Pubmed du 17/09/20

jeudi 17 septembre 2020

1. Byiers BJ, Payen A, Feyma T, Panoskaltsis-Mortari A, Ehrhardt MJ, Symons FJ. Associations Among Diurnal Salivary Cortisol Patterns, Medication Use, and Behavioral Phenotype Features in a Community Sample of Rett Syndrome. Am J Intellect Dev Disabil ;2020 (Sep 1) ;125(5):353-368.

Rett syndrome (RTT) is a severe neurodevelopmental disorder resulting from mutations of the MECP2 gene. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal stress responses have been observed in animal models of RTT, but little is known about HPA axis function among individuals with RTT. Diurnal salivary cortisol patterns from 30 females with RTT were examined in relation to mutation type, medication use, and features of the RTT behavioral phenotype. Cortisol patterns were significantly related to mutation severity, anticonvulsant medication status, and bruxism (tooth grinding). This study provides preliminary support for the hypothesis that RTT may be at risk for outcomes associated with aberrant HPA axis function, and that this risk may be mediated by mutation type.

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2. Cascio MA, Weiss JA, Racine E. Person-Oriented Research Ethics to Address the Needs of Participants on the Autism Spectrum. Ethics Hum Res ;2020 (Sep) ;42(5):2-16.

Research ethics scholarship often attends to vulnerability. People with autism may be vulnerable in research, but are also vulnerable to unjust exclusion from participation. Addressing the needs of participants with autism can facilitate inclusion and honor the bioethics principle of respect for persons while accounting for risk and vulnerability. Drawing from a review of the literature and informed by a moral deliberation process involving a task force of stakeholders (including autistic people and parents of autistic people), we use the model of person-oriented research ethics to identify several practical strategies researchers can use to address these needs and foster inclusion. Strategies include using multiple means of communication, addressing the sensory environment, preparing participants in advance, and accounting for social context. These practical strategies are not just methodological or design choices ; they are inherently related to ethical issues. Method and design choices fulfill ethical aspirations by facilitating inclusion, reducing discomfort, and focusing on individuals.

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3. Cibrian FL, Madrigal M, Avelais M, Tentori M. Supporting coordination of children with ASD using neurological music therapy : A pilot randomized control trial comparing an elastic touch-display with tambourines. Res Dev Disabil ;2020 (Sep 17) ;106:103741.

AIM : To evaluate the efficacy of Neurologic Music Therapy (NMT) using a traditional and a technological intervention (elastic touch-display) in improving the coordination of children with Autism Spectrum Disorder (ASD), as a primary outcome, and the timing and strength control of their movements as secondary outcomes. METHODS : Twenty-two children with ASD completed 8 NMT sessions, as a part of a 2-month intervention. Participants were randomly assigned to either use an elastic touch-display (experimental group) or tambourines (control group). We conducted pre- and post- assessment evaluations, including the Developmental Coordination Disorder Questionnaire (DCDQ) and motor assessments related to the control of strength and timing of movements. OUTCOMES AND RESULTS : All participants improved their coordination, according to the DCDQ scores, and exhibited better control of their movements according to the strength and timing assessments after the intervention. Participants who used the elastic touch-display scored higher on the DCDQ. CONCLUSIONS AND IMPLICATIONS : NMT is an efficacious treatment to improve the coordination skills of children with ASD. Elastic touch-displays provide more benefits than the use of tambourines.

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4. Deb S, Nancarrow T, Limbu B, Sheehan R, Wilcock M, Branford D, Courtenay K, Perera B, Shankar R. UK psychiatrists’ experience of withdrawal of antipsychotics prescribed for challenging behaviours in adults with intellectual disabilities and/or autism. BJPsych Open ;2020 (Sep 17) ;6(5):e112.

