Journal of Autism and Developmental Disorders

Abstract Autistic young adults experience substantial gaps in services supporting community living and participation. The Community Autism Peer Support (CAPS) program is a community-based intervention in which trained autistic peer specialists provide individualized support to autistic young adults pursuing self-determined goals related to community participation and independent living. We conducted a single-site, two-arm randomized controlled trial to evaluate the feasibility of implementing the CAPS program. Forty autistic adults aged 18 to 30 years were randomized to CAPS (n = 20) or services as usual alone (n = 20) and assessed at baseline, 3 months, and 12 months. Study findings showed that CAPS attracted autistic young adults with diverse demographic and diagnostic backgrounds, and most intervention participants remained engaged in services for extended periods. While the study was underpowered to detect statistical differences in outcomes because it was not a main focus of the research, a consistent pattern of results favored the CAPS condition across all outcomes. The largest positive signals were observed for overall and social quality of life, with additional favorable changes in internalized stigma, unmet needs, social functioning, loneliness, and positive autistic identity. Findings provide support for the feasibility and promise of an autistic-delivered peer specialist model focused on community living and participation. The consistent pattern of favorable changes supports continued development of CAPS as a person-centered approach to addressing outcomes important to autistic adults.

Autistic adults face considerable challenges in receiving adequate support, from both paid/formal (such as from disability services) and unpaid/informal (for example, from friends and family) sources. Having adequate support can lead to better health and well-being outcomes. However, most instruments designed to assess adequacy of support were not made specifically for/with autistic adults. This paper presents a psychometric validation of the AASPIRE Adequacy of Supports and Information Scale (AASIS), a community-informed adaptation of a previously developed instrument (the Quality of Care and Support scale; Lucas-Carrasco et al., 2011), designed to be relevant and accessible to autistic adults. We also used the AASIS to explore correlates of perceptions of support in a sample of 798 autistic adults. Our confirmatory factor analysis supported a two factor structure for the AASIS (factor one: Supports; factor two: Information). Further testing confirmed the instrument was invariant across several groups, including race/ethnicity, gender, intellectual disability, communication fluency, and self versus proxy-report. Regression analyses suggested that the way in which participants joined the study (i.e., through community advertisements or via established healthcare/disability services) impacted whether they viewed their support as adequate. Additionally, a higher number of adverse childhood events and greater experience of discrimination were related to worse perceptions of support adequacy across both factors. Our findings support the preliminary validity of the AASIS across a variety of autistic people, though further testing is warranted. Findings also point to the importance of addressing the needs of autistic people who are minoritized and/or who have complex trauma histories.

Purpose: This study examined whether word-based and non-word natural language sampling (NLS) measures complement standardized language scores in characterizing expressive communication among preschool children with autism with language impairment (AUT-LI), Down syndrome (DS), and fragile X syndrome (FXS). Method: Participants included 82 preschool children with AUT-LI (n = 32), DS (n = 34), or FXS (n = 16). Expressive communication was characterized using the Preschool Language Scales and 10-minute natural language samples collected during a standardized play-based protocol. NLS measures included traditional word-based metrics, such as lexical diversity, intelligibility, and word approximations, as well as tiered non-word vocalization measures, including non-speech, single-phoneme, and multi-phoneme vocalizations. Analyses examined age associations, diagnostic group differences, between group differences in variability, and exploratory communication profiles derived using principal component analysis and partitioning around medoids clustering. Results: Diagnostic groups did not significantly differ on standardized expressive language scores. Children with FXS showed higher performance than the AUT-LI and DS groups on several word-based NLS measures, whereas non-word vocalization measures primarily revealed differences in within-group variability. Word-based NLS measures were consistently associated with standardized expressive language skills, while associations for non-word vocalizations varied by vocalizations type. Cluster-validity indices factored a two-cluster solution. A hypothesis-informed three cluster solution that included non-word vocalizations suggested Higher Language, Lower Output, and High Output-Low Structure profiles. Conclusions: Standardized and NLS measures provide complementary descriptions of expressive communication in children with neurodevelopmental disorders. Non-word vocalization coding may be especially useful for describing clinical meaningful variation among children with limited expressive language. Keywords: Natural language sampling; expressive language; neurodevelopmental disorders; autism spectrum disorder; Down syndrome; Fragile X syndrome

