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Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD., Competing Interests: Declaration of competing interest L.M.H., J.M.S., J.T., D.V., L.M., C.C., E.C.O., S.C., P.S. are full-time employees of F. Hoffmann - La Roche Ltd, Basel, Switzerland. H.S. is a full-time employee of Roche Products Ltd, Welwyn Garden City, UK. G.P. is a full-time employee of Janssen Research & Development, LLC, Raritan, NJ, USA . P.W. is an employee of Clinical Research Associates, LLC, CT, USA. M.K. has received (non-related) research funding from Novartis during the researching and writing of the manuscript. C.A. has been a consultant to or has received honoraria or grants from Acadia, Abbot, Ambrosetti, AMGEN, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Forum, Gedeon Richter, Janssen-Cilag, Lundbeck, Merck, Otsuka, Pfizer, Roche, Servier, Shire, Schering-Plough, Sunovion, and Takeda. D.M. has received funding for a PhD studentship from Compass, and for consulting from Jaguar Therapeutics and Hoffman La Roche., (Copyright © 2024. Published by Elsevier B.V.)

Aim: To conduct a bibliometric analysis of the top 100 most-cited papers in dentistry for individuals with neurodevelopmental disorders., Methods and Results: A search strategy was constructed and conducted at the Web of Science in the category of "Dentistry, Oral Surgery, and Medicine". The following information was extracted from each paper: title, authorship, year of publication, title of the journal, study subject, study design, age range of sample participants, type of disability, institution, country and continent, number of citations and citation density. Google Scholar and Scopus were used to crosscheck the number of citations of the most-cited papers. The VOSviewer software was used to generate bibliometric network maps. The papers received 4453 citations in Web of Science, ranging from 30 to 106 citations. Most papers were published by the USA (35%), had an observational design (78%) and the main subject was epidemiology (31%). Most studies focused on individuals with Down syndrome (34%) and Autism Spectrum Disorder (18%) and were published in the Journal of Periodontology (10%) and the Pediatric Dentistry Journal (7%)., Conclusion: Most of the studies included in this review were characterized as epidemiological studies. Future research should focus on behavior guidance, dental education, and access to dental services., (© 2021 Special Care Dentistry Association and Wiley Periodicals LLC.)

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that can affect up to 2.6% of the population. Most of these people will have at least one other psychiatric disorder, often diagnosed with a delay or not recognized at all. This study describes the epidemiology, diagnostic difficulties and potential treatment of patients with ASD and comorbid bipolar disorder (BD). The prevalence of bipolar disorder in ASD is estimated at 5-8%. The study with the most numerous group included 700,000 children out of which 9,062 fulfilled ASD criteria at 16 - BD was found to be 6 times more prevalent in this group compared to the control group. Many factors affect the diagnosis. Patients with ASD often have limited insight into understanding the complex emotional states and difficulty in expressing them due to their impairment. The symptoms of bipolar disorder are in their case unspecific and differ from those occurring in the general population, which makes it difficult to make proper diagnosis. Despite the lack of research on the group of patients with ASD, psychometric tools designed to evaluate the general population are used to examine patients. This work aims to show the current state of knowledge and highlight areas that require further investigation.

Introduction: Autism spectrum conditions (ASC) develop early in life and are thought to last a lifetime. However, ASC research has two major knowledge gaps that hinder progression in understanding the concept of ASC and in providing proper support for autistic adults: (1) the majority of knowledge about ASC mainly stems from childhood studies so little is known about older autistic adults and (2) while it is broadly recognised that ASC is a heterogeneous condition, we do not yet understand the differences in trajectories leading to their future outcome. We aim to fill both knowledge gaps., Methods and Analysis: A multistage overlapping cohort design assessing (cognitive) ageing in ASC is designed to obtain an accelerated longitudinal data set. Data, including a multitude of questionnaires, diagnostics and cognitive tests, are collected over four waves within a 10-year time frame. This will provide information regarding actual changes in quality of life, co-occurring health conditions and cognition as well as the possibility to test external validity and temporal stability in newly formed behavioural subtypes. Participants consist of three groups of adults aged 20-90 years: (1) with a clinical diagnosis of ASC, (2) with a clinical diagnosis of attention deficit hyperactivity disorder (ADHD) but no ASC, (3) no ASC/ADHD (ie, comparison group). The sample size differs between waves and instruments. Detailed analysis plans will be preregistered in AsPredicted or at the Open Science Framework., Ethics and Dissemination: Ethical approval for this study was obtained from the ethical review board of the Department of Psychology of the University of Amsterdam (wave 1 2011-PN-1952 and 2013-PN-2668, wave 2 2015-BC-4270, waves 3 and 4 2018-BC-9285). In line with the funding policies of the grant organisation funding this study, future papers will be published open access., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Abstract Autistic individuals often experience a wide range of barriers and challenges with employment across their lifetime. Despite their strengths and abilities to contribute to the workforce, many individuals experience unemployment, underemployment and malemployment. However, current supports and services are often inadequate to meet their needs. To allow autistic people to achieve vocational success, we explore four contributors to employment and expand upon the issues and potential solutions to each. These positions include the importance of family support and its consideration in the application of vocational support interventions, addressing transitional needs for autistic youth, building employer capacity, and conducting research that advises the development of meaningful programs and policies. By advocating for these positions, we aim to foster greater inclusivity and support for individuals with ASD in the workplace.