BACKGROUND : A high proportion of adults with intellectual disabilities are prescribed off-licence antipsychotics in the absence of a psychiatric illness. The National Health Service in England launched an initiative in 2016, ’Stopping over-medication of people with a learning disability [intellectual disability], autism or both’ (STOMP), to address this major public health concern. AIMS : To gain understanding from UK psychiatrists working with adults with intellectual disabilities on the successes and challenges of withdrawing antipsychotics for challenging behaviours. METHOD : An online questionnaire was sent to all UK psychiatrists working in the field of intellectual disability (estimated 225). RESULTS : Half of the 88 respondents stated that they started withdrawing antipsychotics over 5 years ago and 52.3% stated that they are less likely to initiate an antipsychotic since the launch of STOMP. However, since then, 46.6% are prescribing other classes of psychotropic medication instead of antipsychotics for challenging behaviours, most frequently the antidepressants. Complete antipsychotic discontinuation in over 50% of patients treated with antipsychotics was achieved by only 4.5% of respondents (n = 4) ; 11.4% reported deterioration in challenging behaviours in over 50% of patients on withdrawal and the same proportion (11.4%) reported no deterioration. Only 32% of respondents made the diagnosis of psychiatric illness in all their patients themselves. Family and paid carers’ concern, lack of multi-agency and multidisciplinary input and unavailability of non-medical psychosocial intervention are key reported factors hampering the withdrawal attempt. CONCLUSIONS : There is an urgent need to develop national guidelines to provide a framework for systematic psychotropic drug reviews and withdrawal where possible.

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5. Diener ML, Wright CA, Taylor C, D’Astous V, Lasrich L. Dual perspectives in autism spectrum disorders and employment : Toward a better fit in the workplace. Work ;2020 (Sep 17)

BACKGROUND : Compared with people with other disabilities, individuals with autism spectrum disorder (ASD) have the lowest rates of employment and switch jobs at a higher frequency. Thus, understanding how to support workplace success for people with ASD is important. OBJECTIVE : Grounded in an ecological conceptual model, this study explores the dual employment perspectives of adults with ASD and supervisors who worked with individuals with ASD. METHODS : Using participatory research methods, a purposive sample of ten adults with ASD (all verbal with high school diplomas) and ten supervisors participated in semi-structured interviews on employment experiences. Qualitative analyses were used to identify themes. RESULTS : Four major themes emerged from an ecological framework to create a strong person-environment fit in the workplace : 1) building on interest/experiences/strengths/skills, 2) reducing social demands, 3) clear communication and expectations, and 4) ASD awareness for work environment. Comparisons between the two groups of participants showed substantive differences in expectations and accommodations. CONCLUSIONS : Supervisors, although eager to employ individuals with ASD, could benefit by employing an ecological model to successful employment. Results indicate that multiple lenses on the process of employment for those with ASD can lead to better outcomes in the workplace.

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6. Georgiou G, Fanti KA. Physiological reactivity in children with high callous-unemotional and autistic traits : investigating unique and interactive effects. Eur Child Adolesc Psychiatry ;2020 (Sep 17)

Empathy deficits are a hallmark sign of both callous-unemotional (CU) and autistic traits. Despite these similarities, prior work did not investigate how these traits relate to physiological reactivity (heart rate and skin conductance) in response to emotional or empathy-eliciting stimuli. Understanding the physiological mechanisms associated with emotional processing deficits among individuals with autistic or CU traits is a critical step for improving both assessment and interventions. The current study was designed to investigate the unique and interactive contributions of CU and autistic traits in predicting physiological reactivity. Heart rate (HR) and skin conductance (SC) activity in response to sad, fearful and happy emotional videos were collected form young children. Participants for the current study (n = 163 ; M(age) = 7.30, SD= 1.42 ; 44.2% girls) were recruited from a larger community sample of 1652 children and were selected based on their levels of empathy. Regression analysis revealed that boys, but not girls, with high levels of CU traits exhibited low SC reactivity during sad and fearful stimuli. No significant associations were revealed for autistic traits. Finally, an interesting interaction effect suggested that CU traits were associated with stronger HR reactivity to fear stimuli only when autistic traits were low. The identified differences in physiological reactivity can inform etiological hypothesis by providing evidence for the underlying physiological mechanisms related to emotional processing among children high in CU traits but not in autistic traits.

