Journal of Child Psychology and Psychiatry

Research has demonstrated the transdiagnostic importance of irritability in psychopathology pathways but the contribution of developmentally-unfolding patterns has only recently been explored. To address this question, irritability patterns of 110 youth from a large and diverse early childhood cohort were assessed at preschool age and at school age ([~]2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum. Participants then returned at Pre-adolescence ([~]6 years later) for an assessment with a structured clinical interview (internalizing/externalizing symptoms) and a magnetic resonance imaging scan. When only preschool age irritability was considered, this was a transdiagnostic predictor of internalizing and externalizing symptoms. However, a model including both preschool and school age irritability provided a more nuanced picture. A high preschool and decreasing school age profile of irritability predicted elevated pre-adolescence internalizing symptoms, potentially reflecting emerging coping/internalizing behavior in pre-adolescence. In contrast, a stable irritability profile across these timepoints predicted increased pre-adolescence externalizing symptoms. Further, preschool irritability (a period of rapid growth) did not predict pre-adolescent gray matter volume abnormality, an indicator of transdiagnostic clinical risk. However, irritability at school age (when gray matter volume growth is largely finished) demonstrated an interactive effect among regions; increased school age irritability predicted reduced volume in pre-adolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). Expanding the impact of RDoCs approach yielding transdiagnostic phenotypes and multiple units of analysis, a developmentally informed approach provides critical new insights into the complex unfolding of mechanisms underlying emerging psychopathology.

Behaviors and disorders characterized by difficulties with self-regulation, such as problematic substance use, antisocial behavior, and symptoms of attention-deficit/hyperactivity disorder (ADHD), incur high costs for individuals, families, and communities. These externalizing behaviors often appear early in the life course and can have far-reaching consequences. Researchers have long been interested in direct measurements of genetic risk for externalizing behaviors, which can be incorporated alongside other known risk factors to improve efforts at early identification and intervention. In a preregistered analysis drawing on data from the Environmental Risk (E-Risk) Longitudinal Twin Study (N=862 twins) and the Millennium Cohort Study (MCS; N=2,824 parent-child trios), two longitudinal cohorts from the UK, we leveraged molecular genetic data and within-family designs to test for genetic effects on externalizing behavior that are unbiased by the common sources of environmental confounding. Results are consistent with the conclusion that an externalizing polygenic index (PGI) captures causal effects of genetic variants on externalizing problems in children and adolescents, with an effect size that is comparable to those observed for other established risk factors in the research literature on externalizing behavior. Additionally, we find that polygenic associations vary across development (peaking from age 5-10 years), that parental genetics (assortment and parent-specific effects) and family-level covariates affect prediction little, and that sex differences in polygenic prediction are present but only detectable using within-family comparisons. Based on these findings, we believe that the PGI for externalizing behavior is a promising means for studying the development of disruptive behaviors across child development. Significance StatementExternalizing behaviors/disorders are important but difficult to predict and address. Twin models have suggested that externalizing behaviors are heritable ([~]80%), but it has been difficult to measure genetic risk factors directly. Here, we go beyond heritability studies by quantifying genetic liability for externalizing behaviors using a polygenic index (PGI) and employing within-family comparisons to remove sources of environmental confounding typical of such polygenic predictors. In two longitudinal cohorts, we find that the PGI is associated with variation in externalizing behaviors within families, and the effect size is comparable to established risk factors for externalizing behaviors. Our results suggest that genetic variants associated with externalizing behaviors, unlike many other social-science phenotypes, primarily operate through direct genetic pathways.

BackgroundAdolescents are particularly vulnerable to developing psychopathological symptoms, yet neurobiological markers that can identify these vulnerabilities in a personalized and interpretable manner remain limited. Dual Systems Models suggest that this vulnerability may result from asynchronous development of neural systems subserving cognitive-control and socioemotional functions. Given that rigorous empirical evidence is sparse, this study aimed to quantify developmental imbalances and evaluate their predictive value for psychopathology. MethodsBased on Dual Systems Models, the dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VS) were selected as key regions for the two brain systems, respectively. Using longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (baseline: n=11,238, ages 9.92{+/-}0.625 years; 2-year follow-up: n=7,870, ages 12.2{+/-}0.652 years; 4-year follow-up: n=2972, ages 14.1{+/-}0.693 years), we derived a personalized imbalance score based on brain morphometric features, including surface area, thickness and gray-matter volume. Nested linear mixed models were employed to assess associations between the imbalance scores and psychopathology. Additionally, generalized additive models were used to capture developmental trajectories of the imbalance scores and explore potential non-linear associations with psychopathology. To examine reproducibility, data from the Lifespan Human Connectome Project in Development study (HCP-D, N=652, ages 8-21 years) were interrogated. ResultsThe imbalance score, quantified as the difference between VS volume and DLPFC surface area, exhibited strong reliability and validity. During adolescence, the score exhibited a declining trend, with decreasing growth rates and variability between individuals. The score was positively associated with externalizing symptoms and showed a U-shaped relationship with internalizing symptoms. These findings were replicated in the HCP-D sample. ConclusionsThe novel neuroanatomical imbalance score empirically supports Dual Systems Models and may function as a transdiagnostic marker for internalizing and externalizing psychopathology. These findings enhance understanding of the neurodevelopmental mechanisms underlying adolescent psychopathology and offer potential implications for precision prevention and intervention strategies.

