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Individuals with developmental language disorder (DLD) are disproportionately represented in the criminal justice system. The prospective associations between DLD and offending, and the educational and criminal justice pathways through which DLD might increase the risk of offending and reoffending, remain unclear. We analysed existing data from the Avon Longitudinal Study of Parents and Children (maximum N = 6,800; 51% female; 9% with DLD) with linked school data (national pupil database) and crime records (Avon and Somerset police records for offences committed between ages 13 and 29 years in the region). DLD was determined when the individuals were aged 7-9 years using direct assessments and parent reports. Regression and mediation models were fitted to the data. Individuals with DLD were more likely (odds ratio 1.74, 95% confidence intervals 1.25, 2.44) to have a recorded offence (i.e. charged or cautioned by the police) compared to those without DLD. School suspension was a significant mediator of the relationship between DLD and recorded offending. However, SEN identification was not associated with recorded offending for those with DLD. There was also no difference in the odds of being given an out of court disposal or reoffending for individuals with DLD compared to those without DLD. Individuals who have DLD are more likely to be cautioned or convicted for an offence by the police than those without DLD, and this may in part be because they are more likely than those without DLD to be suspended from school.

Childhood adversity is a potent and modifiable risk factor for depression. Few studies have investigated how the developmental timing of adversity exposure shapes depression risk. We investigated whether there were sensitive periods, or age stages when two types of adversity (caregiver abuse, financial hardship) had stronger associations with depressive symptoms in late adolescence. Data came from a prospective, longitudinal birth cohort of children in Avon, England (Avon Longitudinal Study of Parents and Children). Caregivers reported their children's adversity exposure at least seven times between 0 and 18 years of age. Child participants self-reported depressive symptoms (Short Mood and Feelings Questionnaire) at 18.5 years old. We used a structured life course modeling approach (SLCMA) to characterize how sensitive period and accumulation hypotheses explained variation in depressive symptoms. For females, accumulation best explained variation in depressive symptoms for both adversity types, with each additional developmental period of exposure associated with a 0.33-unit increase in depressive symptoms for caregiver abuse and 0.31-unit increase for financial hardship. For males, sensitive period hypotheses were selected for exposure to caregiver abuse (exposure at age 9 =2.13-unit and age 3.9 =1.46-unit increase), while an accumulation hypothesis was selected for exposure to financial hardship (0.40-unit increase in depression). Accumulation rather than sensitive period hypotheses generally best explained the relationship between adversity and depressive symptoms in late adolescence, but findings varied by sex and adversity type. These findings highlight the importance of considering multiple life course hypotheses, sex, and adversity type when investigating the downstream impacts of adversity.

Irritability is highly heterogeneous and a common challenge in youth clinical services. Albeit transdiagnostic, the diagnostic manuals conceptualize severe irritability differently: the ICD-11 primarily recognizes it as behavioral (oppositional defiant disorder specifier), and the DSM-5-TR, as depressive (core to disruptive mood dysregulation disorder). Irritability is also highly prevalent in, and genetically linked to, neurodevelopmental conditions. It is unclear whether irritability represents a unitary construct or multiple different types. We examined whether distinct behavioral, neurodevelopmental, and depressive irritability types, differentiated by their developmental course, sex-preponderance, clinical, genetic, and environmental covariates, could be observed. Using data from the Avon Longitudinal Study of Parents and Children (female participants: 5,085; male participants: 5,028), we explored sex-stratified irritability latent profiles across 5 time points (∼ages 7-25 years) for irritability measured with the Development and Well-Being Assessment. We investigated associations with various clinical, genetic, and environmental covariates typifying behavioral, neurodevelopmental, and depressive conditions. We identified 5 irritability profiles similar across sexes (low, child-limited, child/adolescent-limited moderate, child/adolescent-limited high, high-stable) and 2 sex-specific profiles: adolescent-onset (female participants) and fluctuating (male participants). Although most profiles were not distinguished by condition-specific covariates, 2 profiles showed some specificity with neurodevelopmental or depressive conditions: (1) the male high-stable profile was associated with attention-deficit/hyperactivity disorder diagnosis and genetic liability, and autism-like traits, and (2) the female adolescent-onset profile was associated with depression diagnosis and genetic liability, and adolescent/adult stressful life events. Irritability appears to be developmentally heterogeneous. Albeit often transdiagnostic, for some individuals irritability may align with neurodevelopmental or depressive conditions. This could have potential implications for classification and treatment. Exploring Possible Behavioural, Neurodevelopmental and Depressive Types of Irritability, Using a Developmental Approach; https://osf.io/av2s8/. Irritability is highly impairing and linked to different mental health conditions. Using data from the Avon Longitudinal Study of Parents and Children (n = 10,113), the authors characterized irritability in female and male youths. Five irritability profiles common to female and male youths were identified, as well as adolescent-onset irritability in female youths and fluctuating irritability in male youths. Irritability persisting from childhood to adulthood in male individuals was linked to attention-deficit/hyperactivity disorder and autism, whereas adolescent-onset irritability in female individuals was linked with depression.