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7. 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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8. Hus Y, Segal O. Functional Communication Profiles of Children and Youth with Autism : A Roadmap to Therapeutic and Educational Interventions. Folia Phoniatr Logop ;2020 (Sep 16):1-17.

BACKGROUND : Autism spectrum disorder (ASD) entails varied developmental pathways along the entire lifespan, demanding early and ongoing diverse and responsive interventions to children’s needs. This study examined in situ education and development attained by children and youth with ASD in a school with a therapeutic and educational curriculum. OBJECTIVES : (1) Construct individual communication profiles in educational and developmental aspects. (2) Examine for associations between variables. (3) Demonstrate the clinical and educational utility of including cognitive-linguistic integrative variables. (4) Showcase how the profiles guide interventions tailored to students’ individual needs. METHODS : Functional communication profiles (FCPs) of 21 students, aged 5.0-16.8 years, mostly from bilingual middle-high socioeconomic status families, were constructed with input from their educational and therapeutic staff. Students’ performance was examined with an array of instruments and tasks, including person and clock drawings, false belief, and bouba-kiki metaphor screens. Qualitative and quantitative analyses were performed to uncover associations, weaknesses, and strengths. RESULTS : The profiles revealed associations between cognitive, linguistic, social, and educational abilities, indicating that some abilities from different domains tend to co-occur. CONCLUSIONS : Including cognitive linguistic integrative variables was a novelty that revealed additional aspects of the children’s abilities. Staff feedback confirmed the utility of FCPs in providing "a roadmap" to needed individual and common curriculum adjustments.

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9. Ishizuka K, Yoshida T, Kawabata T, Imai A, Mori H, Kimura H, Inada T, Okahisa Y, Egawa J, Usami M, Kushima I, Morikawa M, Okada T, Ikeda M, Branko A, Mori D, Someya T, Iwata N, Ozaki N. Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia. J Neurodev Disord ;2020 (Sep 17) ;12(1):25.

BACKGROUND : Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders ; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS : To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS : Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS : The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.

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10. Jeste S, Hyde C, Distefano C, Halladay A, Ray S, Porath M, Wilson RB, Thurm A. Changes in access to educational and healthcare services for individuals with intellectual and developmental disabilities during COVID-19 restrictions. J Intellect Disabil Res ;2020 (Sep 17)

BACKGROUND : COVID-19 restrictions have significantly limited access to in-person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals. METHODS : This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation. RESULTS : Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy-four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele-education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele-education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home. CONCLUSIONS : COVID-19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.

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11. 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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12. Jouravlev O, Kell AJE, Mineroff Z, Haskins AJ, Ayyash D, Kanwisher N, Fedorenko E. Reduced Language Lateralization in Autism and the Broader Autism Phenotype as Assessed with Robust Individual-Subjects Analyses. Autism Res ;2020 (Sep 15)

One of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls is reduced language lateralization. However, most prior reports relied on comparisons of group-level activation maps or functional markers that had not been validated at the individual-subject level, and/or used tasks that do not isolate language processing from other cognitive processes, complicating interpretation. Furthermore, few prior studies have examined functional responses in other brain networks, as needed to determine the spatial selectivity of the effect. Using functional magnetic resonance imaging (fMRI), we compared language lateralization between 28 adult ASD participants and carefully pairwise-matched controls, with the language regions defined individually using a well-validated language "localizer" task. Across two language comprehension paradigms, ASD participants showed less lateralized responses due to stronger right hemisphere activity. Furthermore, this effect did not stem from a ubiquitous reduction in lateralization of function across the brain : ASD participants did not differ from controls in the lateralization of two other large-scale networks-the Theory of Mind network and the Multiple Demand network. Finally, in an exploratory study, we tested whether reduced language lateralization may also be present in NT individuals with high autism-like traits. Indeed, autistic trait load in a large set of NT participants (n = 189) was associated with less lateralized language responses. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population, and this lateralization reduction appears to be restricted to the language system. LAY SUMMARY : How do brains of individuals with autism spectrum disorders (ASD) differ from those of neurotypical (NT) controls ? One of the most consistently reported differences is the reduction of lateralization during language processing in individuals with ASD. However, most prior studies have used methods that made this finding difficult to interpret, and perhaps even artifactual. Using robust individual-level markers of lateralization, we found that indeed, ASD individuals show reduced lateralization for language due to stronger right-hemisphere activity. We further show that this reduction is not due to a general reduction of lateralization of function across the brain. Finally, we show that greater autistic trait load is associated with less lateralized language responses in the NT population. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population.