Object personification is the attribution of human characteristics to non-human agents. In online forums, autistic individuals commonly report experiencing this phenomenon. Given that approximately half of all autistic individuals experience difficulties identifying their own emotions, the suggestion that object personification may be a feature of autism seems almost paradoxical. Why would a person experience sympathy for objects, when they struggle to understand and verbalise the emotions of other people as well as their own? An online survey was used to assess tendency for personification in 87 autistic and 263 non-autistic adults. Together, our results indicate that object personification occurs commonly among autistic individuals, and perhaps more often (and later in life) than in the general population. Given that in many cases, autistic people report their personification experiences as distressing, it is important to consider the reasons for the increased personification and identify structures for support.

Background: Responding to one's own name (RtN) has been reported as atypical in children with developmental disorders, yet comparative studies on RtN across syndromes are rare., Aims: We aim to (a) overview the literature on RtN in different developmental disorders during the first 24 months of life, and (b) report comparative data on RtN across syndromes., Methods and Procedures: In Part 1, a literature search, focusing on RtN in children during the first 24 months of life with developmental disorders, identified 23 relevant studies. In Part 2, RtN was assessed utilizing retrospective video analysis for infants later diagnosed with ASD, RTT, or FXS, and typically developing peers., Outcomes and Results: Given a variety of methodologies and instruments applied to assess RtN, 21/23 studies identified RtN as atypical in infants with a developmental disorder. We observed four different developmental trajectories of RtN in ASD, RTT, PSV, and FXS from 9 to 24 months of age. Between-group differences became more distinctive with age., Conclusions and Implications: RtN may be a potential parameter of interest in a comprehensive early detection model characterising age-specific neurofunctional biomarkers associated with specific disorders, and contribute to early identification., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

DNA methylation is a biochemical process that modifies gene expression without changing the underlying DNA sequence, and this represents the molecular basis for imprinting and epigenetics. Recent reports have revealed alterations in DNA methylation profiles in the placenta of babies born from assisted reproductive technologies (ART). This supports several previous observations that suggested an increase in the prevalence of imprinting diseases following ART treatment, and also fits our observations regarding the metabolism and requirements of early human embryos. Human embryo culture media (HECM) are currently formulated according to requirements based on the mouse embryo model, and in fact need to pass the Mouse Embryo Assay test in order to be accepted by the relevant authorities, despite the fact that physiological (especially the time necessary to reach genomic activation) and biochemical requirements of mouse and human embryos are quite different. This commentary aims to explain some of the discrepancies, and emphasize why human embryo metabolism tells us that the composition of HECM, as well as the role of the MEA as a unique model, should be re-evaluated.

Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the "autisms" [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as "steroid metabolism" and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022-1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., (© 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.)

Salivary cortisol may be used as a biomarker of stress and anxiety in children with an autism spectrum disorder (ASD). Some suggestions have been made that the measurement of cortisol needs to be undertaken by repeated days' observations to ensure reliability of the data obtained. These requirements are discussed in regard to 14 studies of the test-retest agreement and stability in cortisol data across repeated daily measurements. Results of those studies almost universally fail to support the argument for repeated daily measurements of cortisol. Implications for the research protocols of studies using cortisol as an index of stress in children with ASD are discussed.

Purpose: To estimate associations between suspected or diagnosed neurodevelopmental or behavioural problems in 7-year-old children and maternal unemployment at child age 7 and 10, in a Portuguese birth cohort., Methods: We evaluated 5754 mothers and their children of the population-based birth cohort Generation XXI in Porto, Portugal. Data on suspected and diagnosed child neurodevelopmental and behavioural problems (exposures)-learning, attention and language problems, externalising behaviours, developmental delay, autism spectrum disorders, and other neurodevelopmental problems-were retrieved at 7 years of age by interviewing caregivers. Maternal employment status (outcome) was collected at the 7- and 10-year follow-up waves. Robust Poisson regression models were used to estimate associations., Results: After adjustment for maternal and household characteristics, women were more likely to be unemployed at child age 10 if the child had, up to age 7, any of the following suspected problems: an autism spectrum disorder (PR = 1.73; 95% CI 1.07, 2.79), developmental delay (PR = 1.58; 95% CI 1.20, 2.06), externalising behaviours (PR = 1.29; 95% CI 1.11, 1.50) or learning problems (PR = 1.26; 95% CI 1.07, 1.48). When the exposure was restricted to clinically diagnosed disorders, the magnitude of associations remained similar but estimates were less precise. Associations with unemployment were stronger at child age 10 (prospective analyses), than at child age 7 (cross-sectional)., Conclusion: Having a child with learning, developmental or behavioural problems, or an autism spectrum disorder up to age 7 was associated with maternal unemployment three years later, even in a less affluent European economy where the dual-earner family structure is often necessary to make ends meet., (© 2023. The Author(s).)

