Pubmed du 26/08/22

Pubmed du jour

1. Bernier A, Ratcliff K, Hilton C, Fingerhut P, Li CY. Art Interventions for Children With Autism Spectrum Disorder: A Scoping Review. Am J Occup Ther;2022 (Sep 1);76(5)

IMPORTANCE: Autism spectrum disorder (ASD) is a neurological condition characterized by impairments in social interaction, communication, and behavior. Occupational therapy practitioners use creative arts interventions for children with ASD, but relevant evidence for these interventions is lacking. OBJECTIVE: To provide occupational therapists evidence of the benefit of creative arts interventions for children with ASD by evaluating treatment efficacy and connecting the evidence with the Occupational Therapy Practice Framework: Domain and Process (4th ed.; OTPF-4). DATA SOURCES: We searched peer-reviewed articles in six databases: CINAHL, Cochrane, PubMed, Ovid, PsycInfo, and Scopus. Eighteen articles published between 2000 and 2020 met Level 1b or 2b evidence criteria and were retrieved for full review; 15 were included in this scoping review. STUDY SELECTION AND DATA COLLECTION: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to extract data. Inclusion criteria were as follows: (1) Level 1b or 2b study; (2) quantitative data; (3) published in English; (4) population of children (ages <18 yr); (5) primary diagnosis of ASD; and (6) creative arts intervention in the forms of drawing, painting, or coloring; music; or theater. FINDINGS: Creative arts interventions benefited children with ASD in two OTPF-4 areas (process and social interaction) pertaining to the Performance Skills domain and one OTPF-4 area (body functions) pertaining to the Client Factors domain. We found similar effects for group and individual intervention sessions, and significant improvements required multiple sessions. CONCLUSIONS AND RELEVANCE: Our findings provide evidence for the efficacy of creative arts interventions to enhance occupation-based outcomes for children with ASD. What This Article Adds: Our findings support occupational therapy practitioners' use of creative arts interventions to improve OTPF-4-based client factors and process and social interaction skills for children with ASD.

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2. Bin-Khattaf RM, Alonazi MA, Al-Dbass AM, Almnaizel AT, Aloudah HS, Soliman DA, El-Ansary AK. Probiotic Ameliorating Effects of Altered GABA/Glutamate Signaling in a Rodent Model of Autism. Metabolites;2022 (Aug 4);12(8)

Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, such as marked impairment in verbal and nonverbal communication, social skills, and cognition. Excitatory/inhibitory (E/I) imbalances have been recorded as an etiological mechanism of ASD. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, is known to be much lower in both patients and rodent models of ASD. We propose correcting GABA signaling as a therapeutic strategy for ASD. In this study, 40 young male western Albino rats, 3-4 weeks in age, weighing about 60-70 g, were used. The animals were randomly assigned into six experimental groups, each including eight rats. Group I served as the control group and was orally administered phosphate-buffered saline. Groups II and III served as rodent models of ASD and were orally administered a neurotoxic dose of propionic acid (PPA). The rats in the three therapeutic groups (IV, V, and IV) received the same doses of PPA, followed by 0.2 g/kg body weight of pure Bifidobacterium infantis, a probiotic mixture of ProtexinR, and pure Lactobacillus bulgaricus, respectively, for 3 weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six groups. Both pure and mixed Lactobacillus and Bifidobacterium&nbsp;were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects mostly involved the correction of oxidative stress, restoration of depleted GABA, and up-regulation of GABA receptor gene expression. Pure Bifidobacterium was the most effective, followed by the mixture of probiotics and finally lactobacillus.&nbsp;In conclusion, Bifidobacteria and lactobacilli can be used independently or in combination as psychobiotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut-brain axis.

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3. Bo J, Shen B, Dong L, Pang Y, Xing Y, Zhang M, Xiang Y, Lasutschinkow PC, Li D. Response Time Modulates the Relationship Between Implicit Learning and Motor Ability in Children With and Without Autism Spectrum Disorders: A Preliminary Study. Motor Control;2022 (Aug 25):1-11.

