Pubmed du 11/09/20

vendredi 11 septembre 2020

1. Barokova MD, La Valle C, Hassan S, Lee C, Xu M, McKechnie R, Johnston E, Krol MA, Leano J, Tager-Flusberg H. Eliciting Language Samples for Analysis (ELSA) : A New Protocol for Assessing Expressive Language and Communication in Autism. Autism Res ;2020 (Sep 9)

Expressive language and communication are among the key targets of interventions for individuals with autism spectrum disorder (ASD), and natural language samples provide an optimal approach for their assessment. Currently, there are no protocols for collecting such samples that cover a wide range of ages or language abilities, particularly for children/adolescents who have very limited spoken language. We introduce a new protocol for collecting language samples, eliciting language samples for analysis (ELSA), and a novel approach for deriving basic measures of verbal communicative competence from it that bypasses the need for time-consuming transcription. Study 1 presents ELSA-adolescents (ELSA-A), designed for minimally and low-verbal older children/adolescents with ASD. The protocol successfully engaged and elicited speech from 46 participants across a wide range of ages (6 ;6-19 ;7) with samples averaging 20-25 min. The collected samples were segmented into speaker utterances (examiner and participant) using real-time coding as one is listening to the audio recording and two measures were derived : frequency of utterances and conversational turns per minute. These measures were shown to be reliable and valid. For Study 2, ELSA was adapted for younger children (ELSA-Toddler [ELSA-T]) with samples averaging 29 min from 19 toddlers (2 ;8-4 ;10 years) with ASD. Again, measures of frequency of utterances and conversational turns derived from ELSA-T were shown to have strong psychometric properties. In Study 3, we found that ELSA-A and ELSA-T were equivalent in eliciting language from 17 children with ASD (ages : 4 ;0-6 ;8), demonstrating their suitability for deriving robust objective assessments of expressive language that could be used to track change in ability over time. We introduce a new protocol for collecting expressive language samples, ELSA, that can be used with a wide age range, from toddlers (ELSA-T) to older adolescents (ELSA-A) with ASD who have minimal or low-verbal abilities. The measures of language and communication derived from them, frequency of utterances, and conversational turns per minute, using real-time coding methods, can be used to characterize ability and chart change in intervention research. LAY SUMMARY : We introduce a new protocol for collecting expressive language samples, ELSA, that can be used with a wide age range, from toddlers (ELSA-T) to older adolescents (ELSA-A) with autism spectrum disorder who have minimal or low-verbal abilities. The measures of language and communication derived from them, frequency of utterances and conversational turns per minute, using real-time coding methods, can be used to characterize ability and chart change in intervention research.

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2. Burton JM, Creaghead NA, Silbert N, Breit-Smith A, Duncan AW, Grether SM. Social Communication and Structural Language of Girls With High-Functioning Autism Spectrum Disorder. Lang Speech Hear Serv Sch ;2020 (Sep 11):1-17.

Purpose The purpose of this study was to characterize social communication and structural language of school-age girls with high-functioning autism spectrum disorder (HF-ASD) compared to a matched group of girls who are typically developing (TD). Method Participants were 37 girls between 7 ;5 and 15 ;2 (years ;months)-18 HF-ASD and 19 TD. Children completed the Test of Pragmatic Language-Second Edition (TOPL-2) and Clinical Evaluation of Language Fundamentals-Fifth Edition. Parents completed the Children’s Communication Checklist-2 United States Edition (CCC-2) and Receptive and Expressive Communication subdomains of the Vineland Adaptive Behavior Scales-Second Edition. Results In the area of social communication, girls with HF-ASD earned significantly lower scores and were more often classified as having an impairment on the TOPL-2 and the CCC-2. However, 28% and 33% earned average scores on the TOPL-2 and the CCC-2, respectively. In the area of structural language, no significant differences were found between groups on Clinical Evaluation of Language Fundamentals-Fifth Edition indexes. In contrast, girls with HF-ASD earned significantly lower scores and were more often classified as having an impairment on the Vineland Adaptive Behavior Scales-Second Edition. Sixty-one percent and 83% scored below average on the Receptive and Expressive Communication subdomains, respectively. Conclusions It has been argued that girls with HF-ASD, when compared to boys with HF-ASD, may have advantages for social communication and structural language that mask their impairments. However, when compared to girls who are TD, girls with HF-ASD demonstrated impaired social communication and structural language. Clinicians should include and carefully examine multiple sources of information when assessing girls with HF-ASD.

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3. Chen T, Yang W, Wang Q, Zhang Y, Ma Z. Effects of social stories intervention for children and adolescents with autism spectrum disorders : A protocol for a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) ;2020 (Sep 11) ;99(37):e22018.

