European Child & Adolescent Psychiatry

BackgroundOrganization, time management, and planning (OTMP) difficulties are associated with academic underachievement. OTMP skills training programs are effective in reducing OTMP deficits and improving academic performance. A randomized controlled trial of Homework, Organization, and Planning Skills (HOPS) for students ages 11-14 (1) found it to be effective with medium to large effects. In that study, HOPS was provided by counselors employed by the research team. This study is a replication examining HOPS under more authentic conditions when providers are employed by schools serving enrolled students. The primary aim is to evaluate HOPS offered by school providers in relation to treatment-as-usual/waitlist (TAU/WL). To respond to limited school resources post-COVID-19, HOPS is also provided by research team members, creating the opportunity to replicate the findings from the prior trial (1) and explore differential effectiveness when HOPS is implemented by school vs. research providers. MethodsStudents in about 30 schools serving students ages 11-14 will be enrolled. Schools are randomly assigned to HOPS vs. TAU/WL on a 2:1 ratio. Students assigned to HOPS schools are randomly assigned to a school vs. research provider on a 1:1 basis. Providers receive two hours of training and additional assistance on request. Child outcomes related to OTMP skills, homework, and academic performance are assessed at post-treatment, 6-month (from baseline) follow-up, and 12-month follow-up. HOPS sessions are video recorded for fidelity coding. Potential effect modifiers include student ADHD, oppositional defiant, and internalizing symptoms, and family socioeconomic level. Analyses will use mixed effects modeling. The goal of the study is to enroll 135 participants, yielding a minimal detectable effect size of 0.50, within the expected range based on prior research. DiscussionThe study is unique in examining intervention implementation and effectiveness when intervention is provided under authentic practice conditions. Trial RegistrationThis study was registered with clinicaltrials.gov (NCT04465708).

ImportanceAs the percentage of young people in the United States identifying as transgender and gender diverse increases, more youth face identity-linked social and structural stigma and discrimination. Little is known about the impact of stigma on psychotic-like experiences in gender diverse youth. ObjectiveTo assess the impact of bullying victimization and state-level policies on psychotic-like experiences among gender diverse youth. DesignIn this prospective cohort study, cross-sectional and longitudinal analyses were conducted using data collected between 2017-2022 across 17 states. SettingThe Adolescent Brain Cognitive Development (ABCD) Study is a U.S. population-based longitudinal study that follows and deeply phenotypes adolescents from the age of 9 to 18. ParticipantsCross-sectional analyses included data from 9,112 participants (mean age=13 {+/-} 0.6) collected between 2019 and 2022. Longitudinal analyses comprised 4,529 participants with data collected across 5 waves between 2017 and 2022. ExposuresSelf-reported frequency of bullying victimization and data on annual state-level policies related to gender identity. Main OutcomesSelf-reported psychotic-like experiences and associated distress, measured by the Prodromal Questionnaire - Brief Child Version. ResultsBased on a dimensional measure of gender, 689 adolescents were identified as most gender diverse (i.e., least congruent with birth-assigned sex) and 8,240 as least gender diverse (i.e., most congruent with birth-assigned sex). Rates of bullying victimization and psychotic-like experiences were significantly elevated in the most vs. least gender diverse group, with bullying partially mediating the difference in psychotic-like experiences (indirect effect = 0.11, p < 2x10-16; direct effect = 0.52, p < 1x10-16). Gender diverse adolescents exhibited greater sensitivity to the effects of bullying on psychotic-like experiences (interaction {beta} = 0.14, 95% CI [0.09, 0.19], p = 8.5x10-08). Moreover, the persistence of unsupportive legislation across 4 years was associated with significantly greater increases in psychotic-like experiences over time in gender diverse youth (interaction {beta} = 0.30, 95% CI [0.20, 0.40], p = 2.2x10-8). ConclusionsThese findings indicate that bullying victimization and unsupportive legislation may explain greater and increasing rates of psychotic-like experiences in gender diverse youth. KEY POINTSO_ST_ABSQuestionC_ST_ABSDo bullying and state-level policy related to gender identity contribute to mental health problems in gender diverse youth in the United States? FindingIn this large U.S.-based sample of adolescents (ages 9-13), gender diverse adolescents reported more frequent experiences of bullying, which partially accounted for increased rates of subclinical psychotic-like experiences (PLEs). Between 2017 and 2022, gender diversity was associated with increasing PLEs only in states with consistently unsupportive policies; in all other states, PLE scores remained stable over time or decreased. MeaningResults suggest that PLEs in the context of gender diversity are partially attributable to the sociopolitical environment and that policy decisions at the state-level have far-reaching impacts on the mental health of youth in the United States.

