Pubmed du 15/07/20

mercredi 15 juillet 2020

1. Albantakis L, Brandi ML, Zillekens IC, Henco L, Weindel L, Thaler H, Schliephake L, Timmermans B, Schilbach L. Alexithymic and autistic traits : Relevance for comorbid depression and social phobia in adults with and without autism spectrum disorder. Autism. 2020 : 1362361320936024.

Adults with autism often develop mental health problems such as depression and social phobia. The reasons for this are still unclear. Many studies found that alexithymia plays an important role in mental health problems like depression. People with alexithymia have difficulties identifying and describing their emotions. Almost every second person with autism has alexithymia. Therefore, we explored in this study whether alexithymia is linked to worse mental health in autistic people. We looked at two common diagnoses, depression and social phobia. We found that alexithymia increased symptoms of depression, while autistic traits increased symptoms of social phobia. Our results suggest that alexithymia and autistic traits can increase the risk of mental health problems. An early assessment could help prevent mental health problems and improve quality of life.

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2. Bach MA, Samms-Vaughan M, Hessabi M, Bressler J, Lee M, Zhang J, Shakespeare-Pellington S, Grove ML, Loveland KA, Rahbar MH. Association of Polychlorinated Biphenyls and Organochlorine Pesticides with Autism Spectrum Disorder in Jamaican Children. Res Autism Spectr Disord. 2020 ; 76.

BACKGROUND : Polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides are suspected to play a role in autism spectrum disorder (ASD). OBJECTIVES : To investigate associations of PCBs and OC pesticides with ASD in Jamaican children and explore possible interaction between PCBs or OC pesticides with glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1) in relation to ASD. METHODS : Participants included n=169 age- and sex-matched case-control pairs of Jamaican children 2-8 years old. Socioeconomic status and food frequency data were self-reported by the parents/guardians. Blood from each participant was analyzed for 100 PCB congeners and 17 OC pesticides and genotyped for three GST genes. PCBs and OC pesticides concentrations below the limit of detection (LoD) were replaced with (LoD/√2). We used conditional logistic regression (CLR) models to assess associations of PCBs and OC pesticides with ASD, individually or interactively with GST genes (GSTT1, GSTM1, GSTP1). RESULTS : We found inverse associations of PCB-153 [adjusted MOR (95% CI) = 0.44 (0.23-0.86)] and PCB-180 [adjusted MOR (95% CI) = 0.52 (0.28-0.95)] with ASD. When adjusted for covariates in a CLR the interaction between GSTM1 and PCB-153 became significant (P < 0.01). DISCUSSION : Differences in diet between ASD and typically developing control groups may play a role in the observed findings of lower concentrations of PCB-153 and PCB-180 in individuals with ASD than in controls. Considering the limited sample size and high proportion of concentrations below the LoD, these results should be interpreted with caution but warrant further investigation into associations of PCBs and OC pesticides with ASD.

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3. Berrigan P, Scott CWM, Zwicker JD. Employment, Education, and Income for Canadians with Developmental Disability : Analysis from the 2017 Canadian Survey on Disability. J Autism Dev Disord. 2020.

This study assessed needs and outcomes for people with developmental disability (DD) to understand the socioeconomic status of this group prior to implementation of the Accessible Canada Act in June 2019. The 2017 Canadian Survey on Disability (CSD) was used to analyze data for a sample of individuals with self-reported disability. Data related to employment, education, income, housing, caregivers, and use of government benefits is reported. Compared to the general Canadian public, persons with DD are less likely to : finish high-school or post-secondary education ; participate in the labor force or be employed ; and earn on average less/year in total income. To align with recent accessibility legislation, significant progress is needed to address disparities for people with DD.

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4. Berry-Kravis E, Horrigan JP, Tartaglia N, Hagerman R, Kolevzon A, Erickson CA, Hatti S, Snape M, Yaroshinsky A, Stoms G, Glass L, Jones NE. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome. Pediatric neurology. 2020.

BACKGROUND : We analyze the safety and tolerability of trofinetide and provide a preliminary evaluation of its efficacy in adolescent and adult males with fragile X syndrome. METHODS : This study was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, parallel group study of the safety and tolerability of orally administered trofinetide in 72 adolescent and adult males with fragile X syndrome. Subjects were randomly assigned in a 1:1:1 ratio to 35 or 70 mg/kg twice daily trofinetide or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant phenotypic dimensions of impairment associated with fragile X syndrome. RESULTS : Both 35 and 70 mg/kg dose levels of trofinetide were well tolerated and appeared to be generally safe. Trofinetide at the 70 mg/kg dose level demonstrated efficacy compared with placebo based on prespecified criteria. On the basis of a permutation test, the probability of a false-positive outcome for the achieved prespecified success was 0.045. In the group analysis, improvement from treatment baseline was demonstrated on three fragile X syndrome-specific outcome measures. CONCLUSIONS : Trofinetide was well tolerated in adolescent and adult males with fragile X syndrome. Despite the relatively short duration of the study, a consistent signal of efficacy at the higher dose was observed in both caregiver and clinician assessments, based on a novel analytical model incorporating evaluation of multiple key symptom areas of fragile X syndrome. This finding suggests a potential for trofinetide treatment to provide clinically meaningful improvement in core fragile X syndrome symptoms.

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5. Besterman AD, Sadik J, Enenbach MJ, Quintero-Rivera F, DeAntonio M, Martinez-Agosto JA. The Feasibility and Outcomes of Genetic Testing for Autism and Neurodevelopmental Disorders on an Inpatient Child and Adolescent Psychiatry Service. Autism Res. 2020.

