European Child & Adolescent Psychiatry

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

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

Objectives To explore caregiver and clinicians perspectives on implementing mental health conversations and supports for caregivers of children with chronic conditions in paediatric outpatient clinics. Specifically, views were sought on (a) screening approaches and measures (phase 1) and (b) how feedback and support could be provided to caregivers experiencing mental health difficulties (phase 2). Methods Caregivers and clinicians from two outpatient clinics (neuromuscular and diabetes) at a tertiary paediatric hospital in Melbourne, Australia participated in online focus groups in July and August 2024. Caregivers were recruited from outpatient clinics and clinicians were recruited via email. Both groups were combined for phase 1 before separating into breakout rooms for phase 2. Two authors conducted reflexive thematic analysis of transcripts using NVivo. Results Sixteen participants (caregivers n = 8; and clinicians n = 8) took part in in two semi-structured focus groups. Analysis generated two overarching domains, each comprising multiple themes. Domain 1, Addressing caregiver mental health, captured themes of overwhelm and invisibility, diverse caregiving roles, and the need for time and resources to support wellbeing conversations. Domain 2, Housing the mental health conversation, encompassed themes of screening preferences, caregiver agency in confidentiality, delivery of feedback, and access to tailored supports. Conclusions Caregivers and clinicians support routine caregiver mental health discussions in paediatric outpatient settings. Caregivers favour screening at diagnosis and key transitions, with clear, and actionable feedback delivered away from the child. Questions about record-keeping warrant further exploration, as do the perspectives of fathers.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by persistent inattention, hyperactivity, and impulsivity. While documented in children, research on its persistence into young adulthood in Jordan remains scarce. This gap is critical given the cognitive demands of higher education. This study estimated attention deficit hyperactivity disorder (ADHD) symptom prevalence among Jordanian university students, examined associations with gender and academic performance, and identified barriers to mental health service accessibility. Methods: A descriptive cross-sectional study using web-based sampling recruited 389 university students (aged [&ge;] 18 years) from various Jordanian universities. Participants completed an online survey, incorporating the validated English and Arabic versions of the Adult ADHD Self-Report Scale (ASRS-v1.1) to assess symptom prevalence, alongside inquiries regarding demographics, academic history, and barriers to care. Results: The prevalence of probable ADHD was 37.5% (n=146). Males constituted a significantly higher proportion of positive cases (69.9%) compared to females (30.1%). A strong statistical association was found between positive ADHD screening and negative academic impact (p<0.001), as well as negative effects on emotional well-being (p<0.001). Comorbidities including anxiety disorders and emotional abuse were significantly linked to probable ADHD (p=0.019). Notably, positive-screened participants were significantly more likely to cite social stigma as a primary barrier to seeking professional help (p=0.024). Conclusion: Self-reported ADHD symptoms are highly prevalent among Jordanian university students, correlating with substantial academic underachievement and emotional dysfunction. These findings highlight an urgent need for targeted university-based screening programs, academic accommodations, and de-stigmatization campaigns to facilitate early intervention and improve educational outcomes in this population.

Objective: Cross-sectional studies indicate associations between self-reported social media use and adolescent wellbeing outcomes. We aimed to evaluate longitudinal associations of objectively measured smartphone and social media use with psychosocial wellbeing. Design: Observational study with one year of follow-up Setting: High schools in Finland from 2022 to 2023 Population: 259 adolescent girls (mean age 16.3 years at baseline) Main outcome measures: screenshots depicting smartphone and social media use, Bergen Social Media Addiction Scale (BSMAS), Generalized Anxiety Disorder-7 questionnaire, Body Appreciation Scale 2 (BAS-2) and visual analogue scales (VAS) of mood, tiredness, and loneliness Results: Across one year of follow-up, anxiety, body appreciation, and mood improved, but possible social media addiction increased from 15% to 17%. Social media addiction at baseline was associated with increased anxiety (r=0.29, p<0.001), lower body appreciation (r=-0.15, p=0.022), and more loneliness (r=0.20, p=0.001) at follow-up. Anxiety at baseline was associated with social media addiction at follow-up (r=0.19, p=0.005). The highest quartile of TikTok users reported more social media addiction (BSMAS 19 [IQR 16-21] vs. 17 [IQR 14-20]; p=0.009) and lower body appreciation (BAS-2 32 [IQR 28-38] vs. 35 [IQR 29-40]; p=0.003) than did others. The highest quartile of Snapchat users reported more social media addiction (BSMAS 19 [IQR 15-21] vs. 17 [IQR 14-20]; p=0.007) and tiredness (VAS 21 [IQR 13-32] vs. 26 [IQR 15-35]; p=0.049) than did others. Conclusions: Consistent with cross-sectional studies, social media addiction was associated with poorer psychosocial outcomes across follow-up. Policies to protect adolescents from social media addiction are urgently needed.