Rare copy number variants (CNVs; deleted/duplicated DNA segments) are associated with childhood attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). It is unknown whether carrying a CNV moderates the effect of ADHD/ASD on adult outcomes. In a UK population-based cohort, the Avon Longitudinal Study of Parents and Children, ADHD and ASD difficulties at ages 7-16 years were defined categorically. Outcomes included: General Certificate of Secondary Education non-attainment; depression at ages 18 and 24; functioning at age 25; not in education, employment or training; and receiving state benefits at age 25. Logistic regressions were used to assess associations between ADHD/ASD and outcomes, and to test CNVs as moderators. Multiple imputation was used to account for data missingness. We did not find strong evidence of CNVs moderating the effect of ADHD or ASD on young adult outcomes. However, confidence intervals for the moderating effect were wide, so further research in larger clinical samples is necessary.

Little is known about the provision of diagnoses to young people with mental health disorders. We investigated diagnosis provision by NHS mental health services, focusing on 17-year-olds in South London between 2009-2024, and compared with estimated disorder prevalence. To examine diagnosis provision in the population, we extracted diagnosis data from records of the NHS mental healthcare provider serving South London, using the Maudsley Biomedical Research Centre Clinical Record Interactive Search application; we then compared these data with the corresponding population size, obtained from the Office for National Statistics. To assess diagnosis provision in those with mental health disorders, we compared diagnosis data with the number of young people estimated to have met criteria for a disorder, derived from epidemiological interview data collected in the Environmental Risk (E-Risk) Longitudinal Twin Study and weighted according to characteristics of 17-year-old South Londoners. To assess diagnosis provision in those with mental health disorders within health services, we compared diagnosis data with the number estimated to have met criteria for a disorder and used any health service for their mental health, again derived from weighted E-Risk Study data. Of 17-year-olds from South London in 2009-2024, 4.0% (n=8,958/223,404) had a diagnosis in mental health records during the previous year. This diagnosis provision covered <1 in 16 of those estimated to have had a mental health disorder, and <1 in 4 of those estimated to have also used health services. Diagnosis provision was lower in girls than boys and in young people with Black/Asian/Mixed/Other ethnicity than those with White ethnicity, in those estimated to have had a mental health disorder and used health services. These findings demonstrate gaps and biases in mental health diagnosis provision for young people, including within health services, and reveal the imperative need to strengthen young people's mental healthcare. National Institute for Health Research, Medical Research Council, National Institute of Child Health and Development, Jacobs Foundation, National Society for Prevention of Cruelty to Children, Economic and Social Research Council, Prudence Trust, Wellcome Trust. Evidence before this study: Epidemiological research has found that less than half of young people with a mental health disorder report seeing a health professional for their symptoms and only a quarter to a third have seen a mental health specialist, and these findings are fairly consistent across high-income countries where this research has been conducted. For young people who see health professionals, there are likely to be barriers to the recognition and treatment of mental health disorders. We focused on the recognition of mental health disorders in young people, which is operationalised in clinical practice as provision of diagnoses. To identify studies examining mental health diagnosis provision in young people accessing health services, we searched MEDLINE with the terms "diagnos*" AND ("mental" OR "psychiatr*" OR [various terms for individual disorders]) AND ("young" OR "youth*" OR "child*" OR "adolescen*" OR "paedatric*" OR "pedatric*" OR "juvenile") AND ("clinical" OR "healthcare" OR "health care" OR "service*"). This search was supplemented by reviewing reference lists and forward citations of relevant articles. We identified several studies that found diagnosis provision varied by sociodemographic characteristics and has increased over the past two decades in young people across multiple countries for several disorders, including depression, anxiety disorders, eating disorders, autism, and attention-deficit/hyperactivity disorder (ADHD). Only a small number of studies investigated diagnosis provision within young people who met criteria for a disorder. In the Avon Longitudinal Study of Parents and Children in the UK, of 18-year-olds who met criteria for depression, only 7.0% had a diagnosis of depression documented in their primary care records. In the Child and Adolescent Twin Study in Sweden, of 9-year-olds who met criteria for ADHD, only 18.5% of boys and 12.1% of girls had a diagnosis of ADHD noted in their health records. Within an Irish child and adolescent mental health service, of 12-15-year-olds who met criteria for depressive disorder, only 28.4% received a depressive disorder diagnosis after their usual clinical assessment. These studies suggest large gaps in diagnosis provision, including within health services, and highlight possible bias by sociodemographic characteristics. A better understanding of this topic is needed to enable more effective service planning, commissioning, and policymaking.Added value of this study: This study investigated mental health diagnosis provision in 17-year-olds from South London. We examined diagnosis provision for several mental health disorders in NHS mental healthcare records. We compared these data with population and epidemiological data to calculate diagnosis provision rates in the general population, in those estimated to have met criteria for a disorder, and in those estimated to have also seen a health professional. We found that diagnosis provision substantially increased during our study period of 2009-2024, demonstrating an increase in the number of young people whose mental health needs were recognised in specialist services. However, we estimated that diagnoses were only provided to a small proportion of young people with a mental health disorder, including those within health services. Estimated diagnosis gaps were largest for those with generalised anxiety disorder and multiple disorders. We also found evidence of biases in diagnosis provision, based on gender, neighbourhood deprivation, and ethnicity.Implications of all the available evidence: Barriers to mental healthcare access for young people should be reduced by policymakers and commissioners, including through investment in adequately staffed services with skilled clinicians, enabling more young people with mental health disorders to receive cost-effective evidence-based healthcare that has long-term benefits. Greater awareness among clinicians of the under-diagnosis and bias in diagnosis of young people's mental health disorders, alongside strategies to address these problems, could improve young people's mental healthcare. Innovative scalable interventions that can reach many more young people need to be developed, evaluated, and implemented by researchers. Prevention strategies are also required, including addressing risk factors for young people's mental health disorders, and intervening early for those with symptoms before disorders develop, to reduce the future burden of mental health disorders in young people.