Diagnostic genetic testing is recommended for children with autism spectrum disorder and other neurodevelopmental disorders. One approach to improve access to genetic testing is to offer it on the inpatient child and adolescent psychiatry (CAP) service. We provided medical genetics education to CAP fellows and retrospectively compared the genetic testing rates and diagnostic yield pre- and post-education. We compared demographics to similar patients who received testing on other clinical services and assessed rates of outpatient genetics follow-up post-discharge. The genetic testing rate on the inpatient CAP service was 1.6% before the educational intervention and 10.7% afterward. Genetic risk factors were identified in 4.3% of inpatients. However, 34.8% had variants of unknown significance. 39.1% of patients who received genetic testing while inpatients were underrepresented minorities, compared to 7.7% of inpatients who received genetic testing from other clinical services. 43.5% of patients were lost to outpatient genetics follow-up. We have demonstrated that it is feasible to provide medical genetics education to CAP fellows on an inpatient service, which may improve genetic testing rates. This preliminary evidence also suggests that genetic testing for inpatients may identify variants of unknown significance instead of well-known neurodevelopmental disorder risk variants. Genetic testing on an inpatient CAP service may also improve access to genetic services for underrepresented minorities, but assuring outpatient follow-up can be challenging. LAY SUMMARY : Genetic testing is recommended for children with autism and related developmental conditions. We provided genetic testing to a group of these children who were in a psychiatric hospital by teaching their doctors how it can be helpful. We identified a genetic risk factor in a small percentage of children and a possible genetic risk factor in a large percentage of children. However, many children did not end up receiving their genetic test results once they left the hospital. These results tell us that the psychiatric hospital may be a good place for children with autism and behavioral problems to get genetic testing, but that it is really important that doctors assure follow-up is feasible for all patients to receive their genetic test results once they leave the hospital.

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6. Brondino N, Damiani S, Politi P. Effective Strategies for Managing COVID-19 Emergency Restrictions for Adults with Severe ASD in a Daycare Center in Italy. Brain Sci. 2020 ; 10(7).

The COVID-19 pandemic has posed a serious challenge for the life and mental health of people with autism spectrum disorder (ASD). COVID-19 sanitary restrictions led to significant changes in the lives of people with ASD, including their routines ; similarly, these modifications affected the daily activities of the daycare centers which they attended. The present retrospective study evaluated the impact of COVID-19 restrictions on challenging behaviors in a cohort of people with severe ASD attending a daycare center in Italy at the beginning of the pandemic. During the first two weeks of the pandemic, we did not observe variations in challenging behaviors. This suggests that adaptations used to support these individuals with ASD in adapting to the COVID-19 emergency restrictions were effective for managing their behavior.

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7. Chan WK, Griffiths R, Price DJ, Mason JO. Cerebral organoids as tools to identify the developmental roots of autism. Mol Autism. 2020 ; 11(1) : 58.

Some autism spectrum disorders (ASD) likely arise as a result of abnormalities during early embryonic development of the brain. Studying human embryonic brain development directly is challenging, mainly due to ethical and practical constraints. However, the recent development of cerebral organoids provides a powerful tool for studying both normal human embryonic brain development and, potentially, the origins of neurodevelopmental disorders including ASD. Substantial evidence now indicates that cerebral organoids can mimic normal embryonic brain development and neural cells found in organoids closely resemble their in vivo counterparts. However, with prolonged culture, significant differences begin to arise. We suggest that cerebral organoids, in their current form, are most suitable to model earlier neurodevelopmental events and processes such as neurogenesis and cortical lamination. Processes implicated in ASDs which occur at later stages of development, such as synaptogenesis and neural circuit formation, may also be modeled using organoids. The accuracy of such models will benefit from continuous improvements to protocols for organoid differentiation.

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8. Cook A, Ogden J, Winstone N. The effect of school exposure and personal contact on attitudes towards bullying and autism in schools : A cohort study with a control group. Autism. 2020 : 1362361320937088.

Autistic children are more likely than non-autistic children to be bullied at school. This study therefore explored whether the kind of school setting and the level of personal contact with autistic people can affect children’s attitudes towards bullying and autism. Surveys were completed at the beginning and end of the school year by 775 children aged 11-12 years, from six schools : three with specialist centres for autistic children and three without. Participants read stories describing bullying situations, then provided their views in relation to the story and in relation to autism. Children in schools with centres increased their feelings of anger, pity, sadness and shame in response to the bullying situations. In contrast, children in schools with no centre showed less sociable responses to bullying, except in response to a story describing an autistic child, being excluded by classmates. Furthermore, children who increased the time they spent with autistic individuals over the course of the year showed a greater rise in positive attitudes towards autistic people. This highlights the need for both personal contact and an inclusive school environment, to improve attitudes towards autism and reduce tolerance for bullying.

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9. Coughlan B, Duschinsky R, O’Connor ME, Woolgar M. Identifying and managing care for children with autism spectrum disorders in general practice : A systematic review and narrative synthesis. Health & social care in the community. 2020.

Many healthcare systems are organised such that General Practitioners (GPs) often have a key role in identifying autism spectrum disorders (hereafter collectively referred to as autism) in children. In this review, we explored what GPs know about autism and the factors that influence their ability to identify and manage care for their patients with autism in practice. We conducted a systematic narrative review using eight electronic databases. These included Embase and MEDLINE via Ovid, Web of Knowledge, PsycINFO via Ebscohost, PubMed, Scopus, ProQuest Dissertations and Thesis, and Applied Social Sciences Index and Abstracts (ASSIA) via ProQuest. Our search yielded 2,743 citations. Primary research studies were included, and we did not impose any geographical, language or date restrictions. We identified 17 studies that met our inclusion criteria. Studies included in the review were conducted between 2003 and 2019. We thematically synthesised the material and identified the following themes : the prototypical image of a child with autism ; experience, sources of information, and managing care ; barriers to identification ; strategies to aid in identification ; and characteristics that facilitate expertise. Together, the findings from this review present a mixed picture of GP knowledge and experiences in identifying autism and managing care for children with the condition. At one end of the continuum, there were GPs who had not heard of autism or endorsed outmoded aetiological theories. Others, however, demonstrated a sound knowledge of the conditions but had limited confidence in their ability to identify the condition. Many GPs and researchers alike called for more training and this might be effective. However, framing the problem as one of a lack of training risks silences the array of organisational factors that impact on a GP’s ability to provide care for these patients.