BACKGROUND : Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, which lacks specific medical treatment. Intervention is the key point of rehabilitation training for ASD. Social stories (SS) are a commonly used intervention practice in individuals with ASD. However, there is mixed evidence on the effectiveness of SS. Thus, the objective of this systematic review and meta-analysis is to assess studies of the effects of SS for children and adolescents with ASD. METHODS : To identify relevant studies, we will search PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar and trials registers (the World Health Organization International Clinical Trial Registration Platform,, and Chinese Clinical Trial Register) from inception to May 2020. In addition, we will also perform handsearching of grey literature, such as conference proceedings and academic degree dissertations. Only the randomized control trials will be accepted, no matter what the languages they were reported. We will first focus on the effectiveness of the intervention on the behavior of the targets. Then we will do further analysis of the study design, including the length and intensity of intervention, the characteristics of participants and interveners, the methods of assessment, the place, the medium, and the economic feasibility. Two independent reviewers will carry out literature identification, data collection, and study quality assessment. Discrepancies will be resolved by a third reviewer. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Data analysis will be calculated using the STATA 13.0 software. RESULT : This study will offer new evidence whether the SS is an appropriate intervention of benefiting the children and adolescents with ASD, and to determine which factors affect the effectiveness of SS. CONCLUSION : The conclusion drawn from this systematic review will benefit the children and adolescents with ASD.

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4. Douard E, Zeribi A, Schramm C, Tamer P, Loum MA, Nowak S, Saci Z, Lord MP, Rodríguez-Herreros B, Jean-Louis M, Moreau C, Loth E, Schumann G, Pausova Z, Elsabbagh M, Almasy L, Glahn DC, Bourgeron T, Labbe A, Paus T, Mottron L, Greenwood CMT, Huguet G, Jacquemont S. Effect Sizes of Deletions and Duplications on Autism Risk Across the Genome. Am J Psychiatry ;2020 (Sep 11):appiajp202019080834.

OBJECTIVE : Deleterious copy number variants (CNVs) are identified in up to 20% of individuals with autism. However, levels of autism risk conferred by most rare CNVs remain unknown. The authors recently developed statistical models to estimate the effect size on IQ of all CNVs, including undocumented ones. In this study, the authors extended this model to autism susceptibility. METHODS : The authors identified CNVs in two autism populations (Simons Simplex Collection and MSSNG) and two unselected populations (IMAGEN and Saguenay Youth Study). Statistical models were used to test nine quantitative variables associated with genes encompassed in CNVs to explain their effects on IQ, autism susceptibility, and behavioral domains. RESULTS : The "probability of being loss-of-function intolerant" (pLI) best explains the effect of CNVs on IQ and autism risk. Deleting 1 point of pLI decreases IQ by 2.6 points in autism and unselected populations. The effect of duplications on IQ is threefold smaller. Autism susceptibility increases when deleting or duplicating any point of pLI. This is true for individuals with high or low IQ and after removing de novo and known recurrent neuropsychiatric CNVs. When CNV effects on IQ are accounted for, autism susceptibility remains mostly unchanged for duplications but decreases for deletions. Model estimates for autism risk overlap with previously published observations. Deletions and duplications differentially affect social communication, behavior, and phonological memory, whereas both equally affect motor skills. CONCLUSIONS : Autism risk conferred by duplications is less influenced by IQ compared with deletions. The model applied in this study, trained on CNVs encompassing >4,500 genes, suggests highly polygenic properties of gene dosage with respect to autism risk and IQ loss. These models will help to interpret CNVs identified in the clinic.

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5. Fernandez-Prieto M, Moreira C, Cruz S, Campos V, Martínez-Regueiro R, Taboada M, Carracedo A, Sampaio A. Executive Functioning : A Mediator Between Sensory Processing and Behaviour in Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Sep 11)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, executive functioning, sensory-perceptual abilities and behaviour, such as anxious/depressed states, attention problems, aggression, or somatic complains. However, the dynamic relationship between these dimensions remains to be addressed. Therefore, we explored the link between executive functions, sensory processing and behaviour in 79 children and adolescents with ASD. Results showed significant associations between all dimensions-executive functions, sensory processing and behaviour. Furthermore, using structural equation modelling methods, we observed a mediation effect of executive functioning, specifically the domain pertaining to emotion regulation and control, and in the relationship between sensory processing abnormalities and behavioural problems. We discuss the importance of emotion regulation as a mediator between sensory processing and behavioural impairments and its impact in social competence in ASD.

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6. Forseth B, Papanek PE, Polfuss ML. Feasibility and applicability of Evenson sedentary behavior cut points applied to children with and without intellectual and developmental disabilities. Disabil Rehabil ;2020 (Sep 10):1-6.

AIM : Sedentary behavior (SB) is widely studied as it is associated with cardiometabolic health and obesity issues. However, children with Intellectual and Developmental Disabilities (IDD) have been understudied. Accelerometers are commonly used to measure SB in typically developing populations but may be inappropriate for IDD populations due to differences in body movement and physiologic responses to the activity. The use of Evenson sedentary cut-points, created based on typically developing children, has yet to be applied and/or examined in children with IDD. PURPOSE : A descriptive cross-sectional study was conducted to (1) Assess the feasibility of applying Evenson sedentary cut-points in children with IDD (2) Describe SB over a two-week period between diagnosis groups. METHODS : The SB of 22 participants (8 children with Down syndrome, 6 children with spina bifida, 8 children with no chronic illness) was assessed on two separate occasions : (1) during a 7-minute sedentary protocol, and (2) over a two-week period. RESULTS : The study supports the preliminary efficacy of using Evenson cut-points for this population, with 100% of participants being within the Evenson counts per minute (0-100 cpm) during the 7-minute sedentary protocol. The total volume of SB over a two-week period was not significantly different between diagnosis groups (8.8 h, 8.6 h, and 7.1 h of SB for children with Down syndrome, spina bifida, or those with no chronic illness, respectively ; p = 0.36). CONCLUSIONS : Evenson sedentary cut-points can be used for children with IDD. Preliminary data suggest that children with IDD do not engage in significantly different SB than children without a chronic illness. Further study is warranted. Implications for rehabilitation Objective measures of physical activity and sedentary behavior for children with Down syndrome or spina bifida are rarely used due to potential differences in body movement (e.g., gait) during ambulation compared to typically developing peers that may influence the accuracy of cut-points. This study supports that Evenson sedentary cut-points can be used in children with Down syndrome or spina bifida to assess sedentary activity. Preliminary findings from this study demonstrate similarities in patterns of sedentary behaviors exhibited by our sample of children with Down syndrome, spina bifida, or no chronic illness.

