Objective:There is little longitudinal research investigating links between violence exposure and mental disorders among children in low- and middle-income countries (LMICs), despite high rates of violence. We examined cross-sectional and longitudinal violence-mental health associations among children in a large South African birth cohort, the Drakenstein Child Health Study, including direct clinical interviews capturing children's mental disorders. Method:In this birth cohort (N=974), we assessed lifetime violence exposure and four subtypes (witnessed community, community victimization, witnessed domestic, domestic victimization) at ages 4.5 and 8-years via caregiver reports. At 8-years, caregivers completed the Child Behaviour Checklist; and psychiatric disorders were assessed using the Mini-International Neuropsychiatric Interview for Children and Adolescents, a self-report measure. We tested for associations using linear/logistic regressions, adjusted for confounders. Results:Most children (91%) had experienced violence by 8-years. Cross-sectionally, total violence exposure was associated with total (B =0.49 [95% CI 0.32, 0.66]), internalizing (0.32 [0.17, 0.47]), and externalizing problems (0.46 [0.31, 0.61]), and with increased odds of disorder at 8 years (aOR=1.09 [1.05, 1.13]). Longitudinally, total violence exposure up to 4.5-years was associated with total (B=0.27 [0.03, 0.52]), internalizing (0.24 [0.04. 0.44]), and externalizing scores (0.23 [0.008, 0.45]) at 8-years, but not with increased risk of psychiatric disorders. The strongest and most consistent associations were observed for domestic versus community violence subtypes. Conclusion:Our strong cross-sectional but weaker longitudinal findings suggest that recent violence exposures may be more critical than early exposures for children's mental health. Longitudinal exploration of other violence-affected LMIC populations is urgently needed.

Maternal antenatal psychological distress can negatively affect child development, particularly in low- and middle-income countries (LMICs) where women are at heightened risk for distress. This study examined the association between maternal antenatal distress and child amygdala-prefrontal cortex functional connectivity in a South African birth cohort using resting-state fMRI. Children aged 2-3 years who were either exposed to maternal distress in utero (n=27) or unexposed (n=85) were analyzed using region-of-interest analysis. Multivariate analysis of covariance assessed group differences, adjusting for confounders, and Pearson correlations examined associations with externalizing behaviors 6-18 months later across the whole sample (n=111). Exposed children showed weaker amygdala-medial PFC and amygdala-lateral PFC connectivity than unexposed peers (medial PFC: mean=0.099 vs 0.164, p=0.034; lateral PFC: mean=0.095 vs 0.132, p=0.025). These differences were significant in boys only (medial PFC: p=0.016; lateral PFC: p=0.019). Additionally, hippocampus-PFC connectivity at ages 2-3 was negatively associated with later externalizing behaviors. Findings suggest exposure to maternal psychological distress in utero impacts amygdala-PFC connectivity in early childhood, while exploratory associations between hippocampus-PFC and externalizing behavior point to potential links with later behavioral outcomes. Understanding these neural correlates may inform early interventions to disrupt intergenerational transmission of psychological risk.

Background:Depression is the most common mental health disorder worldwide and frequently leads to workplace absence. As face-to-face treatment can be difficult to access, app-based interventions are a popular solution, although their effectiveness in working populations and their mechanisms of action are unclear. Deficits in executive function may contribute to the onset and maintenance of depression, and executive function training is proposed to improve symptoms by enhancing executive function. Responders to cognitive behavioral therapy (CBT) show improvements in executive function, suggesting that this may be one mechanism of action. Objective:This study investigated the effectiveness of app-based interventions (executive function or CBT-based) for reducing depressive and anxiety symptoms and improving workplace well-being, and assessed whether changes in executive function mediated improvements. Methods:A total of 228 participants (147 female participants) with mild-to-moderate symptoms of depression and anxiety were recruited online and randomly assigned to a waitlist control group, an executive function training group (NeuroNation app, Synaptikon GmbH), or a self-guided CBT group (Moodfit app, Roble Ridge LLC) for a 4-week intervention period. Participants assigned to the active intervention groups were asked to use their apps a minimum of 21 times during the intervention. Participants completed measures of depressive symptoms, anxiety symptoms, and workplace well-being, and a working memory task at baseline, postintervention, and follow-up (12 weeks). Results:Executive function training reduced anxiety (β=-2.79; P=.004) and depressive (β=-2.77; P=.02) symptoms at follow-up but not at postintervention, and it did not affect workplace well-being. There were no reductions in depressive or anxiety symptoms in the self-guided CBT group, though workplace well-being was improved at postintervention (β=3.72; P=.02) and follow-up (β=4.46; P=.02). Improvements in executive function did not mediate intervention-related changes in symptoms or workplace well-being. Self-reported adherence rates were high (executive function training: 48/54, 89%; self-guided CBT: 52/54, 96%), although attrition was high at follow-up (58% missing). Conclusions:These results suggest that app-based executive function training may be effective at managing symptoms of anxiety and depression in a working population, while self-guided CBT apps may improve workplace well-being. However, improving executive function did not appear to be a mechanism of action of either intervention.