Depressive symptoms increase during puberty and females experience higher rates of depression compared to males. However, it is unclear whether the increase in depressive severity is due to general increases in all symptoms, or whether there are specific symptoms that are more prominently influenced by pubertal development. Therefore, we examined whether pubertal status and chronological age exert pathoplastic effects (i.e., differential influences on disorder expression) on depressive symptoms. To isolate pathoplastic effects, we controlled for overall depression severity. Data came from 7,362 participants spanning ages 10-18 in the Avon Longitudinal Study of Parents and Children. Depression was assessed via the Short Mood and Feelings Questionnaire. Pubertal status was measured through self- and parent-reports of pubic hair, breast, and gonadal development, and voice changes in male participants. Pubertal changes correlated with overall depression severity in females, but not in males. Certain symptoms were more prominently influenced by pubertal indicators and chronological age, supporting pathoplastic effects. In females, within-person breast development was associated with increases in the symptoms I hated myself and nobody really loved me and decreases in the symptom felt lonely. Pubic hair development was associated with higher levels of miserable/unhappy and I hated myself. In males, within-person testes development was associated with increases of the symptom felt tired. Voice changes were associated with increases in the symptom felt lonely. Chronological age was associated with multiple symptoms, beyond the effects of puberty. Pubertal changes and age independently shape depressive symptoms in different ways by sex.