Parents of Autistic children often modify their participation in leisure, social, and employment activities to meet the caregiving needs of their child. However, few studies have examined the impact this has on caregiver quality of life (QoL). The aim in the current study was to examine the role of participation in a range of activities on QoL amongst primary and secondary caregivers of school-aged Autistic children. Eighty-eight primary (93% mothers) and 63 secondary (91% fathers) caregivers of Autistic children (aged 7- to 12-years) participated in this cross-sectional study, with time pressure, participation, social support, parenting stress, and QoL measured via an online questionnaire. Compared to secondary caregivers, primary caregivers reported fewer employment hours, increased time pressure, less participation in desired activities, and higher perceived responsibility of domestic and child-rearing tasks. Similar levels of leisure frequency, parenting stress, and QoL were identified by both caregivers. Hierarchical regression revealed caregiver participation as important for QoL in both primary and secondary caregivers. However, when measures of caregiver well-being were added to the model, the unique contribution of participation to QoL was reduced, particularly for secondary caregivers. Overall, the findings demonstrate that despite differences in caregiver roles and responsibilities, participation in meaningful activities was important for QoL in all caregivers., (© 2024 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

BackgroundThere is a multitude of systematic reviews of interventions for children and adolescents with autism spectrum disorder (ASD). However, most reviews seem to be based on research conducted in High-Income Countries (HIC). Thus, summary findings may not directly apply to Lower Middle-Income Countries (LMIC). Therefore, we conducted a Meta-Review analyzing systematic reviews on the effectiveness of interventions for target outcomes in children and adolescents with ASD to find out whether there are differences in effectiveness between HIC and LMIC and which interventions can be considered evidence-based in LMIC.MethodsElectronic databases (PsycINFO, PubMed, Cochrane database of systematic reviews) were searched for reviews on interventions for ASD in children and adolescents from January 2011 through December 2021, which included studies not coming from HIC. Systematic reviews with qualitative and quantitative syntheses of findings were included. Two investigators independently assessed studies against predetermined inclusion/exclusion criteria and extracted relevant data including quality and evidence assessments. Evidence for different types of interventions in HIC vs. LMIC was planned to be compared, but none of the reviews assessed potential differences. Therefore, a narrative review of the studies from LMIC was conducted including an assessment of quality and evidence.ResultsThirty-five reviews fulfilled the inclusion criteria. Eleven considered findings from HIC and LMIC. Sixty-nine percent included studies with various research designs; 63% provided a qualitative synthesis of findings; 77% percent assessed the quality of studies; 43% systematically assessed the level of evidence across studies. No review compared evidence from HIC and LMIC. A review of the studies from LMIC found some promising results, but the evidence was not sufficient due to a small number of studies, sometimes poor quality, and small sample sizes.ConclusionSystematic reviews on interventions for children and adolescents with ASD did not look for potential differences in the effectiveness of interventions in HIC and LMIC. Overall, there is very little evidence from LMIC. None of the interventions can be considered evidence-based in LMIC. Hence, additional research and mutually agreed methodological standards are needed to provide a more secure basis for evidence-based treatments in LMIC trying to establish evidence-based practices.