Purpose Autistic adults have diverse communication characteristics that are not well captured by standard demographic measures. Communication affects self-determination, relationships, access to healthcare, and services. Characterizing communication differences may improve research and intervention targeting for meaningful subgroups of autistic adults. Methods The Academic Autism Spectrum Partnership in Research and Education (AASPIRE) Outcomes Project team used a community based participatory research (CBPR) approach to develop a self- or caregiver-report module to characterize communication among autistic adults. The 10-item module asks about receptive and expressive communication, literacy, speech reliability, usage of digital communication, use of alternatives to speech, and communication fluency. It can be completed directly, with or without support, or via a caregiver. We used baseline survey data from 844 autistic adults to evaluate the module and derived a five-level variable, Communication Profile, from selected module items to stratify participants. We examined completion feasibility, response consistency, and construct validity. We also assessed test-retest reliability in a 15% random subsample who completed a 2-week retest following the 6-month survey, with oversampling of caregiver-report respondents. Results The Communication Characteristics module demonstrated high completion feasibility, minimal systematic error, and strong construct validity. The Communication Profile variable stratified participants into five meaningful communication profiles and demonstrated strong construct validity and substantial test-retest reliability ({kappa} = .69). Conclusion The Communication Characteristics module and Communication Profile variable provide a valid approach for characterizing communication diversity among autistic adults for research, clinical, and service settings. The full AASPIRE Measurement Toolkit is available at https://aaspire.org/measurement. Lay Summary Autistic people communicate in many different ways, and their communication may change in different situations. We developed and tested a set of survey questions to describe an individuals communication. We also used the results to describe 5 groups of autistic people based on how they communicate, without treating these groups as different types of autism.

Objective: Mental health challenges are highly prevalent in autism, but the degree to which they are similar in experience and etiology to the general population remains unclear. This study's objective was characterization of phenotypic and genetic architectures of psychiatric symptomatology in versus out-of-autism. Methods: Psychiatric symptoms were evaluated using the Child Behavior Checklist (CBCL) in 22,152 children (8-15 years): 11,111 autistic children with verbal abilities from SPARK and 11,041 non-autistic children from ABCD. The CBCL's canonical, population-wide factor structure and genetic associations were compared between cohorts. In parallel, exploratory factor analysis was conducted in SPARK, with resulting dimensions associated with key clinical phenotypes (cognitive ability, co-occurring neuropsychiatric diagnoses), polygenic scores (PGS) for psychiatric disorders, and de novo burden in autism-associated genes. Results: Confirmatory factor analysis supported the canonical structure in ABCD but not in SPARK. Psychiatric PGS associations with canonical CBCL subscales were weaker in SPARK than in ABCD, with the ADHD PGS association to Attention problems lower in SPARK ({beta}=0.05 [CI: 0.04,0.06] than in ABCD ({beta}=0.17 [0.13,0.21]). SPARK exploratory factor analysis replicated canonical internalizing factors while revealing other structural departures, including a distinct Developmental Delays factor and dispersion of social problems across multiple factors. The Developmental Delays factor had the strongest associations with de novo burden and lower cognitive ability but was weakly associated with psychiatric PGS. In contrast, common genetic variation explained larger proportions of variances in somatic and inattentive factors and had stronger PGS associations. Conclusions: Correlation structures and genetic architectures of psychiatric symptoms differed in autism compared to the broader population, emphasizing the need for autism-specific approaches in assessment and treatment.

