Journal of Child Psychology and Psychiatry

BackgroundScreen use is pervasive in childhood and adolescence, yet its role in antisocial behaviour (ASB) remains uncertain. While cross-sectional studies consistently link higher screen use to elevated ASB, longitudinal evidence is mixed, and few studies have controlled adequately for prior behaviour and genetic liability. Thus, it remains unclear whether these associations reflect prospective influences of screen exposure, or underlying vulnerabilities shared with ASB. We investigated whether screen use is a modifiable risk factor or a marker of underlying vulnerability. MethodsWe analysed data from up to 41,562 children in the Norwegian Mother, Father, and Child Cohort Study (MoBa). ASB traits and ICD-10-based conduct disorder (CD) diagnoses were assessed at ages 5, 8 and 14 years, together with screen use (total exposure and modality). Cross-sectional logistic regression models examined associations between screen use and ASB traits/CD at each age, adjusting for sex and parental education. Polygenic risk scores for ASB (PRSASB) were used to assess genetic susceptibility and gene-environment interplay. Lagged logistic models tested whether screen use predicted later ASB, adjusting for prior ASB. Linear mixed-effects models examined developmental patterns across age. ResultsHigher screen use was positively associated with ASB traits and CD across all ages, with dose-response patterns across screen-use modalities. Social media showed the strongest modality-specific association at adolescence. In lagged models, screen use did not predict later ASB after adjustment for prior ASB. Longitudinal models showed significant but attenuating associations across development. PRSASB was independently and additively associated with ASB outcomes but did not interact with screen use. ConclusionsWe found that higher screen use was consistently associated with antisocial outcomes across childhood and adolescence. However, the absence of prospective associations after accounting for prior behaviour, together with independent genetic contributions, suggests that screen use may be better understood as a marker of underlying vulnerability rather than an independent driver of antisocial development.

Background: Adverse childhood experiences (ACEs) are traumatic or adverse events in early life that can have lasting effects on behavioral, emotional, and psychological functioning. Prior research suggests ACEs relate to later psychiatric outcomes through threshold, cumulative, and individual-specific risk patterns. Few studies, however, have operationalized all three models to test ACE-specific associations with diagnosed psychiatric disorders in individuals who are adopted or with foster care histories. Methods: We conducted a cross-sectional retrospective study using electronic health record data from foster care and adopted patients aged 0-21 years old seen at the University of Minnesota Adoption Medicine Clinic (UMN-AMC) between 2014-2024. Extracted measures included ACE history, demographics, and psychiatric diagnoses. We used latent class analysis and logistic regression to identify clusters of adversity and estimate associations with psychiatric diagnosis domains, adjusting for Sex and Age at Initial Visit. Results: ACEs showed a threshold pattern across psychiatric domains, with higher ACE counts associated with greater odds of psychiatric diagnoses. Individual risk modeling indicated that exposure to abuse or violence was associated with higher odds of psychiatric diagnoses. Across cumulative and individual risk approaches, Anxiety Disorders, Mood Disorders, and Behavioral or Emotional Disorders showed the greatest sensitivity to adversity. Conclusion: Current ACE models may not fully capture neurodevelopmental impacts reflected in diagnosed psychiatric disorders among adolescents, particularly in high-risk groups such as foster and adopted individuals. In a large clinic sample our findings support a nuanced association between ACEs and later psychiatric diagnoses and highlight the need for ACE-focused assessment, prevention, and treatment strategies tailored to foster care and adopted populations.