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7. Gilmore D, Harris L, Longo A, Hand BN. Health status of Medicare-enrolled autistic older adults with and without co-occurring intellectual disability : An analysis of inpatient and institutional outpatient medical claims. Autism ;2020 (Sep 9):1362361320955109.

Little is known about the extent to which the healthcare needs of autistic older adults with intellectual disability differ from autistic older adults without intellectual disability. Our study is the first, to our knowledge, to use US national data to compare physical and mental health conditions among autistic older adults with and without intellectual disability. The data analyzed in this study consisted of records from inpatient hospitalizations as well as "institutional outpatient" healthcare visits, which include visits to hospital outpatient departments, rural health clinics, renal dialysis facilities, outpatient rehabilitation facilities, Federally Qualified Health Centers, and community mental health centers. Autistic older adults with intellectual disability were significantly more likely to have thyroid disorders, epilepsy, respiratory infections, gastrointestinal conditions, osteoporosis, cognitive disorders, and schizophrenia/psychotic disorders. In contrast, autistic older adults without intellectual disability were significantly more likely to have obesity, diabetes, high blood pressure, cerebrovascular disease, chronic obstructive pulmonary disease, arthritis, back conditions, attention deficit disorders, substance use disorders, and suicidal ideation or intentional self-injury. These findings highlight the importance of developing distinct, tailored health management strategies for the autistic older adults with and without intellectual disability.

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8. Goin-Kochel RP, Fombonne E, Mire SS, Minard CG, Sahni LC, Cunningham RM, Boom JA. Beliefs about causes of autism and vaccine hesitancy among parents of children with autism spectrum disorder. Vaccine ;2020 (Sep 11) ;38(40):6327-6333.

Vaccine hesitancy may be more common among parents of children with autism spectrum disorder (ASD). We examined factors associated with ASD-specific vaccine hesitancy among caregivers of children with ASD who participated in the SPARK study (Simons Foundation Powering Autism Research for Knowledge). 225 participants completed an online survey containing the Parent Attitudes About Childhood Vaccines (PACV) questionnaire (measure of vaccine hesitancy) and the Illness Perception Questionnaire revised for parents of children with ASD (IPQ-R-ASD ; measure of parents’ views about ASD). 65 participants (28.8%) were vaccine hesitant (PACV score ≥ 50) ; children of vaccine-hesitant parents (VHPs) were less likely to be first born (n = 27, 41.5%), had greater ASD-symptom severity (mean Social Communication Questionnaire score = 23.9, SD = 6.9), and were more likely to have experienced developmental regression (n = 27, 50.9%) or plateau (n = 37, 69.8%). Compared to non-hesitant parents, VHPs significantly more often endorsed accident/injury, deterioration of the child’s immune system, diet, environmental pollution, general stress, parents’ negative views, parents’ behaviors/decisions, parents’ emotional state, and vaccines as causes for ASD. VHPs also had higher scores on the Personal Control, Treatment Control, Illness Coherence, and Emotional Representations subscales of the IPQ-R than did non-hesitant parents. In the final model, ASD-related vaccine hesitancy was significantly associated with higher scores on the Emotional Representations subscale (OR = 1.13, p = 0.10), agreement with deterioration of the child’s immunity as a cause of ASD (OR = 12.47, p < 0.001), the child not having achieved fluent speech (OR = 2.67, p = 0.17), and the child experiencing a developmental plateau (OR = 3.89, p = 0.002). Findings suggest that a combination of child functioning and developmental history, as well as parents’ negative views about and their sense of control over ASD, influence vaccine hesitancy among parents of children with ASD.

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9. Griffiths AJ, Hanson AH, Giannantonio CM, Mathur SK, Hyde K, Linstead E. Developing Employment Environments Where Individuals with ASD Thrive : Using Machine Learning to Explore Employer Policies and Practices. Brain Sci ;2020 (Sep 11) ;10(9)

An online survey instrument was developed to assess employers’ perspectives on hiring job candidates with Autism Spectrum Disorder (ASD). The investigators used K-means clustering to categorize companies in clusters based on their hiring practices related to individuals with ASD. This methodology allowed the investigators to assess and compare the various factors of businesses that successfully hire employees with ASD versus those that do not. The cluster analysis indicated that company structures, policies and practices, and perceptions, as well as the needs of employers and employees, were important in determining who would successfully hire individuals with ASD. Key areas that require focused policies and practices include recruitment and hiring, training, accessibility and accommodations, and retention and advancement.