ObjectiveAlthough mental health and healthy lifestyle interventions are associated with functional outcomes in adolescence, the extent to which particular lifestyle factors explain relationships between mental health and outcome are unclear. Here we examined mediating effects of lifestyle factors on relationships between mental health and two functional outcomes measured 2-3 years later as well as the moderating effect of environmental risk factors on mediation strength in early adolescence. MethodsThis study analyzed data from 3 waves of the Adolescent Brain Cognitive Development Study (ages 10-11, 11-12, and 12-13). Mediating effects of sleep quality, screen time, physical activity and Mediterranean diet on the relationships between depression, anxiety, psychotic-like experience (PLE) distress, and total problems with two subsequent functional outcomes (academic functioning and social problems) were examined. Secondary analyses included environmental factors as moderators. ResultsSleep quality mediated 18.5%, 36.3%, 8.3%, and 3.4% of the relationships between depression, anxiety, PLE distress and total problems with academic functioning, respectively. Screen time was the second strongest mediating factor. For social problems, only sleep quality showed > 3% mediation (19.6% - 23.3%). Mediating effects of sleep and screen time on academic functioning decreased as financial adversity increased. Conversely, mediating effects of sleep quality on social problems increased with worsening family conflict, financial adversity, and school environment. ConclusionsThese results suggest that healthy lifestyle factors (in particular sleep quality) may partially explain the associations between mental health and functioning in adolescents and suggest that these effects are modulated by environmental factors. These results may have important implications for future intervention studies.

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.

ObjectiveTo analyze the structure of mental disorders in children in the outpatient practice of a specialized mental health center for optimization of care organization for this patient category. MethodsA retrospective analysis of medical records of 23 children (out of 44 patients) at the Insight Mental Health Center (Dushanbe, Tajikistan) was conducted for the period from December 9, 2025, to January 8, 2026. Diagnosis was performed according to ICD-10 criteria using standardized instruments: M-CHAT-R, ADOS-2, and ADI-R for autism spectrum disorder (ASD); SNAP-IV for attention deficit hyperactivity disorder (ADHD); CGI; and pediatric versions of PHQ and GAD. ResultsChildren accounted for 52% of all patients. Primary school-age children (7-12 years) predominated at 43.5%. Disorders of psychological development (F80-F89) dominated the nosological structure at 82.6%, with ASD comprising 56.5%. ADHD was diagnosed in 30.4% of cases. Comorbidity was registered in 47.7% of patients. ConclusionThe structure of pediatric psychiatric pathology is characterized by a predominance of developmental disorders and high comorbidity levels, justifying the need for a multidisciplinary approach.

