt, wie hoch die Prävalenz psychischer Störungen in dieser Population ist. Das Hauptziel dieses Beitrages ist es, die Prävalenzen psychischer Störungen bei Care Leavern zu beschreiben und Implikationen für Versorgungssysteme zu diskutieren. Methodik: Die psychischen Störungen, inklusive Persönlichkeitsstörungen, wurden anhand des Strukturierten Klinischen Interviews bei 175 Schweizer Care Leavern (Durchschnittsalter = 26.53 Jahre, 32.00 % Frauen) erfasst. Deskriptive Informationen wurden in absoluten und relativen Häufigkeiten präsentiert und Zusammenhänge wurden anhand t-Tests und χ 2 -Tests berechnet. Ergebnisse: 58.29 % der Teilnehmenden erfüllten die Diagnosekriterien für mindestens eine psychische Störung, wobei die Substanzkonsumstörungen (37.71 %), Persönlichkeitsstörungen (35.43 %) und die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (19.43 %) die häufigsten Diagnosen waren. Frauen zeigten häufiger Angststörungen sowie Cluster-C-Persönlichkeitsstörungen, während Männer häufiger eine Alkoholkonsumstörung aufwiesen. Schlussfolgerungen: Ungefähr die Hälfte der Schweizer Care Leaver erfüllt die Diagnosekriterien für mindestens eine psychische Störung. Das junge Erwachsenenalter stellt für Care Leaver – ähnlich wie für die Gleichaltrigen aus der Allgemeinbevölkerung – eine sensible Phase für psychische Störungen dar. Dies stellt sozialpädagogische und psychiatrische Versorgungssysteme vor die Herausforderung, das Angebot für psychisch belastete junge Menschen entlang der Transition ins Erwachsenenalter weiter präventiv zu gestalten.

Objective: Formerly out-of-home placed young adults (i. e., care leavers) were exposed to a variety of cumulative psychosocial stress factors during their childhood. However, the knowledge about the prevalence of mental disorders among care leavers in German-speaking countries is scarce. This article addresses the prevalence of mental disorders among care leavers and discusses the implications for care systems. Method: Mental disorders, including personality disorders, were assessed using structured clinical interviews among 175 Swiss care leavers (mean age = 26.53 years, 32.00 % women). Descriptive information was presented as absolute and relative frequencies, and correlations and group comparisons were calculated using t-tests and chi 2-tests. Results: 58.29 % of participants met the diagnostic criteria for at least one mental disorder, with substance use disorders (37.71 %), personality disorders (35.43 %), and attention-deficit/hyperactivity disorder (19.43 %) being the most common diagnoses. In comparison, women were more likely to have anxiety disorders and Cluster C personality disorders, while men were more likely to have alcohol use disorders. Conclusions: Our results indicate that approximately half of the Swiss care leavers meet the criteria for the diagnosis of at least one mental disorder in young adulthood. Young adulthood thus represents a sensitive phase for care leavers regarding mental disorders - similar to their peers in the general population. This poses a challenge for residential care institutions and psychiatric care systems to design and further expand preventive services for care leavers with high mental health burdens throughout the transition to adulthood.

Adverse childhood experiences (ACE) are common risk factors for many psychiatric disorders. Their underlying biological mechanisms may involve oxidative stress (OS), which has deleterious effects on cells through its own actions and through its interactions with inflammation and the stress axes, particularly in the brain. In order to assess the role of OS in the association between ACE and psychopathology, we performed a systematic review of animal and human research (PROSPERO CRD42023378418 and CRD42022378376), funded by the Swiss National Science Foundation (grant number 204033). PubMed, Web of Science, PsycInfo, Scopus and Embase were searched from inception until 31 October 2024. We included 130 studies involving animal models exposed to stressor-paradigms recognized as ACE analogs before they reached adulthood, or human participants with a history of ACE and assessment of psychopathology, and reporting outcomes on OS-related markers. Animal studies overall show increased OS and psychopathology after stress, thus supporting the hypothesis that OS mediates the relationship between ACE and psychopathology. Human studies are heterogeneous and less conclusive. Although the association between ACE exposure and OS, in animals and humans, was likely affected by the nature, the timing, and the intensity of the exposure, these parameters were only evaluated in a small fraction of studies. Similarly, though some studies hinted at sex differences in the OS response to ACE in animals, the majority of studies did not address this issue. Further research, using longitudinal designs and more thorough examination of ACE history in participants, is therefore needed.