Dysglycaemia in youth results from complex interactions between genetic and environmental factors, yet their individual and combined contributions remain unclear. We aimed to: (1) evaluate the predictive performance of polygenic risk scores (PRSs) for glycaemic traits from childhood to early adulthood; (2) identify gene-environment interactions shaping glucose homeostasis trajectories; and (3) explore underlying mechanisms using pathway-specific PRSs. Data from 8783 participants (aged 7-24 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to compute 12 PRSs for type 2 diabetes, fasting glucose, insulin and BMI. Glycaemic outcomes, including insulin resistance, prediabetes (impaired fasting glucose) and type 2 diabetes, were assessed using fasting glucose and insulin (ages 7, 15, 18 and 24 years) and HbA1c (age 9 years). We evaluated whether PRSs could distinguish between transient (resolved by adulthood) and persistent glycaemic abnormalities using multinomial regression. We performed univariate and multivariate regressions, incorporating environmental factors (lifestyle, diet and maternal characteristics), and evaluated model performance using R2 and AUC. We tested interactions between PRS quintiles and environmental factors and explored pathophysiological mechanisms using pathway-specific PRSs. Prediabetes prevalence was up to 24% at age 24 years. PRS-enhanced models outperformed those using environmental factors alone (e.g. AUC for dysglycaemia at age 15 improved by 0.12, reaching 0.78). Fasting glucose PRS showed moderate ability to differentiate transient from persistent prediabetes (AUC=0.70). Gene-environment analyses revealed that high genetic risk combined with increased screen time or younger maternal age increased insulin resistance risk. Physical activity and health awareness attenuated this risk. Pathway analyses indicated insulin secretion as a key mechanism earlier in life, with insulin resistance emerging later. Genes interact with environment to define glucose homeostasis in youth, highlighting modifiable factors as actionable targets for early prevention.

Externalising behaviours are among the most common childhood mental health problems and have been linked to numerous adverse psychosocial outcomes including antisocial behaviour and depression. Parental negativity (PNeg) and child behaviours have been shown to mutually influence each other, leading to coercive cycles of negative behaviour over time. Interrupting these negative cycles is a common target for clinical intervention but little is known about what factors moderate these cycles over time in the general population. Using data on 9943 families from The Avon Longitudinal Study of Parents and Children across ages 4, 7 and 8, we explored the reciprocal associations between PNeg and externalising behaviour and tested whether they differed as a function of high versus low parent-reported interpersonal social support and neighbourhood social cohesion. Using random-intercept cross-lagged panel models, we found bidirectional associations between PNeg and child externalising behaviour across ages 7 to 8 (&#x3b2;s&#xa0;=&#xa0;0.13-0.15) but not ages 4 to 7 (&#x3b2;s&#xa0;=&#xa0;0.01-0.03). Moreover, we did not find evidence of moderation of any of the cross-lagged paths by social support or neighbourhood cohesion. Parent-reported interpersonal social support and neighbourhood social cohesion do not appear to play a role in interrupting negative parent-child interaction cycles in the general population.

Mendelian randomization (MR) is increasingly used to strengthen causal inference in nutritional epidemiology. However, dietary MR studies often rely on instruments selected from genome-wide association studies of self-reported intake based solely on statistical significance, increasing vulnerability to pleiotropy and reverse causation and potentially violating key MR assumptions. We aimed to develop and evaluate a biologically informed framework for selecting valid genetic instruments for dietary exposures, leveraging genes encoding taste and olfactory receptors that influence chemosensory perception and shape food preferences and dietary behaviour. We prioritised 1,214 nonsynonymous variants (minor allele frequency&#x2009;&#x2265;&#x2009;1%) across 30 taste and 295 olfactory receptor genes. Associations with 140 food-liking traits were tested in UK Biobank participants aged 37 to 73 years. Candidate variants were evaluated using a multi-stage filtering pipeline comprising replication in an independent younger cohort (Avon Longitudinal Study of Parents and Children, age 25), concordance between food liking and intake, exclusion of associations with socioeconomic status, assessment of food specificity accounting for linkage disequilibrium and co-consumption, and directionality testing to reduce reverse causation. Retained variants were used as instruments in MR analyses of cardiometabolic outcomes. We identified 268 variants within 101 olfactory and 16 taste receptor genes associated with 96 food-liking traits. Filtering yielded 24 candidate instruments for 20 foods. The instrument for onion liking satisfied all pre-defined criteria for classification as high confidence. As an illustrative MR application, genetically proxied onion liking was associated with lower systolic and diastolic blood pressure and reduced risk of type 2 diabetes, with no evidence of effects on body mass index, glycaemic traits, or serum lipid levels. Instrument selection guided by chemosensory genetics provides a scalable strategy for dietary MR that can improve instrument credibility and reduce susceptibility to pleiotropy and reverse causation. However, this approach prioritises biological specificity at the cost of fewer available instruments. This framework supports more robust causal evaluation of diet-disease relationships and strengthens inference in nutritional epidemiology and public health research.