Background Elevated resting gamma power is a reproducible, robust neurophysiology marker across species in fragile X syndrome (FXS), a major known cause of autism spectrum disorders (ASD). In FXS, this neurophysiological phenotype is well described and particularly prominent in males harboring fully methylated full CGG repeat expansions. However, gamma power evaluations in idiopathic ASD have yielded variable results. As a single-gene model of ASD, FXS hold promise to biologically model some of the autism spectrum. Exaggerated gamma power in FXS is thought to reflect increased cortical excitability, a common feature of ASD, and has been shown to correlate with symptoms in both human FXS individuals and the Fmr1 knockout mouse model of FXS. A recent clinical trial of the BK channel positive modulator, Codabakalner, provided encouraging signs that normalization of gamma power in FXS may provide therapeutic benefit [14]. Interventional and biomarker studies in ASD provide support that this may also be the case in ASD. We utilized gamma band power to evaluate neurophysiological overlap between ASD and FXS seeking to determine the prevalence and clinical characteristics of those with ASD who exhibit a FXS-like elevated resting state gamma phenotype. Methods This cross-sectional resting EEG analysis included 159 individuals with non-syndromic ASD and 41 males with fully methylated full mutation FXS. Relative gamma power was calculated as 30-100 Hz power divided by 1-100 Hz power across 10-20-equivalent electrodes, excluding 55-65 Hz. We defined the cutoff for elevated resting gamma band power in ASD as relative gamma power of greater than or equal to the median minus one standard deviation of gamma power in our FXS male sample. Results A FXS-derived relative-gamma threshold of 0.185 or greater was met by 22% of participants with ASD (n=35). As expected, the mean ASD group resting state gamma was lower than the male FXS sample (p < 0.001). ASD participant threshold proportions by age group were 3/37 (8.1%) below 13 years, 9/50 (18.0%) age 13-18 years, and 23/72 (31.9%) in the 18+ years group. Within the ASD group, there were no observable clinical characteristics that readily differentiated participants with an elevated gamma phenotype from those without this phenotype. Conclusions Approximately one fifth of all participants and slightly over 30 percent of adults with ASD met the FXS-derived elevated resting gamma band power criterion. This represents the first investigation using a translational brain neurophysiology marker in a syndromic form of autism to parse a clinical idiopathic ASD sample to identify potential overlapping brain features. The results will work to support potential targeting of ASD subgroups in the future utilizing therapeutic approaches initially established in a single-gene form of developmental disability.

Background Psychiatric diagnoses and psychotropic medication use among children, adolescents, and young adults have increased in high-income countries, with concerns about geographic variation. We described national trends and geographic variation in Denmark from 2010 to 2025 and developed an interactive online tool to explore these patterns. Methods We conducted a nationwide, descriptive, repeated cross-sectional register-based study of all Danish residents aged 0-24 years in 2010-2025 (n=2,930,744), using the Danish National Patient Registry and the Danish National Prescription Registry. We estimated annual incidence, prevalence, and, for selected diagnoses, lifetime prevalence, by age and sex, and age- and sex-standardised rates across regions, health councils, and municipalities. We assessed geographic variation using deviations from national means, coefficients of variation, Gini coefficients, and funnel plots. Findings Psychiatric diagnoses and psychotropic medication use increased from 2010 to 2025. The annual prevalence of attention-deficit hyperactivity disorder (ADHD) increased from 0.41 to 2.3 per 100 individuals, autism spectrum disorders from 0.20 to 1.2, and melatonin use from 0.14 to 3.0. ADHD and autism spectrum disorders were more prevalent among boys and anxiety disorders among girls. Sertraline use was also more prevalent among girls. Geographic variation was observed across diagnoses and psychotropic medications at regional, health council, and municipal levels. For example, lifetime prevalence of autism ranged from 1.3 to 5.9 per 100 across municipalities, and in 2025 regional coefficients of variation ranged from 0.11 (sertraline) to 0.41 (atomoxetine). Results can be explored in the interactive online tool (https://bupstat.sdu.dk/?lang=en). Interpretation Psychiatric diagnoses and psychotropic medication use increased among Danish children, adolescents, and young adults, with marked geographic variation. Descriptive data cannot establish the causes of this variation, but the findings identify areas for further review and support continued monitoring. Funding Best for Us project (www.bedstforos.dk), funded by the Novo Nordisk Foundation (NNF24SA0093635) and the Obel Family Foundation (69348).

Pharmacological treatments targeting core autistic features remain limited. In neurotypical adults, cannabidiol (CBD) alters mismatch negativity (MMN), an electrophysiological marker of automatic auditory deviance detection that has been associated with autistic traits. The effects of CBD on MMN, as measured using electroencephalography (EEG), in autistic children remain unknown. This secondary analysis of a pilot randomised, double-blind, placebo-controlled crossover trial examined the effects of 12 weeks of oral CBD oil on MMN during a duration-deviant auditory oddball task. We hypothesised that CBD would produce more negative MMN amplitudes and shorter peak latencies relative to placebo. Nineteen autistic children (6-12 years, 8 female) received CBD (dose) and placebo in randomised order, separated by an 8-week washout. Age-adjusted linear mixed-effects models tested Time (baseline, follow-up) x Treatment (CBD, placebo) effects on mean MMN amplitude and peak latency separately at Fz and FCz. Exploratory Spearman correlations examined baseline associations between MMN and Developmental Behaviour Checklist-2 (DBC-2) Social Relating scores. At FCz, latency decreased following CBD but increased following placebo but did not survive FDR correction (p = .029, pFDR = .058) and no other interactions were significant. Higher baseline DBC-2 Social Relating scores were associated with more negative MMN amplitude at FCz (rho = -.58, pFDR = .028) and Fz (rho = -.59, pFDR = .028). These findings provide tentative evidence that CBD may modulate MMN latency in autistic children. Larger trials should clarify CBDs effects on MMN and further examine the association between MMN amplitude and social-relating difficulties.