Autism spectrum disorder is an increasingly prevalent and debilitating neurodevelopmental condition and an electroencephalogram (EEG) diagnostic challenge. Despite large amounts of electrophysiological research over many decades, an EEG biomarker for autism spectrum disorder (ASD) has not been found. We hypothesized that reductions in complex dynamical system behaviour in the human central nervous system as part of the macroscale neuronal function during cognitive processes might be detectable in whole EEG for higher-risk ASD adults. In three studies, we compared the medians of correlation dimension, largest Lyapunov exponent, Higuchi's fractal dimension, multiscale entropy, multifractal detrended fluctuation analysis and Kolmogorov complexity during resting, cognitive and social skill tasks in 20 EEG channels of 39 adults over a range of ASD risk. We found heterogeneous complexity distribution with clusters of hierarchical sequences pointing to potential cognitive processing differences, but no clear distinction based on ASD risk. We suggest that there is indication of statistically significant differences between complexity measures of brain states and tasks. Though replication of our studies is needed with a larger sample, we believe that our electrophysiological and analytic approach has potential as a biomarker for earlier ASD diagnosis., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Few autism spectrum disorder (ASD) screening tools have been developed and validated in Africa. This study aimed to examine the psychometric properties of the Social Communication Questionnaire (SCQ) when used with Nigerian adolescents. Parents and caregivers of two hundred and five adolescents completed the SCQ Lifetime form while the adolescents were assessed for ASD using the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2). Factor structure and convergent and discriminative validity were examined, along with the sensitivity and specificity of the SCQ in identifying participants with an autism spectrum disorder. The confirmatory factor analysis (CFA) was used to examine the factor structure, while logistic regression and Pearson's correlation coefficient were used to examine the validities. The SCQ had good internal consistency, discriminative, and convergent validity. A cut-off score of 10 revealed sensitivity = 0.81 and specificity = 0.88 for the identification of autism spectrum disorder. AUC was 0.83, p < 0.001, 95% CI [0.77, 0.90]. The results of this study provide evidence to support the retention of the original four factors of the SCQ. The SCQ has good psychometric properties when used with Nigerian adolescents., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders characterized by aberrant neural networks. Cerebellum is best known for its role in controlling motor behaviors; however, recently, there have been significant reports showed that dysfunction in cerebellar-cerebral networks contributes significantly to many of the clinical features of ASD. Hereby, this is a randomized controlled trial (RCT) study examining the potential modulating effects of bilateral anodal tDCS stimulation over cerebellar hemispheres on the resting-state brain complexity in children with ASD., Methods: Thirty-six children with ASD (aged 4-14) years old were divided equally and randomly into a tDCS treatment group, which underwent 10 sessions (20-min duration, five sessions/per week) of bilateral anodal tDCS stimulation applied over left and right cerebellar hemispheres, and control group underwent the same procedures, but with sham tDCS stimulation. Resting-state brain complexity was evaluated through recording and calculating the approximate entropy (ApxEnt) values of the resting-state electroencephalograph (EEG) data obtained from a 64-channel EEG system before and after the interventions., Results: Repeated measures of ANOVA showed that tDCS had significant effects on the treatment group (Wilks' Lambda = 0.29, F (15, 16) = 2.67, p = 0.03) compared with the control group. Analyzed data showed a significant increase in the averaged ApxEnt values in the right frontal cortical region (F (1, 16) = 10.46, p = 0.005) after the bilateral cerebellar anodal tDCS stimulation. Besides, the Cohen's d effect size showed a large effect size (0.70-0.92) of bilateral cerebellar anodal tDCS on the ApxEnt values increases in the left and right frontal cortical regions, the right central cortical region, and left parietal cortical region. However, there were no any significant differences or increases in the brain complexity before and after the sham tDCS stimulation of the control group., Conclusion: Bilateral cerebellar anodal tDCS modulated and increased the brain complexity in children with ASD with no any reported adverse effect. Hereby, cerebellum and cerebellar-cerebral circuitry would serve as a promising target for non-invasive brain stimulation and neuro-modulation as a therapeutic intervention., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Social skills interventions are commonly recommended to help children and young people with autism spectrum disorder develop social skills, but some struggle to engage in these interventions. LEGO ® (LEGO System A/S, Billund, Denmark) based therapy, a group social skills intervention, aims to be more interesting and engaging., Objective: To evaluate the clinical effectiveness of LEGO ® based therapy on the social and emotional skills of children and young people with autism spectrum disorder in school settings compared with usual support. Secondary objectives included evaluations of cost-effectiveness, acceptability and treatment fidelity., Design: A cluster randomised controlled trial randomly allocating participating schools to either LEGO ® based therapy and usual support or usual support only., Setting: Mainstream schools in the north of England., Participants: Children and young people (aged 7-15 years) with autism spectrum disorder, their parent/guardian, an associated teacher/teaching assistant and a facilitator teacher/teaching assistant (intervention schools only)., Intervention: Schools randomised to the intervention arm delivered 12 weekly sessions of LEGO ® based therapy, which promotes collaborative play and encourages social problem-solving in groups of three children and young people with a facilitator (trained teacher or teaching assistant). Participants received usual support from school and community services. Participants in the control arm received usual support only. Research assistants and statisticians were blind to treatment allocation., Main Outcome Measure: The social skills subscale of the Social Skills Improvement System (SSIS), completed by the children and young people's unblinded teacher pre randomisation and 20 weeks post randomisation. The SSIS social skills subscale measures social skills including social communication, co-operation, empathy, assertion, responsibility and self-control. Participants completed a number of other pre- and post-randomisation measures of emotional health, quality of life, loneliness, problem behaviours, academic competence, service resource utilisation and adverse events., Results: A total of 250 children and young people from 98 schools were randomised: 127 to the intervention arm and 123 to the control arm. Intention-to-treat analysis of the main outcome measure showed a modest positive difference of 3.74 points (95% confidence interval -0.16 to 7.63 points, standardised effect size 0.18; p  = 0.06) in favour of the intervention arm. Statistical significance increased in per-protocol analysis, with a modest positive difference (standardised effect size 0.21; p  = 0.036). Cost-effectiveness of the intervention was found in reduced service use costs and a small increase in quality-adjusted life-years. Intervention fidelity and acceptability were positive. No intervention-related adverse events or effects were reported., Conclusions: The primary and pre-planned sensitivity analysis of the primary outcome consistently showed a positive clinical difference, with modest standardised effect sizes of between 0.15 and 0.21. There were positive health economics and qualitative findings, corroborated by the difference between arms for the majority of secondary outcomes, which were not statistically significant but favoured the intervention arm. Post hoc additional analysis was exploratory and was not used in drawing this conclusion. Given the small positive change, LEGO ® based therapy for children and young people with autism spectrum disorder in schools should be considered., Limitations: The primary outcome measure was completed by an unblinded teacher (rather than by the facilitator)., Future Work: The study team recommends future research into LEGO ® based therapy, particularly in school environments., Trial Registration: This trial is registered as ISRCTN64852382., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/49/32) and is published in full in Public Health Research ; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.