Objective: ADHD has been associated with obesity indicators, including BMI, across the lifespan. A possible mechanism linking ADHD and BMI is binge eating. Previous research has found associations between ADHD, binge eating and BMI. However, the role of genetic and environmental influences on these associations remains unclear. Method: We utilized data from the Twins Early Development Study (TEDS), comprising 3,675 monozygotic and 7,063 dizygotic twin pairs. ADHD symptoms in childhood and adolescence were assessed using parent-reported questionnaires. Adult ADHD symptoms were measured using both self-report and parent-report questionnaires. Phenotypic mediation models examined whether binge eating mediated the association between ADHD and BMI, without controlling for genetic confounding. Subsequently, the etiological architecture underlying the associations among the three traits across childhood, adolescence, and adulthood were investigated by incorporating genetic and environmental influences into the models. Results: Binge eating significantly mediated the association between ADHD symptoms and BMI in both adolescence and adulthood. However, these mediation effects were no longer present once genetic and environmental influences were incorporated into the models. The best-fitting model in childhood, adolescence and adulthood was Cholesky decomposition models, where covariance between traits was explained by shared aetiology. Conclusions: This twin study reveals shared liability across ADHD, binge eating, and BMI. The mediating role of binge eating in the relationship between ADHD symptoms and BMI was largely confounded by shared genetic influences. Intervention strategies could focus more on common underlying behavioural and self-regulatory mechanisms across these traits, as well as placing more emphasis on symptom patterns within families.

I ntroduction: Prospective memory (PM) deficits in children with attention-deficit/hyperactivity disorder (ADHD) significantly impact academic and daily functioning. Through two experiments, this study investigated how cognitive load and encoding strategies modulate PM performance. Methods: Experiment 1 included 43 children (21 ADHD, 22 typically developing) who completed an n-back task under high and low cognitive load. Experiment 2 included 44 children with ADHD who were randomly assigned to either a standard encoding group or an implementation intention encoding group, also completing the n-back task under both load conditions. Results: Experiment 1 showed that children with ADHD had significantly lower PM accuracy than typically developing peers. Signal detection analysis revealed that this deficit stemmed from a more conservative response bias rather than impaired perceptual sensitivity. Unexpectedly, PM accuracy and perceptual sensitivity were higher under high cognitive load than low load for both groups. Experiment 2 demonstrated that implementation intention encoding significantly enhanced PM accuracy and perceptual sensitivity in children with ADHD, with stable effects across load conditions and no interference with ongoing task performance. Discussion: These findings indicate that PM deficits in children with ADHD reflect a conservative response strategy rather than an inability to detect target cues. Implementation intention encoding provides an effective, load-independent cognitive strategy for enhancing PM performance. These results offer novel insights into the cognitive mechanisms underlying PM deficits in ADHD and provide evidence-based guidance for targeted interventions.

ImportancePrenatal exposure to gestational diabetes mellitus (GDM) has been associated with adverse metabolic, neurodevelopmental, and psychiatric outcomes in offspring. However, whether GDM-exposed youth exhibit heterogeneous neuroanatomical patterns remains unclear. ObjectiveTo identify distinct cortical thickness subtypes among GDM-exposed youth and examine their associations with anthropometric, neurocognitive, psychiatric/behavioral and neuroimaging measures both cross-sectionally and longitudinally. Design, Setting, and ParticipantsThis cohort study used the Adolescent Brain Cognitive Development (ABCD)(R)data, a multisite longitudinal population study. Subtype and Stage Inference (SuStaIn), an unsupervised machine learning framework, was applied to cross-sectional structural MRI data to identify cortical thickness patterns in 573 GDM-exposed youth and 2854 healthy controls. Posthoc longitudinal analyses included 1,853 observations from a subset of GDM-exposed youth with 1-, 2-, and 4-year follow-up visits to examine subtype differences in developmental trajectories over time. Exposure(s)Prenatal exposure to GDM. Main Outcome(s) and Measure(s)The primary outcomes included identification of cortical thickness subtypes and their inferred regional ordering patterns. Secondary outcomes included subtype-specific anthropometric, neurocognitive, psychiatric/behavioral and neuroimaging measures. ResultsThe GDM-exposed sample had a mean age of 119.02 {+/-} 7.34 months and was 47.5% female. Two cortical thickness subtypes were identified. Between subtypes, Subtype 1 (63.2%) was characterized by earlier inferred insula involvement and was associated with greater height (d = 0.36, pFDR < 0.001) and weight (d = 0.26, pFDR = 0.007), whereas Subtype 2 exhibited earlier inferred frontal involvement and nominally higher Attention-Deficit/Hyperactivity Disorder (ADHD) prevalence (d = 0.08, p = 0.036), steeper longitudinal cortical thinning across all six cortical regions of interest ({beta} range: -0.05 to -0.13, all pFDR < 0.05), and a smaller decline in Obsessive-Compulsive Disorder (OCD) prevalence over time ({beta} = -1.02, pFDR = 0.049). Conclusions and RelevanceGDM exposure was associated with two distinct offspring cortical thickness subtypes, each showing different inferred regional ordering patterns and clinical associations. One subtype showed an insula-cingulate-predominant pattern associated with anthropometric measures, whereas the other showed a frontal-predominant pattern associated with nominally higher psychiatric measures and faster cortical thinning over time.