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13. Kang E, Lerner MD, Gadow KD. Atypical communication characteristics among clinic-referred youth with and without autism spectrum disorder : Stability and associations with clinical correlates. Dev Psychopathol ;2020 (Sep 17):1-14.

Atypical communication characteristics (ACCs), such as speech delay, odd pitch, and pragmatic difficulties, are common features of autism spectrum disorder (ASD) as are the symptoms of a wide range of psychiatric disorders. Using a simple retrospective method, this study aimed to better understand the relation and stability of ACCs with a broad range of psychiatric symptoms among large, well-characterized samples of clinic-referred children and adolescents with and without ASD. Youth with ASD had higher rates and a more variable pattern of developmental change in ACCs than the non-ASD diagnostic group. Latent class analysis yielded three ACC stability subgroups within ASD : Stable ACCs, Mostly Current-Only ACCs, and Little Professors. Subgroups exhibited differences in severity of ASD symptomatology, co-occurring psychiatric symptoms, and other correlates. Our findings provide support for the clinical utility of characterizing caregiver-perceived changes in ACCs in identifying children at risk for co-occurring psychopathology and other clinically relevant variables.

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14. Katsuki R, Tateno M, Kubo H, Kurahara K, Hayakawa K, Kuwano N, Kanba S, Kato TA. Autism Spectrum Conditions in Hikikomori : A Pilot Case-Control Study. Psychiatry Clin Neurosci ;2020 (Sep 17)

AIM : Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of hikikomori are associated with ASD including undiagnosed autism spectrum conditions (ASC) in clinical settings. METHODS : 416 clinical patients were recruited through the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. 103 hikikomori cases and 221 clinical controls without hikikomori conditions were extracted using a semi-structured interview, and completed a series of self-rated scales including Autism-Spectrum Quotient (AQ-J). RESULTS : Compared to non-hikikomori controls, hikikomori cases were likely to have higher autistic tendency based on AQ-J. The cases showed more severe subjective depressive symptoms based on self-rated BDI-II, whereas no significant difference was found on interview-based severity evaluation using HAMD. Comparison within hikikomori cases based on the cut-off score of AQ-J revealed that hikikomori cases with high ASC were significantly more likely to have higher traits of modern-type depression (MTD), smaller social networks and less social support. CONCLUSION : The present data has suggested hikikomori sufferers are more likely to have autistic tendency, and hikikomori sufferers with high ASC may have much more difficulty in social communication and social interaction. In addition, those with high ASC may also have lower self-esteem and higher complaint tendencies as aspects of MTD traits, which may relate to the occurrence of hikikomori. Thus, evaluating autistic tendencies is important for appropriate interventions in hikikomori. Further investigations should be conducted to validate our pilot findings using structured diagnostic systems of ASD. This article is protected by copyright. All rights reserved.

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15. Klin A, Micheletti M, Klaiman C, Shultz S, Constantino JN, Jones W. Affording autism an early brain development re-definition. Dev Psychopathol ;2020 (Sep 17):1-15.

The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD in early brain development terms, with a view to revisit the world of opportunities afforded by current science to optimize children’s outcomes despite the risks that they are born with. This view is presented here to counter outdated notions that potentially devastating disability is determined the moment a child is born, and that these burdens are inevitable, with opportunities for improvement being constrained to only alleviation of symptoms or limited improvements in adaptive skills. The impetus for this piece is the concern that such views of complex neurodevelopmental conditions, such as ASD, can become self-fulfilling science and policy, in ways that are diametrically opposed to what we currently know, and are learning every day, of how genetic risk becomes, or not, instantiated as lifetime disabilities.

