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Sensory-Based Interventions (SBIs) are often recommended to enable function/participation in children with ASD. Still, there are limited studies to evaluate their effectiveness. Acceptability studies are an important step towards establishing effective interventions. We examined parents' perceptions of the uptake and acceptability of such interventions. An online survey was sent to 399 families; response rate was 39%. The most frequently therapist-recommended interventions were trampoline (54.6%), massage (47.8%), and oral-motor tools (43.8%). Highest use was reported for massage (96.3%), trampoline (89.2%) and joint compressions and brushing (89.2%). The majority of parents viewed these interventions to be very important /important, (74.8%) but barriers to their use were identified. High acceptability of SBIs was reported by parents of children with ASD.

The aim of this study was to generate a patient-centered conceptual model of the impact of living with autism spectrum disorder, which can be used to support the selection of outcome measures for clinical trials. Following an initial literature review to identify preliminary concepts and inform an interview guide, in-depth face-to-face interviews were conducted with adolescents and adults with autism spectrum disorder (IQ ? 70) (n = 10), as well as parents of children, adolescents, and adults with autism spectrum disorder (IQ ? 70) (n = 26). Data were analyzed using established qualitative research methods. The resultant conceptual model contains three interrelated domains reflecting core symptoms of autism spectrum disorder (communication deficits, socialization deficits, and restrictive, repetitive patterns of behavior), three domains reflecting associated symptoms of autism spectrum disorder (physical, cognitive, and emotional/behavioral), and three domains representing the impacts of living with autism spectrum disorder (impacts on activities of daily living, school/work, and social life). Interview respondents also cited social communication deficits as priority targets for new treatments. The conceptual model provides a patient-centered perspective of relevant concepts of autism spectrum disorder from the perspectives of people with autism spectrum disorder and their parents and offers a valuable tool for identifying valid patient-centered outcome measures for future clinical trials.

This study aimed to describe rates of antipsychotic medication use and the association between their use and demographics, clinical variables, and the use of behavioral/education services among children with ASD. For children with ASD ages 2-11 (n = 4749) and those 12-17 (n = 401), 5.4 and 17.7% were prescribed at least one atypical antipsychotic medication respectively. In the multivariable model of young children, older age, use of multiple psychotropic medications, prior ASD diagnosis, non-white Hispanic race/ethnicity, and oppositional defiant problems were associated with antipsychotic use. Among older children, only older age was associated with antipsychotic use. In at least one age group, antipsychotic medication use was also related to behaviour, family and occupational therapy, public insurance, site region, externalizing problems, body mass index, and sleep and gastrointestinal problems.

Children with autism spectrum disorder (ASD) exhibit social-communicative impairments. Less is known about the neuropsychological profile of ASD, although cognitive and neuropsychological deficits are evident. We modelled neuropsychological function in 20 children with ASD and 20 sex, age and IQ matched typically-developing controls (ages 7-14) as a network of interacting parameters. Graph theoretical analysis was applied to identify critical topographic regions within this network. Two areas were significantly stronger hubs in typically-developing children, the ability to shift attention (p < 0.001) and overall executive function (p < 0.001). Planning/organization was a stronger hub in the cognitive networks of children with ASD (p = 0.001). We show that ASD is not only characterized by impairments in various neurocognitive domains, but also alterations in their interaction.

Recent research suggests that brain development follows an abnormal trajectory in children with autism spectrum disorders (ASD). The current study examined changes in diffusivity with age within defined white matter tracts in a group of typically developing children and a group of children with an ASD, aged 6 to 14 years. Age by group interactions were observed for frontal, long distant, interhemispheric and posterior tracts, for longitudinal, radial and mean diffusivity, but not for fractional anisotropy. In all cases, these measures of diffusivity decreased with age in the typically developing group, but showed little or no change in the ASD group. This supports the hypothesis of an abnormal developmental trajectory of white matter in this population, which could have profound effects on the development of neural connectivity and contribute to atypical cognitive development in children with ASD.