It has been proposed that bilinguals have better executive function (EF) arising from the constant selection of one language while inhibiting the other, and gray matter has been found to differ in bilinguals in regions linked to EF (frontal-parietal and subcortical structures). Attention Deficit Hyperactivity Disorder (ADHD) is associated with poorer EF and neuroanatomical differences underlying EF. Given the EF advantage in bilinguals, we investigated whether a bilingual experience affects EF performance and brain structure differentially in those with ADHD. Using the Adolescent Brain and Cognitive Development Study, we compared early Spanish-English bilinguals and English-speaking monolinguals with and without ADHD. ANOVAs for the Flanker, Working Memory, and Card Sort Tasks revealed no main effects of Language Experience (Bilingual versus Monolingual), a main effect of Diagnostic Group for Card Sort (ADHD worse than Controls), and no interaction effects on performance for any task. ANOVAs for gray matter volume (GMV) revealed a main effect of Language Experience in many regions, a main effect of Diagnostic Group in some regions, but no interactions. GMV in left thalamus was affected by both ADHD and bilingualism, but the effect of ADHD was not significantly diminished or enhanced by the dual-language experience. For cortical thickness, there was a main effect of Language Experience in several regions, no main effect of Diagnostic Group, and no interactions. Taken together, bilingualism has some impact on EF performance, a strong impact on neuroanatomy, but there was no disproportionate impact by bilingualism on the differences caused by ADHD for any measure. Research HighlightsExecutive function and brain structure differ in ADHD and in bilinguals, prompting the need to investigate interactive effects. Bilingualism did not disproportionately affect performance differences in ADHD for executive function, nor for gray matter volume or for cortical thickness differences in ADHD. Gray matter volume was less in ADHD than non-ADHD, as well as greater in bilinguals than monolinguals in the left thalamus, but without interaction effect. These independent effects indicate that the brain basis of ADHD is not impacted by a dual-language experience.

Abstract Parental depression and early child neurodevelopment are closely interconnected, yet few population-based studies have examined both maternal and paternal depression in relation to early neurodevelopmental risk. This study aimed to examine the association between child neurodevelopmental risk and parental depression in the French national birth cohort Etude Longitudinale Francaise depuis l'Enfance (ELFE). We conducted a cross-sectional analysis of 12,953 children and their parents who participated in the 2-year follow-up. Child neurodevelopmental risk was assessed at age 2 years using the Modified Checklist for Autism in Toddlers and categorized as low, intermediate, or high risk. Parental depression was assessed using the Kessler Psychological Distress Scale and defined as maternal depression, paternal depression, or depression in at least one parent. Multivariable logistic regression models were adjusted for sociodemographic, pregnancy-related, and child characteristics. Compared with low child neurodevelopmental risk, intermediate risk was associated with higher odds of maternal depression and depression in at least one parent. High child neurodevelopmental risk was associated with substantially higher odds of maternal depression and depression in at least one parent. Associations with paternal depression were weaker and were no longer statistically significant after adjustment. These findings suggest that parental depression, particularly maternal depression, is associated with early child neurodevelopmental risk from the stage of initial developmental concerns. They support an integrated, family-centred approach combining early identification of child developmental vulnerability with attention to parental mental health.

Adolescence is a critical developmental window for the emergence of substance use and psychosis-spectrum symptoms, yet early risk for these outcomes remains poorly understood. Using longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study (n=10,134), we tested whether demographic, clinical, and structural and functional neuroimaging measures assessed in childhood (mean baseline age=9.96 years) predict later adolescent substance use, psychotic-like experiences, and/or their co-occurrence. Multivariate machine learning models reliably predicted later emergence of psychotic-like experiences (AUROC=0.780) and their co-occurrence with substance use (AUROC= 0.828), as well as substance use on its own (AUROC=0.626). Distinct patterns of functional brain connectivity, task-related brain activation, demographic, and clinical factors differentiated each outcome. Findings suggest that partially dissociable developmental risk profiles are detectable as early as childhood, and results underscore the importance of explicitly modeling comorbidity when interrogating risk factors for mental health outcomes.