A combination of genetic and environmental factors working in interplay is thought to underlie differences in symptoms of psychopathology between adolescents. Yet, studies that have investigated gene-environment interaction in isolated aspects of developmental psychopathology lack robust effects, highlighting the need for a more comprehensive approach. We adopted a multivariable framework to investigate gene-environment interaction in internalising and externalising symptoms of psychopathology in a sample of 3,337 16-year-olds from the Twins Early Development Study. We used penalised regression models to examine the main effects of genetic factors (G), indexed combining 13 polygenic scores for psychopathology, and environmental factors (E), measured by combining multiple environmental exposures during childhood and adolescence, on symptoms of psychopathology. We also examined their additive effects (G+E) and their interaction (GxE). Polygenic scores accounted for, on average, 2.7% of the variance in symptoms of psychopathology, with stronger predictions for externalising symptoms, while environmental measures alone accounted for an average of 7.1% of the variance. G+E accounted for an average of 9.1% of differences between adolescents in symptoms of psychopathology. We observed small GxE effects for internalising symptoms, accounting for an average of 1.1% of the variance. Children with a higher genetic risk showed higher levels of internalising symptoms, especially when exposed to more chaos at home and harsher parenting. Our findings indicate that genetic and environmental influences contribute additively, underscoring the importance of jointly considering both factors to enhance our understanding of youth psychopathology. At the same time, our results highlight the persistent challenges involved in identifying robust GxE effects.

BackgroundEarly relational health (ERH) is thought to buffer the association between early life stress (ELS) and child psychopathology, but limited work has directly tested this hypothesis. ObjectiveWe evaluate mother-infant emotional connection, a facet of ERH, as a buffer of combined and individual impacts of specific ELS exposures (maternal mental health and interpartner conflict) on child psychopathology. MethodsParticipants included mother-infant dyads (n=100) followed longitudinally in the COMBO cohort, a convenience sample recruited during the COVID-19 pandemic. ERH was assessed via a remote mother-infant face-to-face interaction at ~4mo postpartum coded for emotional connection. An ELS Index was estimated using measures of maternal self-reported postpartum anxiety, depression, stress, and inter-partner conflict. Mothers rated emerging signs of child psychopathology symptoms at 2-3yrs on the Child Behavior Checklist for Ages 1[1/2]-5 (CBCL/1[1/2]-5). Main and interactive effects of ELS and ERH on emerging signs of child psychopathology were tested in generalized linear models. ResultsGreater ELS Index scores were associated with a higher rate of emerging psychopathology symptoms (aRR=1.32, p<.001), but this association was moderated by a significant interaction between the ELS Index and emotional connection (aRR=0.99, p=.03), such that at higher levels of emotional connection, the association of ELS with child psychopathology symptoms was weaker (aRR=1.16, p<.001). ConclusionParent-infant emotional connection may buffer the impact of ELS exposure in infancy on child emerging symptoms of psychopathology in toddlerhood, supporting efforts to invest in pediatric interventions that target ERH.