BackgroundAutism spectrum disorder (ASD) is frequently associated with speech and language difficulties, yet empirical data from Central Asian countries remain scarce. This study examined the association between a diagnosis of childhood autism (ICD-10: F84.0) and the presence of speech development difficulties in a clinical sample from Tajikistan MethodA retrospective cross-sectional study was conducted using clinical records of 85 patients (36 with F84.0; 49 with other psychiatric diagnoses) at the Insight Mental Health Center in Dushanbe, Tajikistan (December 2025-January 2026). Speech difficulties were identified through systematic review of clinical notes. Between-group comparisons were performed using Pearsons {chi}2 test, odds ratios (OR), relative risk (RR), and effect size measures ({varphi} coefficient, Cohens h). ResultsSpeech difficulties were present in 72.2% of the autism group versus 36.7% of the comparison group. The association was statistically significant ({chi}2 = 10.47, p <.01). Children with autism had substantially higher odds of speech difficulties (OR = 4.48, 95% CI [1.76, 11.38]), with a large effect size (Cohens h = 0.73). ConclusionsAutism diagnosis was significantly associated with elevated rates of speech difficulties in this Tajik clinical sample. Practical implicationsThese findings support the systematic inclusion of speech-language assessment and intervention within autism care protocols, particularly in Central Asian healthcare settings where such integration remains limited. HighlightsO_LISpeech difficulties were identified in 72.2% of children with autism (F84.0) in a Tajik clinical sample. C_LIO_LIChildren with autism were 4.5 times more likely to present with speech difficulties than those with other diagnoses (OR = 4.48, 95% CI [1.76, 11.38]). C_LIO_LIThe most prevalent speech pattern was complete absence of expressive speech (nonverbal presentation). C_LIO_LIFindings support the integration of speech-language assessment into standard autism care protocols in Central Asia. C_LIO_LIThis is one of the first empirical reports on autism and speech profiles from Tajikistan. C_LI

BackgroundAdults with intellectual disabilities who display behaviours that challenge (BtC) are more prone to poor health. This study seeks to evidence the long-term health outcomes for this population. MethodsWe conducted a longitudinal cohort study of adults with intellectual disabilities aged 18+ years in England using data from Clinical Practice Research Datalink Aurum (01/2003-12/2023) linked to Hospital Episode Statistics and Office for National Statistics. Main outcome measures were Annual Health Checks (AHCs), GP referrals, emergency visits, outpatient attendance, inpatient admissions, and mortality. ResultsAmong 83,166 adults with intellectual disabilities (mean age 38.6 years), 18.5% had a record of BtC with similar sociodemographic distributions to those without BtC but higher rates of physical and mental health comorbidities and uptake of AHCs. 72.5% of participants with BtC were receiving psychotropic medication(s). Adults with BtC had higher rates of mental health outpatient attendance (OR: 1.42, 95% CI: 1.33 to 1.52) and inpatient admissions (IRR: 1.19, 95% CI: 1.09 to 1.29) but consistently lower rates of physical health outpatient attendance (IRR: 0.81, 95% CI: 0.78 to 0.84) and inpatient admissions (IRR: 0.77, 95% CI: 0.74 to 0.79), after adjusting for demographic and clinical characteristics. BtC was not associated with mortality after adjustment for comorbidities (HR: 0.97, 95% CI: 0.93 to 1.00). ConclusionThis longitudinal study not only corroborated the markedly elevated burden of physical and mental health comorbidities among individuals displaying BtC but also indicated that repeated efforts to improve health outcomes have yielded minimal measurable benefit over time. The apparent absence of progress is likely underpinned by a combination of insufficiently effective or poorly tailored interventions and wider systemic constraints that limit the capacity of services to respond to the complex needs of this population.

BackgroundThe present study examines the link between DNA methylation at the nerve growth factor-induced protein A (NGFI-A) binding domain of the NR3C1 1F promoter and later cognitive functions in children from families living in disadvantaged psychosocial conditions. MethodsParticipants were 132 children who took part in a Swiss Parents as Teachers (PAT) randomized controlled trial (72 in the intervention group, 60 in the control group). DNA methylation was quantified from saliva samples collected at age three using sodium bisulfite next-generation sequencing (NGS). Cognitive functions were assessed at age five using the SON-R 2.5-7 Intelligence Test. Results(a) DNA methylation at age three predicted lower IQ at age five through increased concentration problems; (b) participation in the three-year PAT program predicted lower methylation levels at the end of the intervention; and (c) early life stressors predicted lower IQ through increased methylation and concentration problems with descriptively stronger effects in the control group. ConclusionsThese findings demonstrate a link between early DNA methylation at the NGFI-A binding site of the NR3C1 1F promoter and later cognitive functions in children and highlight the role of early life stressors and the PAT intervention in shaping these associations.