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10. Hand BN, Coury DL, Darragh AR, White S, Moffatt-Bruce S, Harris L, Longo A, Gilmore D, Garvin JH. Patient and caregiver experiences at a specialized primary care center for autistic adults. J Comp Eff Res ;2020 (Sep 11)

Background : Little is known about the extent to which patient-centered medical homes meet the needs of autistic adults. Materials & methods : We conducted a cross-sectional survey of autistic adult patients (n = 47) and caregivers of autistic adult patients (n = 66) receiving care through one patient-centered medical home specifically designed to meet the needs of this population. We performed post hoc comparisons of our results to previously published data from a national sample of autistic adults. Results : Participants reported high levels of satisfaction with care, frequent preventive healthcare use and few unmet healthcare needs. Autistic adults in our sample reported significantly higher satisfaction and fewer unmet healthcare needs. Conclusion : A patient-centered medical home tailored to the needs of autistic adults is a promising approach to healthcare delivery for meeting this population’s needs.

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11. Hand BN, Coury DL, White S, Darragh AR, Moffatt-Bruce S, Harris L, Longo A, Garvin JH. Specialized primary care medical home : A positive impact on continuity of care among autistic adults. Autism ;2020 (Sep 9):1362361320953967.

There is a nationally recognized need for innovative healthcare delivery models to improve care continuity for autistic adults as they age out of pediatric and into adult healthcare systems. One possible model of care delivery is called the "medical home". The medical home is not a residential home, but a system where a patient’s healthcare is coordinated through a primary care physician to ensure necessary care is received when and where the patient needs it. We compared the continuity of care among autistic adult patients at a specialized primary care medical home designed to remove barriers to care for autistic adults, called the CAST, to matched national samples of autistic adults with private insurance or Medicare. Continuity of primary care among CAST patients was significantly better than that of matched national samples of autistic adult Medicare beneficiaries and similar to that of privately insured autistic adults. Our findings suggest that medical homes, like CAST, are a promising solution to improve healthcare delivery for the growing population of autistic adults.

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12. Joga-Elvira L, Jacas C, Joga ML, Roche-Martínez A, Brun-Gasca C. Bullying Victimization in Young Females with Fragile-X-Syndrome. Genes (Basel) ;2020 (Sep 11) ;11(9)

The aim of this study is to investigate the risk associated with girls with fragile X syndrome (FXS) suffering bullying in the role of a victim and its effects on their adaptive behavior, socialization style, and emotional state. A neuropsychological assessment was carried out on a sample of 40 participants (26 FXS positive and 14 control group) using the following instruments : WISC-V, SENA, BAS-2, ABAS-II. The results show that the group of girls with FXS presented higher ratios of lack of social support and isolation from classmates. This finding suggests that problems with social interaction and communication in the group of girls with FXS could lead to difficulties in interpreting social signals and identifying situations of bullying correctly, placing them in a very vulnerable situation.

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13. Johnson KL. US Pilot Curriculum for Transitioning Students with Autism Spectrum Disorders from High School to College and the Workforce. Folia Phoniatr Logop ;2020 (Sep 11):1-7.

OBJECTIVES : Few, evidence-based programs have been developed to prepare social skills for students with autism spectrum disorder (ASD) transitioning to the workplace or college setting. This article describes a pilot curriculum developed for Tarrant County College (TCC) to address the transitional needs of high school students with ASD to a vocation or college. METHODS : TCC enrolled 123 high school students across the ASD who were taught a 2-h, 2-semesters course on how to apply for college as well as employment applications, job interviews, and interpersonal skills. Work preparation and college preparatory skills such as communicating with professors regarding specific student learning accommodations were also included. Publicly available enrollment TCC data were utilized to describe the curricular program outcomes. Program Outcomes : No statistically significant success rate increase was identified among enrolled ASD students obtaining college acceptance by participating in the TCC program. However, 14 students were successful in attaining employment. TCC enrollment data also showed that 1 course addressing high school ASD students’ transitional needs to a vocation or college is not enough to ensure student success. Ongoing mentorship and advising should play a major role in the development of several semester long transitional courses to assist ASD students as they seek employment or a college program. Such a curriculum should include parental support and ongoing employer and college advisor communication regarding curriculum expectations for long-term success in the lives of ASD students, as they gain the skills requisite for independent living.

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14. Kerr-Gaffney J, Mason L, Jones E, Hayward H, Harrison A, Murphy D, Tchanturia K. Autistic Traits Mediate Reductions in Social Attention in Adults with Anorexia Nervosa. J Autism Dev Disord ;2020 (Sep 10)

Anorexia nervosa (AN) is associated with difficulties in social and emotional functioning. A significant proportion of individuals with AN show autistic traits, which may influence social attention. This study examined attention to faces and facial features in AN, recovered AN (REC), and healthy controls, as well as relationships with comorbid psychopathology. One hundred and forty-eight participants’ eye movements were tracked while watching a naturalistic social scene. Anxiety, depression, alexithymia, and autistic traits were assessed via self-report questionnaires. Participants with AN spent significantly less time looking at faces compared to REC and controls ; patterns of attention to individual facial features did not differ across groups. Autistic traits mediated the relationship between group and time spent looking at faces.

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15. Kim B, Lee D, Min A, Paik S, Frey G, Bellini S, Han K, Shih PC. PuzzleWalk : A theory-driven iterative design inquiry of a mobile game for promoting physical activity in adults with autism spectrum disorder. PLoS One ;2020 ;15(9):e0237966.