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10. Dempsey EE, Moore C, Richard AE, Smith IM. Moral foundations theory in autism spectrum disorder : A qualitative investigation. Autism. 2020 : 1362361320939331.

Morality is important for how humans treat each other and non-human animals. Differences in moral thinking have been found between autistic and neurotypical individuals. This research has relied on ways of thinking about moral psychology that suggest that mature morals develop as individuals learn to take the perspectives of others. Yet, even autistic individuals, who sometimes differ in their ability to take others’ perspectives, make moral judgements that are similar to neurotypical individuals. Moral foundations theory suggests that moral psychology is not hierarchical but differs depending on culture. This theory could therefore help make sense of similarities and differences in autistic and neurotypical moral thinking. Moral foundations theory has not yet been investigated among autistic individuals. In this study, we interviewed autistic adults as a first attempt at understanding how moral foundations theory fits with autistic moral thinking. We found that all five moral foundations of moral foundations theory were represented in the interviews, yet certain foundations appeared more prominent than others. The autistic adults interviewed in our study discussed issues of care and fairness more than of loyalty, authority or purity when prompted to discuss moral transgressions. Future research should use quantitative methods to compare groups of autistic and neurotypical individuals to clarify similarities and differences in moral thinking between the groups.

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11. Di Liberto D, D’Anneo A, Carlisi D, Emanuele S, De Blasio A, Calvaruso G, Giuliano M, Lauricella M. Brain Opioid Activity and Oxidative Injury : Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder. Brain Sci. 2020 ; 10(7).

Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of wheat gliadin and related prolamins from other cereals, such as barley and rye. Immunity against these cereal-derived proteins is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. Peptides generated in this condition are absorbed across the gut barrier, which in these patients is characterized by the deregulation of its permeability. Here, we discuss a possible correlation between CD and Autistic Spectrum Disorder (ASD) pathogenesis. ASD can be induced by an excessive and inappropriate brain opioid activity during the neonatal period. Cereal-derived peptides produced in celiac patients cross the blood-brain barrier and bind to endogenous opioid receptors interfering with neurotransmission and generating deleterious effects on brain maturation, learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the proposed relationship between ASD and CD and the possible usefulness of a gluten-free diet in ASD patients.

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12. Failla MD, Schwartz KL, Chaganti S, Cutting LE, Landman BA, Cascio CJ. Using phecode analysis to characterize co-occurring medical conditions in autism spectrum disorder. Autism. 2020 : 1362361320934561.

People with autism spectrum disorder often have a number of other medical conditions in addition to autism. These can range from constipation to epilepsy. This study uses medical record data to understand how frequently and how long people with autism have to be seen by a medical professional for these other medical conditions. This study confirmed that people with autism often have a number of other medical conditions and that they have to go see a medical professional about those conditions often. We also looked to see if children diagnosed with autism after age 5 years might have different medical conditions compared to children diagnosed earlier. Children diagnosed later had more conditions like asthma, hearing loss, and mood disorders. This work describes how much medical care people with autism get for different medical conditions and the burden of seeking additional medical care for people with autism and their families.

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13. Flower RL, Richdale AL, Lawson LP. Brief Report : What Happens After School ? Exploring Post-school Outcomes for a Group of Autistic and Non-autistic Australian Youth. J Autism Dev Disord. 2020.

Young autistic Australians are less likely to attend higher education and have lower employment rates than non-autistic Australians (in : Australian Bureau of Statistics, Survey of disability, ageing and carers Australia : Summary of Findings 2018. Australian Bureau of Statistics, Canberra, 2019a). Few studies have examined post-school outcomes among this population. Using data from the first phase of a national longitudinal study including autistic (n = 79) and non-autistic (n = 107) 17-25-year olds, we found young autistic adults were (a) less likely to be employed, (b) more likely to attend technical and further education (TAFE) than university, (c) more likely to enrol in higher education on a part-time basis and (d) less likely to be engaged in both higher education and employment, than their non-autistic peers. Findings highlight a need to understand post-school trajectories of young autistic adults.

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14. Gómez LE, Monsalve A, Morán ML, Alcedo M, Lombardi M, Schalock RL. Measurable Indicators of CRPD for People with Intellectual and Developmental Disabilities within the Quality of Life Framework. Int J Environ Res Public Health. 2020 ; 17(14).

This article proposes the quality of life (QOL) construct as a framework from which to develop useful indicators to operationalize, measure, and implement the Articles of the Convention on the Rights of Persons with Disabilities (CRPD). A systematic review of the scientific literature on people with intellectual and developmental disabilities (IDD) was carried out, with the aim of identifying personal outcomes that can be translated into specific and measurable items for each of the CRPD Articles aligned to the eight QOL domains. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the systematic review was conducted across the Web of Science Core Collection, Current Contents Connect (CCC), MEDLINE, KCI-Korean Journal Database, Russian Science Citation Index and SciELO Citation Index, for articles published between 2008 and 2020. A total of 65 articles focusing on people with IDD were selected. The results were grouped into four broad categories : conceptual frameworks used to monitor the CRPD ; instruments used to assess the rights set out in the CRPD ; recommendations on the use of inclusive research ; and indicators or personal outcomes associated with specific rights contained in the CRPD.