OBJECTIVE:Although conduct problems (CPs) are continuously distributed, little is known about how dimensional measures of CPs map onto brain structure. Therefore a large sample was used to comprehensively assess associations between dimensionally measured CPs and brain structure. METHOD:T1-weighted structural brain magnetic resonance imaging scans from 14,160 youths (5-21 years old, 46.2% female) across 18 international case-control, community-based, and population-based cohorts were preprocessed using ENIGMA-standardized protocols. Regression models examined associations between CPs and cortical thickness, surface area, and subcortical volumes, adjusting for age, sex, and intracranial volume. Moderation by sex, age, and callous-unemotional traits was also investigated. RESULTS:Widespread but small (β = -0.02 to -0.07) negative associations were observed between CPs and surface area (total surface area, 23/34 regions), cortical thickness (average thickness, 15/34 regions), and amygdalar and hippocampal volumes. Sex was a key moderator, with many surface area associations limited to boys and some thickness associations limited to girls. Some associations were stronger in younger children and at lower levels of callous-unemotional traits. The impact of adjusting for IQ and other psychopathology varied by outcome (eg, most surface area findings survived IQ adjustment, whereas cortical thickness associations did not). CONCLUSION:CPs were associated with subtle, yet widespread, alterations in brain structure. Findings overlapped with differences observed in categorically measured conduct disorder, but novel associations with cortical thickness were identified. This provides further evidence that neuroanatomical differences are not limited to youth with clinically elevated CPs. Our findings have potential implications for neurocognitive models of CPs as they extend beyond the regions highlighted in these models. STUDY REGISTRATION INFORMATION:Investigating dimensional relationships between conduct problems and brain structure: an ENIGMA mega-analysis; https://osf.io/nzj3r/.

Conduct disorder (CD) is the leading global cause of mental health burden in children and adolescents and has recently been hypothesized to be a neurodevelopmental disorder. Although prior research has identified neuroanatomical differences associated with CD, it remains unclear whether these differences reflect atypical brain development. Here, we investigated the difference between an individual's brain age and chronological age as a proxy for variations in brain maturation. Using a pretrained model, we estimated brain age from structural neuroimaging data obtained from 1,119 youth with CD and 1,183 typically developing controls across 14 international cohorts participating in the ENIGMA-Antisocial Behavior Working Group. Youth with CD exhibited a statistically robust but small acceleration in brain age compared to typically developing youth (around 0.50 years), which was restricted to the adolescence-onset subtype of the disorder. Our large-scale, coordinated analysis provides the first evidence of accelerated neurodevelopment as a potential mechanism underlying CD.

BACKGROUND: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared with typically developing control participants (TDCs). METHODS: A total of 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate a), we investigated group differences for the 3 learning conditions in whole-brain and region of interest (ROI) analyses, including the ventral striatum and insula. RESULTS: Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in participants with CD compared with TDCs. CONCLUSIONS: Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD that contributes to punishment insensitivity/hyposensitivity as a hallmark of the disorder. Because the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.

BACKGROUND:Strength-based approaches are increasingly common in neurodevelopmental research, but the positive characteristics that may be features of attention-deficit/hyperactivity disorder (ADHD) remain underexplored. The extent to which people with ADHD recognize and use their personal strengths, and whether these play a role in their life outcomes, is also unknown. Tackling these gaps in the literature, we conducted the first study of self-reported strengths, strengths knowledge, and strengths use in ADHD. METHODS:Adults with (n = 200) and without (n = 200) ADHD were recruited online and rated their endorsement of 25 putative ADHD-related strengths. Participants also completed self-report measures assessing strengths knowledge, strengths use, subjective wellbeing, quality of life, and mental health. Using both Frequentist and Bayesian methods, we compared the groups and explored the associations of strengths knowledge and use with outcomes across both groups. RESULTS:The ADHD group endorsed 10 strengths more strongly than the non-ADHD group, including hyperfocus, humor, and creativity, but reported similar endorsement for 14 of the strengths. Adults with and without ADHD did not differ on their strengths knowledge and use but, in both groups, increased strengths knowledge and, to some extent, greater strengths use were associated with better wellbeing, improved quality of life, and fewer mental health symptoms. CONCLUSIONS:We conclude that, while adults with and without ADHD may have both similarities and differences in strengths, interventions that focus on enhancing people's strength knowledge and promoting the everyday use of their personal strengths could have universal applications to improve wellbeing in adulthood.