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with intellectual disability and increased vulnerability to traits such as anxiety, perseveration, and belief inflexibility. In the general population, these traits are linked to self-reported thought disturbances such as paranoia and delusions. However, little is known about how such disturbances present in WS, largely due to concerns regarding the validity of self-report in this population. To address this gap, we collected self- and caregiver-reported measures characterizing thought disturbances and related cognitive traits in adults with WS, assessing inter-rater reliability and correlations among measures. Total scores were similar across reporters, except for delusional ideation, which participants endorsed more strongly than caregivers. Several participants also reported clinically significant levels of paranoia, delusions, and worry that were not captured by caregiver report. These findings suggest that self-report is a valid method for accurately characterizing the severity and nature of thought disturbances in WS.

BackgroundTourette syndrome is a childhood-onset neuropsychiatric disorder characterised by recurrent motor and vocal tics. It shows a marked male predominance and is frequently associated with comorbid conditions such as attention-deficit/hyperactivity disorder (ADHD) and obsessive- compulsive disorder (OCD). Histaminergic dysregulation in the brain has been proposed as one of the mechanisms underlying Tourette syndrome. Vitamin B6, a key cofactor in histamine metabolism, may therefore play a contributory role in its pathophysiology. MethodThe clinical features of 25 children diagnosed with Tourette syndrome were assessed using the Yale Global Tic Severity Scale. Plasma vitamin B6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and compared with those of a control group. ResultMost participants were males, and 16% had comorbid ADHD or OCD. The most common motor tics were eye blinking, shoulder shrugging, head jerking, and orofacial movements. Frequent vocal tics included throat clearing, sniffing, uttering syllables, and breathing-related tics. Coprolalia was observed in four children. The median plasma vitamin B6 level in the Tourette syndrome group was 25.01ng/ml, which was significantly lower than the 36.33ng/ml in the control group (Mann-Whitney U = 225, p = 0.03). The rank-biserial correlation indicated a moderate effect size (r = 0.35). ConclusionTourette syndrome in children predominantly affects males and is commonly associated with ADHD and OCD. Coprolalia-a clinically distressing symptom - was present only in a small subgroup. The lower plasma vitamin B6 levels observed in children with Tourette syndrome suggest a possible role for vitamin B6 in disease pathogenesis, potentially through its involvement in histaminergic and GABAergic neurotransmission, as well as in the modulation of neuroinflammatory processes.

Dialectical Behavioural Therapy for Adolescents (DBT-A) is an effective treatment for adolescents exhibiting features of borderline personality disorder (BPD). However, some do not benefit, potentially leading to major negative outcomes later in life. Previous quantitative studies have highlighted the importance of dynamic (changeable) factors in determining treatment success, including the therapeutic alliance, emotional dynamics between therapist and adolescent, and the motivation of those involved. Nevertheless, the specific contribution of these factors to the therapeutic process and perceived treatment success remains unclear. This study protocol outlines a multicenter, qualitative longitudinal study designed to explore how dynamic factors in DBT-A are experienced by adolescents, parents, and therapists at various stages of therapy. The study will track treatment journeys (trajectories) of fifteen youth during DBT-A therapy across four child and adolescent psychiatry institutions in the Netherlands. The triad of adolescent, parent(s), and therapist will be interviewed separately at four time points during treatment: at the start and after three, six, and nine months (resulting in 180 interviews in total). The semi-structured interviews, based on a theoretical framework, will be analyzed using reflexive thematic analysis, employing a combination of deductive framework analysis and inductive open coding methods. By bringing together the triad of perspectives, and monitoring how these perspectives evolve over time, this study will yield valuable, practice-based insights into how dynamic factors unfold during DBT-A. Insights from this study will offer therapists specific, actionable guidance for modifying dynamic factors to better address the unique needs of adolescents with BPD features.