Background: Female individuals tend to be diagnosed with autism later. One factor suggested to contribute to diagnostic timing is verbal ability, in which autistic females may show strengths relative to male peers. Social drivers of health (SDOH) predict higher verbal skills, yet access to resources may facilitate diagnosis; thus, SDOH likely contributes to diagnostic timing in complex ways. We use data from two autism cohorts with substantial representation of those assigned female at birth (AFAB) to examine interactions among assigned sex at birth (sex), verbal IQ (VIQ), and SDOH in predicting autism diagnostic timing. Methods: We used multiple linear regression to examine sex assigned at birth and VIQ as predictors of diagnostic timing in an assigned-sex-balanced research sample (N=164, AFAB: 71) and an independent clinical sample (N=641, AFAB: 177). We hypothesized VIQ would positively predict diagnostic age, particularly among AFAB. Available data in the clinical sample also permitted us to explore the contributions of SDOH and inclusion criteria to model fit in this cohort. Results: In the research sample, VIQ, but not sex, positively predicted diagnostic age. In the clinical sample, VIQ and VIQ x SDOH, but not sex, predicted diagnostic age. Fitting the same model in a subsample of the clinical cohort formed by applying exclusion criteria used in the research sample (N=484, AFAB: 110), VIQ x SDOH x Sex became significant. For AFAB, higher VIQ and lower SDOH together were associated with later diagnosis in the clinical subsample, while for AMAB the opposite was true. Conclusions: Autistic youth with strong verbal ability may experience diagnostic delays. SDOH interacts with VIQ in a complex fashion, with lower SDOH generally exacerbating the tendency for VIQ to be associated with later diagnosis across a large clinical sample. However, among autistic youth without complicating medical factors or intellectual disability, this relationship is dependent upon sex.

Abstract Background Gene dosage disorders impact cognition and psychopathology, but outcomes vary widely amongst carriers of the same variant. Recent work has sought to better predict proband outcomes using measures of corresponding traits in family members. However, family-based models have not yet been prospectively quantified across several traits in different genetic disorders, nor evaluated for the precision they afford: both crucial issues for clinical implementation. Methods In a first test case for these questions, we apply regression analyses to quantify and compare family-based prediction of 12 traits (including IQ, autism- and ADHD-related traits) in 433 individuals from families including a proband with XXY or XYY syndrome (N=93 and 58, respectively). Results The 12 traits vary substantially in their proband-family associations (0.001<|r|<0.55) - with differences emerging between XXY and XYY syndrome. Only two traits also show significant and similar proband-family associations in both aneuploidies, with the greatest concordance found for IQ. A family-based model for IQ prediction in male sex chromosome trisomies significantly reduces error vs. a group mean IQ model (F = 7.4, p = 0.006), but only in 65% of probands, and with mean error reduction of ~2 IQ points. Conclusions Family-based prediction of neuropsychiatric traits in genetic syndromes likely requires trait- and syndrome- specific models. Family models can significantly improve outcome prediction for IQ, but to variable degrees across individuals and with a small mean improvement. By mapping and quantifying these limits, our work helps draft a roadmap for refinement of family-based prediction of proband outcomes in gene dosage disorders.