Longitudinal evidence on the dual-energy X-ray absorptiometry measures of body composition from childhood with changes in cardiac structure and function in youth is scarce. This study examined whether the increase in total and trunk fat mass during growth from childhood is associated with progressive cardiac remodeling and whether increased systolic blood pressure and inflammation explained the associations. From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1803 children aged 9 years who had repeated dual-energy X-ray absorptiometry-measured fat mass at ages, 9, 11, 15, and 17 and 24 years clinic visits were included. Echocardiography at 17 and 24 years assessed left ventricular mass indexed for height2.7 (LVM). Each unit increase of total fat mass from age 9-24 years (&#x3b2; = -0.48&#x2005;g/m2.7 [95% CI, -0.50--0.48], P < .001) and trunk fat mass (-0.78&#x2005;g/m2.7 [-0.83 to -0.74], P < .001) were independently associated with progressively decreased LVM over 7 years. However, each unit increase of total fat mass from age 17-24 years (&#x3b2; = 0.12&#x2005;g/m2.7 [95% CI, 0.09-0.15], P < .001) and trunk fat mass (0.23&#x2005;g/m2.7 [0.18-0.28], P < .001) were independently associated with increased LVM. Each unit increase of lean mass from age 9-24 years (&#x3b2; = 0.31&#x2005;g/m2.7 [95% CI, 0.29-0.33], P < .001) and body mass index (0.24&#x2005;g/m2.7 [0.20-0.27], P < .001) were independently associated with increased LVM. Increased systolic blood pressure and high-sensitivity C-reactive protein partly mediated (10.6% and 7.4% mediation, respectively), the association between increased fat mass and increased cardiac mass during growth from adolescence to young adulthood. Increased total and trunk fat mass from adolescence but not from childhood predicted progressive cardiac structural and functional pathologies by young adulthood.

Affective instability (AffI) is associated with psychosis, and cannabis use is a known risk factor for psychosis. Previous evidence suggests that AffI may itself be a risk factor for cannabis use. This study aimed to investigate the longitudinal relationship between AffI and cannabis use during adolescence and the development of psychosis in early adulthood. Data from the Avon Longitudinal Study of Parents and Children were analyzed to estimate the prevalence of AffI at age 12 and cannabis use frequency at ages 13, 14, 15, 17, 20, and 22. Psychotic experiences (PEs) and psychotic disorder (PD) were measured at age 24 using the Psychosis-like Symptoms Interview. Latent class growth analysis identified cannabis use trajectories and odds ratios (OR) were calculated to assess associations between adolescent AffI, different cannabis use patterns and psychotic outcomes. Path analysis was used to examine cannabis use as a mediator between AffI and psychotic outcomes. Individuals with AffI were significantly more likely to develop psychotic outcomes at age 24 [PEs: OR&#x2009;=&#x2009;4.08 (2.35-7.08); PD: OR&#x2009;=&#x2009;4.74 (2.00-11.27)]. Regular cannabis users from ages 13-22 had an increased likelihood of developing psychotic outcomes compared with non-users [PEs: OR&#x2009;=&#x2009;4.40 (2.79-6.92); PD: OR&#x2009;=&#x2009;3.13 (1.25-7.88)]. Regular cannabis use partially mediated the relationship between AffI and both PEs and PD. Adolescents with AffI are at a higher risk of developing psychosis in early adulthood. Regular cannabis use mediates this risk, suggesting the potential benefit of targeted prevention strategies for at-risk youth.