Interparental conflict and parental stress are well-established risk factors for child psychopathology, including elevated internalizing and externalizing symptoms. From a family systems framework, these stressors may spill over into the parent-child relationship, undermining emotional attachment and co-regulation processes central to childrens mental health. Neural synchrony, defined as the dynamic, mutual alignment of brain activity between a parent and child, offers a biological index of these dyadic processes. Using functional near-infrared spectroscopy, researchers have shown that greater neural synchrony (NS) in prefrontal brain regions is associated with more attuned caregiving and positive child adjustment. Yet, NS is not uniform; it varies across dyads in pattern and regional distribution, potentially reflecting differences in relational dynamics, regulation, or stress exposure. To capture this heterogeneity, we used latent profile analysis to identify distinct synchrony patterns along the right and left ventrolateral and dorsolateral prefrontal cortices during the DB-DOS:Biosynch - a mild stress, three-context task. We further examined whether interparental conflict and perceived parental stress predicted profile membership, and whether childrens internalizing and externalizing behaviors differed by profile. Among 194 dyads, two profiles emerged: lower baseline synchrony (LB; n = 132) and higher baseline synchrony (HB; n = 62). Greater interparental conflict reduced the odds of membership in HB, while parental stress was not predictive of profile membership. Additionally, children in LB exhibited higher levels of internalizing behaviors compared to HB, with no group differences observed for externalizing behaviors. These findings underscore the value of capturing synchrony heterogeneity in understanding family stress and child psychopathology.

Cognitive function, psychological processes, mental states, and behaviors are key dimensions of human subjective experience that separately relate to mental disorders across diagnostic categories. However, whether these dimensions are linked to common or distinct brain morphological patterns that convey risk or resilience for psychiatric disorders remains unclear. The current study is a longitudinal investigation on 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study aged 9-10 years at baseline. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of cortical morphology (4 metrics: surface area, cortical and subcortical volume, cortical thickness, and sulcal/gyral depth) with multidomain behavioral assessments including cognitive scores and psychological measures indexing motivation, impulse control, mental states, and behaviors across a normative continuum from healthy to pathological. Across morphological measures, we identified a robust latent brain structural variate that correlated positively with cognitive performance and negatively with psychological measures indexing greater psychology. Notably, higher scores on this brain variate reflected larger cortical surface area and cortical volume--especially in the temporal gyri--together with a posterior-anterior gradient in cortical thickness, showing relatively greater thickness in occipital, parietal, and temporal cortices and lower thickness in cingulate and frontal regions. This brain variate and the related cognitive-psychological-behavioral variate remained stable at the 2-year follow-up, demonstrating temporal consistency. Importantly, the brain variate showed a dose-dependent relationship with the cumulative number of psychiatric diagnoses assessed concurrently and at 2-year follow-up, with lower brain variate scores being associated with higher numbers of comorbid diagnoses. In addition, the brain scores were associated with longitudinal transitions between healthy and diagnosed states over the 2-year study period, in which lower scores at baseline were associated with persistent psychiatric diagnoses whereas higher scores at baseline were associated with persistent healthy states, suggesting that the brain scores capture a vulnerability- resilience continuum for psychopathology. By revealing shared brain structural substrates across conventional diagnostic boundaries, these findings advance the neurodevelopmental understanding of psychiatric disorders and highlight the potential utility of morphology-informed approaches for early screening and intervention in youth.