BACKGROUND:Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits. METHODS:Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions. RESULTS:When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females < TD females; CD/LCU males > TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males). CONCLUSIONS:The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.

Background: A large body of evidence links stressful life events with depression. However, little is understood about the role of perceived impact in this association. Methods: We performed regression analysis to investigate whether self-reported stress reactivity (derived by regressing the impact-weighted life event score on the unweighted score) moderated the association between stressful life events and depressive symptoms in adolescents from the Avon Longitudinal Study of Parents and Children cohort (n = 4791), controlling for age at outcome, sex, ethnicity, and maternal education. Depressive symptoms were assessed using the self-report Short Mood and Feelings Questionnaire (score range 0-26) at 16 years of age. Adolescents also reported on their exposure to 23 possible stressful life events since age 12 and their impact, which were used to define stress reactivity groups using a residual regression approach. Results: We identified a moderating effect of stress reactivity. Adolescents with high stress reactivity showed a stronger association between the number of stressful life events and depressive symptoms than adolescents with low (b = 0.32, 95 % CI = 0.13, 0.50, p < 0.001) or typical (b = 0.44, 95 % CI = 0.28, 0.60, p < 0.001) stress reactivity. Limitations: Limitations include the use of retrospective life event measures and limited generalisability of findings to other population-based, high-risk, or clinical samples. Conclusions: When resources are limited, interventions should prioritise individuals with high stress reactivity who have experienced multiple stressful life events, as these individuals may be at greater risk for depression.

Childhood maltreatment is a key risk factor for conduct disorder (CD), and the "ecophenotype hypothesis" suggests that maltreatment-related versus non-maltreatment-related CD are neurobiologically distinct. This may explain inconsistent findings in previous structural connectivity studies of CD. We tested this hypothesis by comparing youth with CD with (CD/+) versus without (CD/-) childhood physical or sexual abuse in white-matter microstructure. Diffusion tensor imaging data were collected from 100 CD and 169 control participants aged 9-18 years. Using Tract-Based Spatial Statistics, we compared the CD and control groups in fractional anisotropy, and axial, radial and mean diffusivity, then compared the CD/+ (n = 39) and CD/- (n = 61) subgroups and controls. The combined CD group had higher fractional anisotropy in the corpus callosum than controls. When divided by abuse history, only the CD/- subgroup exhibited higher corpus callosum fractional anisotropy than controls; the CD/+ subgroup did not differ from controls. Comparing the CD subgroups, the CD/+ subgroup displayed higher superior longitudinal fasciculus axial diffusivity than the CD/- subgroup. Notably, sex-stratified analyses yielded different findings in all-male and all-female samples. Findings support the ecophenotype hypothesis, demonstrating microstructural differences between the CD/+ and CD/- subgroups and emphasizing the importance of considering abuse/maltreatment (and sex) in future studies.

Facial emotion recognition (FER) biases refer to systematic tendencies to recognize specific emotions when processing facial expressions. In youths with conduct disorder (CD), who are characterized by highly impairing antisocial behavior, research on FER biases has focused on hostile attribution biases. This work has shown that youths with CD perceive ambiguous social cues as angry. However, youths with CD may not only show biases towards anger, which is why we investigated FER biases in youths with CD towards the six basic emotions. Within the European FemNAT-CD study, we analyzed data from 610 youths with CD (60% female) and 818 typically developing controls (TDCs; 68% female), aged 9 to 18 years (M = 14.1, SD = 2.41 years). FER biases were assessed using the Emotion Hexagon Task by showing morphed emotional expressions and asking participants to choose the predominant emotion. Biases were calculated as tendency towards an emotion shown at 0%, 10%, 30%, or 50% intensity. Our findings from hierarchical linear modelling indicate that youths with CD exhibited stronger FER biases than TDCs across all emotions, meaning that they misclassified each emotion more often. However, this difference varied by intensity, with youths with CD displaying weaker biases at higher intensity levels and a smaller increase in bias with increasing intensity level. Our findings indicate that youths with CD not only show a hostile attribution bias but rather misclassify emotions as predominant when they are present at low intensity, regardless of type of emotion.