Exposure to parental depression is a risk factor for offspring mental illness. To examine the association between the timing of exposure to parental depression, from pregnancy to young adulthood, and adult offspring mental health. This prospective longitudinal cohort study of adult offspring aged 22 to 27 years in the Avon Longitudinal Study of Parents and Children, a British birth cohort, was conducted from September 1990 to July 2020. Data were analyzed from March 2024 to January 2026. Parental depressive symptoms were assessed repeatedly using the Edinburgh Postnatal Depression Scale (score range, 0 to 30, with higher scores indicating more severe depressive symptoms) beginning in pregnancy through offspring age of 21 years. The main outcomes were offspring symptoms of depression at age 27 years, anxiety at age 25 years, psychotic disorders at age 24 years, and alcohol use disorder (AUD) at age 22 years. Covariates included socioeconomic status and maternal-offspring polygenic risk for multiple psychiatric disorders. A total of 5329 adult offspring (3276 females [61.5%]) provided at least 1 outcome measure, which included 3795 participants providing symptoms of depression (mean [SD] age, 27.8 [0.5] years), 3505 participants providing symptoms of anxiety (mean [SD] age, 25.3 [0.6] years), 3342 participants with assessments for psychotic disorders (mean [SD] age, 24.5 [0.8] years), and 3392 participants reporting on symptoms of AUD (mean [SD] age, 22.9 [0.5] years). Cumulative exposure to parental depression across all time points was associated with increased odds of offspring depression (maternal: AOR, 2.36 [95% CI, 1.91-2.92]; paternal: AOR, 2.13 [95% CI, 1.60-2.83]) and anxiety (maternal: AOR, 2.58 [95% CI, 2.06-3.23]; paternal: AOR, 1.98 [95% CI, 1.49-2.63]). Only maternal depression was associated with increased odds of psychosis symptoms (maternal: AOR, 1.90 [95% CI, 1.27-2.82]; paternal: AOR, 1.63 [95% CI, 0.95-2.80]). There were no statistically significant associations with AUD. Significant associations between maternal depression and adult offspring depression were observed from 32 weeks' gestation (AOR, 1.08 [95% CI, 1.01-1.15]) to age 18 years (AOR, 1.08 [95% CI, 1.01-1.16]). Maternal depression from the 8-month postnatal period (AOR, 1.06 [95% CI, 1.01-1.11]) onward (aged 21 years: AOR, 1.13 [95% CI, 1.02-1.24]) was associated with offspring anxiety symptoms. Paternal depression was significantly associated with offspring depression from mid-childhood (AOR, 1.08 [95% CI, 1.01-1.15]) onward (aged 21 years: AOR, 1.22 [95% CI, 1.04-1.43]), with similar associations between paternal depression and offspring anxiety from mid-childhood (aged 5 years: AOR, 1.11 [95% CI, 1.03-1.18]) onward (aged 21 years: AOR, 1.22 [95% CI, 1.04-1.43]). Only maternal prenatal depression at 32 weeks' gestation was associated with offspring psychotic symptoms (AOR, 1.20 [95% CI, 1.03-1.41]). In this cohort study, analyses of 2 decades of data found distinct temporal associations between maternal and paternal depression and offspring psychiatric symptoms, and pregnancy was found to be a sensitive period in the association between maternal depression and offspring psychotic experiences. The findings suggest a substantial role of timing for specifying the association between parental depression and psychiatric outcomes in young adults and emphasize the need to support parental mental health from pregnancy onward.

Psychopathologies are interrelated and often co-occur, suggesting shared genetic and environmental influences. We examined the mediated associations between children's genetic predispositions for higher-order psychopathology-represented by polygenic scores (PGS)-and the development of psychopathology symptoms from childhood to adolescence via baseline levels of psychopathology symptoms in childhood. We performed the same set of analyses in 2 longitudinal birth cohorts (Generation R Study, N = 4,657; Avon Longitudinal Study of Parents and Children [ALSPAC], N = 4,368) and assessed the consistency of our results. PGS for externalizing, internalizing, and neurodevelopmental psychopathology were calculated using the LDpred2-automatic technique. Using growth curve modeling, we modeled the developmental slopes of child psychopathology symptoms into adolescence (ages 6-14 years, assessed by mothers using the Child Behavior Checklist [Generation R Study] and the Development and Well-Being Assessment [DAWBA; ALSPAC]). We next performed 3 sets of mediation analyses (one per PGS) predicting the development of psychopathological symptoms via baseline levels (at age 6 years) of psychopathology during childhood. The PGS for neurodevelopmental problems was linked to most baseline levels and developmental slopes of psychopathological symptoms through direct or mediated effects (ie, via higher levels of symptomatology at baseline). The PGS for neurodevelopmental problems could serve as a broad index of susceptibility to psychopathological symptoms in the general youth population. Direct and Indirect Developmental Pathways From Genetic Predispositions to Mental Health Symptomatology in Adolescence; https://osf.io/hwv9a/.