Objectives: To assess the occurrence rate, characteristics, and impact of eating disorders (EDs) in adolescents with epilepsy., Methods: In this observational study, adolescents with epilepsy seen in a single center between 2013 and 2022 who had comorbid EDs were compared to two control groups of adolescents with only epilepsy and only EDs. Patients with intellectual disability or autism spectrum disorder were excluded. Data retrieved included demographic and anthropometric details and clinical variables relating to seizure types, EDs, and psychiatric disorders and behaviors., Results: A total of 376 subjects were included in the study: 84 adolescents with both epilepsy and eating disorders, 135 with only epilepsy, and 157 with only EDs. The rate of EDs in adolescents with epilepsy was 7.0% (95% confidence interval [CI] 5.6%-8.5%) overall, 11.3% (95% CI 8.8%-14.3%) in females, and 3.1% (95% CI 1.9%-4.8%) in males. The median (interquartile range [IQR]) time difference between the onset of epilepsy to an ED was 1.6 (.5-3.6) years. Among adolescents with epilepsy, those with an ED were more likely to be female (p = .001) and have a lower body mass index z-score (zBMI) percentile (p < .001). Epilepsy type, seizure frequency, or seizure duration were not specific for having or not having EDs. Among adolescents with EDs, those with epilepsy had a younger onset of their EDs (p < .001), included relatively more males (p = .007), and consisted of more cases of anorexia-nervosa-restrictive type (p < .001), and fewer cases of bulimia nervosa (p = .04) and binge eating disorder (p = .003). Adolescents with epilepsy and a comorbid ED were more likely to have psychiatric comorbidities such as depression, anxiety, and suicidality than adolescents with only epilepsy or EDs., Significance: EDs should be suspected and screened for in intellectually intact female and male adolescents with epilepsy, irrespective of their epilepsy type. If disturbed eating behaviors or EDs are identified, further evaluation should be directed at detecting other psychopathologies, including suicidality., (© 2023 International League Against Epilepsy.)

Purpose: To investigate serum levels of VEGF, IGF-1 and FGF-2, and relationships with several clinical characteristics in children and adolescents with autism spectrum disorder (ASD) with and without bipolar disorder (BD)., Method: 40 subjects with ASD + BD as study group, and 40 subjects with ASD as control group were included. Serum levels of VEGF, IGF-1, and FGF-2 were measured using commercial enzyme-linked immunosorbent assay kits., Results: The study group was significantly higher than the control group in terms of ASD severity, self-harming behavior and sleep disturbance. Serum VEGF and FGF-2 levels were significantly higher in the ASD + BD group than in the control group. There was no significant difference in serum IGF-1 levels between the two groups. There was no correlation between VEGF, IGF-1 and FGF-2 serum levels and ASD severity in the study group. However there was a negative correlation between VEGF levels and age at first diagnosis of BD, and a positive correlation between IGF-1 levels and the number of bipolar episodes in the study group., Conclusion: Growth factors like VEGF and FGF-2 may be potential biomarkers of bipolar disorder in young subjects with ASD. Given the difficulty of clinical management of BD in young subjects with ASD, potential biomarkers would help clinicians in the diagnosis and follow up of BD in this special population. Further research is needed whether VEGF and FGF-2 can be potential biomarkers in the clinical management of young subjects with ASD and BD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neurodevelopmental conditions frequently co-occur. The aim of this paper was to determine whether there is a cumulative association between (1) the number of neurodevelopmental conditions, specifically hyperkinetic disorder (hereafter referred to as attention deficit hyperactivity disorder), autism spectrum disorder (hereafter referred to as autism) and intellectual disability, and (2) behavioural and socio-emotional problems and the level of clinician-rated functioning for young males and females., Methods: In this cross-sectional study, diagnostic information, caregiver-rated behavioural and socio-emotional data (as conceptualised by the Strengths and Difficulties Questionnaire) and clinician-rated functioning scores (as conceptualised by the Children's Global Assessment Scale) were extracted from electronic patient records for 2768 young people aged 3-17 years (mean = 11.55, SD = 3.46). All data were extracted at baseline, that is, at the time the young person was diagnosed with attention deficit hyperactivity disorder, autism and/or an intellectual disability. Ordinal regression analyses tested associations between the number of neurodevelopmental conditions met (i.e. 1, 2 or 3) and behavioural and socio-emotional outcomes and functioning., Results: After controlling for age and biological sex, the number of neurodevelopmental conditions was associated with higher levels of inattention/hyperactivity and peer problems, lower levels of prosocial behaviour and poorer clinician-rated functioning. Although these findings were consistent for males, a cumulative association was not identified for females, except for clinician-rated functioning., Conclusions: For young people, the presence of multiple neurodevelopmental conditions may have a cumulative impact across domains, but this may differ between males and females., (© 2024 The Author(s). Journal of Intellectual Disability Research published by John Wiley & Sons and MENCAP.)