Neuroimaging studies suggest that resilience to adversity is linked to reduced emotional reactivity or enhanced emotion regulation. However, such studies are scarce and mainly use adult samples and categorical definitions of resilience. Using a novel, data-driven approach to define resilience dimensionally, based on cumulative adversity exposure across childhood and psychopathology, we investigated associations between resilience and brain activation during facial emotion processing in youth. We also tested for sex differences in the relationship between resilience and brain activation. fMRI data were acquired from 208 youths (aged 9–18 years; Mean age = 13.28), while viewing angry, fearful, and neutral faces. Whole-brain analyses were performed, followed by region-of-interest analyses focusing on the amygdala, hippocampus, and prefrontal cortex. Resilience was positively correlated with bilateral inferior frontal gyrus responses to fearful (versus neutral) faces, and negatively correlated with right superior temporal gyrus, left hippocampal, and right inferior frontal gyrus responses to neutral faces (versus fixation). Sex-by-resilience interactions were observed in the medial prefrontal cortex: males showed positive, while females showed negative, associations between resilience and brain activation, though these results did not survive correction for multiple comparisons. These findings provide further evidence that resilience in youth is associated with enhanced emotion regulation at a neural level.

Childhood maltreatment has been associated with multimorbidity of depression, coronary artery disease and type 2 diabetes. However, the biological mechanisms underlying this association remain unclear. We employed two-step and multivariable Mendelian randomisation (MR) to understand the role of three potential biological mediating mechanisms - inflammation (92 proteins), metabolic processes (54 markers), and cortisol - in the link between childhood maltreatment liability and multimorbidity. Using summary statistics from large-scale genome-wide association studies of European ancestry for childhood maltreatment (N = 185,414) and multimorbidity (Neffective = 156,717), we tested for the presence of an indirect effect via each mediator individually. We found a potential role of metabolic pathways. Up to 11% of the effect of childhood maltreatment on multimorbidity was mediated by triglycerides (indirect effect [95% CI]: 0.018 [0.009-0.027]), 8% by glycated haemoglobin (indirect effect: 0.013 [0.003-0.023]), and up to 7% by high-density lipoprotein cholesterol (indirect effect: 0.011 [0.005-0.017]). We did not find evidence for mediation via any inflammatory protein or cortisol. Our findings shed light on the biological mechanisms linking childhood maltreatment liability to multimorbidity, highlighting the role of metabolic pathways. Future studies may explore underlying pathways via non-biological mediators (e.g., lifestyle factors) or via multiple mediators simultaneously.

The adverse impacts of psychological stress during pregnancy are well established, with negative outcomes reported for both mothers and children. Intimate partner violence (IPV) represents a significant stressor, with high prevalence in low- and middle-income countries (LMICs). In a high-adversity South African birth cohort, the Drakenstein Child Health Study (DCHS), we prospectively investigated whether maternal exposure to IPV during pregnancy and in the first 2 years was associated with child brain structure at age 2-3 years. Structural magnetic resonance imaging (sMRI) data was analysed from 171 children (n=70 exposed to prenatal IPV; n=55 to postnatal IPV). Regression modelling explored associations between IPV exposures and measures of brain structure derived using FreeSurfer. Voxel- and surface-based morphometry were conducted using Statistical Parametric Mapping to explore differences in cortical architecture. Analyses adjusted for sociodemographic and clinical confounding variables. Both prenatal and postnatal IPV exposure were associated with increased mean cortical thickness (β=0.037, p=0.030, 95% CI [0.004, 0.070], and β=0.041, p=0.023, 95% CI [0.006, 0.074], respectively), when compared to unexposed controls. Exploratory analyses identified a prenatal IPV-by-child sex interaction in right medial orbitofrontal cortex thickness (p=0.025, FWE-corrected); with greater thickness in boys (β= 0.14, p=0.008, 95% CI [0.04 to 0.24]), but not girls (β=-0.04, p=0.44, 95% CI [-0.15 to 0.07]).Early exposure to IPV may impact cortical structure in childhood, with potential sex-specific effects. These results emphasise the importance of addressing IPV as a public health priority to mitigate long-term impacts on child brain development.