BackgroundParental genetics matters for childrens behavioural difficulties, but the extent to which this is due to direct genetic transmission versus environmentally mediated indirect genetic effects remains unclear. MethodsWe studied eight European birth cohorts with over 33,000 family-based trio samples. We analysed polygenic scores (PGSs) for 13 mental health and neurodevelopmental conditions and their composite indices (PC1 and mean) representing general neuropsychiatric liabilities, as well as educational attainment (EA) and alcohol and cigarette use, from children (PGSc), mothers (PGSm), and fathers. Child internalising, externalising, and total difficulties reported by mothers and/or fathers were examined at preschool and school ages. We then conducted multivariate meta-analyses to combine cohort-level results. FindingsWe observed several direct genetic effects on externalising difficulties, while indirect genetic influences were mainly identified for internalising difficulties. Specifically, child PGSs for attention-deficit/hyperactivity disorder (ADHD) and EA predicted higher and lower levels, respectively, of child externalising and total difficulties (all pFDR<0{middle dot}001; for school-aged externalising difficulties, PGSc-ADHD: {beta}=0{middle dot}121 [95% CI 0{middle dot}091 to 0{middle dot}151], pFDR<0{middle dot}0001; PGSc-EA: {beta}=-0{middle dot}095 [95% CI -0{middle dot}127 to -0{middle dot}063], pFDR<0{middle dot}0001), whereas maternal PGSs for major depressive disorder (MDD) and general neuropsychiatric liabilities were associated with internalising and total difficulties across parental raters and child ages (all pFDR<0{middle dot}05; for school-aged internalising difficulties, PGSm-MDD: {beta}=0{middle dot}049 [95% CI 0{middle dot}017 to 0{middle dot}081], pFDR=0{middle dot}016; PGSm-PC1: {beta}=0{middle dot}056 [95% CI 0{middle dot}022 to 0{middle dot}091], pFDR=0{middle dot}011). No statistically significant effects from paternal PGSs were identified. InterpretationIn this multi-cohort study, findings across multiple traits, raters, and ages supported several direct genetic effects of ADHD and EA on child externalising difficulties and indirect genetic effects on internalising difficulties, especially maternal depression and general neuropsychiatric liabilities. These suggest that child internalising difficulties are not solely driven by direct genetic transmission. More comprehensive research is needed to better understand the mechanisms involved, and ultimately how to ameliorate child behavioural difficulties. FundingEU, ERC, RCN, RCF, UKRI, SERI, DFG Research in contextO_ST_ABSEvidence before this studyC_ST_ABSIndirect genetic effects (IGEs) refer to the influence of parental genotypes on offspring outcomes beyond direct genetic effects (DGEs), for example via environmental pathways. While IGEs on offspring cognitive traits are well-established for educational attainment, evidence for IGEs of parental liabilities to mental health and neurodevelopmental conditions remains limited. To assess the current state of evidence, we conducted a systematic search of published studies applying trio-based polygenic score (PGS) designs to child and adolescent mental health outcomes. We identified 141 primary studies in MEDLINE, Embase, PsycInfo, and Web of Science, by 6 March 2025, after removing duplicates; following screening, 12 studies met inclusion criteria (see supplement for a full description including results). Ten out of the 12 studies focused on externalising outcomes, with little or inconsistent support for IGEs. When observed, IGEs were mainly driven by maternal liabilities to autism, educational attainment, and cognitive performance on child outcomes. The current evidence was too limited and heterogeneous to synthesize findings quantitatively, therefore a qualitative synthesis was conducted. Many studies were statistically underpowered, and the observed IGEs were in all cases sample-specific. There were no published multi-cohort studies. Added value of this studyWe integrated information across over 33,000 mother-father-child trios from eight European cohorts, investigating 18 PGSs from parents and children, using maternal and paternal ratings of offsprings internalising, externalising, and total difficulties as outcomes at both preschool and school age. We mainly observed DGEs on externalising difficulties, consistent with previous studies. Some evidence of IGEs was found for internalising and total difficulties. IGEs were often found to be maternally driven, with the most robust evidence across ages and raters emerging for maternal depression and general neuropsychiatric liabilities. Implications of all the available evidenceThe current evidence suggests that childrens behavioural difficulties, especially internalising difficulties, may be partly driven by the environment shaped by maternal neuropsychiatric liabilities. Ours and previous findings highlight a pressing need for more comprehensive studies across different cohorts, raters, outcomes, and time points to understand the true extent of IGEs in the intergenerational transmission of mental health.

BackgroundTemperament traits, which reflect early emerging individual differences in reactivity and regulation, are well-established correlates of psychopathology. However, studies have historically examined static temperament-psychopathology associations within limited age ranges. Research is required to understand the developmental dynamics of these associations. MethodsWe leveraged data from a longitudinal cohort (N = 767) with repeated measures in infancy and at ages 2 years, 3 years, 5 years, 7 years, and 11 years to examine predictive and concurrent associations between temperament traits (negative affectivity, surgency, effortful control, behavioral inhibition) and psychopathology (internalizing, externalizing) symptoms. We estimated time-varying associations using generalized additive mixed models to quantify variation in the significance and magnitude of associations from infancy through early adolescence. ResultsGreater negative affectivity consistently predicted higher internalizing and externalizing symptoms from infancy through 11 years. Surgency showed differential patterns, with higher surgency associated with lower internalizing symptoms but greater externalizing symptoms. Surgency from 2 years was associated with both internalizing and externalizing symptoms over proximal developmental intervals, whereas at 3 years, associations with externalizing extended distally through 11 years, while associations with internalizing remained proximal. Higher effortful control was associated with fewer internalizing and externalizing symptoms, with stronger effects for externalizing symptoms. Behavioral inhibition at 3 years was associated with internalizing symptoms ages 3 and 5 years. The significance and magnitude of associations between temperament domains and psychopathology symptoms varied based on developmental timing. ConclusionsTemperament traits show differential associations with psychopathology symptoms, depending on the specific temperament trait and psychopathology domain. Further, the significance and magnitude of associations vary based on developmental timing. These findings highlight the importance of considering differential traits, domains, and developmental timing when considering the potential role of temperament in psychopathology.