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16. Lee CE, Kim KM. Future planning for individuals with intellectual and developmental disabilities : Perspectives of siblings in South Korea. J Appl Res Intellect Disabil ;2020 (Sep 17)

BACKGROUND : Future planning has emerged as a global issue for families of individuals with intellectual and developmental disabilities due to the longer lives and limited long-term services and supports in the adult disability system. While it has received greater attention, most future planning studies only included parents of individuals with intellectual and developmental disabilities within the context of European or American countries. The purpose of this study was to examine future planning among siblings of individuals with intellectual and developmental disabilities in South Korea. METHOD : In this study, 185 Korean siblings of individuals with intellectual and developmental disabilities responded to a survey. RESULTS : Few siblings engaged in future planning activities and reported a range of barriers to conduct future planning. Further, greater future planning involvement was associated with older siblings, greater advocacy level and greater sibling caregiving. CONCLUSION : For future research, culturally relevant measures and intervention should be addressed.

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17. Lindly O, Crossman M, Eaves M, Philpotts L, Kuhlthau K. Health Literacy and Health Outcomes Among Children With Developmental Disabilities : A Systematic Review. Am J Intellect Dev Disabil ;2020 (Sep 1) ;125(5):389-407.

Developmental disabilities (DDs) are prevalent and associated with health disparities among children. Family health literacy of parents and/or children is one modifiable factor associated with child health ; however, little is known about family health literacy for children with DDs. This systematic review was conducted to determine evidence on associations of health literacy with health outcomes among children with DDs. Medline, CINAHL, Embase, ERIC, PsycInfo, and Web of Science were searched through August 2018. Of 2,768 unique records, 53 full text articles were reviewed and four articles were included. Associations of family health literacy with health outcomes among children with DDs were mixed. Future research should include more diverse samples, greater breadth in health outcomes assessed, and increased methodological rigor.

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18. Linke AC, Mash LE, Fong CH, Kinnear MK, Kohli JS, Wilkinson M, Tung R, Jao Keehn RJ, Carper RA, Fishman I, Müller RA. Dynamic time warping outperforms Pearson correlation in detecting atypical functional connectivity in autism spectrum disorders. Neuroimage ;2020 (Sep 17) ;223:117383.

Resting state fMRI (rsfMRI) is frequently used to study brain function, including in clinical populations. Similarity of blood-oxygen-level-dependent (BOLD) fluctuations during rsfMRI between brain regions is thought to reflect intrinsic functional connectivity (FC), potentially due to history of coactivation. To quantify similarity, studies have almost exclusively relied on Pearson correlation, which assumes linearity and can therefore underestimate FC if the hemodynamic response function differs regionally or there is BOLD signal lag between timeseries. Here we show in three cohorts of children, adolescents and adults, with and without autism spectrum disorders (ASDs), that measuring the similarity of BOLD signal fluctuations using non-linear dynamic time warping (DTW) is more robust to global signal regression (GSR), has higher test-retest reliability and is more sensitive to task-related changes in FC. Additionally, when comparing FC between individuals with ASDs and typical controls, more group differences are detected using DTW. DTW estimates are also more related to ASD symptom severity and executive function, while Pearson correlation estimates of FC are more strongly associated with respiration during rsfMRI. Together these findings suggest that non-linear methods such as DTW improve estimation of resting state FC, particularly when studying clinical populations whose hemodynamics or neurovascular coupling may be altered compared to typical controls.

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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. Miller M, Austin S, Iosif AM, de la Paz L, Chuang A, Hatch B, Ozonoff S. Shared and distinct developmental pathways to ASD and ADHD phenotypes among infants at familial risk. Dev Psychopathol ;2020 (Sep 16):1-12.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are believed to share partially overlapping causal mechanisms suggesting that early risk markers may also overlap. Using latent profile analysis (LPA) in a sample of infants enriched for ASD and ADHD, we first examined the number of distinct groups of 3-year-old children, based on ADHD and ASD symptomatology. To investigate early predictors of ASD and ADHD symptom profiles, we next examined differences in trajectories of infant behaviors among the LPA classes spanning general development, negative affect, attention, activity level, impulsivity, and social behavior. Participants included 166 infants at familial risk for ASD (n = 89), ADHD (n = 38), or low-risk for both (n = 39) evaluated at 12, 18, 24, and 36 months of age. A three-class solution was selected reflecting a Typically Developing (TD) class (low symptoms ; n = 108), an ADHD class (high ADHD/low ASD symptoms ; n = 39), and an ASD class (high ASD/ADHD symptoms ; n = 19). Trajectories of infant behaviors were generally suggestive of a gradient pattern of differences, with the greatest impairment within the ASD class followed by the ADHD class. These findings indicate a mixture of overlapping and distinct early markers of preschool ASD- and ADHD-like profiles that can be difficult to disentangle early in life.