The positive association between childhood asthma and attention deficit hyperactivity disorder (ADHD) has not been adequately explained. We aimed to investigate whether it is causal or whether shared genetics and/or shared early-life risk factors explain the link. We used a two-sample Mendelian randomization (MR) to test whether there is a causal relationship between asthma and ADHD. In the Avon Longitudinal Study of Parents and Children (ALSPAC), we defined doctor-diagnosed asthma, its endotypes according to atopy determined by skin-prick tests, and the risk of ADHD by using the Strengths and Difficulties Questionnaire, all at 7&#xa0;years of age. We explored whether the asthma-ADHD association was attenuated when controlling for an extensive number of early-life risk factors (N&#x2009;=&#x2009;7165). Child polygenic risk scores (PRSs) for asthma and ADHD were calculated by using published genome-wide association studies across seven P-value thresholds (<5&#x2009;&#xd7;&#x2009;10-8 to <.5) (N&#x2009;=&#x2009;5425-5503). We found little evidence of a causal effect between asthma and ADHD in both directions. In ALSPAC, asthma [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.10&#x2009;-&#x2009;1.65], particularly non-atopic asthma (OR 1.51, 95% CI 1.09&#x2009;-&#x2009;2.08), was associated with ADHD in crude models, while atopic asthma was not (OR 1.00, 95% CI 0.69&#x2009;-&#x2009;1.45). These associations were largely attenuated after adjusting for 15 shared early-life risk factors (OR 1.14, 95% CI 0.92&#x2009;-&#x2009;1.41 for asthma and OR 1.24, 95% CI 0.88&#x2009;-&#x2009;1.74 for non-atopic asthma). There was little evidence of association between asthma PRSs and ADHD at any P-value threshold. We found evidence of an association between ADHD PRSs and asthma and non-atopic asthma at most thresholds; the strongest association was at P&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-3 (OR 1.12, 95% CI 1.04&#x2009;-&#x2009;1.22, P&#x2009;=&#x2009;.004) for asthma and at P&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-2 (OR 1.18, 95% CI 1.04&#x2009;-&#x2009;1.34, P&#x2009;=&#x2009;.01) for non-atopic asthma. The association between asthma and ADHD in childhood is unlikely to be causal and is largely explained by shared early-life risk factors, with some evidence for a shared genetic background.

Observational evidence suggests ultra-processed food (UPF) may contribute to obesity, but some people who consume a larger amount of UPF remain at normal weight. This study examined whether childhood UPF consumption was associated with obesity in early adulthood and whether the association was modified by genetic susceptibility to body mass index (BMI). This prospective cohort study included data from 3061 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) in England with follow-up from 7 to 24&#xa0;years. UPF consumption was calculated from food diaries based on the NOVA classification. LDpred2 was used to construct a polygenic score (PGS) for body mass index (BMI). Linear regression models were used to estimate the association between UPF intake at 7&#xa0;years and BMI at 24&#xa0;years. The PGS-UPF interaction was examined to see whether genetic susceptibility modifies the association between childhood UPF consumption and early adulthood BMI. Each 10% increase in the proportion of total energy intake coming from UPF at 7 was associated with 0.21 (95% CI 0.05-0.37) kg/m2 higher BMI at 24, after adjusting for BMI at 7, age, sex, ethnicity, physical activity, socioeconomic position, and total energy intake. There is evidence for PGS-BMI interaction (0.19; 95% CI 0.02-0.36), and the UPF-BMI association was only retained in children with the highest genetic predisposition to higher BMI (0.74, 95% CI 0.07-1.42) in the subgroup analysis. UPF consumption in childhood is only associated with early adulthood obesity among children more genetically predisposed to higher BMI.