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. depressive or anxiety) disorders, in youth accessing mental health care. MethodsActigraphy monitoring was completed for 5-23 days in 250 participants (aged 12-30) presenting to youth-focused early intervention services in Sydney, Australia. Participants were followed longitudinally as part of the Optymise cohort for 6+ months (up to 8 years; median 2.5 years). Logistic regression and Cox proportional hazard models estimated associations between SCRDs and illness progression, after controlling for relevant baseline clinical and demographic covariates (e.g., age, sex, social and occupational functioning, mania-like and psychotic-like experiences, medication use). ResultsLonger sleep duration at baseline predicted higher odds of transition (OR = 2.23 [95%CI = 1.38-3.74]), and shorter time-to-transition (HR = 2.05 [95%CI = 1.23-3.40]) to full-threshold bipolar or psychotic disorders. This effect remained significant after controlling for clinical covariates. Later sleep midpoint predicted transition to any full-threshold mental disorder (OR = 1.46 [95%CI = 1.02-2.17]) at the uncorrected significance level. ConclusionsExcessive sleep duration may represent an early marker of vulnerability for progression to severe mental illness. Findings support the prognostic utility of objective measures of SCRDs to guide indicated prevention and early intervention.

Misophonia is the adverse emotional reaction to everyday sounds (e.g., chewing or pen clicking). Since atypical sensory experiences are a key feature of autism, we investigated whether autistic individuals are more liable for experiencing misophonia symptoms. In addition, we explore the contribution of sensory sensitivity to misophonia symptoms in autism. Autistic adults (N=1050) filled out the Amsterdam Misophonia Scale-Revised (AMISOS-R), the Autism Spectrum Quotient (AQ-28), and the Sensory Processing Questionnaire (SPQ). Autistic people reported higher scores on the AMISOS-R compared to population levels, reflecting more misophonia symptoms. In particular autistic females and those with co-occurring disorders scored higher. In addition, we found that autistic traits strongly predicted misophonia symptoms. Hearing or vision sensitivity subscales of the SPQ significantly mediated the effect of autism on misophonia symptoms. The increased level of misophonia symptoms in autism and the mediation analyses suggest that autistic traits and sensory sensitivity are factors to consider for a subset of misophonia sufferers, with possible consequences for their clinical interventions.

BackgroundLight plays a critical role in mental health, as the primary input to the circadian system, which regulates mood, energy, and the sleep-wake cycle. Altered light sensitivity is a potential mechanism in circadian-associated mental disorders. MethodsActigraphy-derived sleep, physical activity, and circadian rhythm correlates of the pupillary light reflex were explored in young people with emerging mental disorders. Participants were 27 healthy controls (Mean age=25.67 {+/-} 2.83, 52% female) and 155 young people from the Neurobiology Youth Follow-up Study (Mean age=25.48 {+/-} 5.65; 60% female), recruited from an early intervention mental health service. 32% of the latter group were re-assessed over 12 months. Pupil constriction, average and maximal constriction velocity, and constriction latency were recorded by the PLR-3000 monocular pupillometer in response to dim ([~]10 lux) and bright ([~]1500 lux) pulses. ResultsCompared to healthy controls, young people with emerging mental disorders had a smaller change in pupil diameter (p=0.037) and a slower maximal constriction velocity (p=0.018) in response to dim light. In the full sample, decreased dim light sensitivity was correlated with later timing of actigraphy-derived sleep midpoint. Within the clinical cases, increased genetic risk for bipolar disorder was correlated with increased dim light sensitivity, and higher insomnia clinical scores were correlated with decreased dim light sensitivity. Pupillometry measures were stable across time and seasons. ConclusionAltered light sensitivity may be associated with the emergence of mood disorder in young people and with altered sleep-wake timing.