BACKGROUNDVariation in pubertal maturation relative to same-age, same-sex peers (pubertal timing) has been linked to increased risk for depressive symptoms during adolescence. This developmental period is also characterized by substantial reorganization of functional brain networks. However, how pubertal timing relates to resting-state functional connectivity (rsFC) changes and depression risk remains unclear. METHODSWe examined pubertal timing and rsFC associations in preadolescents aged 9-11 years from the Adolescent Brain Cognitive Development (ABCD) Study. Pubertal timing was estimated using a puberty age gap approach based on parent-reported physical development. Linear mixed-effects and Bayesian multilevel models were used to assess cross-sectional and longitudinal associations between pubertal timing and rsFC across large-scale functional brain networks. We also tested whether rsFC differences explained associations between pubertal timing and later depressive symptoms. RESULTSEarlier pubertal timing was associated with heterogeneous rsFC patterns, with stronger and more widespread effects in females. In females, earlier pubertal timing was associated with rsFC increases and decreases across sensory-motor and association networks, whereas in males, associations were more limited and localized to sensorimotor and cerebellar systems. Longitudinally, earlier pubertal timing in females predicted reductions in rsFC at the 2-year follow-up, with no significant associations in males. rsFC differences did not explain the pubertal timing and later depressive symptoms association. CONCLUSIONSPubertal timing is associated with sex-specific patterns of brain functional connectivity during early adolescence, with greater heterogeneity and broader network involvement in females. These findings suggest that pubertal maturation contributes to early reorganization of functional brain networks, although these changes did not explain subsequent depressive symptoms.

Background: Body-focused repetitive behaviours (BFRBs), including hair pulling, skin picking and nail biting, are common but under-recognised behaviours that often emerge during adolescence. Their prevalence, associated distress, and relationship with mental health and social factors remain poorly characterised. Methods: 5,437 adolescents aged 11-18 years reported engagement in BFRBs, associated distress, and functional interference as part of the 2025 OxWell Student Survey. Participants. Problematic BFRBs were defined as at least one BFRB with moderate or high distress. Associations with gender, neurodivergence, bullying, and internalising symptoms were examined using multivariable logistic regression. Results: Overall, 58.5% of participants reported at least one BFRB. Nail biting was most common (43.6%), followed by skin picking (31.3%) and hair pulling (14.5%). Among those with BFRBs, 22.2% reported moderate-to-high distress, and 3.3% of the total sample reported the highest level of distress. Co-occurrence was common: more than half of those with BFRBs reported multiple behaviours. BFRBs were more common and more distressing in girls and trans/gender-diverse participants than in boys. Problematic BFRBs showed strong associations with internalising symptoms (6.3% in the normal range vs 34.2% in the clinical range) and bullying (9.6% with no bullying vs 27.1% with >weekly bullying). Internalising symptoms were the strongest predictor in multivariable models (OR 1.97 per 10-point increase), alongside independent contributions from gender and frequent bullying. Conclusions: BFRBs are common in adolescents, frequently co-occur, and are strongly associated with emotional distress and social adversity. Recognition of distress, rather than behaviour alone, may be important for identifying unmet need and guiding intervention.

BackgroundAutism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) share substantial clinical and physiological overlap. While naturalistic and sensory-driven paradigms increasingly capture evoked neurophysiological responses, the intrinsic baseline physiology of these conditions remains poorly defined. We aimed to characterize resting-state autonomic arousal and oculomotor stability across the ASD-ADHD spectrum using both continuous (RDoC) and categorical (DSM-5) analytical frameworks. MethodsWe analyzed resting-state eye-tracking data from a large pediatric cohort (N = 2,640) from the Healthy Brain Network. During an unconstrained baseline, we extracted Pupil Relative Volatility (Coefficient of Variation [CV]) to index intrinsic autonomic arousal, and the Bivariate Contour Ellipse Area (BCEA) to index spatial gaze instability. Data were evaluated using continuous dimensional regressions against the Social Responsiveness Scale (SRS) and SWAN inventories, followed by 2x2 factorial ANCOVAs based on clinical diagnoses. Sensitivity analyses accounted for clinical collinearity, spatial outliers, and psychostimulant medication. ResultsDimensional models revealed that Pupil CV was significantly and uniquely associated with continuous autistic traits (q = 0.0043, joint model), exhibiting a strong statistical suppression effect when controlling for ADHD trait covariance. However, this pupillary biomarker lost significance in binary categorical models. Conversely, spatial gaze instability (BCEA) demonstrated robust categorical threshold effects; isolated ASD and ADHD diagnoses significantly impaired baseline gaze stability. Furthermore, comorbid ASD+ADHD produced a distinct, sub-additive interaction for BCEA (q = 0.005) that remained robust to extreme spatial outliers. Both physiological phenotypes were independent of active psychostimulant use. LimitationsWhile this study included a large and diverse group of children, the eye-tracking data were collected during a brief resting period -- watching a simple cross on a screen -- which may not capture how children behave in everyday, real-world situations. Because holding still for eye-tracking can be difficult, particularly for children with more severe symptoms, some data were lost; however, we statistically accounted for how much data each child contributed. Finally, while we confirmed that ADHD medication taken on the day of testing did not explain our findings, complete medication records were not available for every participant in this large observational study. ConclusionsPupillary dynamics and oculomotor stability associate with the ASD-ADHD spectrum through differing analytical patterns during resting states. Baseline autonomic volatility is more strongly captured by dimensional models of autistic trait severity, whereas baseline gaze instability is more clearly differentiated across categorical diagnostic groups, exhibiting a sub-additive interaction in comorbidity. Integrating both dimensional and categorical frameworks provides a more comprehensive understanding of these physiological variations, establishing a necessary foundation for future naturalistic and sensory-evoked research.