Atopic dermatitis (AD) may impair school performance through sleep disturbance, comorbidities, or psychosocial effects; however, population-based longitudinal evidence is limited. To investigate the association of AD with academic performance and whether this association is modified or confounded by disease phenotype and socioeconomic background. Parallel, population-based cohort studies in Denmark and England, including children with or without AD. In Denmark, children born between 1986 and 2000 from nationwide linked registries were followed up through 2018. In England, children born between 1991 and 1992 from the Avon Longitudinal Study of Parents and Children, linked to the National Pupil Database, were followed up through 2009. Data analysis was conducted from October 2022 to April 2024. AD, defined as hospital diagnosis before age 13 years (Denmark) or 2 or more maternal reports of AD by age 11.5 years (England). Danish analyses were repeated in exposure-discordant full siblings to account for family factors. Academic performance on final compulsory national examinations at approximately age 16 years: nonpassing grade (binary outcome; Poisson regression prevalence ratios) and mean academic performance score (continuous outcome; linear regression mean differences). A total of 782&#x202f;837 children were included between both studies. In Denmark (n&#x2009;=&#x2009;776&#x202f;214; 10&#x202f;259 children with AD; 386&#x202f;408 [49.8%] female), the prevalence of nonpassing grades (12.0% vs 11.2%; fully adjusted prevalence ratio [aPR], 1.06 [95% CI, 1.01-1.12]) and mean academic performance scores (fully adjusted mean difference, -0.06 points [95% CI, -0.11 to -0.01]) were similar between children with vs without AD. Active AD was associated with a higher prevalence of nonpassing grades than no AD (aPR, 1.19 [95% CI, 1.03-1.37]). Sibling analyses yielded similar results. In England (n&#x2009;=&#x2009;6623; 2967 children with AD; 3332 [50.3%] female), nonpassing grades were slightly less common (37.7% vs 47.4%; aPR, 0.88 [95% CI, 0.83-0.93]) and mean performance scores were higher (10.48 points [95% CI, 6.49-13.86]) in children with vs without AD. Phenotype analyses showed that better performance in children with moderate-declining and moderate-frequent AD primarily explained these results, whereas those with mild-intermittent or severe-frequent AD performed similarly to the unaffected or rare comparator. Overall, no consistent variation by disease phenotype or socioeconomic background was found across academic performance outcomes and settings. In these parallel cohort studies, triangulation across 2 large cohorts and multiple analyses provided reassurance that AD is likely not associated with meaningfully diminished academic performance among adolescents taking national compulsory examinations.

The United Kingdom has the fourth highest estimated prevalence globally of maternal alcohol consumption during pregnancy (41%). It is therefore important to understand the long-term impacts of prenatal alcohol exposure (PAE) by examining its impact on the development of adolescent multiple risk behaviors (MRBs) that may increase morbidity and premature mortality across the life-course. Using Avon Longitudinal Study of Parents and Children (ALSPAC) cohort data with multiple imputation (n&#x2009;=&#x2009;6752), we examined the impacts of "infrequent," "frequent," and "binge" PAE groups on the development of seven MRBs at 16&#x2009;years old, encompassing substance misuse, risky sexual behavior, and antisocial behavior. Data were analyzed using multiple regression, using q-statistics to adjust for multiple comparisons. Adolescents with "infrequent" and "frequent" PAE were more likely to develop hazardous alcohol use at 16&#x2009;years old compared to those without PAE, with the strongest association being for the "frequent" group (adjusted odds ratio [aOR] 1.45 [1.19-1.76], p&#x2009;<&#x2009;0.001, q value&#x2009;=&#x2009;0.005). Adolescents exposed to binge drinking prenatally had an increased risk of engaging in underage sexual intercourse (aOR 1.34 [1.09-1.64], p&#x2009;=&#x2009;0.005, q value&#x2009;=&#x2009;0.044). Binge drinking predicted a higher total MRB score (Coefficient&#x2009;=&#x2009;+0.21 [+0.08 to +0.33], p&#x2009;=&#x2009;0.001, q value&#x2009;=&#x2009;0.017). This study supports the UK Chief Medical Officer's Low Risk Drinking Guidelines that the safest approach if pregnant, or if there is a possibility of becoming pregnant, is to avoid drinking alcohol, with the more alcohol consumed during pregnancy the greater the risks of long-term harm to the baby. Given the findings that PAE may increase the risk of adolescent hazardous alcohol use and risky sexual behavior, this study highlights the need for further research to understand the intergenerational effects of PAE.