Autistic individuals with intellectual disability (ASD+ID) and profound autism are rarely studied in neuroscience research due to barriers including communication challenges, sensory sensitivities, anxiety, and elevated behavioral support needs. Consequently, biomarker development in autism fails to include the portion of the autistic population with highest support needs and greatest potential to benefit from treatments derived from imminent advances in personalized medicine. Here we present a multimodal, participant-centered protocol for simultaneous electroencephalography (EEG) and eye-tracking (ET) acquisition to advance clinical trial readiness research in this underserved population. The protocol combines individualized behavioral supports and an adaptive EEG-ET acquisition platform. Pre-visit caregiver interviews informed participant-specific research plans, including customized visual supports, reinforcement strategies, and EEG net desensitization procedures. A gaze-contingent stimulus presentation system used participant-preferred videos to support attention to experimental stimuli and behavior consistent with data acquisition (e.g., refraining from movement) while dynamically adapting stimulus delivery based on visual engagement with the assay and real-time assessment of data quality. By quantifying attended trials in real time and prioritizing unattended stimulus classes, the paradigm maximizes acquisition efficiency to minimize participant burden. This approach was utilized to deploy candidate biomarkers with demonstrated replicability in the Autism Biomarkers Consortium for Clinical Trials (ABC-CT): the N170 event-related potential to faces, resting-state EEG, and visual attention to human faces (measured with ET). Feasibility was evaluated in 76 children with ASD+ID (M age = 8.76 years; IQ = 32.4) and a small comparison sample of 8 children with intellectual disability without autism (M age = 8.91 years; IQ = 45.9). Usable EEG data (>7 minutes) were acquired in 61% (ASD+ID) and 88% (ID) of participants, respectively. Sufficient ET data were obtained from 67% (ASD+ID) and 63% (ID) of participants, respectively. Findings demonstrate the feasibility of inclusive biomarker acquisition and provide a framework for expanding participation of individuals with ASD+ID and profound autism in neuroscience research. Ongoing research seeks to evaluate this approach in larger samples and to demonstrate feasibility in multisite research studies.

BackgroundAtypical antipsychotics (AAPs) are increasingly prescribed for paediatric patients with autism spectrum disorder (ASD). However, pharmacovigilance data from Saudi Arabia remain scarce. The aim of this study is to detect and characterise signals associated with AAPs and assess gender- and age-related ADR reporting patterns. MethodsA retrospective cross-sectional study with disproportionality analysis was conducted on paediatric patients (0-19 years) using the Saudi Food and Drug Authority (SFDA) database (2021-2024). Disproportionality analyses were performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). Age and gender were assessed using odds ratios (ORs), with Firth penalized logistic regression to confirm associations. ResultsOverall, 701 ADR reports were analysed. Most involved males (59.91%) and children aged 0-9 years (82.88%). Olanzapine had the highest proportion of serious reports (44.44%). At the system organ class (SOC) level, signals included nervous system disorders with risperidone (ROR 32.61 [16.62-64.00]; PRR 3.49 [2.22-5.47]; IC025 0.08); cardiac and general disorders with quetiapine; haematological, metabolic, and psychiatric disorders with olanzapine; and gastrointestinal disorders with aripiprazole. Gender-adjusted analyses indicated significant variation in selected ADR signals across age groups, while no significant differences were observed by gender. ConclusionsThis study highlights disproportionality signals associated with AAP use in paediatric patients. Age-related ADR variation supports consideration of age-specific ADR monitoring within current paediatric recommendations. While these findings do not establish causality, they generate hypotheses for further evaluation. Regional pharmacovigilance may complement international paediatric safety monitoring frameworks.