Psychotic-like experiences (PLEs) are common in youth and predict later mental health problems. Bullying victimization is a robust environmental risk factor for psychopathology including PLEs, but whether its association with PLEs reflects shared genetic liability, individual-specific putatively causal effects, or reciprocal processes is unclear. We analyzed seven waves of longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, examining associations across the sample in addition to leveraging within-family comparisons among twin and sibling pairs who were concordant or discordant for exposure to bullying victimization. Using linear mixed-effects and cross-lagged models, we found that youth reporting bullying victimization were more likely to endorse significantly distressing PLEs than non-victimized youth (caregiver-reported odds ratio=2.35; youth-reported odds ratio=4.10). Longitudinal analyses revealed bidirectional associations: prior bullying predicted subsequent increases in distressing PLEs, and prior PLEs predicted elevated risk of later bullying victimization. Genetically-informed within-family analyses indicated that both shared genetic influences and individual-specific factors contributed to these associations; critically, bullied youth exhibited higher odds of distressing PLEs than their non-exposed siblings (youth-reported odds ratio=6.67; 95%CI:4.96-8.96), consistent with an individual-specific effect of victimization. Together, these findings suggest that bullying and PLEs are linked through reciprocal developmental processes that are not fully explained by familial confounding. More broadly, our results highlight bullying prevention as a plausible leverage point for reducing early psychosis-spectrum risk and illustrate the value of integrating within-family designs to help disentangle genetic and environmental contributions to mental health outcomes in adolescence. Significance StatementUnderstanding how early adversity shapes mental health trajectories is important for science and public policy. Using nationally representative, longitudinal twin and sibling data, analyses show that bullying victimization and psychotic-like experiences in youth are linked through reciprocal processes that cannot be fully explained by shared genetics or family background. Bullied youth were more likely to endorse distressing psychotic-like experiences than their own non-bullied siblings, providing rare evidence for individual-specific effects of bullying victimization. Early psychotic-like experiences also increased subsequent risk of being bullied, suggesting a potential feedback loop that may compound risk. These findings demonstrate how social environments and mental health dynamically interact and point to bullying prevention as a population-level strategy with potential to reduce early psychopathology risk.

ImportanceMotor skill impairments affect up to 87% of children with autism spectrum disorder (ASD) and are associated with greater severity of repetitive behaviors. Yet, most research examining this relationship has treated ASD as a unitary condition. Understanding whether motor-behavior relationships differ by genetic etiology could inform stratified approaches to ASD research and clinical care. ObjectiveTo determine whether the relationship between motor function and restricted and repetitive behaviors (RRBs) differs between children with monogenic forms of ASD (SHANK3, DYRK1A, or SCN2A variants) and children with idiopathic ASD. Design, Setting, and ParticipantsMatched cohort cross-sectional study using data from the Simons Foundation Powering Autism Research for Knowledge (SPARK) database. Children with loss-of-function variants in SHANK3, DYRK1A, or SCN2A were matched to children with idiopathic autism and intellectual disability. Main Outcomes and MeasuresMotor function was assessed using the Developmental Coordination Disorder Questionnaire (DCDQ). Repetitive behaviors were assessed using the Repetitive Behavior Scale-Revised (RBS-R), with subscales categorized as lower-order (stereotyped, self-injurious) or higher-order (compulsive, ritualistic, sameness, restricted interests). The primary analysis compared motor-RRB correlations between groups. ResultsThe sample included 93 children with monogenic autism (SHANK3, n=34; DYRK1A, n=46; SCN2A, n=13) and 787 matched children with idiopathic ASD. In idiopathic ASD, motor function was negatively correlated with RRBs (r = -0.156); in monogenic ASD, this reversed to a positive correlation (r = +0.185; {Delta}r = 0.341, P = 0.002). This reversal was specific to higher-order RRBs (idiopathic r=-0.106; monogenic r=+0.234; {Delta}r=0.339, 95% CI 0.124-0.535, P=0.002) and was not observed for lower-order RRBs ({Delta}r=0.212, P=0.05). All three genes showed positive correlations (SHANK3 r=+0.033; DYRK1A r=+0.262; SCN2A r=+0.623) with no significant heterogeneity (P=0.153). Conclusions and RelevanceThe relationship between motor function and repetitive behaviors differs by genetic etiology, with children with monogenic ASD showing a positive motor-RRB correlation specific to higher-order behaviors, opposite to the negative correlation observed in idiopathic ASD. This reversal was consistent across three molecularly distinct genes. These findings support stratifying autism research and clinical care by genetic etiology. KEY POINTSO_ST_ABSQuestionC_ST_ABSDoes the relationship between motor function and restricted and repetitive behaviors (RRBs) differ between children with autism spectrum disorder (ASD) attributable to SHANK3, DYRK1A, or SCN2A variants and children with idiopathic ASD? FindingsWe conducted a matched cohort cross-sectional study comparing correlations between motor function and RRBs in children with monogenic ASD versus children with idiopathic ASD and intellectual disability. Motor function was negatively correlated with RRBs in children with idiopathic ASD but positively correlated in children with monogenic ASD. MeaningGenetic variants may alter behavioral organization, supporting the value of stratifying populations of individuals with ASD by genetic etiology in both research and clinical care.