Functional handwriting involves complex interactions among physical, cognitive and sensory systems. Impairments in many aspects of these systems are associated with Autism spectrum disorders (ASD), suggesting a heightened risk of handwriting difficulties in children with ASD. This scoping review aimed to: (1) survey the existing evidence about potential contributions to compromised handwriting function in children with ASD, and (2) map out the existing studies documenting handwriting difficulties in children with ASD. The current evidence implicates impairments in fine motor control and visual-motor integration as likely contributors to handwriting difficulties in children with ASD, though the role of the latter is not well-understood. Moreover, diminished overall legibility and compromised letter formation are emerging points of convergence among existing studies of handwriting quality in children with ASD. (Contains 1 table and 2 figures.)

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research.

Background: Gender clinic and single‐item questionnaire‐based data report increased co‐occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under‐studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. Methods: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4–12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi‐dimensionally using a well‐validated parent‐report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex‐assigned‐at‐birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. Results: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC‐derived scores. Instead, higher early‐childhood dimensional autistic social‐communication traits correlated with higher current overall gender incongruence (as defined by GIQC‐14 score). This correlation was potentially moderated by sex‐assigned‐at‐birth: greater early‐childhood autistic social‐communication traits were associated with higher current overall gender incongruence in assigned‐males‐at‐birth, but not assigned‐females‐at‐birth. For fine‐grained gender diversity domains, greater autistic restricted‐repetitive behavior traits were associated with greater diversity in gender identity across sexes‐assigned‐at‐birth; greater autistic social‐communication traits were associated with lower stereotypical male expression across sexes‐assigned‐at‐birth. Conclusions: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early‐childhood autistic social‐communication traits and overall current gender diversity was most evident in assigned‐males‐at‐birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender‐diverse populations. [ABSTRACT FROM AUTHOR]

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 ([+ or -] 3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials. Keywords Autism * Serotonin reuptake inhibitors * Citalopram * Double-blind method * Repetitive behavior, Introduction Pervasive Developmental Disorders (PDDs, autism, Asperger's disorder and pervasive developmental disorder-not otherwise specified) are chronic conditions beginning in early childhood. The PDDs share the common feature of profoundly impaired [...]