Objective: Parent-adolescent disagreement in ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms can complicate clinical assessment. This study examined parent - adolescent agreement in ADHD symptom ratings and characteristics associated with disagreement. Method: Participants were 1,008 parent-adolescent dyads recruited from a nationally stratified U.S. community sample. Adolescents were 12--18 years old (49.6% female) and along with their parents completed measures of ADHD and depressive symptoms. Agreement on Inattention (IN), Hyperactivity/Impulsivity (HI), and Total ADHD scores was examined. Item-level agreement was assessed using weighted kappa, Gwet 's AC2, percent agreement, and polychoric correlations. Associations between age, sex, and severity of ADHD and depression with levels of agreement were analyzed. Results: Agreement for ADHD factor and total symptom scores was moderate (intraclass correlations = 0.67--0.71), with moderate-to-strong rank-order correspondence. Adolescents reported slightly higher ADHD symptom levels than parents, although the mean difference was small. Item-level agreement was moderate to high (Gwet 's AC2 = 0.79--0.95). Several HI items demonstrated the kappa's paradox, with relatively low kappa values despite high Gwet's AC2 and percent agreement. Q-correlations revealed low agreement on relative strengths and weaknesses. Age and sex were not associated with disagreement and parent-reported ADHD severity and adolescent-reported depressive symptoms were associated with disagreement. Conclusions: Parent and adolescent ratings showed moderate agreement across boys and girls ages 12-- 18; however, disagreement related to relative strengths and weaknesses. Disagreement was associated with ADHD and depressive symptom severity. Findings suggest that ratings from parents and adolescents offer unique perspectives on the assessment of ADHD symptoms.

Individuals with autism spectrum disorder (ASD) and co-occurring mood or psychotic disorders face substantially elevated suicide-attempt risk, but prior research is largely limited to population-level incidence and cross-sectional risk-factor studies, leaving unclear whether individual-level, prospective prediction is possible in this population. We conducted a retrospective prediction model study using Epic Cosmos electronic health record (EHR) data from 322,879 individuals with ASD and co-occurring mood or psychotic disorders to predict suicide attempts at the next clinical encounter using only information available at or before the preceding encounter. Five machine-learning algorithms were compared, with performance evaluated across discrimination, calibration, and clinical utility. All algorithms achieved strong discrimination using the full predictor set (AUROC 0.87-0.91). A parsimonious feature set (22 predictors) matched or exceeded full-model performance, with extreme gradient boosting (XGBoost) achieving the highest discrimination and standardized net benefit post-ablation (AUROC = 0.90; AUPRC = 0.34), though net benefit was comparable for elastic net and logistic regression. A prior suicide attempt was the strongest individual predictor. Decision-curve analysis indicated that model-guided decisions provided greater net benefit than treating all or no individuals across a broad range of clinically plausible thresholds. These findings demonstrate that near-term suicide-attempt risk can be predicted with high decision utility in this high-risk population using data already captured in routine care, suggesting a feasible basis for future EHR-based clinical decision-support tools.

Objective: To provide national norms, percentiles, and results of factor analyses for the ADHD symptoms and performance items on the parent-report and self-report versions of the Vanderbilt Assessment Scale (VAS) for youth ages 6 to 17. We hypothesized that symptom items would demonstrate separate inattention and hyperactivity/impulsivity factors, performance items would demonstrate interpretable latent dimensions, measurement invariance would be supported across age and sex, and symptom ratings would vary systematically by age and sex. Method: In a nationally stratified survey conducted in July 2025-March 2026, 2,230 parents of youth aged 6-17 years and 996 adolescents aged 12-17 years completed Vanderbilt Assessment Scale items. Both versions asked about the frequency of 18 ADHD symptoms and performance in 8 domains. To evaluate the psychometric properties and age-related normative curves of the VAS across parent- and youth-report forms, we conducted exploratory factor analysis, confirmatory factor analysis, and measurement invariance testing. We also generated age and sex-specific norms. Results: Factor analyses produced the expected two symptom factors and two performance factors. Developmental and sex-specific patterns of ratings of inattention and hyperactivity/impulsivity symptoms indicated that after increasing slightly during the preadolescent years, parent ratings of inattention symptoms declined and remained stable. In contrast, ratings of hyperactivity/impulsivity declined steadily with age. Normative data were generated using GAMLSS estimated centiles from fitted probability distributions. Conclusions: This study provides norms for the parent-report and adolescent self-report VAS. Findings underscore the importance of using sex- and age-based norms to better inform estimates of severity and diagnostic decision making.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition, and co-occurring autistic traits may shape its phenotypic expression. Although creativity has been discussed as a relative strength in ADHD, it remains unclear whether autistic traits are associated with different dimensions of creativity in adults with ADHD and whether large-scale brain networks contribute to these associations. Methods: We compared divergent thinking (DT) and real-life creativity between 65 adults with ADHD and 73 neurotypical controls. We used subgroup comparisons, partial correlation analyses, and multiple regression models to determine the effects of autistic traits (ATs) on creativity dimensions within the ADHD cohort. Guided by prior creativity-network research, we analyzed resting-state functional connectivity (FC) of the Default Mode Network (DMN) and Frontoparietal Network (FPN) to uncover the neural mechanisms. Results: The ADHD cohort demonstrated significantly higher scores on both DT (ps = 0.002-0.009) and real-life creativity measures (ps = 0.011-0.017) compared to the neurotypical control group. Importantly, increased ATs within the ADHD group were associated with a dissociated creativity profile, showing positive associations with DT but negative associations with real-life creativity. At the neural level, stronger right DMN FPN connectivity mediated positive associations between ATs and DT performance (ps = 0.007-0.018), but mediated a negative association between ATs and self-reported imagination (p = 0.029). Conclusions: In individuals with ADHD, co-occurring ATs exert a paradoxical effect on creativity, enhancing DT while compromising real-life creative achievement. In this subgroup with ADHD and elevated ATs, interventions should capitalize on ATs-associated ideational strengths while circumventing translational barriers, to enhance real-world creative outcomes.