BackgroundAdolescence is a period of rapid neurobiological and behavioural change, yet it remains unclear how deviations from normative brain maturation relate to the development of internalising and externalising symptoms. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study, we combined brain age prediction with bivariate latent growth curve (BLGC) models to test whether deviations in brain maturation - indexed by the brain age gap (BAG) - relate to mental health development across late childhood and adolescence. Brain age was estimated using T1-weighted, diffusion (dMRI), resting-state fMRI, and multimodal MRI data across four waves (ages [~]8.3-17.5). Internalising and externalising symptoms were assessed across ten waves with the self-report Brief Problem Monitor (BPM). ResultsAcross T1, dMRI, and multimodal models, deviations from age-expected brain maturation and internalising and externalising symptoms showed coordinated nonlinear development across adolescence. Adolescents whose brains increasingly diverged from age-expected maturation over time also showed increasing symptom trajectories. These associations were small to moderate in magnitude and were most consistent for internalising symptoms in females (r = .15-.23), whereas externalising symptoms showed broader but less selective nonlinear associations across modalities in both males and females (r = .15-.23). Intercept-level associations were weaker and modality-specific (r = .06-.11). Formal tests provided no evidence for robust sex differences in these associations after correction for multiple comparisons. ConclusionThese results indicate that adolescent development of mental health problems is more strongly linked to nonlinear changes in how individuals diverge from age-expected brain trajectories, rather than to fixed differences in brain age. Shifts in brain maturational tempo may therefore be a key feature underlying vulnerability to psychopathology in youth.

IntroductionSickle cell disease is a chronic hematologic disorder associated with significant physical and psychological challenges, including depression. Children with SCD experience recurrent pain crises, hospitalizations, and social limitations, which can contribute to mental health issues. This study aimed to determine the prevalence of depression and associated factors among school-age children with SCD at Jinja Regional Referral Hospital (JRRH), Eastern Uganda. MethodsA cross-sectional study was conducted among 200 randomly selected children aged 6-12 years receiving care at JRRH. Depression was assessed using the Childrens Depression Inventory (CDI). We assessed the association between depression and several factors including sociodemographic characteristics, clinical factors and health related quality of life. Multivariate logistic regression was used to identify factors that were statistically significantly associated with depression at a 95% confidence interval. ResultsMajority of the participants 55.5% (111/200) were female, 49.5% (99/200) were in pre-primary with a mean age of 6.7 (SD{+/-}1.4) years -The prevalence of depression among children with SCD was 43% (95% CI= 40-46%). Among these, 27.9% had mild depression, 58.1% had moderate depression, and 14.0% had severe depression. Factors significantly associated with depression included lack of assured income among caregivers (AOR=3.67, 95% CI=1.35-7.56, p=0.001), having more than one sibling with SCD (AOR=2.54, 95% CI=1.45-4.72, p=0.02), frequent hospital admissions (AOR=2.12, 95% CI=1.56-4.39, p=0.01), and frequent pain crises (AOR=2.10, 95% CI=1.56-4.67, p<0.001). ConclusionDepression is prevalent among children with SCD at JRRH, with socio-economic status of the caregiver, number of siblings with SCD, health facility admission frequency and frequent pain crises playing significant roles. Improving access to financial and social support for caregivers and ensuring adequate pain management are recommended.