Aim: To determine whether the neural phenotype (whole-brain resting-state functional connectivity pattern) of attention deficit hyperactivity disorder associated with prenatal alcohol exposure (ADHD+PAE) differs from that in unexposed children with ADHD of probable familial origin (ADHD-PAE). Method: Resting-state functional MRI was acquired from 26 children with ADHD+PAE, 25 with ADHD-PAE, and 25 typically developing (TD) children, all aged 8-13 years. Mean connectivity matrices based on the Cole-Anticevic Brainwide Network Parcellation of the brain were compared between the groups. Results: Within the frontoparietal network (FPN), children with ADHD+PAE showed widespread lower group-mean connectivity than children with ADHD-PAE; effects were concentrated primarily in cerebellar-cerebral cortical and cerebral cortical-cerebral cortical connections. Children with ADHD-PAE showed widespread hyperconnectivity relative to TD children. Children with ADHD+PAE showed mixed hyper- and hypoconnectivity relative to TD. Interpretation: These results are consistent with other MRI findings indicating that ADHD+PAE is neurally distinct from ADHD-PAE; PAE may be associated with broadly reduced connectivity, especially across cerebellar-cerebral cortical systems.

Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

Aim: To systematically evaluate evidence on the effects of post-discharge early developmental intervention programs (EI) on behavioral development, quality of life, participation, executive functioning, parent-child interaction, and use of medical services from infancy through adolescence in children born preterm. Method: Four bibliographic databases and one trial registry were systematically searched for randomized controlled trials up to April 23, 2024. Two reviewers independently screened studies and extracted data. In clinically and methodologically comparable studies, random-effects meta-analysis were performed. Risk of bias was assessed with the Cochrane RoB 2 tool, and certainty of evidence with the GRADE approach. Results: Twenty-six studies met inclusion criteria, eleven studies including 2,315 preterm born infants reported relevant outcomes, and seven contributed to meta-analyses. Most reported results showed some concerns or high risk of bias; certainty of evidence ranged from very low to moderate across outcomes. EI may offer small benefits for selective attention, behavioral problems and parent-child interaction. Little to no effect was found for special educational needs, language skills, executive functioning and the use of medical services. No included studies evaluated the effect of EI on ADHD, quality of life, or participation related to mobility or leisure activities. Interpretation: EI may improve problems typically seen in preterm children and should be offered especially to those with additional medical or social risk factors. High-quality, contemporary trials are needed to establish reliable clinical recommendations regarding EI strategies and complementary interventions throughout childhood.