Importance. Anorexia nervosa (AN) is a severe metabo-psychiatric disorder with heterogeneous outcomes and elevated mortality. Characterizing severity trajectories may improve early risk stratification and targeted intervention. Objective. To identify AN severity trajectories using a register-based severity index (AN-RSI) and examine their associations with polygenic scores (PGS), preceding (prior to AN diagnosis) as well as subsequent (5 years post AN diagnosis) psychiatric and somatic disorders. Design. Population-based cohort study. Setting. Nationwide study in Denmark. Participants. Individuals born between 1969 and 2013 with diagnosed AN (N = 9,534 individuals). Genetic data were available in a subsample comprising 5,126 individuals. Exposures. Forty-one PGS indexing traits relevant to AN, and psychiatric and somatic disorders prior to AN diagnosis. Main Outcomes and Measures. The main outcomes of interest were the AN-RSI trajectories and psychiatric and somatic disorders 5 years post AN diagnosis. Results. Three trajectories were identified: "low and stable" (32.6%), "medium and stable" (53.5%), and "high increasing" (14.0%). The "low and stable" group was used as the comparison group for all analyses. Each 1 standard deviation (SD) increase in AN PGS corresponded with 13% greater odds of following the "high increasing" trajectory. Increases in BMI and attention-deficit/hyperactivity disorder PGS corresponded with 15% and 14% lower odds of following the "high increasing" trajectory, respectively. No preceding psychiatric or somatic disorders were significantly associated with trajectory assignment. In contrast, psychiatric and somatic disorders were more likely to occur subsequent to an AN diagnosis in those in the "high increasing" trajectory with odds ratios (OR) ranging between 1.73 and 3.81 for psychiatric disorders and between 1.61 and 5.38 for somatic disorders with a notable exception of obesity which showed a lower OR of 0.27. Conclusions and Relevance. Our findings hold significant clinical relevance by demonstrating that individuals with AN follow distinct severity trajectories that have different genetic risk as measured by PGS and clear differences in post-diagnosis morbidity patterns but no discernable differences in pre-diagnosis psychiatric or somatic morbidity. As the eating disorders genetics field progresses, incorporating PGS into comprehensive assessments at first presentation may aid in early identification, personalized intervention, and resource allocation for individuals at higher risk of developing a severe illness trajectory.