Background: This study examined the association between caregiving demands and depression symptoms among caregivers of individuals with Down syndrome during the COVID-19 pandemic. Method: We conducted an online survey of 200 caregivers of children and adults with Down syndrome, including demographic data, the Patient Health Questionnaire-8 (PHQ-8), and questions about lack of childcare and taking over instruction during the pandemic. A multiple linear regression analysis identified predictors of caregiver depression symptoms. Results: Household income (B = -3.45, p < .001) and having to take over instruction (B = 2.24, p < .001) were significant predictors of PHQ-8 scores. Child age, caregiver gender, difficulty paying for health insurance, and lack of childcare were not significant predictors. Conclusions: Lower income and instructional caregiving demands were associated with higher depression symptoms among caregivers of individuals with Down syndrome, suggesting potential targets for policy and intervention during future public health emergencies.

Mental health problems, including emotional problems, are linked to adverse educational outcomes among children and adolescents. This study examines the association between early onset of mental health problems generally, and emotional problems specifically, at ages 5-14, and outcomes from the General Certificate of Secondary Education (GCSE), a secondary education qualification, at age 16 for 4,783 students in England, using the Millennium Cohort Study dataset linked to the National Pupil Database. We found that the onset of mental health problems at ages 5, 7, 11 and 14 had a significant and negative association with all GCSE outcomes. We also found negative associations between early onset emotional problems and GCSE outcomes, although results were most stark for emotional problems that onset at age 11, with statistically significant negative associations with all GCSE outcomes. School absence was identified as a potential mediator of the negative association. Furthermore, this study found that the potential loss of productivity related to mental health problems in general and emotional problems in particular was over 23,000 sterling and 11,000 sterling per affected individual, respectively, which could translate into approximately 2.57 billion sterling and 1.6 billion sterling, respectively at the population level for England. These findings highlight the importance of early intervention for children and adolescents with mental health problems to improve educational and future outcomes.

Background: Sleep debt and irregular sleep patterns are highly prevalent amongst adolescents. However, whether the absence of these sleep behaviours protects against subsequent depression remains unclear. Here, we examined the association of sleep debt, weekend catch-up sleep (WCS), and social jetlag (SJL) in adolescence with depression in young adulthood and identified underlying biopsychosocial mechanisms. Methods: Secondary data analyses were conducted using the Avon Longitudinal Study of Parents and Children. Bedtimes and wake-up times on school days and weekends (i.e., sleep duration) and sleep need were self-reported at 15 years. This was used to generate sleep debt (sleep need minus school day sleep duration), WCS (weekend sleep duration minus school day sleep duration), and SJL (absolute difference in the midpoint of sleep times between school days and weekends). Depression was assessed at 24 years with the Clinical Interview Schedule-Revised. Common mental health symptoms, biological, and school-related factors at 17 years were the mediators. Results: Logistic regression analyses revealed that greater WCS (adjusted odds ratio [AOR]=0.90; 95% CI=0.84-0.97; p=0.004) and lower sleep debt (AOR=1.10; 95% confidence interval [CI]=1.03-1.18; p=0.005) at age 15 reduced the likelihood of depression at 24 years. Irritability at 17 years partially mediated the relationship between sleep debt and depression (bias-corrected estimate=0.003; 95% CI=0.002-0.004; p<0.001). Conclusions: Adolescents who experience less sleep debt (i.e., less discrepancies between their actual sleep and their perceived sleep need) and those who extend their sleep duration on weekends are at reduced risk for depression in young adulthood. These findings underscore the need for greater opportunities for adolescents to obtain more hours of sleep to protect them against later poor mental health outcomes, such as depression. Keywords: Sleep; longitudinal studies; depression; ALSPAC

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

BackgroundA high proportion of autistic people receive off-license antipsychotic medication, often in the absence of a mental illness, primarily for behaviours that challenge, which is a public health concern. Although meta-analyses have been published recently, there is a lack of a comprehensive network meta-analysis to inform clinicians about the relative efficacy and safety of antipsychotic medications. AimsTo conduct a network meta-analysis of available RCTs of antipsychotic medications involving autistic participants to assess the relative efficacy of different antipsychotics and their adverse effects. MethodWe searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts, and full papers, extracted data, and assessed their quality. ResultsWe analysed data from 22 RCTs involving 1562 autistic people. The largest mean difference with 95% confidence interval in the Aberrant Behaviour Checklist-Irritability (ABC-I) score compared with placebo was from the combined intervention with risperidone and parent training: -11.16 (-15.13, -7.18), followed by risperidone: -7.59 (-9.22, -5.95), and aripiprazole: -5.59 (-7.18, -4). The largest effect on Clinical Global Impression-Improvement (CGI-I) scores was from risperidone, 7.65 (2.17, 27.04), followed by aripiprazole, 7.02 (1.92, 25.72), compared with placebo. Risperidone (4; 1.57, 10.21) and aripiprazole (2.77; 1.20, 6.39) had significantly higher odds ratios for adverse effects, but aripiprazole showed the least weight gain. ConclusionsCombined parent training and risperidone followed by risperidone and aripiprazole showed the best effects on the ABC-I score, whereas risperidone and aripiprazole showed the greatest effect on the CGI-I score. However, risperidone and aripiprazole showed significantly increased adverse effects.