Primary symptoms of adults with autism spectrum disorder (ASD), such as pervasive social deficits in social interaction and communication, cause adults with ASD to adopt a sedentary lifestyle. Meanwhile, gamified and behavioral theory-based interventions have been shown to improve physical activity in a fun and unobtrusive way. In this paper, we describe the iterative design inquiry process of PuzzleWalk, a gamified, physical activity-promoting mobile app designed for adults with ASD. We report the design rationales and lessons learned across four user-centered design phases with ASD experts and adults with ASD, including user requirement gathering, iterative participatory design, usability evaluation, and field deployment. The design insights generated from this work could inform future research focusing on designing sociotechnical systems, games, and interventions for people with ASD.

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16. Lasat E, Willems K, Huysmans S. [Autistic female with anxiety disorder and superior mesenteric artery syndrome]. Tijdschr Psychiatr ;2020 ;62(9):805-809.

An anxiety disorder can manifest in multiple ways. We saw a 21-year-old woman with an anxiety disorder in combination with superior mesenteric artery syndrome. For we know, this is the first description of this combination. There was also hypersensitivity to certain foods and rigid thinking patterns, and an autism spectrum disorder was discovered later. The recognition of the influence of autism on comorbid disorders is important in order to create an individual adapted treatment protocol.

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17. Levinson S, Neuspiel J, Eisenhower A, Blacher J. Parent-Teacher Disagreement on Ratings of Behavior Problems in Children with ASD : Associations with Parental School Involvement Over Time. J Autism Dev Disord ;2020 (Sep 9)

ASD symptomology and behavioral problems pose challenges for children with ASD in school. Disagreement between parents and teachers in ratings of children’s behavior problems may provide clinically relevant information. We examined parent-teacher disagreement on ratings of behavior problems among children with ASD during the fall and spring of the school year. When child, teacher, and class characteristics were considered simultaneously, only ASD symptom severity predicted informant disagreement on internalizing and externalizing behavior problems. We also examined associations between informant disagreement and parent school involvement. Cross-lagged panel analyses revealed that higher informant disagreement on children’s behavior problems in the fall predicted lower parent school involvement in the spring, suggesting that greater informant agreement may foster parental school involvement over time.

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18. Lo JYT, Shum KK. Brief Report : A Randomized Controlled Trial of the Effects of RECALL (Reading to Engage Children with Autism in Language and Learning) for Preschoolers with Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Sep 11)

This study investigated the effects of a parent-implemented dialogic reading approach-Reading to Engage Children with Autism in Language and Learning (RECALL)-on the engagement in reading and inference-making ability for preschoolers with autism spectrum disorder (ASD). Thirty-one preschoolers (mean age = 5.90 years, SD = 0.69 ; 26 boys, 5 girls) were randomly assigned to a treatment or control group. Six weeks of RECALL significantly enhanced story comprehension, emotion knowledge, and reading engagement among preschoolers in the treatment group. This might be the first randomized controlled trial testing the effects of RECALL on children with ASD. Our findings suggest that additional instructional support such as the application of a prompting hierarchy during dialogic reading might help children with ASD reap greater benefits from shared book reading.

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19. Luu S, Province H, Berry-Kravis E, Hagerman R, Hessl D, Vaidya D, Lozano R, Rosselot H, Erickson C, Kaufmann WE, Budimirovic DB. Response to Placebo in Fragile X Syndrome Clinical Trials : An Initial Analysis. Brain Sci ;2020 (Sep 11) ;10(9)

Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and autism spectrum disorder. Individuals with FXS often present with a wide range of cognitive deficits and problem behaviors. Educational, behavioral and pharmacological interventions are used to manage these and other complex issues affecting individuals with FXS. Despite the success of preclinical models and early-phase drug clinical studies in FXS, large-scale randomized-controlled trials have failed to meet primary endpoints. Currently, no targeted or disease-modifying treatments for FXS have received regulatory approval. Here, we examined the placebo response in FXS clinical trials conducted between 2006 and 2018. Specifically, we performed a meta-analysis of placebo-treated groups in eight double-blind, randomized controlled trials. Placebo groups demonstrated significant improvements on caregiver-rated efficacy endpoints, which were greater in adolescents and adults than in children. Among the latter measures, the Visual Analog Scale scores displayed the greatest improvements, whereas the positive effects on the Vineland-II Adaptive Behavior Composite and the Aberrant Behavior Checklist-Community/fragile X version were statistically significant in both children and adolescents/adults. Although the Clinical Global Impression scale Improvement appears to have exhibited a substantial placebo effect in multiple clinical trials in FXS, limited data availability for meta-analysis, prevented us from drawing conclusions. No placebo-related improvements were observed in performance-rated measures. These findings raise substantial concerns about placebo effects in outcome measures commonly used in the randomized-controlled trials in FXS and suggest several potential improvements in the study design and implementation of such trials. Considering the small number of trials available for this study, larger and more detailed follow up meta-analyses are needed. Meanwhile, efforts to improve the measurement properties of endpoints and rater training in drug trials in FXS should be prioritized.