Whilst childhood adversities have been shown to be risk factors for mental, physical, and comorbid health problems in childhood and middle-to-late adulthood, there is less evidence for these associations in early adulthood. It is also unclear if lifestyle factors can modify the risk of these health outcomes following childhood adversities. This study aims to examine childhood adversities as risk factors for psychological distress, obesity, and their comorbidity, and further quantify the moderating impact of lifestyle factors. This could provide insight into potential protective influences against the detrimental health consequences of childhood adversities, particularly mental-physical comorbidity. Analyses were conducted on data from the 1970 British Cohort Study (n = 16,407). The cumulative impact of parent- and self-reported adversities (range: 0–33) were consolidated across childhood (0–16 years) and examined as a predictor of psychological distress (Malaise Inventory ≥ 8), obesity (BMI ≥ 30 kg/m2) and their comorbidity in early adulthood (30 years) using multinomial logistic regression. Self-reported lifestyle factors in adolescence (16 years), including physical activity, diet, sleep duration, smoking, and alcohol consumption were assessed as moderators of the association between childhood adversities and the specified outcome categories. A one-item increase on the childhood adversities scale elevated the risk of psychological distress (OR [95

Background The mental health consequences of exposure to childhood trauma have been little studied among adolescents in low-income and-middle-income countries (LMICs), despite a relatively high burden of trauma in LMIC populations. We investigated associations between trauma and adolescent psychiatric disorders in the 2004 Pelotas Birth Cohort, Brazil. Methods In the 2004 Pelotas Birth Cohort, current psychiatric diagnoses (anxiety, mood, attention-hyperactivity, and conduct-oppositional disorders) were assessed at age 15 years (caregiver-report Development and Well-being Assessment), and age 18 years (self-report Mini-International Neuropsychiatric Interview). Lifetime cumulative trauma was assessed via caregiver report up to age 11 years and combined self-report and caregiver-report thereafter. Exposure to 12 trauma types were assessed (serious accident, fire, other disaster, attack or threat, physical abuse, sexual abuse, witnessed domestic violence, witnessed attack, witnessed accident, heard about attack, heard about accident, and parental death). Due to the high prevalence of trauma exposure in the sample, the number of different types of trauma exposure reported was extracted as a proxy for cumulative trauma load. We assessed both crosssectional and longitudinal associations between cumulative trauma load and psychiatric disorders during adolescence using logistic regression, adjusting for confounders and pre-existing child psychopathology at 48 months. We also computed population attributable fractions (PAFs) for trauma-mental health associations at age 18 years. Findings 4229 adolescents (519% male, 481% female) were included in logistic regression analyses based on imputed data. Trauma exposure affected 812% of adolescents by age 18 years. At age 15 years, the odds of any disorder (adjusted odds ratio [aOR] 119 [95% CI 103-138]), anxiety disorders (145 [121-175]), and conduct- oppositional disorders (160 [113-227]) increased for each category increase in cumulative trauma, but mood and attention-hyperactivity disorders were not related to cumulative trauma. At age 18 years, the odds of any disorder (134 [124-144]), anxiety disorders (123 [113-134]), mood disorders (133 [122-146]), attention-hyperactivity disorders (124 [109-141]), and conduct-oppositional disorders (159 [136-186]) all increased for each category increase in cumulative trauma. In longitudinal analyses, each category increase in cumulative trauma by age 11 years was associated with an increased odds of any disorder (aOR 126 [95% CI 111-144]), anxiety disorders (127 [104-156]), and conduct-oppositional disorders (143 [104-197]) at 15 years; and trauma up to age 15 years was associated with increased odds of any disorder (132 [121-145]), anxiety disorders (127 [114-140]), mood disorders (126 [112-141]), and conduct-oppositional disorders (152 [124-187]) at age 18 years. Trauma up to age 11 years was not predictive of disorders at age 18 years, and there were no longitudinal associations between trauma and attention-hyperactivity disorders. PAF estimates indicated that trauma exposure accounted for 306% (95% CI 212-387) of psychiatric disorders at age 18 years. Interpretation Increasing exposure to trauma is associated with mental disorders among Brazilian adolescents. Given the high prevalence of trauma in LMIC populations, strategies to reduce exposure, identify those at greatest risk of mental disorders following trauma, and mitigate the consequences are crucial. Funding Wellcome Trust, WHO, National Support Program for Centers of Excellence, Brazilian National Research Council, Brazilian Ministry of Health, Children's Pastorate, S & atilde;o Paulo Research Foundation, Rio Grande do Sul Research Foundation, L'Or & eacute;al-Unesco-ABC Program for Women in Science in Brazil-2020, All for Health Institute, University of Bath, Economic and Social Sciences Research Council.Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.