Impairments in emotional face processing are demonstrated by individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which is associated with altered emotion processing networks. Despite accumulating evidence of high rates of diagnostic overlap and shared symptoms between ASD and ADHD, functional connectivity underpinning emotion processing across these two neurodevelopmental disorders, compared to typical developing peers, has rarely been examined. The current study used magnetoencephalography to investigate whole-brain functional connectivity during the presentation of happy and angry faces in 258 children (5–19 years), including ASD, ADHD and typically developing (TD) groups to determine possible differences in emotion processing. Data-driven clustering was also applied to determine whether the patterns of connectivity differed among diagnostic groups. We found reduced functional connectivity in the beta band in ASD compared to TD, and a further reduction in the ADHD group compared to the ASD and the TD groups, across emotions. A group-by-emotion interaction in the gamma frequency band was also observed. Greater connectivity to happy compared to angry faces was found in the ADHD and TD groups, while the opposite pattern was seen in ASD. Data-driven subgrouping identified two distinct subgroups: NDD-dominant and TD-dominant; these subgroups demonstrated emotion- and frequency-specific differences in connectivity. Atypicalities in specific brain networks were strongly correlated with the severity of diagnosis-specific symptoms. Functional connectivity strength in the beta network was negatively correlated with difficulties in attention; in the gamma network, functional connectivity strength to happy faces was positively correlated with adaptive behavioural functioning, but in contrast, negatively correlated to angry faces. Our findings establish atypical frequency- and emotion-specific patterns of functional connectivity between NDD and TD children. Data-driven clustering further highlights a high degree of comorbidity and symptom overlap between the ASD and ADHD children. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles. Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0–17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd editionTM. Secondary outcome measures include the CGI–S (Clinical Global Impression–Severity), CGI–I (Clinical Global Impression–Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach. Discussion: The outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development. Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has led to an increase in screen time for children and families. Traditionally, screen time has been associated with negative physical and mental health outcomes, and children with autism spectrum disorder (ASD) are at increased risk of these outcomes. The primary objectives of this study were to (1) characterize the change in screen time during COVID-19 school closures for children with ASD, and (2) examine the parent perceived impact of screen time on mental health and quality of life of children and their families. Canadian parents and caregivers of children 19 years of age and younger were eligible to participate in an anonymous, online survey study. This survey was available in English, consisted of 28 questions, took ~10-min to complete, and was available for 6 weeks (May 22 through July 6, 2020). The total sample consisted of 414 responses (ASD: n = 127, mean age = 11.7 ± 4.06 years; community sample: n = 287, mean age = 9.4 ± 4.26 years). Seventy-one respondents were missing responses to our primary question and removed from the analyses (final sample n = 344). Compared to the community sample, the ASD group had a significantly higher screen time use before and during the COVID-19 pandemic school closures [weekdays: difference = 1.14 (SE = 0.18), t = 6.56, p < 0.0001; weekends: difference = 1.41 (SE = 0.20), t = 6.93, p < 0.0001]. Mean total screen time during the pandemic was 6.9 h (95% CI 6.49, 7.21) on weekdays and 6.3 h (95% CI 5.91, 6.63) on weekends for the ASD group, and 5.6 h (95% CI 5.28, 5.92) on weekdays and 5.0 h (95% CI 4.70, 5.34) on weekends for the community sample. There was a significant increase in screen time during the COVID-19 pandemic as compared to before the pandemic period in the ASD group [weekdays: mean difference = 3.8 h (95% CI 3.35–4.25), p < 0.0001; weekends: mean difference = 1.5 h (95% CI 1.17–1.92), p < 0.0001]. Gender was a significant predictor of parent perceived mental health and quality of life, with male gender associated with a higher likelihood of negative impact [quality of life (child/family) OR = 1.8 (95% CI 1.1–2.9), corrected p = 0.040; mental health OR = 1.9 (95% CI 1.1–3.1), corrected p = 0.0028]. Parents' most frequently endorsed emotions toward screen time were guilt, frustration, and worry. Results of this survey study revealed that children with ASD were less likely to benefit from screen time to cope with social isolation, and screen time resulted in significantly more lost time on social interactions than the community sample, which may exacerbate difficulties in social domains. Given the unprecedented circumstances of the COVID-19 pandemic and the novel context of technology use, the findings of this study highlight the need for revision of screen time recommendations to reflect the current needs of children and families. [ABSTRACT FROM AUTHOR]

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research. [ABSTRACT FROM AUTHOR]

Background: Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation. Methods: We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha‐2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random‐effects model. Results: Twenty‐five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent‐rated: standardized mean difference [SMD] = −.63, 95%CI = −.95,−.30; teacher‐rated: SMD = −.81, 95%CI = −1.43,−.19) and inattention (parent‐rated: SMD = −.36, 95%CI = −.64,−.07; teacher‐rated: SMD = −.30, 95%CI = −.49,−.11). Atomoxetine reduced inattention (parent‐rated: SMD = −.54, 95%CI = −.98,−.09; teacher/investigator‐rated: SMD = −0.38, 95%CI = −0.75, −0.01) and parent‐rated hyperactivity (parent‐rated: SMD = −.49, 95%CI = −.76,−.23; teacher‐rated: SMD = −.43, 95%CI = −.92,.06). Indirect evidence for significant reductions in hyperactivity with second‐generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events. Conclusions: Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long‐term continuation is undertaken to help guide clinical decision‐making regarding treatment of co‐occurring ADHD symptoms in children and youth with ASD. [ABSTRACT FROM AUTHOR]

An introduction to articles in the issue is presented on topics including an overview of the reach of the HRSA-MCHB Autism and Other Developmental Disabilities Program, the special needs of families of children with ASD, and barriers and factors to promote personal- and family-centered care in the emergency department.