Importance: 22q11.2 deletion syndrome (22q11DS) is among the strongest genetic risk factors for neuropsychiatric disorders and has marked effects on brain structure. Yet, it remains unclear which neuroanatomical features reflect uniform effects of the deletion versus inter-individual biological processes relevant to psychiatric outcomes. Identifying these features is critical for developing targeted treatments and interventions. Objective: To identify brain regions where 22q11DS exerts its most consistent and most variable impacts, and to test whether these patterns align with normative neurotransmitter receptor distributions and cortical growth trajectories. Design: Multisite cross-sectional case-control study. Setting: T1-weighted brain MRI data were obtained across 15 scanners. MRI data underwent standardized processing, quality control procedures and statistical site-adjustment using ComBat. Participants: A total of N = 438 individuals with 22q11DS (5-54 years, 48% females) and 380 typically developing controls (6-58 years, 48% females). Main Outcomes and Measures: Primary outcomes were global and regional cortical thickness and surface area . Mean and dispersion estimates were calculated using double generalized linear models, correcting for age, age2, sex (and intracranial volume for surface area). Quantile shift functions characterized fine-scale distributional differences. Sensitivity analyses adjustedt for co-occurring neuropsychiatric disorders, antipsychotic use and deletion subtype. Secondary outcomes included spatial correspondence between regional structural alterations and normative maps of neurotransmitter receptor density and cortical expansion. Results: Compared with controls, individuals with 22q11DS showed widespread mean differences in cortical thickness and surface area. Notably, 22q11DS was associated with greater regional heterogeneity in both measures, except for reduced dispersion in the anterior cingulate. Effects were attenuated after covariate adjustment. Cortical thickness differences spatially overlapped with regions enriched for glutamatergic and GABAergic receptors. There was partial evidence linking surface area dispersion patterns to normative cortical growth trajectories. Conclusions and Relevance: 22q11DS exerts broad effects on cortical structure consistent with a global developmental mechanism, reflected in widespread mean shifts. Beyond these, region-specific variability, particularly in cortical thickness, suggests individualized neurobiological processes. The anterior cingulate emerges as a region of consistent structural deviation. Overall, structural variability in 22q11DS aligns with normative patterns of excitatory-inhibitory signaling and cortical development, implicating these pathways as potential targets for intervention.

Background: Prenatal substance exposure (PSE) occurs when an individual is exposed to substances in utero. PSEs may have lasting effects on mental health. We tested whether PSEs show threshold, cumulative, or individual substance associations with childhood psychiatric diagnoses. Methods: Clinical variables (demographics, ICD-9/10 diagnoses, PSE history) were extracted from electronic health records from the University of Minnesota Adoption Medicine Clinic. PSEs were identified from caregiver and child-protective-services narratives and/or toxicology (cord tissue/blood, meconium). For each ICD-9/10 diagnostic category, we fit logistic regression models comparing (1) exposure thresholds (0, 1, 2, 3, 4+ exposures), (2) a cumulative exposure count, and (3) individual substances to estimate marginal odds ratios (ORs) with 95% Confidence Intervals (CIs). Results: Psychiatric diagnoses increased with the number of PSEs. Relative to no exposure, odds of an Anxiety Disorder rose from OR 1.47 (95% CI 1.16-1.87) with one exposure to OR 2.03 (1.64-2.52) with >=4 exposures. Higher cumulative exposure scores were associated with Anxiety Disorders (OR 1.28, 1.18-1.38), Behavioral and Emotional Disorders (OR 1.42, 1.31-1.54), Substance Use Disorders (OR 1.52, 1.29-1.79), and Mood Disorders (OR 1.16, 1.04-1.30). Alcohol, tobacco, and marijuana exposures were associated with increased odds of at least one psychiatric diagnosis, and each substance showed at least one significant diagnostic cluster when modeled independently. Conclusion: Increasing numbers of PSEs were associated with higher odds of psychiatric diagnoses, with patterns varying by substance and outcome. These findings motivate research on exposure timing and combinations to support earlier identification and intervention for at-risk children.

Excessive screen use is associated with childhood behavioral problems, but whether associations differ between typically developing (TD) children and those with autism spectrum disorder (ASD) is unclear. Our cross-sectional study included 108 children aged 5-9 years (61 TD, 47 ASD). ASD was diagnosed using standardized clinical instruments. Measures included parent-reported screen time (excluding TV/DVD), cognitive ability (K-ABC), and behavioral problems (Vineland-II). Screen time and externalizing problems were associated in the TD group (Spearmans {rho} = 0.361, p < 0.01), but not in the ASD group. In the regression model, screen time ({beta} = 0.40, t = 2.60, p < 0.05), ASD status ({beta} = 0.70, t = 8.30, p < 0.001), and their interaction ({beta} = -0.34, t = -2.06, p < 0.05) significantly predicted externalizing problems. Considering the diversity within the autism spectrum, future studies with larger sample sizes should consider individual heterogeneity when examining the association between behavioral outcomes and screen time.