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15. Grigg I, Ivashko-Pachima Y, Hait TA, Korenková V, Touloumi O, Lagoudaki R, Van Dijck A, Marusic Z, Anicic M, Vukovic J, Kooy RF, Grigoriadis N, Gozes I. Tauopathy in the young autistic brain : novel biomarker and therapeutic target. Translational psychiatry. 2020 ; 10(1) : 228.

Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer’s disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c.2244Adup/p.His559Glnfs*3 allowed exploration of tauopathy, reflecting on a general unexplored mechanism. The tested subject exhibited autism, fine motor delays, severe intellectual disability and seizures. The patient died after multiple organ failure following liver transplantation. To compare to other ADNP syndrome mutations, immortalized lymphoblastoid cell lines from three different patients (including ADNP p.Arg216*, p.Lys408Valfs*31, and p.Tyr719* heterozygous dominant mutations) and a control were subjected to RNA-seq. Immunohistochemistry, high-throughput gene expression profiles in numerous postmortem tissues followed. Comparisons to a control brain and to extensive datasets were used. Live cell imaging investigated Tau-microtubule interaction, protecting against tauopathy. Extensive child brain tauopathy paralleled by multiple gene expression changes was discovered. Tauopathy was explained by direct mutation effects on Tau-microtubule interaction and correction by the ADNP active snippet NAP. Significant pathway changes (empirical P value < 0.05) included over 100 genes encompassing neuroactive ligand-receptor and cytokine-cytokine receptor interaction, MAPK and calcium signaling, axon guidance and Wnt signaling pathways. Changes were also seen in steroid biosynthesis genes, suggesting sex differences. Selecting the most affected genes by the ADNP mutations for gene expression analysis, in multiple postmortem tissues, identified Tau (MAPT)-gene-related expression changes compared with extensive normal gene expression (RNA-seq) databases. ADNP showed relatively reduced expression in the ADNP syndrome cerebellum, which was also observed for 25 additional genes (representing >50% of the tested genes), including NLGN1, NLGN2, PAX6, SMARCA4, and SNAP25, converging on nervous system development and tauopathy. NAP provided protection against mutated ADNP disrupted Tau-microtubule association. In conclusion, tauopathy may explain brain-imaging findings in ADNP syndrome children and may provide a new direction for the development of tauopathy protecting drug candidates like NAP in ASD/ID.

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16. Hahn LJ, Hamrick LM, Kelleher BL, Roberts JE. Autism Spectrum Disorder-Associated Behaviour in Infants with Down Syndrome. Journal of health science & education. 2020 ; 4(2).

BACKGROUND : Individuals with Down syndrome (DS) are at high risk for autism spectrum disorder (ASD) with 20% of individuals meeting diagnostic criteria for ASD. Despite the high risk, there is no research documenting early signs of ASD in infants with DS or potential prodromal ASD-associated behaviors. AIM : This preliminary case-control study described ASD-associated behaviors in infants with DS contrasted to typically developing (TD) infants. PATIENTS AND METHODS : The Autism Observation Scale for Infants (AOSI) was used to describe ASD-related behaviors in 18 infants with DS (7-18 months) and 18 TD infants (9-14 months). RESULTS : Thirty nine percent (7 out of 18) of infants with DS in our sample were designated "at risk" for ASD on the AOSI with 100% of infants with DS demonstrating at least one feature of ASD. In contrast, only 11% (2 out of 18) of TD infants were designated "at risk" for ASD on the AOSI. Social and communication impairments appear to represent early signs of elevated ASD-associated behavior in infants with DS. CONCLUSIONS : Early signs of ASD-associated behavior appear present and detectable in infants with DS. These early signs mirror findings of other populations at risk for ASD with social communication as the primary behavioral impairment to signal elevated risk for the emergence of ASD. This study contributes to the refinement of the DS behavioral phenotype and identifies important next steps to help improve the identification, diagnosis, and treatment of ASD in DS.

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17. Hashem S, Nisar S, Bhat AA, Yadav SK, Azeem MW, Bagga P, Fakhro K, Reddy R, Frenneaux MP, Haris M. Genetics of structural and functional brain changes in autism spectrum disorder. Translational psychiatry. 2020 ; 10(1) : 229.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social impairment and restricted interactive and communicative behaviors. It may occur as an isolated disorder or in the context of other neurological, psychiatric, developmental, and genetic disorders. Due to rapid developments in genomics and imaging technologies, imaging genetics studies of ASD have evolved in the last few years. Increased risk for ASD diagnosis is found to be related to many specific single-nucleotide polymorphisms, and the study of genetic mechanisms and noninvasive imaging has opened various approaches that can help diagnose ASD at the nascent level. Identifying risk genes related to structural and functional changes in the brain of ASD patients provide a better understanding of the disease’s neuropsychiatry and can help identify targets for therapeutic intervention that could be useful for the clinical management of ASD patients.

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18. Hatch B, Iosif AM, Chuang A, de la Paz L, Ozonoff S, Miller M. Correction to : Longitudinal Differences in Response to Name Among Infants Developing ASD and Risk for ADHD. J Autism Dev Disord. 2020.

The original version of this article unfortunately contained a consistency mistake in Figure 1 legend. The legend for Figure 1 refers to "Non-ADHD/Non-ASD Concerns" instead of "Comparison," which is the wording used in the text/tables, but that these terms are synonymous. The figure 1 with the correct legend is given below.

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19. Kanellis VG. Barriers to sun safety in autism spectrum disorder. Biophysical reviews. 2020.

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20. Kelly E, Meng F, Fujita H, Morgado F, Kazemi Y, Rice LC, Ren C, Escamilla CO, Gibson JM, Sajadi S, Pendry RJ, Tan T, Ellegood J, Albert Basson M, Blakely RD, Dindot SV, Golzio C, Hahn MK, Katsanis N, Robins DM, Silverman JL, Singh KK, Wevrick R, Taylor MJ, Hammill C, Anagnostou E, Pfeiffer BE, Stoodley CJ, Lerch JP, du Lac S, Tsai PT. Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits. Nat Neurosci. 2020.

Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs) ; however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice ; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors ; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.

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21. Leadbitter K, Macdonald W, Taylor C, Buckle KL. Parent perceptions of participation in a parent-mediated communication-focussed intervention with their young child with autism spectrum disorder. Autism. 2020 : 1362361320936394.

Paediatric Autism Communication Therapy is an intervention for young children with autism spectrum disorder that focuses on parent-child communication. In Paediatric Autism Communication Therapy, the therapist and parent watch videos of the parent and child playing together. The therapist coaches the parent to carefully observe the child’s communication and to interact with their child in a more sensitive and responsive way. Parents are encouraged to use the strategies with their child at home. Paediatric Autism Communication Therapy has been shown to lead to long-term improvements in parent-child communication and family quality of life. This study aimed to explore parents’ perceptions of their participation in Paediatric Autism Communication Therapy. Interviews were carried out by an independent researcher with 18 parents. Parents discussed the learning processes they went through when working with Paediatric Autism Communication Therapy therapists and carrying out home practice. Some parents described initial doubts about the approach and hesitations about being videoed and analysing video material. In time, most parents came to really value the therapy and their relationship with the therapist. They reported positive changes in their interaction and relationship with their child and improvements to their child’s communication and interaction. Some also highlighted poignant realisations and emotional challenges associated with taking part in this post-diagnosis therapy. Practical difficulties were also emphasised, including the time commitment, accessibility of therapy venues and difficulties in occupying the child during therapist-parent discussion. Implications for the clinical practice of parent-mediated interventions are discussed.

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22. Ouellette J, Toussay X, Comin CH, Costa LDF, Ho M, Lacalle-Aurioles M, Freitas-Andrade M, Liu QY, Leclerc S, Pan Y, Liu Z, Thibodeau JF, Yin M, Carrier M, Morse CJ, Dyken PV, Bergin CJ, Baillet S, Kennedy CR, Tremblay M, Benoit YD, Stanford WL, Burger D, Stewart DJ, Lacoste B. Vascular contributions to 16p11.2 deletion autism syndrome modeled in mice. Nat Neurosci. 2020.

While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2(df/+) mouse model of 16p11.2 deletion ASD syndrome. We discover that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2(df/+) mice, endothelial dysfunction results in impaired cerebral angiogenesis at postnatal day 14, and in altered neurovascular coupling and cerebrovascular reactivity at postnatal day 50. Moreover, we show that there is defective angiogenesis in primary 16p11.2(df/+) mouse brain endothelial cells and in induced-pluripotent-stem-cell-derived endothelial cells from human carriers of the 16p11.2 deletion. Finally, we find that mice with an endothelium-specific 16p11.2 deletion (16p11.2(ΔEC)) partially recapitulate some of the behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.

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23. Pattison E, Papadopoulos N, Marks D, McGillivray J, Rinehart N. Behavioural Treatments for Sleep Problems in Children with Autism Spectrum Disorder : a Review of the Recent Literature. Curr Psychiatry Rep. 2020 ; 22(9) : 46.

PURPOSE OF REVIEW : Behavioural sleep problems in children with autism spectrum disorder (ASD) are common and burdensome for both the child and their family. We provide an up-to-date review on behavioural sleep interventions and their core features and conclude with expert recommendations regarding the modification of interventions for children with ASD. RECENT FINDINGS : In the past 3 years, four original research studies (n ≥ 10) have evaluated behavioural sleep interventions for children with ASD (one RCT, three pre-post studies). All four studies reported significant improvements across various sleep outcomes and daytime behaviours. The interventions varied, however, in assessment comprehensiveness, nature of implementation support, length and delivery of intervention, outcome measurements, and follow-up periods. Clinically, behavioural sleep interventions are regarded as the first-line of treatment for sleep problems experienced by children with ASD. However, there is still much to be learnt regarding their clinical effectiveness.

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24. Quick VBS, Wang B, State MW. Leveraging large genomic datasets to illuminate the pathobiology of autism spectrum disorders. Neuropsychopharmacology. 2020.

"Big data" approaches in the form of large-scale human genomic studies have led to striking advances in autism spectrum disorder (ASD) genetics. Similar to many other psychiatric syndromes, advances in genotyping technology, allowing for inexpensive genome-wide assays, has confirmed the contribution of polygenic inheritance involving common alleles of small effect, a handful of which have now been definitively identified. However, the past decade of gene discovery in ASD has been most notable for the application, in large family-based cohorts, of high-density microarray studies of submicroscopic chromosomal structure as well as high-throughput DNA sequencing-leading to the identification of an increasingly long list of risk regions and genes disrupted by rare, de novo germline mutations of large effect. This genomic architecture offers particular advantages for the illumination of biological mechanisms but also presents distinctive challenges. While the tremendous locus heterogeneity and functional pleiotropy associated with the more than 100 identified ASD-risk genes and regions is daunting, a growing armamentarium of comprehensive, large, foundational -omics databases, across species and capturing developmental trajectories, are increasingly contributing to a deeper understanding of ASD pathology.

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25. Riglin L, Leppert B, Langley K, Thapar AK, O’Donovan MC, Davey Smith G, Stergiakouli E, Tilling K, Thapar A. Investigating attention-deficit hyperactivity disorder and autism spectrum disorder traits in the general population : What happens in adult life ?. J Child Psychol Psychiatry. 2020.