Irritability refers to the dispositional tendency toward angry emotion with both mood and behavioral elements. The dimensional spectrum of irritability is an RDoC-informed transdiagnostic marker of psychopathology risk, specifically the common and modifiable internalizing and externalizing disorders. Despite substantial interest in this robust developmentally based transdiagnostic indicator of psychopathology risk, its early brain markers are understudied. Here, we present data (n=31) from an imaging sub-study of the When to Worry study, in which we examined prospective associations between volume in three subcortical regions implicated in irritability (the caudate, putamen, and amygdala) around the infants first birthday (Baseline) and the dimensional spectrum of observed irritability using the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) around toddlers second birthday (Follow-up). Both left (q<.04, FDR corrected) and right caudate volumes (q<.04, FDR corrected) at Baseline were negatively associated with a measure of irritability measured at Follow-up. We did not find support for associations between putamen and amygdala volumes at Baseline and observed irritability at Follow-up. These findings identify early prospective neuroanatomical correlates of toddler irritability and provide preliminary support for the caudate being an important brain region for understanding the developmental sequalae of irritability.

BACKGROUNDAdolescent peer victimization (PV) is a prevalent social stressor associated with potential long-term psychological and physiological consequences. Yet, the mechanisms underlying enduring alterations in stress-regulatory systems remain underexplored. This multimodal study examines autonomic, endocrine, and affective reactivity in young adults with a history of severe PV. METHODSEyeblink startle electromyograms, pupil dilation, hair cortisol, resting heart rate variability, and self-reported state anxiety were assessed in 182 young adults (age 22) with longitudinal data on adolescent PV (ages 11-20). Effects were estimated using a counterfactual framework with genetically informed inverse probability weighting--leveraging polygenic risk scores and genetic ancestry--and adjustment for time-varying confounders. RESULTSVictims exhibited heightened startle amplitudes compared to controls, with negative stimuli (angry faces) further exaggerating amplitude and prolonging latency. Pupil dilation increased in response to negative stimuli, but was otherwise blunted. Victims also showed reduced resting heart rate variability, elevated hair cortisol, and slower state anxiety recovery across the session. Depression moderated several effects; more depressed victims showed hypocortisolism and reduced autonomic reactivity. CONCLUSIONSFindings provide converging evidence and mechanistic insight into potential links between PV and trauma-like physiological effects, suggesting sustained alterations into young adulthood. Targeted interventions are needed to reduce PV and its stress-related dysregulation, preventing potential long-term psychiatric and societal sequelae.

Common genetic variants make a significant contribution to neurodevelopmental characteristics such as cognitive abilities and ADHD symptoms. The relevance and structure of these associations amongst children with transdiagnostic difficulties in cognition, attention and learning has not been explored. Polygenic scores (PGS) derived from the largest genome-wide association study (GWAS) data at the time of this study on ADHD (38,691 individuals with ADHD and 186,843 controls) and Intelligence (269,867 individuals) were calculated for 524 children and young people (5-18 years old) referred to the Centre for Attention, Learning and Memory (CALM). PGS-trait associations were assessed via linear regression analyses, for a range of cognitive and behavioural dimensional measures, and factor scores from a hierarchical model of psychopathology. PGS associations were explored with and without co-varying for socio-economic status (SES). Within this sample, we found the expected positive associations between ADHD-PGS and ADHD primary symptoms, and between Intelligence-PGS and IQ. ADHD-PGS were also associated with broader externalising behaviours and intelligence scores, and these associations remained significant after removing ADHD-diagnosed participants, or after covarying with SES. Intelligence-PGS showed associations with verbal and non-verbal cognitive skills, but no significant associations with ADHD traits were detected. For the hierarchical model of psychopathology, ADHD-PGS, but not intelligence-PGS, showed associations with the general mental health factor, externalising factor, and social maladjustment factor, only when SES was not included as a covariate. In summary, PGS for neurodevelopmental traits may contribute to both general and specific cognitive and behavioural dimensions in a paediatric transdiagnostic sample. Future studies investigating PGS associations with neural correlates, as well as gene-by-environment interactions, will contribute to our understanding of developmental pathways and risk-resilience mechanisms in child mental health.