BackgroundAttention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attentional deficits, hyperactivity and impulsivity that often persists into adulthood. While dysfunction of dopaminergic neurotransmitter systems has been observed, underlying mechanisms remain incompletely understood. Current treatments with methylphenidate and amphetamines show limited long-term effectiveness and do not address broader clinical needs. The endocannabinoid system represents a promising therapeutic target. Cannabinoid type 1 (CB1) receptors are highly concentrated in the prefrontal cortex and striatum, brain regions central to ADHD pathophysiology. The "dual pathway model of ADHD" describes deficits in inhibition-related executive functions and reward-related functions, both mediated by fronto-striatal networks. Striatal CB1 receptor availability correlates negatively with impulsivity. Given the interaction between dopaminergic and endocannabinoid systems, CB1 receptors may play a key role in ADHD pathogenesis. MethodsThis controlled study will investigate CB1 receptor availability in ADHD using positron emission tomography (PET) with the CB1-selective radiotracer [18F]MK-9470. The primary outcome is the CB1 receptor distribution volume (VT) in the striatum. Secondary outcomes include CB1 receptor availability in prefrontal cortex and other ADHD-relevant brain regions, plasma concentrations of endocannabinoids (anandamide, 2-arachidonoylglycerol), and validated neuropsychological assessments of attention and impulsivity. We will compare three groups (n=34 each): medication-naive participants with ADHD, methylphenidate-treated participants with ADHD, and healthy controls. Statistical analysis will employ ANOVA with post-hoc comparisons and correlation analyses between neuroimaging and behavioral measures. DiscussionThis first investigation of the endocannabinoid system in ADHD will provide crucial insights into disease mechanisms and identify potential therapeutic targets. Results may inform development of novel cannabinoid-based treatments and improve evidence-based therapeutic strategies for ADHD management. Trial registration: German Clinical Trials Register (DRKS-ID: DRKS00037526, Registration date: 25 September 2025)

Predictive processing has been proposed as an explanatory framework for symptom development in both autism (ASD) and schizophrenia (SSD) spectrum disorders, with ASD being associated with an overweighting of (low-level) sensory evidence whereas SSD is characterized by an overweighting of (high-level) prior beliefs. The goal of the present study was to investigate these hypotheses in subclinical expressions of ASD and SSD in the domain of language processing. To test this, we used an auditory comprehension task designed to directly manipulate the precision of high-level semantic prior beliefs and low-level sensory evidence. We applied hierarchical Bayesian belief updating modeling to quantify this effect and used EEG to examine whether an imbalance in the weighting of prior beliefs and sensory evidence would be characterized by altered processing of semantic precision-weighted prediction errors as indexed by alterations in mean N400 amplitudes. Computational modeling revealed that increasing schizotypal traits were associated with a significant overweighting of prior beliefs, while autistic traits did not show a significant shift. Linear mixed models on the mean N400 amplitudes further indicated that this schizotypy-related overweighting of semantic prior beliefs was reflected in a reduced semantic prediction error signal, indexed by smaller N400 differences between low entropy sentences and both high and low-mismatch sentences. A similar pattern emerged for increasing autistic traits, though the effect was weaker and less distinct, pointing to a subtle overweighting of semantic prior beliefs, only. Overall, our findings provide converging computational and electrophysiological support for an overweighting of semantic prior beliefs with increasing subclinical schizotypy, consistent with predictive processing accounts of SSD, whereas we did not find evidence for an overweighting of sensory evidence with increasing autistic traits, with electrophysiological results instead pointing toward subtle alterations in the weighting of semantic prior beliefs.