Difficulty with implicit learning plays an important role in the symptomology of autism spectrum disorder (ASD). However, findings in motor learning are inconsistent. This study evaluated implicit sequence learning and its relationship with motor ability in children with and without ASD. We adopted a classic serial reaction time task with a retention task and three awareness tests. The Movement Assessment Battery for Children was administered to assess children’s motor ability. Significant learning differences between children with and without ASD were only found in retention but not immediately after the serial reaction time task. These findings suggest that the impaired implicit learning in ASD is characterized as impaired consolidation where the relatively permanent changes are missing. Exploratory moderation analyses revealed a significant relationship between implicit learning and motor ability for individuals with faster response time. We argue the importance of response speed for optimal learning and should be weighted more for future intervention in children with ASD.

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4. Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev;2022 (Aug 25);8(8):CD013845.

BACKGROUND: Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child’s quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness. OBJECTIVES: To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child’s weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence). AUTHORS’ CONCLUSIONS: It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.

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5. Coulter H, Donnelly M, Mallett J, Kernohan WG. Heart Rate Variability Biofeedback to Treat Anxiety in Young People With Autism Spectrum Disorder: Findings From a Home-Based Pilot Study. JMIR Form Res;2022 (Aug 26);6(8):e37994.

BACKGROUND: People with autism spectrum disorder (ASD) frequently experience high levels of anxiety. Despite this, many clinical settings do not provide specialist ASD mental health services, and demand for professional support frequently outstrips supply. Across many sectors of health, investigators have explored digital health solutions to mitigate demand and extend the reach of professional practice beyond traditional clinical settings. OBJECTIVE: This critical appraisal and pilot feasibility study examines heart rate variability (HRV) biofeedback as an approach to help young people with ASD to manage anxiety symptoms outside of formal settings. The aim is to explore the use of portable biofeedback devices to manage anxiety, while also highlighting the risks and benefits of this approach with this population. METHODS: We assessed the feasibility of using home-based HRV biofeedback for self-management of anxiety in young people with ASD. We adopted coproduction, involving people with ASD, to facilitate development of the study design. Next, a separate pilot with 20 participants with ASD (n=16, 80% male participants and n=4, 20% female participants, aged 13-24 years; IQ>70) assessed adoption and acceptability of HRV biofeedback devices for home use over a 12-week period. Data were collected from both carers and participants through questionnaires and interviews; participants also provided single-lead electrocardiogram recordings as well as daily reports through smartphone on adoption and use of their device. RESULTS: Pre-post participant questionnaires indicated a significant reduction in anxiety in children (t(6)=2.55; P=.04; Cohen d=0.99) as well as adults (t(7)=3.95; P=.006; Cohen d=0.54). Participant age was significantly negatively correlated with all HRV variables at baseline, namely high-frequency heart rate variability (HF-HRV: P=.02), the root mean square of successive differences in normal heartbeat contractions (RMSSD: P=.02) and the variability of normal-to-normal interbeat intervals (SDNN: P=.04). At follow-up, only SDNN was significantly negatively correlated with age (P=.05). Levels of ASD symptoms were positively correlated with heart rate both before (P=.04) and after the intervention (P=.01). The majority (311/474, 65.6%) of reports from participants indicated that the devices helped when used. Difficulties with the use of some devices and problems with home testing of HRV were noted. These initial findings are discussed within the context of the strengths and challenges of remotely delivering a biofeedback intervention for people with ASD. CONCLUSIONS: HRV biofeedback devices have shown promise in this pilot study. There is now a need for larger evaluation of biofeedback to determine which delivery methods achieve the greatest effect for people with ASD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04955093; https://clinicaltrials.gov/ct2/show/NCT04955093.

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6. Coutelle R, Boedec M, Vermeulen K, Kummeling J, Koolen DA, Kleefstra T, Fournier C, Colin F, Strehle A, Geneviève D, Burger P, Mandel JL. The impact of lockdown on young people with genetic neurodevelopmental disabilities: a study with the international participatory database GenIDA. BMC Psychiatry;2022 (Aug 25);22(1):572.