BACKGROUNDEarly childhood has increasingly been recognized as an important neurodevelopmental period. However, the links between specific forms of early educational activities and cognition and mental health remain unclear. METHODSA large-scale analysis on the attainments of childhood Reading for Pleasure (early RfP) and its relationship with young adolescent measures of cognition, mental health and brain structure was conducted, using linear mixed-effects model, structural equation and mediation analyses. Participants were from the Adolescent Brain and Cognitive Development (ABCD) study, a USA national cohort (n=11,878). A two-sample Mendelian randomization (MR) analysis using genetic instruments from two independent genome-wide association studies (GWAS) based on ABCD and GWAS meta-analyses including UK-biobank datasets were conducted to assess potential causal inference. RESULTSEarly RfP was positively associated with cognitive assessments, which in contrast, was negatively associated with dimensional psychiatric problems in young adolescents. MR analysis revealed a beneficial relationship between early RfP and later-life cognitive performance, and a trend towards a protective relationship between early RfP and later-life attention disorder. Brain regions in which larger cortical areas were positively associated with early RfP included the superior temporal, prefrontal, left angular, parahippocampal, right anterior cingulate (ACC), occipital, supramarginal and orbital regions and subcortical ventral diencephalon (DC), thalamus, and brainstem volumes. Mediation analysis indicated that the brain regions significantly mediated the effects of early RfP with better cognitive performance and lower psychiatric problems. INTERPRETATIONOur results highlight the importance of encouraging RfP in young children during the critical early childhood stage, as it was associated with beneficial outcomes for cognition, mental health, and brain structure later in life.

Externalizing psychopathology in childhood is a predictor of poor outcomes across the lifespan. Children exhibiting elevated externalizing psychopathology also commonly show emotion dysregulation and callous-unemotional (CU) traits. Examining cross-sectional and longitudinal neural correlates across dimensions linked to externalizing psychopathology during childhood may clarify shared or distinct neurobiological vulnerability for psychopathological impairment later in life. We used tabulated brain structure and behavioural data from baseline, year 1, and year 2 timepoints of the Adolescent Brain Cognitive Development Study (ABCD; baseline n=10,534). We fit separate linear mixed effect models to examine whether baseline brain structures in frontolimbic and striatal regions (cortical thickness or subcortical volume) were associated with externalizing symptoms, emotion dysregulation, and/or CU traits at baseline and over a two-year period. At baseline, cortical thickness in the right rostral middle frontal gyrus and bilateral pars orbitalis was positively associated with CU traits ({beta}=|0.027-0.033|, pcorrected=0.009-0.03). Subcortical volume in the left caudate, right amygdala, and bilateral nucleus accumbens was negatively associated with emotion dysregulation ({beta}=|0.026 - 0.037|, pcorrected=<0.001-0.02). Over the two-year follow-up period, higher baseline cortical thickness in the left pars triangularis and rostral middle frontal gyrus predicted greater decreases in externalizing symptoms (F=6.33-6.94, pcorrected=0.014). The results of the current study suggest that unique regions within frontolimbic and striatal networks may be more strongly associated with different dimensions of externalizing psychopathology. The longitudinal findings indicate that brain structure in early childhood may provide insight into structural features that influence behaviour over time.

This study identified latent trajectories of physical aggression from infancy to preschool age and tested for (a) early parent, parenting and child predictor effects on trajectory membership and (b) trajectory-effects net of parent, parenting, and child predictor effects on Grade 2 social, behavioral and academic functioning. We used data from the Behavior Outlook Norwegian Developmental Study (BONDS), comprising 1,159 children (559 girls). Parents reported on risk and protective factors, and on physical aggression from 1 to 5 years; teachers reported on Grade 2 outcomes. We employed latent class growth curve analyses to identify nine aggression trajectories. In fully adjusted models testing simultaneously all associations among predictors, trajectories, and outcomes, maternal and paternal harsh parenting, child gender, and sibling presence predicted trajectory membership, which significantly predicted Grade 2 externalizing. Child gender had a pervasive influence on all outcomes as well as on trajectory membership. This is the first trajectory study that attempts to sort out which predictors are most proximal, more distal, or just confounded, with their relative direct effect sizes, and to link early paternal as well as maternal harsh parenting with childrens development of physical aggression from infancy to preschool age. Our findings underscore the need to include fathers in developmental research and early prevention and intervention efforts.