Background: Adolescent mental health disorders represent a growing public health concern globally, with a substantial proportion of young people experiencing unmet mental health needs. Despite this burden, help-seeking behavior among adolescents remains low, particularly in low- and middle-income countries (LMICs), where structural, social, and cultural barriers persist. In Tanzania, limited context-specific evidence exists on factors influencing mental health help-seeking among adolescents, particularly within school settings. Methods: A cross-sectional qualitative study was conducted among adolescents aged 15-19 years attending secondary schools in Moshi Urban, Kilimanjaro region, Tanzania, between April and May 2025. A total of 11 participants, including students, teachers, a school administrator, and a school healthcare provider, were recruited using convenience sampling. Data were collected using semi-structured questionnaires and focus group discussions, and audio-recorded for accuracy. Transcripts were analyzed using thematic analysis, following a systematic six-step approach. Codes were organized into subthemes and overarching themes. Results: Three major themes emerged: facilitators, barriers, and suggested strategies for improving mental health help-seeking behavior. Key facilitators included the presence of school-based support systems, encouragement from trusted individuals (peers, parents, and teachers), perceived severity of mental health problems, and positive experiences from others. Major barriers included lack of trust and concerns about confidentiality, fear of information disclosure, stigma and fear of judgment, rigid school schedules, and poor teacher-student relationships. Participants highlighted the need for confidential, professionally led counselling services, increased mental health education, strengthened school-based programs, and improved access to mental health information as critical strategies to enhance help-seeking behavior. Conclusion: Mental health help-seeking behavior among adolescents in Moshi Urban is influenced by a complex interplay of interpersonal, institutional, and individual factors. While supportive environments and social networks facilitate help-seeking, persistent barriers particularly related to trust, confidentiality, and stigma limit access to care. Strengthening school-based mental health services, improving mental health literacy, and ensuring confidential, youth-friendly support systems are essential to enhance help-seeking behavior and improve adolescent mental health outcomes in Tanzania and similar settings. Keywords: Adolescents; mental health; help-seeking behavior; qualitative study; Tanzania; barriers; facilitators; school-based interventions

Background: Biopsychosocial factors associated with functional changes, including changes in personality, communication, movement, and weight, were evaluated in individuals with Down syndrome (DS) during the COVID-19 pandemic. Method: Caregivers of individuals with DS (aged [&ge;]12, n = 118) completed an online survey. Elastic net regression with bootstrap resampling assessed 31 candidate predictors. Results: Pandemic-related mental health was most strongly associated with functional changes ({beta} = 0.388). Healthcare access barriers were also reliably selected: inability to access mental health treatment, difficulty affording insurance, difficulty accessing specialists, and residing in a low-income health professional shortage area. The model explained 35.2% of variance. Conclusions: Mental health and healthcare access barriers were biopsychosocial correlates of functional changes for people with DS during COVID-19.

Abstract Introduction: Over 30% of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) show an insufficient response to standard pharmacological treatments, which underscores the need for evidence-based alternative interventions. Methods: In this sham-controlled study, 30 adult outpatients with ADHD were randomized to 12 weeks of active or sham transcranial direct current stimulation (tDCS) as add-on to a digital cognitive behavioral therapy application (dCBT app). Participants received either active (2 mA, 20 min/day, 5 days/week) or sham tDCS with anodal (left) and cathodal (right) stimulation applied over the dorsolateral prefrontal cortex (DLPFC). In parallel, access to the dCBT app was provided for three months. ADHD symptoms were measured before and after treatment and after a three-month follow-up using the Adult Self-Report Scale (ASRS v1.1). Results: All scales showed an improvement over time with medium-to-large within-subjects effects (Cohens d: -.48 to -.75), irrespective of group allocation. Two additional sensitivity analyses including (1) participants with over 75% of planned (sham)-tDCS sessions and (2) those who logged into the dCBT app on at least 5 days (median split) confirmed results. Response was observed in 1/15 (6.7%) of the tDCS group and 2/15 (13.3%) of the sham-tDCS group, with no difference between groups (p = .543, phi = -.111). Compliance to (sham-)tDCS was high. tDCS usability was rated marginally lower in the tDCS group. Conclusions: tDCS as an add-on therapy could not produce additional improvement in ADHS symptoms. The results are discussed in terms of contextual and patient-related aspects. ClinicalTrials.gov Identifier: NCT06766214.