BACKGROUND: Previous publications suggested that lockdown is likely to impact daily living issues of individuals with intellectual disabilities. The authors notably suspected an intensification of behavioural, eating and sleep problems. METHODS: To test these hypotheses, we conducted an international online survey about the impact of COVID-19-associated first lockdown on people with genetic neurodevelopmental disorders. This survey was carried out using GenIDA, an international participatory database collecting medical information on genetic neurodevelopmental disorders. Patients’ relatives took part in this online survey from 30/04/2020 to 09/06/2020. This survey adapted from GenIDA standard questionnaire requested information on diagnosis, lifestyle and was based on yes/no answers to questions regarding behaviour, diet, and sleep, in the 6-months period before lockdown and during lockdown. We also asked relatives to evaluate the intensity of these problems by severity level. Finally, relatives could freely comment in open fields on the medical and/or quality of life problems they had encountered during lockdown. RESULTS: In total 199 participants-144 children and 45 adults-with neurodevelopmental disorders (intellectual disability (79.4%) and/or autism spectrum disorder (21.6%)) of various genetic origins, with near-equal male/female (96/103) contribution and originating mainly from Europe and Northern America, were included. The average lockdown duration at time of the survey was 57 days. We did not find differences in the frequency of behavioural, eating and sleep problems before and during lockdown. Moreover, there was no apparent difference in the intensity of eating and sleep disorders between both periods. However, for persons with behavioural problems at both periods, relatives reported an increase in aggressivity, self-aggressivity, depressiveness, stereotypies, and restricted interests during lockdown, all of which might be interpreted as consequences of a lack of stimulation or a reaction to unexpected changes in daily habits. CONCLUSIONS: Our results support previous studies that suggest that the negative impact of lockdown does not depend on the intellectual disability per se but on the associated comorbidities such as behavioural disorders. This study addresses the need for prevention of behavioural disturbance in the vulnerable population with genetic neurodevelopmental disabilities.

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7. El-Ansary A, Al-Onazi M, Alhowikan AM, Alghamdi MA, Al-Ayadhi L. Author Correction: Assessment of a combination of plasma anti-histone autoantibodies and PLA2/PE ratio as potential biomarkers to clinically predict autism spectrum disorders. Sci Rep;2022 (Aug 25);12(1):14509.

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8. Enkhbat U, Gombojav E, Banzrai C, Batsukh S, Boldbaatar B, Enkhtuya E, Bellinger DC, Lanphear BP, McCandless LC, Allen RW. Portable HEPA filter air cleaner use during pregnancy and children’s autistic behaviors at four years of age: The UGAAR randomized controlled trial. Environ Int;2022 (Jul 25);168:107432.

BACKGROUND: Developmental exposure to airborne particulate matter (PM) may increase children’s risk of developing autism spectrum disorder. We quantified the impact of reducing PM exposure during pregnancy on the development of autistic traits in children. We also assessed associations between indoor fine PM (PM(2.5)) concentrations during pregnancy and autistic traits. METHODS: In this parallel-group randomized controlled trial, we randomized 540 non-smoking pregnant women to receive HEPA filter air cleaners or to a control group, which did not receive air cleaners. We administered the Social Responsiveness Scale (SRS-2) to caregivers when children were a median of 48 months (range: 48 to 51 months). Our primary outcome was the SRS-2 total T-score. We imputed missing data using multiple imputation with chained equations and our primary analysis was by intention to treat. In secondary analyses, we estimated associations between full pregnancy and trimester-specific indoor PM(2.5) concentrations and T-scores. RESULTS: We enrolled participants at a median of 11 weeks’ gestation. Our analysis included 478 children (233 control, 245 intervention). The intervention reduced average indoor PM(2.5) concentrations by 29 % (95 % CI: 21, 37 %). The mean SRS-2 total T-score was 0.5 units lower (95 % CI: -2.5, 1.5) among intervention participants, with evidence of larger benefits for children at the high end of the T-score distribution. An interquartile range (9.6 µg/m(3)) increase in indoor PM(2.5) during pregnancy was associated with 1.8-unit (95 % CI: 0.3, 3.2) increase in mean SRS-2 total T-score. Effect estimates for PM(2.5) concentrations by trimester were smaller and confidence intervals spanned no effect. CONCLUSION: Reducing indoor PM during pregnancy had little impact on mean autism-related behavior scores in children. However, indoor PM(2.5) concentrations during pregnancy were associated with higher scores. Exposure to particulate matter during pregnancy may influence the development of autistic traits in childhood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01741051.