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20. Mercado E, 3rd, Chow K, Church BA, Lopata C. Perceptual category learning in autism spectrum disorder : Truth and consequences. Neurosci Biobehav Rev ;2020 (Sep 7)

The ability to categorize is fundamental to cognitive development. Some categories emerge effortlessly and rapidly while others can take years of experience to acquire. Children with autism spectrum disorder (ASD) are often able to name and sort objects, suggesting that their categorization abilities are largely intact. However, recent experimental work shows that the categories formed by individuals with ASD may diverge substantially from those that most people learn. This review considers how atypical perceptual category learning can affect cognitive development in children with ASD and how atypical categorization may contribute to many of the socially problematic symptoms associated with this disorder. Theoretical approaches to understanding perceptual processing and category learning at both the behavioral and neural levels are assessed in relation to known alterations in perceptual category learning associated with ASD. Mismatches between the ways in which children learn to organize perceived events relative to their peers and adults can accumulate over time, leading to difficulties in communication, social interactions, academic performance, and behavioral flexibility.

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21. Nollace L, Cravero C, Abbou A, Mazda-Walter B, Bleibtreu A, Pereirra N, Sainte-Marie M, Cohen D, Giannitelli M. Autism and COVID-19 : A Case Series in a Neurodevelopmental Unit. J Clin Med ;2020 (Sep 11) ;9(9)

BACKGROUND : COVID-19 has become pandemic and can impact individuals with autism as well. Here, we report a case series admitted to a neurobehavioral unit dedicated to challenging behaviors in patients with autism. METHODS : We describe 16 patients (mean age 20.8 years ; range 12-43 years ; 76% male) with autism hospitalized between March 2020 and mid-April 2020 for challenging behaviors, for which COVID-19 disease has been suspected and who needed both psychiatric and medical care. A close cooperation with the Infectious and Tropical Diseases Department was organized to limit viral spread and training sessions (e.g., hygiene, clinical COVID-19 monitoring, virus testing) were given to staff members. RESULTS : Most patients had severe autism and severe/moderate intellectual disability. Eleven patients were already in the unit when it was hit by the pandemic, and five were admitted from the community. Based on a virus search via reverse transcriptase polymerase chain reaction (RT-PCR) or serology at the 2-month follow-up, we had 11 confirmed COVID-19 cases. The main COVID-19 symptoms included benign upper respiratory infection signs (N = 9, 81.8%), diarrhea (N = 7, 63.6%), fatigue (N = 7, 63.6%), and respiratory signs (N = 5, 45.5%), including one patient who needed oxygen therapy. Three patients remained asymptomatic and COVID-19-free (including two under immunosuppressive treatments). Among the symptomatic patients, five showed atypical behaviors that we understood as idiosyncratic manifestations (e.g., irrepressible licking behavior). On day 14, only one patient with respiratory dysfunction still had a positive RT-PCR SARS-CoV-2 test. CONCLUSIONS : Organizing a COVID+ unit for patients with autism is realistic and requires close collaboration with infectologists. We believe that this initiative should be promoted to limit both the spread of the virus and the ostracism of patients with autism and challenging behaviors.

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22. Pan PY, Bölte S, Kaur P, Jamil S, Jonsson U. Neurological disorders in autism : A systematic review and meta-analysis. Autism ;2020 (Sep 9):1362361320951370.

Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.

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23. Payne KL, Maras KL, Russell AJ, Brosnan MJ. Are Mental Health, Family and Childhood Adversity, Substance Use and Conduct Problems Risk Factors for Offending in Autism ?. J Autism Dev Disord ;2020 (Sep 11)

Mental health difficulties, family and childhood adversity factors, substance use and conduct problems have all been linked to offending behaviour in the general population. However, no large-scale study with comparison groups has investigated these risk factors in relation to autistic offenders. The current research included 40 autistic offenders, 40 autistic non-offenders, 40 typically developed (TD) offenders and 39 TD non-offenders. Conduct problems risk factors differentiated autistic offenders from both non-offender groups (autistic and TD) and mental health risk factors differentiated autistic offenders from both TD groups (offenders and non-offenders). Further research is required to understand more about the role of both conduct problems risk factors in autistic offenders (e.g., age at onset, frequency of behaviours) and the mental health needs of autistic offenders.

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24. Reyes NM, Factor R, Scarpa A. Emotion regulation, emotionality, and expression of emotions : A link between social skills, behavior, and emotion problems in children with ASD and their peers. Res Dev Disabil ;2020 (Sep 7) ;106:103770.

This study aimed to investigate differences between emotion regulation (ER), emotionality, and expression of emotions in children with Autism Spectrum Disorder (ASD) and their typically developing (TD) peers ; and to examine the potential links between these areas of development with social skills in both groups, as well as with behavioral, emotional, and social problems in ASD. Forty-four children (40 males and 4 females, ages 3 to 7 years) with ASD (n = 22) and their TD peers (n = 22) were included in this study. Mothers reported about their children’s ASD symptoms, social, emotional, and behavioral functioning. As predicted, children with ASD were described as showing decreased ER, increased emotionality, and decreased expression of emotions when compared to their TD peers. Moreover, in the ASD group, increased social skills were associated with enhanced ER and increased expression of emotions ; and in the TD group, increased social skills were correlated with decreased emotionality. Finally, enhanced ER was linked to decreased peer problems, and increased prosocial behaviors ; and decreased emotionality was linked to decreased behavior and emotional problems in the ASD group. Implications for further research are discussed.