BACKGROUND : Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are generally considered early-onset disorders so most research has therefore tended to focus on children. Differences between ADHD/ASD in adult life and childhood have been noted, but few population-based studies have examined them in adulthood. Furthermore, the interpretation of findings is hampered by changes in measure and from parent report to self-report. METHOD : We examined continuous/trait measures of parent- and self-rated ADHD and ASD in adulthood (age 25 years) in a UK prospective longitudinal sample ALPSAC (the Avon Longitudinal Study of Parents and Children), using many of the same measures that parents reported on in childhood (N = 6,064). Our aim was to investigate these traits in this population for mean-level sex differences, overlaps with other cognitive, learning and communication problems and their associations with polygenic risk scores (PRS) for neuropsychiatric disorders (ADHD, ASD, schizophrenia, depression and anxiety). RESULTS : ADHD and ASD traits in adulthood, as in childhood, showed associations with childhood cognitive, learning and communication problems and adult communication/language measures, although less so for self-ratings than parent-ratings. Males had higher ADHD and ASD trait levels, but this was not as marked as in childhood. In adulthood, ADHD (both parent- and self-rated) and ASD (parent-rated) symptoms showed associations with ADHD PRS ; self-reported ADHD also showed association with depression PRS, whereas self-reported ASD did not show strong PRS associations. CONCLUSIONS : Our findings suggest that in young adults, ADHD and ASD symptoms have similar characteristics as they do in childhood. Associations with other cognitive, learning and communication problems, and ADHD PRS were somewhat less pronounced for self-reported adult ADHD and ASD symptoms, suggesting that even at age 25, parent reports, where available, could be clinically useful.

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26. Ruffolo G, Cifelli P, Miranda-Lourenço C, De Felice E, Limatola C, Sebastião AM, Diógenes MJ, Aronica E, Palma E. Rare Diseases of Neurodevelopment : Maintain the Mystery or Use a Dazzling Tool for Investigation ? The Case of Rett Syndrome. Neuroscience. 2020 ; 439 : 146-52.

The investigation on neurotransmission function during normal and pathologic development is a pivotal component needed to understand the basic mechanisms underlying neurodevelopmental pathologies. To study these diseases, many animal models have been generated which allowed to face the limited availability of human tissues and, as a consequence, most of the electrophysiology has been performed on these models of diseases. On the other hand, the technique of membrane microtransplantation in Xenopus oocytes allows the study of human functional neurotransmitter receptors thanks to the use of tissues from autopsies or surgeries, even in quantities that would not permit other kinds of functional studies. In this short article, we intend to underline how this technique is well-fit for the study of rare diseases by characterizing the electrophysiological properties of GABA(A) and AMPA receptors in Rett syndrome. For our purposes, we used both tissues from Rett syndrome patients and Mecp2-null mice, a well validated murine model of the same disease, in order to strengthen the solidity of our results through the comparison of the two. Our findings retrace previous results and, in the light of this, further argue in favor of Prof. Miledi’s technique of membrane microtransplantation that proves itself a very useful tool of investigation in the field of neurophysiology. This article is part of a Special Issue entitled : Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.

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27. Salerno-Ferraro AC, Schuller RA. Perspectives from the ASD community on police interactions : Challenges & recommendations. Res Dev Disabil. 2020 ; 105 : 103732.

BACKGROUND : Research shows that a substantial proportion of people with Autism come into contact with the police in their lifetime, and some research suggests that they are largely unsatisfied with their police interactions. METHOD : Thirty-five adults with ASD completed an online questionnaire regarding the challenges police may face when interacting with Autistic people, as well as provided recommendations as to how those interactions could be improved. RESULTS : Respondents reported a variety of different potential challenges that could present in an interaction between the police and people with ASD. For example, respondents felt that typical Autistic behaviours, such as stimming or communication difficulties, could be misinterpreted by police officers and lead to adverse outcomes. Respondents discussed several recommendations aimed at improving police interactions with Autistic people, including involving Autisitc people in the training of police officers. CONCLUSIONS : The information collected in this study provides insights into how interactions between the police and people with ASD can be improved. These findings can be used in the development of police training programs or integrated into pre-existing training programs on Autism, contributing the invaluable perspective of the Autism community.

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28. Schott W, Nonnemacher S, Shea L. Service Use and Unmet Needs Among Adults with Autism Awaiting Home- and Community-Based Medicaid Services. J Autism Dev Disord. 2020.

Autistic adults in need of long-term services and supports spend months on waiting lists before receiving such services through Medicaid. Data from a state-wide survey of adults and their caregivers on a waiting list for autism waivers suggest that the majority have unmet needs for functional skills services (63.6%), employment or vocation services (62.1%), and mental and behavioral health services (52.8%). Almost a third require case management services (28.3%). Predictors of greater service need are African American race and the number of physical and behavioral health diagnoses. Predictors of greater service receipt were employment status, housing type, and school enrollment ; there was lower service receipt for African American race, Hispanic ethnicity, over age 21 years, and college completion.

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29. Shalev I, Uzefovsky F. Empathic disequilibrium in two different measures of empathy predicts autism traits in neurotypical population. Mol Autism. 2020 ; 11(1) : 59.