Background: Autistic people experience substantially higher rates of mental health conditions and are overrepresented in mental health services. However, most interventions and service models have been developed for non-autistic people, and evidence is needed as to whether there are disparities in outcomes. This systematic review aimed to compare outcomes between autistic and non-autistic people receiving the same mental health interventions or services. Methods: We conducted a systematic review following PRISMA guidelines (PROSPERO: CRD420251021068). We searched academic databases (MEDLINE, Embase, PsycINFO, PubMed, CINAHL), a grey literature database (HMIC), a trial registry (ISRCTN), preprint servers (medRxiv and PsyArXiv), Google, and Google Scholar, to identify relevant papers published 01/01/1992-30/04/2026. We conducted backwards and forwards citation searching and contacted experts. Study quality was assessed using a modified Critical Appraisal Skills Programme Cohort Study Checklist and the Autism-Inclusive Research Assessment (AIRA). Data were synthesised narratively, with random effects meta-analyses where appropriate. Results: Thirty-nine studies were included, comprising 4787730 participants, assessing outcomes of psychological therapies (n = 17) and multi-component or service-level approaches (n = 22). Nearly half (46.2%) were UK-based, and under a quarter (23.1%) included people with intellectual disabilities. Ten studies (25.6%) were rated low quality, twenty-two (56.4%) medium quality, and seven (17.9%) high quality. AIRA ratings highlighted concerns about research inclusiveness for autistic people, including limited involvement of autistic people and lack of validated or adapted outcome measures. Findings varied by intervention: for some, multiple large, higher-quality studies showed less favourable outcomes for autistic people (e.g., less improvement in symptoms or functioning, or higher rates of restrictive practices or acute service use). For other interventions, comparable or mixed outcomes were found across studies, with interpretation often limited by small samples. Conclusions: Mental health treatment outcomes for autistic versus non-autistic people varied across interventions and outcome types. Where significant differences were observed, these usually showed poorer outcomes for autistic people, although they generally reflected smaller improvements rather than a lack of benefit. Action is needed to improve the accessibility and appropriateness of mental health care for autistic people, supported by more high-quality, co-produced research across a broader range of countries and service contexts.

Objective: Emotion dysregulation and irritability occur across pediatric disorders, complicating distinctions between general symptom burden and specific clinical presentations. Person-centered analyses can look at profiles of scores to identify groups with similar presentations. We examined whether modeling shared and domain-specific symptom variance identified differentiated profiles in youth. Method: Caregivers of 2,187 US youth ages 6-18 completed 87 items assessing emotion dysregulation, depression, mania-related symptoms, sleep-related impairment, and attention and behavioral problems. An ordinal bifactor model estimated one general and 13 specific factors. Latent profile analyses used standardized scores on all 14 factors, with an expanded raw-score analysis as a comparator. We examined caregiver-reported diagnoses and functioning and approximately two-week classification agreement among 166 recontacted caregivers. Results: The general factor accounted for 62% of common variance ({omega}H=.94), although model fit was mixed (CFI=.884; RMSEA=.058; SRMR=.092). A provisional four-class solution distinguished population-modal (67.4%), internalizing (11.8%), attention/hyperactivity (11.0%), and unusual-thought/elevated-mood (9.8%) profiles. Entropy was .83, but model enumeration and initialization checks did not establish a unique solution. Profiles showed overlapping diagnostic and functional correlates. Recontact agreement was 78.9% ({kappa}=.60). Irritability-specific reliability was limited, constraining interpretation of its weak profile differentiation. Conclusions: General symptom burden coexisted with differentiated residual symptom patterns. These findings support evaluating severity alongside symptom configuration, without equating profiles with diagnoses or weak residual irritability signals with limited clinical relevance. Measurement refinement, model-selection verification, and confirmation of classification-error-adjusted associations are needed before clinical application, but profiles could simplify clinical interpretation of sets of scales.

Abstract Background: The 52-item Ontario Child Health Study Emotional Behavioural Scales (OCHS-EBS) has demonstrated reliability and validity evidence in Canadian population-based samples. This study evaluated an adapted item set of the Ontario Child Health Study Emotional Behavioural Scales (OCHS-EBS-A) intended to measure selected mental disorder symptoms while reducing respondent burden in population-based research. Methods: A prespecified candidate set of 21 items from selected OCHS-EBS disorder scales assessed depression (4 items), generalized anxiety (4 items), oppositional behaviour (6 items), and attention-deficit/hyperactivity (7 items). The 2023 Longitudinal Canadian Health Survey on Children and Youth (L-CHSCY; ages 5-21 years; n= 22,740) provided calibration and internal-validation samples. The Ontario Provincial Assessment and Tracking of Child and Family Health Study (ONPATH; Wave 5: n=719 parent and n=116 youth respondents) provided an independent sample for further evaluation. Analyses examined factorial validity, internal consistency reliability, convergent and discriminant validity, and measurement invariance across sex assigned at birth within age/informant groups. Findings: The analyses supported a refined 20-item OCHS-EBS-A with three correlated factors representing internalizing, oppositional behaviour, and inattention/hyperactivity symptoms. Prespecified criteria for internal consistency reliability and convergent and discriminant validity were met within the reported L-CHSCY age/informant groups. Measurement invariance across sex assigned at birth was supported in the L-CHSCY groups and for children and parents in and youth-reported internalizing symptoms in ONPATH. However, not for ONPATH youth-reported oppositional behaviour symptoms. Interpretation: Results from these population-based samples provide factorial-validity, internal-consistency, and convergent- and discriminant-validity evidence for scores from the 20-item OCHS-EBS-A among children, youth, and emerging adults aged 5-21 years.