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25. Richa S, Khoury R, J JR, Chammay R, Kazour F, Bou Khalil R, Kheir W, Choueifaty D, Kouba-Hreich E, Gerbaka B, Adib S. Estimating the prevalence of autism spectrum disorder in Lebanon. Encephale ;2020 (Sep 11)

This cross-sectional survey examines the prevalence rate of Autism spectrum disorder (ASD) in 818 children (16-48 months) across all Lebanese regions. Screening was done using the revised form of the Modified-Checklist for Autism in Toddlers. Based on the total score of items failed, children were classified into 3 categories of ASD risk (low, moderate and high). Phone calls follow-up interviews and clinical assessments for diagnosis ascertainment were conducted. Given the caregivers’ reluctance to participate, the prevalence rate was estimated between 49 and 513 per 10,000 with a male predominance. Our prevalence estimation, even under restrictive assumptions, is higher than elsewhere in the Arab region. Anti- stigma interventions adapted to the socio-cultural context are needed prior to future research in the field.

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26. Roussin L, Prince N, Perez-Pardo P, Kraneveld AD, Rabot S, Naudon L. Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder : Clinical and Preclinical Evidence. Microorganisms ;2020 (Sep 7) ;8(9)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.

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27. Savino R, Carotenuto M, Polito AN, Di Noia S, Albenzio M, Scarinci A, Ambrosi A, Sessa F, Tartaglia N, Messina G. Analyzing the Potential Biological Determinants of Autism Spectrum Disorder : From Neuroinflammation to the Kynurenine Pathway. Brain Sci ;2020 (Sep 11) ;10(9)

Autism Spectrum Disorder (ASD) etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and the Kynurenine pathway ; here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies have also identified some important polymorphisms in chromosome loci related to the human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates the Kynurenine pathway with an increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in the glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of the Kynurenine branch induces depletion of melatonin and serotonin, worsening ASD symptoms. Thus, in genetically predisposed subjects, aberrant neurodevelopment may derive from a complex interplay between inflammatory processes, mitochondrial dysfunction, oxidative stress and Kynurenine pathway overexpression. To validate this hypothesis a new translational research approach is necessary.

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28. Schiavi S, Carbone E, Melancia F, Buzzelli V, Manduca A, Campolongo P, Pallottini V, Trezza V. Perinatal supplementation with omega-3 fatty acids corrects the aberrant social and cognitive traits observed in a genetic model of autism based on FMR1 deletion in rats. Nutr Neurosci ;2020 (Sep 11):1-14.

Background and objective : Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which no treatments exist. Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most frequent monogenic cause of ASD. Given the lack of pharmacological treatments for ASD, increasing interest is devoted to non-pharmacological approaches, including dietary interventions. Omega-3 polyunsaturated fatty acids (PUFAs) are critical for neurobehavioraldevelopment. This study had two aims : 1. To validatethe recently developed Fmr1-(Δ)exon 8 rat model of FXS ; 2. To assess the impact of omega-3 PUFAs dietary supplementation during pregnancy and lactation on the altered behavior displayed by Fmr1-(Δ)exon 8 rats. Methods : Female Fmr1-(Δ)exon 8 and wild-type Sprague-Dawley rats were fed with either an omega-3 PUFAs enriched diet or with an isocaloric control diet during pregnancy and lactation. Behavioral experiments were carried out on the infant (Postnatal days (PNDs) 9 and 13), juvenile (PND 35) and adult (PND 90) male offspring. Results : Fmr1-(Δ)exon 8 pups showed hypolocomotion, reduced ultrasonic vocalizations (USVs) emission and impaired social discrimination compared to wild-type controls. Juvenile and adult Fmr1-(Δ)exon 8 rats showed deficits in the social and cognitive domains, that were counteracted by perinatal omega-3 PUFAs supplementation. Conclusion : Our results support the validity of the Fmr1-(Δ)exon 8 rat model to mimic key autistic-like features and support an important role of omega-3 PUFAs during of neurodevelopment. Although the mechanisms underlying the beneficial effects of omega-3 PUFAs supplementation in ASD needs to be clarified, this dietary intervention holds promise to mitigate core and comorbid autistic features.

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29. Scott KE, Kazazian K, Mann RS, Möhrle D, Schormans AL, Schmid S, Allman BL. Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing. Autism Res ;2020 (Sep 11)

Autism spectrum disorder (ASD) is characterized by social interaction and communication impairments, as well as restrictive/repetitive patterns of behavior, interests or activities, which can coexist with intellectual disability and altered sensory processing. To study the mechanisms underlying these core features of ASD, preclinical research has developed animal models with manipulations in ASD-linked genes, such as CNTNAP2. In order to fully interpret the findings from mechanistic studies, the extent to which these models display behaviors consistent with ASD must be determined. Toward that goal, we conducted an investigation of the consequences of a functional loss of Cntnap2 on ASD-related behaviors by comparing the performance of rats with a homozygous or heterozygous knockout of Cntnap2 to their wildtype littermates across a comprehensive test battery. Cntnap2(-/-) rats showed deficits in sociability and social novelty, and they displayed repetitive circling and hyperlocomotion. Moreover, Cntnap2(-/-) rats demonstrated exaggerated acoustic startle responses, increased avoidance to sounds of moderate intensity, and a lack of rapid audiovisual temporal recalibration ; indicating changes in sensory processing at both the pre-attentive and perceptual levels. Notably, sensory behaviors requiring learned associations did not reveal genotypic differences, whereas tasks relying on automatic/implicit behaviors did. Ultimately, because these collective alterations in social, stereotypic, and sensory behaviors are phenotypically similar to those reported in individuals with ASD, our results establish the Cntnap2 knockout rat model as an effective platform to study not only the molecular and cellular mechanisms associated with ASD, but also the complex relationship between altered sensory processing and other core ASD-related behaviors. LAY SUMMARY : Autism spectrum disorder (ASD) is characterized by social interaction differences, and restrictive/repetitive patterns of behavior. We studied the behavioral alterations caused by the loss of an autism-linked gene, Cntnap2, in the rat to determine how mutations in this gene contribute to autism-related behaviors. We show the loss of Cntnap2 leads to changes in social, stereotypic, and sensory behaviors, indicating this rat model can be used to better understand the brain changes underlying ASD.