Aim: Schema Therapy (ST) is an evidence-based treatment for complex mental health problems rooted in early Adverse Childhood Experiences (ACEs). Although both individual and group formats have shown effectiveness, little is known about which format works best for whom. This question is particularly relevant for adolescents given their unique developmental needs. Despite over a decade of clinical experience with ST in adolescents, current research offers limited guidance on how to tailor the format to individual needs - resulting in a persistent gap between research and practice. This study aims to develop practice-based indication criteria for individual versus group schema therapy by integrating therapists expertise with experiences from adolescents who underwent ST. Methods: This qualitative study employs a constructivist Grounded Theory approach. Data will be gathered through focus group discussions with schema therapists and individual interviews with adolescents. Therapists will be purposively selected based on experience with both therapy formats and with traumatized adolescents. Adolescents are eligible if they have experienced ACEs and have completed at least 20 sessions of ST. Results: The analysis will result in a theoretical model that integrates therapists clinical reasoning and adolescents preferences. Conclusions: This study integrates schema therapists expertise and adolescents lived experiences to develop actionable indication criteria for choosing between individual and group ST. By supporting informed clinical decision-making, the findings contribute to treatment personalization in adolescent ST and address key challenges such as suboptimal outcomes and treatment dropout. Moreover, the identified criteria provide a foundation for future quantitative validation.

Background Escalating mental health service demands have created a need to better identify young people most likely to require continued support from mental health services at the transition between childhood and adulthood. Anxiety is the most common adolescent mental health condition, yet its clinical significance and prognosis are not well understood. We aimed to examine the risk of young adult-onset psychiatric disorders in individuals with an adolescent anxiety disorder, and identify stratifiers of risk of subsequent psychiatric disorders in this group. Methods Individuals from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with linked health records and aged 18 or over as of the 31st December 2023 were included. Those diagnosed with any ICD-10 anxiety disorder when aged 10-17 years were defined as having an adolescent anxiety disorder (n=2107, controls n=47,582). Polygenic scores (PGS) for psychiatric and neurodevelopmental conditions were calculated using LDpred2. Anxiety, comorbidities, and parental psychiatric history were defined through linked ICD-10 diagnoses. Sex was defined through linked records. Individuals were defined as having a young adult-onset psychiatric disorder if they first received any new psychiatric diagnosis aged 18-24. Results Adolescent anxiety diagnosis was associated with increased risk of all adult-onset psychiatric disorders (HR= 2.33-8.65). Post-traumatic stress disorder PGS, parental history of severe mental illness, and female sex were associated with increased risk of transition to a young adult-onset psychiatric disorder in people with an adolescent anxiety disorder. Conclusions Adolescent anxiety greatly increases the risk of a psychiatric disorder during the transition to adult life. Clinicians should consider female sex and parental psychiatric history when prioritising young people with anxiety for adult mental health service support. Future research needs to further consider whether polygenic scores would aid risk stratification in clinical practice.

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

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

Background 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. Methods 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. Findings 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. Interpretation 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.

Prader-Willi syndrome (PWS) is a rare multisystemic disorder characterized by obesity, endocrine dysfunctions, and psychiatric comorbidities, which imply frequent use of psychotropic medications. They account for atypical responses to standard dosages of psychiatric drugs. Pharmacogenetics could be part of the reason for this situation, potentially offering a valuable tool for individualized treatment. This study analyzed allelic and phenotypic frequency distributions of five of the main cytochrome P450 enzymes (CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A4) involved in psychiatric drug metabolism in 47 patients with genetically confirmed diagnosis of PWS and compared them to reference frequencies in the general European population. Allelic frequency comparisons between the European reference population and the overall PWS cohort revealed a significant global difference for CYP2B6, with CYP2C19 and CYP2D6 showing trends toward significance. Although no global allelic differences remained significant after false discovery rate correction, post-hoc analyses consistently identified an enrichment of reduced- or non-functional alleles CYP2B619 and CYP2D610 in patients with PWS. Predicted metabolizer phenotype analyses showed a significant shift toward intermediate metabolizers of CYP3A4 in the PWS cohort, with corresponding depletion of normal metabolizers. Subgroup analyses indicated that allelic differences were more pronounced in maternal uniparental disomy and non-deletion subtypes, particularly for CYP2B6, although no significant differences were observed between PWS genetic subtypes. Overall, results imply potential differences in metabolizing activity in PWS patients, and subsequent implications in drug efficacy and tolerability. These results support the idea that pharmacogenetic testing may improve therapeutic decision-making in PWS for psychiatric treatment. Larger studies are needed to confirm these preliminary results.

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