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9. Faizo NL. A narrative review of MRI changes correlated to signs and symptoms of autism. Medicine (Baltimore);2022 (Aug 26);101(34):e30059.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that occurs during early childhood. The change from being normal across several contexts to displaying the behavioral phenotype of ASD occurs in infants and toddlers with autism. Findings provided by magnetic resonance imaging (MRI)-based research owing to the developmental phase, including potential pathways underlying the pathogenesis of the condition and the potential for signs and symptomatic risk prediction. The present study focuses on the characteristic features of magnetic resonance imaging autistic brain, how these changes are correlated to autism signs and symptoms and the implications of MRI as a potential tool for the early diagnosis of ASD. PRISMA style was used to conduct this review. Research articles related to the key concepts of this review, which is looking at MRI brain changes in autistic patients, were revised and incorporated with what is known with the pathophysiology of brain regions in relation to signs and symptoms of autism. Studies on brain MRI of autism were revied for major brain features and regions such as brain volume, cortex and hippocampus. This review reveals that brain changes seen in MRI are highly correlated with the signs and symptoms of autism. There are numerous distinct features noted in an autistic brain using MRI. Based on these findings, various developmental brain paths and autistic behavior culminate in a typical diagnosis, and it is possible that addressing these trajectories would improve the accuracy in which children are detected and provide the necessary treatment.

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10. Feldman JI, Dunham K, DiCarlo GE, Cassidy M, Liu Y, Suzman E, Williams ZJ, Pulliam G, Kaiser S, Wallace MT, Woynaroski TG. A Randomized Controlled Trial for Audiovisual Multisensory Perception in Autistic Youth. J Autism Dev Disord;2022 (Aug 26):1-18.

Differences in audiovisual integration are commonly observed in autism. Temporal binding windows (TBWs) of audiovisual speech can be trained (i.e., narrowed) in non-autistic adults; this study evaluated a computer-based perceptual training in autistic youth and assessed whether treatment outcomes varied according to individual characteristics. Thirty autistic youth aged 8-21 were randomly assigned to a brief perceptual training (n = 15) or a control condition (n = 15). At post-test, the perceptual training group did not differ, on average, on TBWs for trained and untrained stimuli and perception of the McGurk illusion compared to the control group. The training benefited youth with higher language and nonverbal IQ scores; the training caused widened TBWs in youth with co-occurring cognitive and language impairments.

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11. Hajri M, Abbes Z, Yahia HB, Jelili S, Halayem S, Mrabet A, Bouden A. Cognitive deficits in children with autism spectrum disorders: Toward an integrative approach combining social and non-social cognition. Front Psychiatry;2022;13:917121.

Autism spectrum disorder (ASD) is associated with neurocognitive impairment, including executive dysfunctioning and social cognition (SC) deficits. Cognitive remediation (CR) is a behavioral training-based intervention aiming to improve cognitive processes. Its first use in psychiatry interested patients with schizophrenia, in whom promising results have been shown. Integrated CR programs targeting both social and non-social cognition have demonstrated to be effective in improving both cognitive domains and functional outcomes. CR studies in children and adolescents with ASD are still new, those regarding CR approaches combining social and executive functioning remediation are scares. One study examining the efficacy of cognitive enhancement therapy (CET) for improving cognitive abilities in ADS adults, showed significant differential increases in neurocognitive function and large social-cognitive improvements. Therefore, taking into account the overlap between ASD and schizophrenia, and considering the close link between executive functions (EF) and SC, we suggest that integrative approach in ASD could result in better outcomes. The present perspective aimed to highlight cognitive remediation (CR) programs contributions in ASD (especially in children and adolescents), and to discuss the value of combining social and non-social programs.