Socio-cognitive difficulties in individuals with autism spectrum disorder (ASD) are heterogenuous and often co-occur with irritability symptoms, such as angry/grouchy mood and temper outbursts. However, the specific relations between individual symptoms are not well-represented in conventional methods analyzing aggregated autistic symptoms and ASD diagnosis. Moreover, the cognitive-behavioral mechanisms linking ASD to irritability are largely unknown. This study investigated the dynamics between autistic (Social Responsiveness Scale) and irritability (Affective Reactivity Index) symptoms and executive functions (Cambridge Neuropsychological Test Automated Battery) in a sample of children and adolescents with ASD, their unaffected siblings, and neurotypical peers (N = 345, aged 6-18 years, 78.6% male). Three complementary networks across the entire sample were computed: (1) Gaussian graphical network estimating the conditional correlations between symptom nodes; (2) Relative importance network computing relative influence between symptoms; (3) Bayesian directed acyclic graph estimating predictive directionality between symptoms. Networks revealed numerous partial correlations within autistic (rs = .07-.56) and irritability (rs = .01-.45) symptoms and executive functions (rs = -.83 to .67) but weak connections between clusters. This segregated pattern converged in all directed and supplementary networks. Plausible predictive paths were found between social communication difficulties to autism mannerisms and between "angry frequently" to "lose temper easily." Autistic and irritability symptoms are two relatively independent families of symptoms. It is unlikely that executive dysfunctions explain elevated irritability in ASD. Findings underscore the need for researching other mood and cognitive-behavioral bridge symptoms, which may inform individualized treatments for co-occurring irritability in ASD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that can affect up to 2.6% of the population. Most of these people will have at least one other psychiatric disorder, often diagnosed with a delay or not recognized at all. This study describes the epidemiology, diagnostic difficulties and potential treatment of patients with ASD and comorbid bipolar disorder (BD). The prevalence of bipolar disorder in ASD is estimated at 5-8%. The study with the most numerous group included 700,000 children out of which 9,062 fulfilled ASD criteria at 16 - BD was found to be 6 times more prevalent in this group compared to the control group. Many factors affect the diagnosis. Patients with ASD often have limited insight into understanding the complex emotional states and difficulty in expressing them due to their impairment. The symptoms of bipolar disorder are in their case unspecific and differ from those occurring in the general population, which makes it difficult to make proper diagnosis. Despite the lack of research on the group of patients with ASD, psychometric tools designed to evaluate the general population are used to examine patients. This work aims to show the current state of knowledge and highlight areas that require further investigation. [ABSTRACT FROM AUTHOR]