BACKGROUND : Features of autism spectrum conditions (ASC) are normally distributed within the population, giving rise to the notion of the autism spectrum. One of the hallmark features of ASC is difficulties in social communication, which relies heavily on our ability to empathize with others. Empathy comprises of both cognitive (CE) and emotional (EE) components that, together, allow us to understand another’s emotions and be affected by them appropriately, while maintaining a self-other distinction. Although CE and EE depend on distinct neural and developmental trajectories, it was suggested that the two empathic capacities can influence, balance, and regulate each other. Previous findings regarding the role of emotional and cognitive empathy in ASC have been mixed. Therefore, our study aimed to investigate whether the intra-personal empathy imbalance between the cognitive and emotional components, a measure we termed empathic disequilibrium (ED), can be associated with autism traits at the neurotypical range. METHODS : Participants were 671 young-adults at the neurotypical range who self-reported their empathy, assessed using two highly validated questionnaires-the Interpersonal Reactivity Index and the Empathy Quotient, autism traits using the Autism-Spectrum Quotient, and the related traits, alexithymia, and systemizing. RESULTS : Controlling for the total empathy score, greater ED was found to be positively correlated with autism traits. Specifically, autism traits were found to be elevated in groups of individuals with relatively higher EE than CE, underscoring their imbalance. CONCLUSIONS : Our study offers a novel perspective on the understanding of the social difficulties associated with autism tendencies in the general population and has potentially important clinical implications for understanding of ASC. We also propose a novel characterization of autism tendencies based on the imbalance between EE and CE, which we term ED, as opposed to examining EE and CE separately.

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30. Sinai-Gavrilov Y, Gev T, Mor-Snir I, Vivanti G, Golan O. Integrating the Early Start Denver Model into Israeli community autism spectrum disorder preschools : Effectiveness and treatment response predictors. Autism. 2020 : 1362361320934221.

Early intensive intervention has been shown to significantly affect the development of children with Autism. However, the costly implementation of such interventions limits their wide dissemination in the community. This study examined an integration of a research-supported early intensive intervention model called the Early Start Denver Model into community preschool programs for children with Autism in Israel. Four community preschools implemented the preschool-based Early Start Denver Model and four implemented the existing multidisciplinary developmental intervention which is widely applied in Israeli community preschools for children with autism. Fifty-one children (aged 33-57 months) participated in the study. Twenty-six attended the preschool-based Early Start Denver Model preschools and twenty-five attended the multidisciplinary developmental intervention preschools. Before the intervention began, groups were comparable on children’s age and developmental functioning and on families’ socio-economic status. Results showed that, compared to the multidisciplinary developmental intervention group, children in the preschool-based Early Start Denver Model treatment group made greater gains on measures of overall cognitive development, language skills, as well as on parent- and teacher-reported adaptive communication and socialization abilities. Children who had lower autism symptom severity, higher adaptive functioning and better language understanding abilities before taking part in the preschool-based Early Start Denver Model program showed greater improvements following it. This study documents the successful implementation of an intensive early intervention program in pre-existing community preschools, underlining the importance of the integration of research-supported intervention programs into community settings.

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31. Sledziowska M, Kalbassi S, Baudouin SJ. Complex interactions between genes and social environment cause phenotypes associated with Autism Spectrum Disorders in mice. eNeuro. 2020.

The aetiology of Autism Spectrum Disorders (ASD) is a complex combination of genetic and environmental factors. Neuroligin3, a synaptic adhesion protein, and Cytoplasmic FMR1 interacting protein 1 (CYFIP1), a regulator of protein translation and actin polymerisation, are two proteins associated with ASD, that interact in neurons, in vivo Here, we investigated the role of the Neuroligin3/CYFIP1 pathway in behavioural functioning and synapse formation in mice and found that it contributes to motor learning and synapse formation in males. Similar investigation in female mice revealed an absence of such phenotypes, suggesting that females are protected against mutations affecting this pathway. Previously, we showed that the social environment influences the behaviour of male mice. We extended this finding and found that the transcriptome of wild type mice housed with their mutant littermates, lacking Neuroligin3, differed from the transcriptome of wild type mice housed together. Altogether, these results identify the role of the Neuroligin3/CYFIP1 pathway in male mouse behaviour and highlight its sensitivity to social environment.Significance statement The causes of Autism Spectrum Disorders remain elusive. In this study, we investigate the combined effect of mutations in two genes associated with ASD : Nlgn3 and Cyfip1, and the effect of the social environment, on phenotypes relevant for ASD. We show that when both mutations are present the behaviour can be restored, emphasising the importance of considering gene interactions. We also show sex differences in behaviour, suggesting that female subjects should be included in the studies of ASD. We show that wild type animals can exhibit phenotypes associated with ASD as a result of being housed with their mutant littermates, highlighting the necessity to re-evaluate the use of wild type animals as controls to define phenotypic traits of mouse models.

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32. Tang JSY, Falkmer M, Chen NTM, Bӧlte S, Girdler S. Development and Feasibility of MindChip™ : A Social Emotional Telehealth Intervention for Autistic Adults. J Autism Dev Disord. 2020.

The study aims to develop and pilot a telehealth social emotional program, MindChip™ delivered with a computer based interventions (CBI) (Mind Reading(©)) for autistic adults. MindChip™ combined four theoretical perspectives and community feedback underpinning the essential mechanisms for targeting the social emotional understanding of autistic adults. A randomised pragmatic pilot trial (N = 25) was conducted to explore the feasibility of MindChip™ (n = 11) and to understand the preliminary efficacy of combining it with CBI compared to CBI only (n = 14). The use of MindChip™ and CBI combined demonstrated partial feasibility, with preliminary efficacy findings revealing increased emotion recognition generalisation outcomes compared to CBI only. Further research is required to improve the engagement and personalisation of the intervention for autistic adults.

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33. Virolainen S, Hussien W, Dalibalta S. Autism spectrum disorder in the United Arab Emirates : potential environmental links. Reviews on environmental health. 2020.

Autism spectrum disorder (ASD) has been experiencing an increase in global prevalence in recent decades. While many factors could account for this reality, certain environmental links have been shown to contribute to ASD development and etiology. The Middle East has had relatively little published research on ASD etiology although statistics indicate that ASD affects 1 in 146 births in the United Arab Emirates (UAE). This review therefore aims to examine potential causes of ASD within the UAE specifically, focusing on environmental links that may contribute to the rise in ASD cases in this population. Significantly, suboptimal breastfeeding practices, high levels of vitamin D deficiency, increased exposure to pollution, pesticides and heavy metals within the UAE may all be potentially important contributing factors to ASD in this population. Our findings support the notion that there are key links between various environmental factors and ASD prevalence in the UAE. The lack of knowledge and much research on ASD within the UAE deeply necessitates further studies on its etiology as it poses a serious public health challenge in the region and globally.