Background Autism spectrum disorder (ASD) shows wide phenotypic variation, from adults without intellectual disability and with low support needs to minimally verbal children with intellectual disability and severe behavioral symptoms. Genetic studies of this heterogeneity have focused mainly on high-impact de novo variants and polygenic scores; here we investigate, at the molecular level, the role of common variants. Materials and methods We analyzed genotypic and phenotypic data from 9,332 individuals with ASD in the SPARK cohort. We considered 31 traits: six latent factors derived from the Social Communication Questionnaire and the Repetitive Behavior Scale-Revised, 22 co-occurring diagnoses, parent-reported IQ range, age at diagnosis, and age at first walking. We performed within-case genome-wide association studies (GWAS) and, for the 10 traits with evidence of SNP heritability, association analyses with genetically predicted gene and protein expression, splicing, and enhancer activity in brain and blood (xWAS). Nominated genes were tested for enrichment in biological processes, brain cell types, and developmental stages. xWAS-derived transcriptional signatures were compared with chemical perturbation signatures from CMap/LINCS L1000 to prioritize candidate drugs. Results GWAS identified seven genome-wide significant loci for five traits, including loci near GABRG3 and TENM2 associated with co-occurring sleep, feeding or toileting problems. xWAS identified seven gene-trait associations involving three phenotypes (FDR < 0.1), including CACNA1G with communication skills and NEGR1 with learning disability. GWAS and xWAS nominated different genes which however converged on synaptic transmission and gated channel activity, with preferential expression in neurons during later stages of brain development. PARP and p38 MAPK inhibitors were predicted to reverse the signatures of both social-communication and repetitive-behavior phenotypes, whereas several compound classes, including histone deacetylase inhibitors and mTOR inhibitors, were predicted to reverse the signatures of some phenotypes while mimicking those of others. Conclusion Combining within-case GWAS with xWAS nominates candidate genes mediating common-variant effects on ASD heterogeneity, provides biological insight, and suggests candidates for phenotypically stratified drug repositioning.

Objective: To compare healthcare access among U.S. children with attention-deficit/hyperactivity disorder (ADHD) only, autism only, and co-occurring ADHD-autism, and to identify social inequities associated with unmet care using recent nationally representative data. Methods: We analyzed combined 2023-2024 National Survey of Childrens Health data for 13,576 children aged 3-17 years with current ADHD and/or autism. Six healthcare-access outcomes were examined: forgone healthcare, unmet mental health care, no medical home, coverage gap or inadequate insurance, unmet specialist care, and unmet care coordination. Survey-weighted modified Poisson regression estimated adjusted prevalence ratios (aPRs) and 95 percent confidence intervals (CIs). Six multiply imputed poverty measures were combined using Rubins rules. Sensitivity models additionally adjusted for functional difficulty. Results: Compared with ADHD only, co-occurring ADHD-autism was associated with higher prevalence of forgone healthcare (aPR, 1.73; 95 percent CI, 1.38-2.16), no medical home (1.11; 1.02-1.20), inadequate or discontinuous insurance (1.14; 1.03-1.28), unmet specialist care (1.49; 1.14-1.94), and unmet care coordination (1.15; 1.04-1.28). Autism only was associated with unmet mental health care (1.49; 1.13-1.97) and care coordination (1.13; 1.02-1.25). Food insufficiency, housing instability, and non-supportive neighborhood conditions were consistently associated with poorer access. After adjustment for functional difficulty, associations remained for co-occurring ADHD-autism with forgone and specialist care and for autism only with unmet mental health care. Conclusions: Healthcare access inequities differed by neurodevelopmental diagnostic group and social context. Pediatric systems should strengthen care coordination, specialty and mental health access, insurance continuity, family navigation, and responses to food and housing hardship. Keywords: attention-deficit/hyperactivity disorder; autism spectrum disorder; healthcare access; health disparities; social determinants of health