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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. Panesar HK, Kennedy CL, Keil Stietz KP, Lein PJ. Polychlorinated Biphenyls (PCBs) : Risk Factors for Autism Spectrum Disorder ?. Toxics ;2020 (Sep 17) ;8(3)

Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1-2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals.

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23. Quebles I, Solomon O, Smith KA, Rao SR, Lu F, Azen C, Anaya G, Yin L. Racial and Ethnic Differences in Behavioral Problems and Medication Use Among Children With Autism Spectrum Disorders. Am J Intellect Dev Disabil ;2020 (Sep 1) ;125(5):369-388.

We examined racial and ethnic differences in the prevalence of behavioral problems measured by the Child Behavioral Checklist (CBCL), sleep disturbances measured by the Child Sleep Habits Questionnaire (CSHQ), and medication use among children with Autism Spectrum Disorders (ASD). We analyzed data from the Autism Treatment Network (ATN) dataset for 2,576 children ages 6 to 18 years of age diagnosed with ASD. Multivariable logistic regression accounting for age, gender, Diagnostic and Statistical Manual of Mental Disorders (4th Edition - Text Revision), diagnosis (Autistic Disorder, PDD-NOS, Asperger’s Disorder), and parents’ education did not show any racial or ethnic differences in behavioral challenges, conduct problems, or sleep disturbances for any of the groups, but Black children had lower odds of Total Problem Behaviors and Asian children had lower odds of Hyperactivity compared to White children. As a group, children from racial and ethnic minorities had lower odds of Total Problem Behaviors and Conduct Problems compared to White children. Hispanic children had lower odds of medication use for Behavioral Challenges, Total Problem Behaviors, Hyperactivity, and Conduct Problems. Asian children had lower odds of medication use for Behavioral Challenges, Total Problem Behaviors, and Hyperactivity ; and had close to lower odds in medication use for Conduct Problems. Black children had lower odds for medication use for Total Problem Behaviors only. As a group, children from racial and ethnic minorities had lower odds for medication use for Behavioral Challenges, Total Problem Behaviors, Hyperactivity, and Conduct problems, but not for Sleep Disturbances. While these results are consistent with previous studies showing that White children are significantly more likely to receive psychotropic medication compared to children from racial and ethnic minority groups, we found no such differences for sleep challenges, suggesting that they are more consistently identified and equitably treated than other behavioral problems associated with ASD. We draw upon Andersen’s (1995) Behavioral Model of Healthcare Use to suggest predisposing, enabling, and needs factors that may contribute to this pattern of racial and ethnic differences in the use of medications among children ASD.

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24. Root JR, Cox SK, Gilley D, Wade T. Using a Virtual-Representational-Abstract Integrated Framework to Teach Multiplicative Problem Solving to Middle School Students with Developmental Disabilities. J Autism Dev Disord ;2020 (Sep 16)

Effective instructional strategies to improve mathematical problem solving skills are critically important to student success in both school-based and real-world mathematics tasks. This study reports effects of a Virtual-Representational-Abstract Integrated framework on the mathematical problem solving skills of three middle school students with developmental disabilities (autism spectrum disorder and intellectual disability). All participants improved in their problem solving accuracy when solving multiplicative comparison word problems using realistic double and triple multipliers. Additionally, all participants maintained their mathematical problem solving accuracy after visual supports (graphic organizer) were removed. Detailed findings and implications for future research and practitioners are discussed.