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34. Wu ZY, Huang SD, Zou JJ, Wang QX, Naveed M, Bao HN, Wang W, Fukunaga K, Han F. Autism spectrum disorder (ASD) : Disturbance of the melatonin system and its implications. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020 ; 130 : 110496.

The molecular mechanisms underlying autism spectrum disorder (ASD) remain elusive, which limits the management options available in the clinic. Accumulating evidence indicates that the pineal gland/melatonin system is associated with the progression of ASD. Here, we review recent advances in our understanding of various mechanisms involving pathological process of ASD, including the abnormal breakdown of melatonin synthesis, the disturbance of intracellular MTNR1A signaling, the effects exerted by melatonin on hippocampal protein serine/threonine kinases, and immune dysregulation/inflammation during ASD. We believe that an in-depth understanding of the interplay between the action of the melatonin system and the onset of autism could promote the development of novel therapeutic strategies against ASD. We anticipate that targeting the neurotransmitters upstream pathway and downstream of melatonin in brain will lead to potential therapeutic treatment for ASD.

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35. Yates L, Hobson H. Continuing to look in the mirror : A review of neuroscientific evidence for the broken mirror hypothesis, EP-M model and STORM model of autism spectrum conditions. Autism. 2020 : 1362361320936945.

The mirror neuron system has been argued to be a key brain system responsible for understanding the actions of others and for imitation. It has therefore been proposed that problems within this system could explain the social difficulties experienced by people with autism spectrum condition. This idea is referred to as the broken mirror hypothesis. However, research has produced insufficient evidence to support the broken mirror hypothesis in its original form. Therefore, two other models have been suggested : EP-M model and the social top-down response modulation (STORM) model. All models suggest something is different regarding the mirror neuron system in autism spectrum condition : either within the mirror neuron system itself or within the systems that control the activity of the mirror neuron system. This literature review compares these three models in regard to recent neuroscientific investigations. This review concludes that there is insufficient support for both the broken mirror hypothesis, but converging evidence supports an integrated EP-M and STORM model.

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36. Yeung MK, Chan AS. Executive function, motivation, and emotion recognition in high-functioning autism spectrum disorder. Res Dev Disabil. 2020 ; 105 : 103730.

BACKGROUND : Several neurocognitive theories have been put forward to explain autism spectrum disorder (ASD). However, the specificity of executive cognitive, motivational (i.e., reward-related), and emotion-recognition impairments in ASD, and the role of early language delay in these impairments remain largely unclear. AIM : This study aimed to examine executive cognitive, motivational, and emotion-recognition functions while considering the potential effect of language delay in ASD. METHODS : Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18 years were recruited. Each completed seven computerized tasks measuring executive cognitive (i.e., set-shifting, inhibition, updating, and access/generativity), motivational (i.e., flexible reinforcement learning and affective decision-making), and emotion-recognition functions (i.e., facial emotion recognition). RESULTS : We found that ASD participants with early language delay (n = 10) had poorer executive cognitive, motivational, and emotion-recognition functioning than TD controls, and had poorer executive cognitive and motivational functioning than ASD participants without language delay (n = 12). ASD participants without language delay only had poorer emotion recognition than TD controls. CONCLUSION AND IMPLICATIONS : These preliminary findings suggest impairments in executive cognitive and motivational functions as well as emotion recognition in ASD with language delay, and impairment only in emotion recognition in ASD without language delay. They implicate a potential partial distinction in mental abilities between ASD with and without early language delay, highlighting the importance of considering language delay when evaluating executive cognitive and motivational functions in ASD.

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37. Zampella CJ, Bennetto L, Herrington JD. Computer Vision Analysis of Reduced Interpersonal Affect Coordination in Youth With Autism Spectrum Disorder. Autism Res. 2020.

Atypical social-emotional reciprocity is a core feature of autism spectrum disorder (ASD) but can be difficult to operationalize. One measurable manifestation of reciprocity may be interpersonal coordination, the tendency to align the form and timing of one’s behaviors (including facial affect) with others. Interpersonal affect coordination facilitates sharing and understanding of emotional cues, and there is evidence that it is reduced in ASD. However, most research has not measured this process in true social contexts, due in part to a lack of tools for measuring dynamic facial expressions over the course of an interaction. Automated facial analysis via computer vision provides an efficient, granular, objective method for measuring naturally occurring facial affect and coordination. Youth with ASD and matched typically developing youth participated in cooperative conversations with their mothers and unfamiliar adults. Time-synchronized videos were analyzed with an open-source computer vision toolkit for automated facial analysis, for the presence and intensity of facial movements associated with positive affect. Both youth and adult conversation partners exhibited less positive affect during conversations when the youth partner had ASD. Youth with ASD also engaged in less affect coordination over the course of conversations. When considered dimensionally across youth with and without ASD, affect coordination significantly predicted scores on rating scales of autism-related social atypicality, adaptive social skills, and empathy. Findings suggest that affect coordination is an important interpersonal process with implications for broader social-emotional functioning. This preliminary study introduces a promising novel method for quantifying moment-to-moment facial expression and emotional reciprocity during natural interactions. LAY SUMMARY : This study introduces a novel, automated method for measuring social-emotional reciprocity during natural conversations, which may improve assessment of this core autism diagnostic behavior. We used computerized methods to measure facial affect and the degree of affect coordination between conversation partners. Youth with autism displayed reduced affect coordination, and reduced affect coordination predicted lower scores on measures of broader social-emotional skills.

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