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12. Halayem S, Bouden A, Amado IR, Leventhal B. Editorial: Advances in social cognition assessment and intervention in autism spectrum disorder. Front Psychiatry;2022;13:962843.

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13. James P, Schafer E, Wolfe J, Matthews L, Browning S, Oleson J, Sorensen E, Rance G, Shiels L, Dunn A. Increased rate of listening difficulties in autistic children. J Commun Disord;2022 (Sep-Oct);99:106252.

INTRODUCTION: Auditory challenges are both common and disruptive for autistic children and evidence suggests that listening difficulties may be linked to academic underachievement (Ashburner, Ziviani & Rodger, 2008). Such deficits may also contribute to issues with attention, behavior, and communication (Ashburner et al., 2008; Riccio, Cohen, Garrison & Smith, 2005). The present study aims to summarize the auditory challenges of autistic children with normal pure-tone hearing thresholds, and perceived listening difficulties, seen at auditory-ASD clinics in the US and Australia. METHODS: Data were compiled on a comprehensive, auditory-focused test battery in a large clinical sample of school-age autistic children with normal pure-tone hearing to date (N = 71, 6-14 years). Measures included a parent-reported auditory sensory processing questionnaire and tests of speech recognition in noise, binaural integration, attention, auditory memory and listening comprehension. Individual test performance was compared to normative data from children with no listening difficulties. RESULTS: Over 40% of patients exhibited significantly reduced speech recognition in noise and abnormal dichotic integration that were not attributed to deficits in attention. The majority of patients (86%) performed abnormally on at least one auditory measure, suggesting that functional auditory issues can exist in autistic patients despite normal pure-tone sensitivity. CONCLUSION: Including functional listening measures during audiological evaluations may improve clinicians’ ability to detect and manage the auditory challenges impacting this population. Learner Outcomes: 1) Readers will be able to describe the auditory difficulties experienced by some autistic patients (ASD). 2) Readers will be able to describe clinical measures potentially useful for detecting listening difficulties in high-functioning autistic children.

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14. Mathew NE, Mallitt KA, Masi A, Katz T, Walker AK, Morris MJ, Ooi CY. Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles. Autism Res;2022 (Aug 26)

Diets of children and adolescents on the autism spectrum often differ when compared to their non-autistic peers. Most dietary studies have been limited by small sample sizes and rarely assess the heterogeneity of autism. Addressing this gap, this study compared the anthropometrics, dietary composition, dietary quality, and food variety of 154 Australian children and adolescents on the spectrum and 213 non-autistic children (71 siblings and 142 unrelated controls). Beyond the case-control approach, within-group comparisons assessed the influence of autism clinical presentations and sensory processing styles on body mass index (BMI) and measures of dietary intake among those on the spectrum. In this word first study of diet that included between-group comparisons with non-autistic peers (siblings and an unrelated comparison group) and within-autism group comparisons, we found that children on the spectrum consumed limited variety and lower quality of food and non-autistic siblings also ate comparably higher levels of energy-dense, nutrient poor food, and less diary. This may be due to autistic traits influencing family’s diets or shared sensory sensitivities driving dietary intake. Within the autism group, higher autistic traits were associated with lower BMIs and a specific dietary pattern higher in simple carbohydrates and lower in unprocessed protein. Contrastingly, greater sensitivity to sensory stimuli was associated with a healthier diet. Increased age was linked to more varied diets but also diets higher in saturated fats and energy-dense, nutrient poor foods. Overall, this research highlights that potential mediators of dietary intake, such as familial influences, autistic traits, sensory processing styles, age and sex, need to be considered when assessing diet in the autistic population. LAY SUMMARY: In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.

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15. Narzisi A, Stavropoulos KKM. Editorial: Enrichment of social skills in adolescent and young adults with high-functioning autism spectrum disorder. Front Psychiatry;2022;13:994914.