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30. Snouckaert VC, Spek AA. [The development of anorexia nervosa in people with an autism spectrum disorder ; a qualitative, retrospective study]. Tijdschr Psychiatr ;2020 ;62(9):760-767.

To improve treatment options for women with autism spectrum disorder (ASD) in combination with anorexia nervosa (an), it is necessary to better understand which risk factors are involved in the development of an in this target audience.
AIM : To identify risk factors for the development of an in people with ASD.
METHOD : Six women with ASD who are, or have been suffering from an, were interviewed about the development of their eating disorder. The data were analyzed using the thematic analysis method.
RESULTS : Regarding these participants, the generally accepted risk factors for developing an also appear to play a role, where it is possible that people with ASD form a vulnerable group for these risk factors. Characteristics specific for ASD were found to also contribute to the development of an in these participants.
CONCLUSION : For women with ASD it is important to be aware of a vulnerability to develop an. Extra support in areas where they experience difficulties is therefore necessary. The ASD specific characteristics can be aggravating or sustaining factors for an and should therefore be included in the treatment.

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31. Trinh S, Arnett A, Kurtz-Nelson E, Beighley J, Picoto M, Bernier R. Transcriptional subtyping explains phenotypic variability in genetic subtypes of autism spectrum disorder. Dev Psychopathol ;2020 (Sep 11):1-9.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes. Recent advances in transcriptomics have provided additional dimensions with which to refine genetic subtyping efforts. In the current study, we investigate phenotypic differences among transcriptional subtypes defined by neurobiological spatiotemporal co-expression patterns. Of the four transcriptional subtypes examined, participants with mutations to genes typically expressed highly in all brain regions prenatally, and those with differential postnatal cerebellar expression relative to other brain regions, showed lower cognitive and adaptive skills, higher severity of social communication deficits, and later acquisition of speech and motor milestones, compared to those with mutations to genes highly expressed during the postnatal period across brain regions. These findings suggest higher-order characterization of genetic subtypes based on neurobiological expression patterns may be a promising approach to parsing phenotypic heterogeneity among those with ASD and related neurodevelopmental disorders.

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32. Wang HE, Cheng CM, Bai YM, Hsu JW, Huang KL, Su TP, Tsai SJ, Li CT, Chen TJ, Leventhal BL, Chen MH. Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder : a nationwide population-based study. Psychol Med ;2020 (Sep 11):1-11.

BACKGROUND : Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive. METHODS : This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan’s National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID). RESULTS : FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls : ASD 17.46 (CI 15.50-19.67), ADHD 3.94 (CI 3.72-4.17), schizophrenia 3.05 (CI 2.74-3.40), BD 2.22 (CI 1.98-2.48) and MDD 1.88 (CI 1.76-2.00). Higher RRs of schizophrenia (4.47, CI 3.95-5.06) and ASD (18.54, CI 16.18-21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only. CONCLUSIONS : The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.

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33. Weir E, Allison C, Warrier V, Baron-Cohen S. Increased prevalence of non-communicable physical health conditions among autistic adults. Autism ;2020 (Sep 9):1362361320953652.

Previous research indicates autistic individuals die at a younger age than others and that this is possibly due in part to chronic physical health conditions. The present study used an anonymous, online survey to determine how common certain physical health conditions are among autistic adults, compared with non-autistic adults. We found autistic adults are more likely to develop heart conditions, lung conditions, and diabetes than non-autistic adults. Autistic females may be at higher risk of developing certain conditions (including respiratory conditions, asthma, and prediabetes) than autistic males. Finally, autistic individuals have increased health risks even when considering lifestyle factors (such as smoking, alcohol, and body mass index). This is still a relatively small study, and future research needs to confirm these findings and identify why these risks exist.

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34. Wilson HA, Creighton C, Scharfman H, Choleris E, MacLusky NJ. Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder. Neuroscientist ;2020 (Sep 11):1073858420952046.

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Numerous genetic and environmental risk factors have been suggested to contribute to the development of ASD. However, no one factor can adequately explain either the frequency of the disorder or the male bias in its prevalence. Gonadal, thyroid, and glucocorticoid hormones all contribute to normal development of the brain, hence perturbations in either their patterns of secretion or their actions may constitute risk factors for ASD. Environmental factors may contribute to ASD etiology by influencing the development of neuroendocrine and neuroimmune systems during early life. Emerging evidence suggests that the placenta may be particularly important as a mediator of the actions of environmental and endocrine risk factors on the developing brain, with the male being particularly sensitive to these effects. Understanding how various risk factors integrate to influence neural development may facilitate a clearer understanding of the etiology of ASD.

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