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25. Russell I, Pearson B, Masic U. A Longitudinal Study of Features Associated with Autism Spectrum in Clinic Referred, Gender Diverse Adolescents Accessing Puberty Suppression Treatment. J Autism Dev Disord ;2020 (Sep 16)

Literature has documented inflated rates of features associated with autism spectrum (AS) in clinic referred, gender diverse young people. This study examined scores on the Social Responsiveness Scale, Second Edition (SRS-2) over time in a group of clinic referred, gender diverse adolescents accessing gonadotropin-releasing hormone analogues (GnRHa) to supress puberty. Primary caregivers of 95 adolescents presenting to the Gender Identity Development Service (GIDS) completed the SRS-2 prior to receiving endocrine input (mean age : 13.6 ± SEM : 0.11) and after approximately one year of accessing GnRHa (mean age : 14.6 ± SEM : 0.13). No significant differences in SRS-2 scores over time and between birth assigned sex were found. No interactions between time and birth assigned sex were established for SRS-2 subscales or total scores.

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26. Sansi A, Nalbant S, Ozer D. Effects of an Inclusive Physical Activity Program on the Motor Skills, Social Skills and Attitudes of Students with and without Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Sep 17)

This study investigated the effects of an inclusive physical activity (IPA) program on the motor and social skills and attitudes of students with and without autism spectrum disorder (ASD). The study sample consisted of 45 ASD and typical development (TD) students aged between 6 and 11 years. The students were randomly divided into two groups : a training group consisting of 27 students (n = 13 with ASD and n = 14 with TD) and a control group consisting of 18 students (n = 9 with ASD and n = 9 with TD). In conclusion, the IPA program increased the motor and social skills of the ASD students and improved the motor skills of the TD students and positively affected their attitudes towards the ASD students.

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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. Shah R, Klumpp L, Negron-Diaz J, Carmain T, Jordan J. Transverse colon volvulus in a patient with autism. J Surg Case Rep ;2020 (Sep) ;2020(9):rjaa284.

Transverse colon volvulus is an extremely rare cause of bowel obstruction with approximately 100 cases reported in literature. Transverse colon volvulus presents with signs and symptoms of large bowel obstruction, but it can become a surgical emergency due to bowel infarction or peritonitis. We present a rare case of transverse colon volvulus in a 36-year-old male patient with severe autism. We hope this case report will raise awareness of this disease.

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29. Singh NN. Implementation Science of Mindfulness in Intellectual and Developmental Disabilities. Am J Intellect Dev Disabil ;2020 (Sep 1) ;125(5):345-348.

Implementation science deals with the translation of evidence-based knowledge into practice in the real world. Mindfulness-based programs for people with intellectual and developmental disabilities (IDD) emerged about 20 years ago. Efficacy and effectiveness studies provide the evidence-base for these programs and the field of IDD is moving towards large scale implementation of these programs. This article presents a model for implementing mindfulness-based programs in community settings, including family and group homes, schools, vocational settings, and congregate care facilities. The model is based on the 3-tier positive behavior support (PBS) system commonly used in school, family, and agency settings. Specific mindfulness-based programs can be linked to each of the three tiers to improve the quality of life of people with IDD.

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30. Song Y, Zhong J, Jia Z, Liang D. Emotional prosody recognition in children with high-functioning autism under the influence of emotional intensity : Based on the perspective of emotional dimension theory. J Commun Disord ;2020 (Aug 17) ;88:106032.

This paper investigated the ability of Mandarin-speaking children with high-functioning autism (HFA) to recognize the four categories of emotional prosody, namely, happiness, anger, sadness and fear, in moderate- and high-intensity emotional conditions using auditory discrimination tasks. Thirty-four children with HFA between 5 and 7 years of age and 34 typically developing (TD) controls participated in this study. In moderate-intensity conditions, children with HFA scored lower than TD children in the recognition of the four categories of emotional prosody, indicating an overall impairment. With an increase in the intensity of emotion, children with HFA showed improved accuracy for anger, decreased accuracy for happiness, but no change in accuracy for either sadness or fear. An analysis of error patterns demonstrated that unlike TD children, children with HFA were inclined to mistake happiness for anger, with the two categories differing in valence, and this inclination deepened as the intensity increased. In discriminating between sadness and fear, which have a slight arousal difference, both groups showed difficulty in moderate-intensity conditions. In high-intensity conditions, TD children were inclined to perceive stimuli as exhibiting fear, which demonstrates comparatively high arousal ; thus, they were more accurate for fear, while HFA children were not sensitive to increases in arousal, showing no noticeable effect. These findings indicated that children with HFA have a mechanism distinct from that of TD children in emotional prosody recognition, exhibiting various degrees of impairment in this regard.