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16. Oakley BFM, Loth E, Jones EJH, Chatham CH, Murphy DG. Advances in the identification and validation of autism biomarkers. Nat Rev Drug Discov;2022 (Aug 25)

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17. Ren H, Ren G, Zhan Y, Jia Z. Examining the efficacy of dance movement and music mixed treatment on social communication impairment in children with autism – Based on family parent-child situation. Front Psychol;2022;13:937564.

Despite impairments in social communication in children with autism spectrum disorder (ASD), existing studies only examine the effects of either MT or DMT interventions. In the family setting, few studies have investigated interventions for social communication impairments in children with ASD. This study designed and tested a mixed intervention program of both MT and DMT through a 3-month intervention and training for children with ASD in the family setting including parent and child. A pre-test and post-test were conducted in the experimental and control groups, and the childhood autism rating scale (CARS) and autism treatment evaluation checklist (ATEC) scales were used to assess the severity of ASD symptoms and the effects of intervention. A t-test and analysis of variance were performed based on the experimental results. The results indicated that the experimental and control groups did not differ significantly on the CARS pre-test (t = 1.218, p > 0.05) and that there was no significant difference in the ATEC pre-test (t = 0.546, p > 0.05; F = 0.074, p > 0.05, partial η(2) = 0.003). There was no significant difference between the pre- and post-test scores for the CARS in the control group (t = 0.635, p > 0.05), and there was no significant difference between the pre- and post-test scores for the ATEC in the control group (t = 0.027, p > 0.05; F = 5.251, p > 0.05, partial η(2) = 0.313). There was a significant difference between the pre- and post-test scores on the CARS in the experimental group (t = 4.327, p > 0.05) and the pre- and post-test scores on the ATEC in the experimental group (t = 5.763, p > 0.01; F = 32.615, p > 0.01, partial η(2) = 0.759), with the post-test scores being lower than the pre-test scores. This demonstrates that the mixed intervention of MT and DMT in the family parent-child setting can reduce autism and improve social communication impairment in children with ASD.

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18. Schachar RJ, Dupuis A, Arnold PD, Anagnostou E, Kelley E, Georgiades S, Nicolson R, Townes P, Burton CL, Crosbie J. Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder: Shared or Unique Neurocognitive Profiles?. Res Child Adolesc Psychopathol;2022 (Aug 25)

Attention-deficit/hyperactivity (ADHD) and autism spectrum (ASD) disorders are commonly co-occurring conditions characterized by neurocognitive impairments. Few studies have directly compared neurocognitive profiles in ADHD and ASD and fewer still have controlled for comorbidity of ADHD and ASD. All direct comparisons have been in clinic samples, leaving the question of generalizability of results unaddressed. We compared neurocognitive performance in clinically ascertained ASD (n = 261) and ADHD (n = 423) cases and controls (n = 162), 6.0-17.9 years of age. We also compared ASD (n = 190) and ADHD (n = 926) cases ascertained in the community with controls (n = 14,842) of similar age. Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time-SSRT), sustained attention (defined as reaction time variability-RTV), and reaction time (RT). We controlled for comorbidity using ADHD and ASD trait scores and categorically-defined ADHD. Compared with controls, both clinic ADHD and ASD had significantly longer SSRT and RTV than controls and did not differ from each other. ADHD traits accounted for neurocognitive impairment in ASD, but not vice versa. There were no group differences for RT. Similar patterns of neurocognitive impairment were observed in the community sample. In the largest direct comparison of ADHD and ASD to date, we found impaired response inhibition and sustained attention in both disorders. However, neurocognitive impairment in ASD was almost completely accounted for by comorbid ADHD. Results generalized in the community sample indicating that referral bias alone did not drive results. Response inhibition and sustained attention likely play a role in ADHD and ASD.