BackgroundComorbidity and heterogeneity in psychiatric disorders may stem from a general psychopathology (p) factor influenced by both genetic and environmental factors. Although the relative contributions of these influences on psychopathology are established, the longitudinal associations between p-factor and specific environmental exposures across development are not well understood. Using a longitudinal genetically informative design, this study investigates the association between the home environment and p-factor across childhood. MethodsData were obtained from the Twins Early Development Study (TEDS). Cross-lagged panel analyses were conducted separately to ascertain the direction of associations between parent-rated p, self-rated p, and self-rated home environment (chaos at home and parental discipline) at ages 9, 12, and 16 (N=6,213). Biometric autoregressive cross-lagged twin models were used to assess the aetiology of these associations, and MZ differences analyses were used to control for familial effects. ResultsBoth latent factors were stable over time, although twin-rated p-factor (r = 0.44-0.40) was more variable than parent-rated p-factor (r = 0.72-0.63). Home environment was more variable than p-factor uniformly. Small, significant bi-directional associations were found between p-factor and home environment, with stronger cross-lagged paths from p-factor to home environment than vice versa. These longitudinal associations persisted over time, though attenuated for parent-rated p-factor. Genetic analyses revealed that bi-directional cross-lagged paths were largely explained by shared environmental factors, with a smaller proportion explained by genetic factors. This pattern of results was confirmed in MZ differences analyses. ConclusionsOur findings suggest a dynamic and bidirectional relationship between p-factor and the home environment across development, predominantly influenced by shared environmental factors. Changes in one can influence the other, highlighting the complexity of psychopathologys environmental influences. This underscores the need for further investigation into gene-environment interplay to inform approaches to psychopathology prevention and intervention. Key points and relevanceO_LIThe relationship between p-factor and the home environment is dynamic and bidirectional, indicating that changes in one can influence the other across different developmental stages. However, the effect sizes of these relationships were modest. C_LIO_LIShared environmental factors played a major role in driving cross-lagged associations between p-factor and the home environment, with some genetic contribution, suggesting that the family environment can significantly shape this relationship. C_LIO_LIThese findings necessitate deeper investigations into gene-environment interplay in shaping psychopathology. A better understanding of these dynamics could inform effective prevention and intervention strategies for developmental psychopathology. C_LI

BackgroundImpulsivity is a multifaceted transdiagnostic trait that emerges in childhood. Research has identified genetic loci and brain systems associated with different facets of impulsivity and risk-taking. However, how these genetic underpinnings overlap across different facets, and how they are associated with brain development during childhood remain unknown. MethodsUsing genomic structural equation modeling on 17 impulsivity and risk-taking traits, we identified latent factors capturing overlapping genetic architecture. We then calculated polygenic scores for these factors using Adolescent Brain Cognitive Development Study data (N = 4,142) and examined their associations with brain structure, development, and behavior in children aged 9-14 years. Finally, we tested whether socioeconomic status modulated the associations between latent polygenic scores and brain structures. ResultsWe identified three distinct genetic latent factors, which we label lack of self-control, reward drive, and sensation seeking. In children, polygenic scores for the three factors showed associations with distinct brain patterns: lack of self-control associated with reduced prefrontal cortical thickness, reward drive with increased subcortical cellular density, and sensation seeking with increased cortical surface area and white matter integrity. Longitudinally, lack of self-control predicted slower white matter development. The association between polygenetic score for lack of self-control and white matter mean diffusivity was modulated by socioeconomic status. ConclusionsWe identified three genetically distinct dimensions of impulsivity and risk-taking with separable neurodevelopmental origins. These genetic predispositions manifested as distinct brain patterns as early as ages 9-10. Environmental experience modulated some of the genetic effects on brain development.

ImportanceAdverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs associates with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain. ObjectiveTo evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents. Design, Setting, and ParticipantsThis cohort study analyzed 4-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11,868 youth aged 9 to 10 years beginning in 2016. Sibling-comparison analysis was performed on 414 non-adopted sibling pairs with discordant APEs. Statistical analysis occurred from March to June 2025. ExposuresCumulative APE burden was calculated by summing six binary prenatal exposures that independently associated with psychopathology at baseline: unplanned pregnancy; early maternal prenatal alcohol, tobacco, or marijuana use; complicated pregnancy; and complicated birth. Main Outcomes and MeasuresOutcomes included annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology, using both continuous and thresholded outcomes; and biennial cortical thickness measures from structural magnetic resonance imaging, analyzed using linear mixed-effects models. ResultsOf 8,515 singleton children (4,055 females [47.6%]), 78% were exposed to at least one APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: odds ratio=2.01-6.75; corrected P=.0065-1.31x10-13). Associations of APEs with attention-deficit/hyperactivity disorder symptoms attenuated over time (interaction: F=13.51; corrected P=7.13x10-8), while those with depressive symptoms potentiated (interaction: F=5.82; corrected P=.0019). Greater APE burden associated with accelerated age-related cortical thinning in 36 of 68 cortical regions (interactions: F=3.26-8.89; corrected Ps=0.039-4.86x10-4). Siblings with more exposures demonstrated persistently higher CBCL total problems (T=2.25; P=0.025) and accelerated cortical thinning (interactions: T=-3.00--2.10; Ps<.05) in 5 of the 36 regions implicated in the larger sample. Conclusions and RelevanceMultiple prenatal adversities associated with altered developmental trajectories of psychopathology and cortical maturation into mid-adolescence. These findings highlight the importance of fetal programming to mental health across life course, and the need for additional study of risk and resiliency-conferring factors in utero. Key PointsO_ST_ABSQuestionC_ST_ABSIs adverse prenatal exposure (APE) burden associated with long-term changes in psychopathology and underlying cortical maturation trajectories in children? FindingsIn this 4-year follow-up cohort study of 8,515 singleton children in the ABCD Study, exposure to multiple APEs associated with persistent, dose-dependent increases in the risk of clinically significant psychopathology and diffuse acceleration in age-associated cortical thinning during adolescence. Findings were further supported by within-family comparisons in 414 sibling pairs discordant for APEs. MeaningThese findings associate multiple prenatal adversities with enduring and developmentally dynamic effects on both cortical development and mental health in adolescence. The results emphasize the need for early identification, longitudinal monitoring, and neurodevelopmentally informed prevention strategies for at-risk youth.

Atypical social functioning is a core feature of autism, yet findings remain fragmented across components and development. We aimed to systematically integrate this literature and characterize the organization, development, and moderators of social functioning in autism. We conducted a systematic review and meta-analysis of behavioral studies published between January 1990 and August 2025, identified through PubMed, Web of Science, and prior reviews, including studies with clinically diagnosed autistic individuals and neurotypical controls. A qualitative synthesis and two complementary quantitative meta-analyses were performed, with risk of bias evaluated through study-level characteristics. A total of 2,622 studies (94,114 autistic and 172,847 neurotypical individuals across 32 countries) were included, covering 22 social components that clustered into five domains. Overall group differences were substantial (Hedges g = -0.744, 95% CI [-0.797, -0.690]). Differences emerged earliest in motivation-based processes ([~]6 months), followed by motor, emotion, and inference domains, and showed age-related divergence alongside improvement in some skills. Cross-domain analyses revealed stronger interdependencies in autism and an organizational pattern most consistent with serial relationships among domains. These findings should be interpreted in light of methodological heterogeneity, underpowered samples, and uneven cultural representation. Together, the results provide an integrative framework for understanding the organization and development of social functioning in autism, with implications for precision subtyping, developmentally timed interventions, and neurodiversity-informed research and policy. This study was pre-registered (PROSPERO: CRD42024566141).

BackgroundAdverse Childhood Experiences (ACEs) are established risk factors for physical and mental health outcomes, yet their associations with pediatric brain development remain underexplored, particularly regarding sex differences. Most studies treat ACEs as a single construct, overlooking the distinct effects of specific subtypes (e.g., sexual abuse, physical neglect) on brain structure and function. This study examines how ACE subtypes and their interaction with sex are linked to brain development in 9-10-year-olds. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study (N{approx}12,000, ages 9-10), we assessed the links between emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect and structural brain measures in the hippocampus, amygdala, lateral orbital frontal cortex (lOFC), medial orbitofrontal cortex (mOFC), and rostral anterior cingulate cortex (rACC). Mixed-effects linear models tested ACE subtype, sex, and interaction effects, adjusting for multiple comparisons (Benjamini-Hochberg FDR correction). ResultsBoys reported higher exposure to emotional abuse (p =.01), emotional neglect (p = .037), and physical neglect (p< .001), while girls had greater exposure to sexual abuse (p < .001). Significant ACE-by-sex interactions emerged: sexual abuse was associated with smaller hippocampal volume in boys (p = .003) but showed no significant effect in girls (p = .433). Emotional abuse was linked to reduced lOFC volume in boys (p = 0.024), while in girls, it was associated with a marginal increase (p = .048). Physical neglect was associated with reduced hippocampal volume regardless of sex (pFDR = .05). ConclusionBoys may be particularly vulnerable to hippocampal and lOFC changes following sexual and emotional abuse, while physical neglect broadly impacts hippocampal development. These findings highlight sex-specific neurodevelopmental effects of ACE subtypes, emphasizing the need for tailored interventions and possible biomarkers for treatment and prevention of sequelae.