Background: Mandarin-speaking children with autism spectrum disorder (ASD) have difficulties producing aspect markers. The difficulties were explained in terms of pragmatic deficits since these children demonstrated strength in the comprehension of aspect markers using the Intermodal Preferential Looking (IPL) task., Aims: To verify whether this dissociation between production and comprehension could be replicated using another technique to the IPL, and if all children with ASD show difficulties in the production of aspect markers., Methods & Procedures: A total of 34 children with ASD without cognitive delay, half with language impairment (ALI; mean age = 61.25 months old) and half with normal language (ALN, mean age = 61.52 months old), as well as 17 age-matched typically developing (TD) children (mean age = 61.38 months old) participated in a sentence-picture-matching task and a priming picture-description task to investigate their comprehension and production of Mandarin aspect markers zai-, -le and -zhe., Outcomes & Results: In the comprehension task, children in the ALN group performed similarly to their TD peers, but those in the ALI group were less accurate on zai- and -le than TD children; children in all groups received higher accuracy when zai- was combined with Activity rather than Accomplishment verbs, and those in the ALI group was also more accurate when -le occurred with Achievement verbs, in contrast to Activity verbs. In the production task, children in the ALI group produced fewer targets and more irrelevant sentences with zai- than their TD peers, and they tended to produce bare verbs for -le and -zhe than TD children; children in all groups tended to combine zai- with Activity verbs, and those in the ALN group also tended to combine -le with Achievement verbs., Conclusions & Implications: The comprehension and production of Mandarin aspect markers by children with ASD are linked to general language abilities, and interactions between lexical and grammatical aspect. Patterns of performance are similar to those of TD peers only for the subgroup with spared global language, while pragmatic deficits are pervasive throughout the spectrum. Therefore, training on formal language, with a specific emphasis on aspectual rather than pragmatic abilities, may be more effective at enhancing the production of aspect markers., What This Paper Adds: What is already known on this subject Mandarin-speaking children with ASD have difficulties producing aspect markers but demonstrate strengths in aspectual comprehension via the IPL task. Therefore, it has been proposed that their 'specific' difficulties in aspectual production should be ascribed to their pragmatic deficits. However, pragmatic deficits are highly pervasive in children with ASD while only a subgroup of children with ASD who are impaired in language development (children with ALI) show difficulties in producing tense/aspect morphology. Pursuing this reasoning, pragmatic deficits might not be the critical factor impacting the performance of children with ASD in aspectual production. What this study adds Children with ASD were divided into one group with ALI and the other with normal language (ALN). Results of a sentence-picture-matching and a priming picture-description task illustrated that both groups preserved the comprehension of Mandarin aspect markers zai-, -le and -zhe. However, children with ALI performed worse than age-matched TD children, while children with ALN demonstrated similar performance to TD children in aspectual production. These findings, coupled with the fact that pragmatic challenges affect individuals throughout the spectrum, suggest that general language abilities rather than pragmatics better explain the performance of children with ASD on aspectual production. What are the potential or actual clinical implications of this work? Since general language abilities rather than pragmatic deficits of children with ASD determine their performance on the production of aspect markers, direct training on the use of aspect markers or more global language therapy could benefit children with ASD in the production of aspect markers., (© 2023 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with severe cognitive impairment. Several studies have reported that brain functional network connectivity (FNC) has great potential for identifying ASD from healthy control (HC) and revealing the relationships between the brain and behaviors of ASD. However, few studies have explored dynamic large-scale FNC as a feature to identify individuals with ASD. This study used a time-sliding window method to study the dynamic FNC (dFNC) on the resting-state fMRI. To avoid arbitrarily determining the window length, we set a window length range of 10-75 TRs (TR = 2 s). We constructed linear support vector machine classifiers for all window length conditions. Using a nested 10-fold cross-validation framework, we obtained a grand average accuracy of 94.88% across window length conditions, which is higher than those reported in previous studies. In addition, we determined the optimal window length using the highest classification accuracy of 97.77%. Based on the optimal window length, we found that the dFNCs were located mainly in dorsal and ventral attention networks (DAN and VAN) and exhibited the highest weight in classification. Specifically, we found that the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly negatively correlated with social scores of ASD. Finally, using the dFNCs with high classification weights as features, we construct a model to predict the clinical score of ASD. Overall, our findings demonstrated that the dFNC could be a potential biomarker to identify ASD and provide new perspectives to detect cognitive changes in ASD., (© 2023 International Society for Autism Research and Wiley Periodicals LLC.)

Background: Maternal folic acid intake has been associated with decreased risk for neurodevelopmental disorders including autism spectrum disorder (ASD). Genetic differences in folate metabolism could explain some inconsistencies. To our knowledge, newborn folate concentrations remain unexamined., Methods: We measured folate in archived newborn dried blood spots of children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) case-control study who were clinically confirmed at 24-60 months to have ASD (n = 380), developmental delay (n = 128), or typical development (n = 247). We quantified monthly folic acid intake from maternally-reported supplements and cereals consumed during pregnancy and 3 months prior. We assessed associations of newborn folate with maternal folic acid intake and with ASD or developmental delay using regression. We stratified estimates across maternal and child MTHFR genotypes., Results: Among typically developing children, maternal folic acid intake in prepregnancy and each pregnancy month and prepregnancy prenatal vitamin intake were positively associated with newborn folate. Among children with ASD, prenatal vitamin intake in pregnancy months 2-9 was positively associated with newborn folate. Among children with developmental delay, maternal folic acid and prenatal vitamins during the first pregnancy month were positively associated with neonatal folate. Associations differed by MTHFR genotype. Overall, neonatal folate was not associated with ASD or developmental delay, though we observed associations with ASD in children with the MTHFR 677 TT genotype (odds ratio: 1.76, 95% CI = 1.19, 2.62; P for interaction = 0.08)., Conclusion: Maternal prenatal folic acid intake was associated with neonatal folate at different times across neurodevelopmental groups. Neonatal folate was not associated with reduced ASD risk. MTHFR genotypes modulated these relationships., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The purpose of this pilot study was to compare video modeling (VM) to a toothbrushing social story (TSS) for improving oral hygiene in children with autism spectrum disorder (ASD)., Methods: Four to 17-year-old children and adolescents with ASD were evaluated at a pre-intervention visit for quality of oral hygiene using plaque and gingival indices. A pre-intervention survey assessed caregivers' perceptions of their children's daily oral hygiene practices. Participants were randomized into VM or TSS groups and caregivers received daily emails to access a VM or TSS presentation when completing toothbrushing for their child for 30 days. At the one-month visit, oral hygiene was re-evaluated, and post-intervention surveys were completed., Results: There were significant improvements in plaque and gingival scores for VM (0.68 ± 0.20; 0.59 ± 0.15) and TSS (0.50 ± 0.11; 0.40 ± 0.10) groups at post-intervention compared to pre-intervention visits. No significant improvements in plaque or gingival scores were noted between the VM and TSS groups. Caregivers' perceptions regarding oral hygiene acceptance by their children was promising for the VM group., Conclusions: VM and TSS interventions improved oral hygiene in subjects with ASD. There was greater acceptance of daily oral hygiene in the VM compared to the TSS group., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)