Children with autism spectrum disorders appear to be at a higher risk of having obesity than their typically developing peers. Although it has been recommended that healthcare providers speak to children with autism spectrum disorders about the potential health risks of unhealthy weight, no previous research has explored how healthcare providers communicate with them about this topic. The purpose of this study was to explore children's perspectives and experiences of discussing weight-related topics in healthcare consultations. Eight children were interviewed, and an interpretive phenomenological analysis informed the research approach and analysis of the data. Results indicated that weight-related discussions with healthcare providers were often met with trepidation, anxiety, anger, and frustration. Children also expressed that they experienced weight stigma in clinical visits and everyday interactions. Weight stigma was often (unwittingly) projected by healthcare providers during appointments and had debilitating effects on children. Finally, higher weights emerged as a repetitive/restricted interest, and children reported body image challenges regarding their higher weights. Frameworks and tools that are specific to the needs and abilities of children with autism spectrum disorders are needed for healthcare providers to foster positive conversations about weight-related topics in an effort to promote lifelong wellness. [ABSTRACT FROM AUTHOR]

Autistic children and youth spend a significant amount of their time interacting with technology, however, the characterization of use remains sparse. The objectives of this study were to 1) characterise the patterns and purpose of technology use among autistic children compared to non-autistic children, 2) explore the impact of how technology use affects child and family well-being, and 3) examine parents' attitudes towards childrens' technology use. A 44-question anonymous parent-report survey developed in consultation with families of autistic children and clinicians was available online for 22 months, from April 2018 through February 2020. Parents and caregivers of children 19-years-old and younger were eligible to complete the survey. 611 survey responses were collected (autism group = 407; community group = 204). The autism group exhibited greater technology use across all time points of interest, with tablets being the most frequently used device type. The autism group was also more likely to use technology for therapeutic and recreational activities. The autism group experienced more positive impacts on quality of life and benefited more in areas of social, motor, language, and emotion regulation skills from technology use than the community group. Parents of older children, males, and those in the autism group were more likely to report displaced socialising with technology use. Positive attitudes were more likely to be reported by parents of autistic children and younger children, whereas negative feelings were more likely to be reported by parents of older and male children. The study findings must be interpreted within the context of several limitations, including the size and representativeness of the sample, potential for bias from parent-report, and limitations in the survey design (closed-ended questions). Autistic children exhibited more technology use than non-autistic children. Parental perceptions of impact were highly mixed, and included potential benefits for recreation and supports. Implications for technology developers and clinical practitioners are discussed. • Children exceeded screen time guidelines. • Autism diagnosis, older age, and being male were associated with greater screen time. • Parental perception of technology impact were mixed. • Parents of autistic children more likely to perceive technology impact as positive. • Educational, recreational, and therapeutic use associated with positive impact. [ABSTRACT FROM AUTHOR]

Highlights • First MEG study of neural underpinnings of theory of mind differences in autism. • Children with autism show decreased LTPJ activity from 300 to 375 and 425 to 500 ms. • Children with autism also show increased RIFG activity from 325 to 375 ms. • Co-incident lower LTPJ and higher RIFG activity implies compensatory use of RIFG. • Executive functions may augment impaired theory of mind in autism. Abstract The social impairments observed in children with autism spectrum disorder are thought to arise in part from deficits in theory of mind, the ability to understand other people's thoughts and feelings. To determine the temporal-spatial dynamics of brain activity underlying these atypical theory-of-mind processes, we used magnetoencephalography to characterize the sequence of functional brain patterns (i.e. when and where) related to theory-of-mind reasoning in 19 high-functioning children with autism compared to 22 age- and sex-matched typically-developing children aged 8–12 during a false-belief (theory-of-mind) task. While task performance did not differ between the two groups, children with autism showed reduced activation in the left temporoparietal junction between 300–375 and 425–500 ms, as well as increased activation in the right inferior frontal gyrus from 325 to 375 ms compared to controls. The overlap in decreased temporoparietal junction activity and increased right inferior frontal gyrus activation from 325 to 375 ms suggests that in children with autism, the right inferior frontal gyrus may compensate for deficits in the temporoparietal junction, a neural theory-of-mind network hub. As the right inferior frontal gyrus is involved in inhibitory control, this finding suggests that children with autism rely on executive functions to bolster their false-belief understanding. [ABSTRACT FROM AUTHOR]