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19. Shaffer RC, Reisinger DL, Schmitt LM, Lamy M, Dominick KC, Smith EG, Coffman MC, Esbensen AJ. Systematic Review: Emotion Dysregulation in Syndromic Causes of Intellectual and Developmental Disabilities. J Am Acad Child Adolesc Psychiatry;2022 (Aug 18)

OBJECTIVE: To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic causes of intellectual disability (S-IDs) in six of the most common forms of S-IDs: Down syndrome (DS), Fragile X syndrome (FXS), tuberous-sclerosis complex (TSC), Williams syndrome (WS), Prader-Willi syndrome (PWS), and Angelman syndrome (AS); and to determine future research directions for identification and treatment of ED. METHOD: PubMed bibliographic database was searched from date of inception to May 2021. PRISMA 2020 guidelines were followed with the flow chart, table of included studies, list of excluded studies, and checklist provided. Filters applied included human research and English. Only original research articles were included in the final set, but review articles were utilized to identify secondary citations of primary studies. All articles were reviewed for appropriateness by two authors and summarized. A total of 145 articles met inclusion criteria (DS=29, FXS=55, TSC=11, WS=18, PWS=24, AS=8). RESULTS: Each syndrome review was summarized separately and further subdivided into articles related to underlying neurobiology, behaviors associated with ED, assessment, and targeted intervention. FXS had the most thorough research base, followed by DS and PWS with the other syndromes having more limited available research. Very limited research was available regarding intervention for all disorders except FXS. CONCLUSION: Core underlying characteristics of S-IDs appear to place youth at higher risk for ED, but further research is needed to better assess and treat ED in S-IDs. Future studies should have a standard assessment measure of ED, such as the Emotion Dysregulation Inventory and explore adapting established curricula for ED from the neurotypical and autism spectrum disorder fields.

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20. Sheela P, Puthankattil SD. MVME-RCMFDE framework for discerning hyper-responsivity in Autism Spectrum Disorders. Comput Biol Med;2022 (Aug 12);149:105958.

BACKGROUND: Autism Spectrum Disorder (ASD), characterized by impaired sensory processing, has a wide range of clinical heterogeneity, which handicaps effective therapeutic interventions. Therefore, it is imperative to develop potential mechanisms for delineating clinically meaningful subgroups, so as to provide individualised medical treatment. In this study, an attempt is being made to differentiate the hyper-responsive subgroup from ASD by analysing the complexity pattern of Visual Evoked Potentials (VEPs), recorded from a group of 30 ASD participants, in the presence of vertical achromatic sinewave gratings at varying contrast conditions of low (5%), medium (50%) and high (90%). METHOD: This study proposes a new diagnostic framework incorporating a novel signal decomposition method termed as Modified Variational Mode Extraction (MVME) and a multiscale entropy approach. MVME segments the signal into five constituent modes with less spectral overlap in lower frequencies. Refined Composite Multiscale Fluctuation-based Dispersion entropy (RCMFDE) is extracted from these constituent modes, thereby facilitating the identification of hyper-responsive subgroup in ASD. RESULTS: When tested on both simulated and real VEPs, MVME displays appreciable performance in terms of root mean square error and minimal spectral overlap in the lower frequencies, in comparison with the other state-of-the-art techniques. Relative Complexity analysis with RCMFDE exhibits a rising trend in 43%-50% of ASD in modes 1, 2, 3 and 4. CONCLUSION: The proposed MVME-RCMFDE approach is efficient in discriminating the hyper-responsive subgroup in ASD in multiple modes namely mode 1, 2, 3 and 4, which correspond to delta, theta, alpha and beta frequency bands of brain signals.

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21. Stagg SD, Thompson-Robertson L, Morgan C. Primary school children rate children with autism negatively on looks, speech and speech content. Br J Dev Psychol;2022 (Aug 24)

Adults and adolescents form negative first impressions of ASD adults and children. We examined the first impression ratings of primary school children (6-9 years) of their ASD peers. 146 school children rated either silent videos, speech or transcribe speech from 14 actors (7 ASD, 7 TD). The ASD actors were rated more negatively than the typically developing actors on all three stimulus types. Children with ASD are likely to be judged more negatively than their peers at the very start of their formal education. Contrary to previous research, for primary school children, the content of the speech was judged as negatively as the delivery of the speech.