The current study examined factorial invariance of the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R) and the Depression Anxiety Stress Scales-21 (DASS-21) using a convenience sample of 434 adults surveyed though Amazon Mechanical Turk. Participants were sorted into two groups based on their score on the Autism-Spectrum Quotient. Results indicated that the CESD-R did not demonstrate configural invariance. The DASS-21 demonstrated evidence of scalar invariance, indicating cross-group equality in factor loadings and factor intercepts. Findings suggest that the DASS-21 measures symptoms of depression, anxiety, and stress consistently across individuals with high and low levels of ASD-related traits, whereas the CESD-R may not be valid when assessing symptoms of depression in those with a high level of ASD-related traits., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An early detection of Neurodevelopmental Disorders (NDDs) is crucial for their prognosis; however, the clinical heterogeneity of some disorders, such as autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD) is an obstacle to accurate diagnoses in children. In order to facilitate the screening process, the current study aimed to identify symptom-based clusters among a community-based sample of preschool and school-aged children, using behavioral characteristics reported by teachers. A total of 6894 children were assessed on four key variables: social communication differences, restricted behavior patterns, restless-impulsiveness, and emotional lability (pre-schoolers) or inattention and hyperactivity-impulsivity (school-aged). From these behavioral profiles, four clusters were identified for each age group. A cluster of ASD + ADHD and others including children with no pathology was clearly identified, whereas two other clusters were characterized by subthreshold ASD and/or ADHD symptoms. In the school-age children, the presence of ADHD was consistently observed with ASD patterns. In pre-schoolers, teachers were more proficient at identifying children who received a diagnosis for either ASD and/or ADHD from an early stage. Considering the significance of early detection and intervention of NDDs, teachers' insights are important. Therefore, promptly identifying subthreshold symptoms in children can help to minimize consequences in social and academic functioning., (© 2024 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Objective: To delineate the comprehensive phenotypic spectrum of SYNGAP1-related disorder in a large patient cohort aggregated through a digital registry., Methods: We obtained de-identified patient data from an online registry. Data were extracted from uploaded medical records. We reclassified all SYNGAP1 variants using American College of Medical Genetics criteria and included patients with pathogenic/likely pathogenic (P/LP) single nucleotide variants or microdeletions incorporating SYNGAP1. We analyzed neurodevelopmental phenotypes, including epilepsy, intellectual disability (ID), autism spectrum disorder (ASD), behavioral disorders, and gait dysfunction for all patients with respect to variant type and location within the SynGAP1 protein., Results: We identified 147 patients (50% male, median age 8 years) with P/LP SYNGAP1 variants from 151 individuals with data available through the database. One hundred nine were truncating variants and 22 were missense. All patients were diagnosed with global developmental delay (GDD) and/or ID, and 123 patients (84%) were diagnosed with epilepsy. Of those with epilepsy, 73% of patients had GDD diagnosed before epilepsy was diagnosed. Other prominent features included autistic traits (n = 100, 68%), behavioral problems (n = 100, 68%), sleep problems (n = 90, 61%), anxiety (n = 35, 24%), ataxia or abnormal gait (n = 69, 47%), sensory problems (n = 32, 22%), and feeding difficulties (n = 69, 47%). Behavioral problems were more likely in those patients diagnosed with anxiety (odds ratio [OR] 3.6, p = .014) and sleep problems (OR 2.41, p = .015) but not necessarily those with autistic traits. Patients with variants in exons 1-4 were more likely to have the ability to speak in phrases vs those with variants in exons 5-19, and epilepsy occurred less frequently in patients with variants in the SH3 binding motif., Significance: We demonstrate that the data obtained from a digital registry recapitulate earlier but smaller studies of SYNGAP1-related disorder and add additional genotype-phenotype relationships, validating the use of the digital registry. Access to data through digital registries broadens the possibilities for efficient data collection in rare diseases., (© 2024 International League Against Epilepsy.)