This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests. Irritability/aggression is a significant comorbid symptom in this population, which greatly impacts burden of care. This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD. This was a 12-week randomized, double-blind, placebo-controlled trial. All efficacy measures were obtained by an independent evaluator blinded to randomization condition and side effects. A total of 55 subjects gavetheir consent and 27 were randomized in a 1 : 1 manner (mean age 9.46±2.46, mean nonverbal IQ 63.3±23.9). Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects (increased irritability). Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, which focused on irritability. Overall, 62.5% of divalproex subjects vs 9% of placebo subjects were responders (CGI-irritability OR: 16.7, Fisher's exact p=0.008). A statistically significant improvement was also noted on the ABC-Irritability subscale (p=0.048). There was a trend for responders to have higher valproate blood levels compared with nonresponders. This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted. [ABSTRACT FROM AUTHOR]

Systemic inflammation is known to alter behaviour, and since it has been reported that individuals with autism spectrum disorder (ASD) have higher levels of circulating cytokines, it has been hypothesized that systemic inflammation may exacerbate behaviours characteristic of ASD. The acute phase proteins α-2-macroglobulin, C-reactive protein, haptoglobin, serum amyloid P, serum amyloid A, ferritin and tissue plasminogen activator, as well as markers of intestinal permeability (intestinal fatty acid binding protein and lipopolysaccharide) were quantitated in the plasma of very young children with ASD. Behaviour severity was measured using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and the Vineland Adaptive Behaviour Scale (VABS). An increase in circulating I-FABP correlated with more severe deficits in communication, communication + social interaction as well as maladaptive behaviour. The acute phase protein haptoglobin was associated with more severe social interaction and communication + social interaction. In summary, I-FABP, a marker of intestinal epithelial damage, was associated with more severe behavioural phenotypes in very young children with ASD. In addition, the acute phase protein, haptoglobin, was associated with behaviour. [Display omitted] • Acute phase proteins and inflammatory markers of intestinal permeability are detectable in a dynamic range in very young children with autism • Intestinal fatty acid binding protein, a marker of intestinal permeability, was associated with an increased severity of behavioural symptoms [ABSTRACT FROM AUTHOR]

Introduction: The N400 is an electrophysiological component that reflects lexical access and integration of words with mental representations. Methods: Thirty‐five young children with a range of language capabilities (n = 21 neurotypical controls, 10 males, mean age = 6.3 ± 0.9 years; n = 14 children with autism, 12 males, mean age = 6.4 ± 1.1 years) completed an auditory semantic categorization paradigm to evoke the N400. Electroencephalograph (EEG) data were acquired with a 64‐channel electrode cap as children listened via ear inserts to binaurally presented single syllable words and decided whether the words were congruent (in) or incongruent (out) with a pre‐specified category. EEG data were filtered, epoched, and averaged referenced, and global field power (GFP) was computed. The amplitude of the N400 peak in the GFP was submitted to a multiple linear regression analysis. Results: N400 amplitude was found to predict language scores only for the children with ASD who have language scores in the normal range (r2 = 0.72). Conclusions: This finding that N400 amplitude only predicted language scores in children with ASD and normal language scores suggests that these children may rely more on basic semantic processing (as reflected by the N400) and less on anticipating and predicting upcoming words. This suggests preferential utilization of a bottom‐up strategy to access higher order language. [ABSTRACT FROM AUTHOR]