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22. Thurman AJ, Dimachkie Nunnally A. Joint attention performance in preschool-aged boys with autism or fragile X syndrome. Front Psychol;2022;13:918181.

Early development marks a period of rapid learning facilitated by children’s natural curiosity about the people around them. In children with typical development, these early social attentional preferences set the foundation for learning about and from the surrounding world of people. Much of this learning happens using joint attention, the ability to coordinate attention between people and objects of mutual interest. It is well documented that decreased gaze use is commonly observed in individuals with autism and individuals with fragile X syndrome (FXS). Despite the growing body of research comparing phenotypic similarities between individuals with autism and individuals with FXS, no studies have directly compared joint attention performance between these groups. In the present study, we considered the similarities and differences in joint attention between preschool-aged boys with autism or FXS, and the relation between joint attention, language, and other phenotypic characteristics known to differ between boys with autism and boys with FXS. Although joint attention appeared similar, between-group differences emerged when controlling for the influence of age, non-verbal IQ, and autism symptom severity. Differences were also observed when considering how joint attention performance related to other aspects of the phenotype. For example, strong positive associations were observed between joint attention and language performance in boys with autism but not boys with FXS, even after controlling for non-verbal IQ. In contrast, the negative association between joint attention and anxiety symptom severity was significant and stronger in boys with FXS than in autism. These data offer preliminary insights into the similarities and differences between the autism and FXS phenotypes.

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23. Wittkopf S, Langmann A, Roessner V, Roepke S, Poustka L, Nenadić I, Stroth S, Kamp-Becker I. Conceptualization of the latent structure of autism: further evidence and discussion of dimensional and hybrid models. Eur Child Adolesc Psychiatry;2022 (Aug 25)

Autism spectrum disorder (ASD) might be conceptualized as an essentially dimensional, categorical, or hybrid model. Yet, current empirical studies are inconclusive and the latent structure of ASD has explicitly been examined only in a few studies. The aim of our study was to identify and discuss the latent model structure of behavioral symptoms related to ASD and to address the question of whether categories and/or dimensions best represent ASD symptoms. We included data of 2920 participants (1-72 years of age), evaluated with the Autism Diagnostic Observation Schedule (Modules 1-4). We applied latent class analysis, confirmatory factor analysis, and factor mixture modeling and evaluated the model fit by a combination of criteria. Based on the model selection criteria, the model fits, the interpretability as well as the clinical utility we conclude that the hybrid model serves best for conceptualization and assessment of ASD symptoms. It is both grounded in empirical evidence and in clinical usefulness, is in line with the current classification system (DSM-5) and has the potential of being more specific than the dimensional approach (decreasing false positive diagnoses).

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24. Wright SE, Rodriguez CM, Monroe J, Xing J, Krans A, Flores BN, Barsur V, Ivanova MI, Koutmou KS, Barmada SJ, Todd PK. CGG repeats trigger translational frameshifts that generate aggregation-prone chimeric proteins. Nucleic Acids Res;2022 (Aug 26);50(15):8674-8689.

CGG repeat expansions in the FMR1 5’UTR cause the neurodegenerative disease Fragile X-associated tremor/ataxia syndrome (FXTAS). These repeats form stable RNA secondary structures that support aberrant translation in the absence of an AUG start codon (RAN translation), producing aggregate-prone peptides that accumulate within intranuclear neuronal inclusions and contribute to neurotoxicity. Here, we show that the most abundant RAN translation product, FMRpolyG, is markedly less toxic when generated from a construct with a non-repetitive alternating codon sequence in place of the CGG repeat. While exploring the mechanism of this differential toxicity, we observed a +1 translational frameshift within the CGG repeat from the arginine to glycine reading frame. Frameshifts occurred within the first few translated repeats and were triggered predominantly by RNA sequence and structural features. Short chimeric R/G peptides form aggregates distinct from those formed by either pure arginine or glycine, and these chimeras induce toxicity in cultured rodent neurons. Together, this work suggests that CGG repeats support translational frameshifting and that chimeric RAN translated peptides may contribute to CGG repeat-associated toxicity in FXTAS and related disorders.

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