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31. Thapar A, Rutter M. Genetic Advances in Autism. J Autism Dev Disord ;2020 (Sep 17)

In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants of large effect size as well as small effect common gene variants all contribute to autism risk. These discoveries challenge traditional diagnostic boundaries and highlight huge heterogeneity in autism. In this review, we consider some of the key findings that are shaping current understanding of autism and what these discoveries mean for clinicians.

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32. Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLoS Genet ;2020 (Sep 17) ;16(9):e1009036.

The polygenic nature and the contribution of common genetic variation to autism spectrum disorder (ASD) allude to a high degree of pleiotropy between ASD and other psychiatric and behavioral traits. In a pleiotropic system, a single genetic variant contributes small effects to several phenotypes or disorders. While analyzed broadly, there is a paucity of research studies investigating the shared genetic information between specific neurodevelopmental domains and ASD. We performed a phenome-wide association study of ASD polygenetic risk score (PRS) against 491 neurodevelopmental subdomains ascertained in 4,309 probands from the Philadelphia Neurodevelopmental Cohort (PNC) who lack an ASD diagnosis. Our main analysis calculated ASD PRS in 4,309 PNC probands using the per-SNP effects reported in a recent genome-wide association studies of ASD in a case-control design. In a high-resolution manner, our main analysis regressed ASD PRS against 491 neurodevelopmental phenotypes with age, sex, and ten principal components of ancestry as covariates. Follow-up analyses included in the regression model PRS derived from brain-related traits genetically correlated with ASD. Our main finding demonstrated that 11-17-year old probands with the highest ASD genetic risk were able to identify angry faces (R2 = 1.06%, p = 1.38 × 10-7, pBonferroni-corrected = 1.9 × 10-3). This ability replicated in older probands (>18 years ; R2 = 0.55%, p = 0.036) and persisted after covarying with other psychiatric disorders, brain imaging traits, and educational attainment (R2 = 0.2%, p = 0.019). We also detected several suggestive associations between ASD PRS and emotionality and connectedness with others. These data (i) indicate how genetic liability to ASD may influence neurodevelopment in the general population, (ii) reinforce epidemiological findings of heightened ability of ASD cases to predict certain social psychological events based on increased systemizing skills (iii) recapitulate theories of imbalance between empathizing and systemizing in ASD etiology.

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33. Xie Y, Zhang X, Liu F, Qin W, Fu J, Xue K, Yu C. Brain mRNA Expression Associated with Cortical Volume Alterations in Autism Spectrum Disorder. Cell Rep ;2020 (Sep 15) ;32(11):108137.

Numerous studies report abnormal cerebral cortex volume (CCV) in autism spectrum disorder (ASD) ; however, genes related to CCV abnormalities in ASD remain largely unknown. Here, we identify genes associated with CCV alterations in ASD by performing spatial correlations between the gene expression of 6 donated brains and neuroimaging data from 1,404 ASD patients and 1,499 controls. Based on spatial correlations between gene expression and CCV differences from two independent meta-analyses and between gene expression and individual CCV distributions of 404 patients and 496 controls, we identify 417 genes associated with both CCV differences and individual CCV distributions. These genes are enriched for genetic association signals and genes downregulated in the ASD post-mortem brain. The expression patterns of these genes are correlated with brain activation patterns of language-related neural processes frequently impaired in ASD. These findings highlight a model whereby genetic risk impacts gene expression (downregulated), which leads to CCV alterations in ASD.

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