Pubmed du 10/05/22
1. Alnemary FM, Simon-Cereijido G, Aldhalaan HM, Hernandez A, Alyahya A, Alenezi S. Factors associated with age of diagnosis of autism spectrum disorder among children in Saudi Arabia: new insights from a cross-sectional study. BMC Res Notes;2022 (May 10);15(1):161.
OBJECTIVES: Research examining the age of diagnosis of autism spectrum disorder (ASD) and its influencing factors mostly originate from developed Western countries, providing little to no systematic information about the understanding and management of ASD in the rest of the world. The present exploratory study examined the influence of child and family characteristics on the age of ASD diagnosis in Saudi Arabia. RESULTS: The median age at diagnosis was 3.0 years and was associated with some child and family characteristics. A 1 year increase in child’s age was associated with a 0.1 year increase in age of diagnosis (95% CI 0.05, 0.12). Children who did not respond to their name were diagnosed 0.3 years earlier than other children (95% CI – 0.60, – 0.05), and engaging in challenging behavior was associated with a 0.5 year increase in age of diagnosis (95% CI 0.20, 0.81). A lack of comorbidity was associated with a 0.6 year increase in the age of diagnosis compared to the diagnosis age of children with comorbidity (95% CI 0.13, 1.01). Finally, those residing outside of Saudi Arabia were diagnosed with ASD 0.9 years earlier than those residing in Saudi Arabia (95% CI – 0.171, – 0.11).
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2. Chen H, Qiao D, Wang C, Zhang B, Wang Z, Tang L, Wang Y, Zhang R, Zhang Y, Song L, Zuo H, Guo F, Wang X, Li S, Cui H. Fragile X Mental Retardation Protein Mediates the Effects of Androgen on Hippocampal PSD95 Expression and Dendritic Spines Density/Morphology and Autism-Like Behaviors Through miR-125a. Front Cell Neurosci;2022;16:872347.
Dysregulated synaptic plasticity is a key feature of neurodevelopmental disorders, including autism. This study investigated whether Fragile X mental retardation protein (FMRP), a selective RNA-binding protein that regulates synaptic protein expression by interacting with miRNAs, mediates the effects of androgens that play an important role in regulating the synaptic plasticity in the hippocampus. Experiments using mouse hippocampal neuron HT22 cells demonstrated that dihydrotestosterone (DHT) increased the expression of postsynaptic density protein 95 (PSD95) by inhibiting FMRP expression. Administration of miR-125a inhibitor upregulated the PSD95 expression and significantly increased the DHT-induced upregulation of PSD95. FMRP knockdown in HT22 cells reduced the expression of miR-125a. Moreover, miR-125a inhibitor upregulated the PSD95 expression in the DHT-treated HT22 cells with FMRP knockdown. Subsequently, the effects of androgen-mediated via FMRP in regulating neural behaviors and PSD95 expression and dendritic spines density/morphology were investigated using Fmr1 knockout (KO) and wild-type littermate (WT) mice. The castration of WT mice reduced the androgen levels, aggravated anxiety and depression, and impaired learning and memory and sociability of mice. DHT supplementation post-castration reversed the alterations in density and maturity of dendritic spines of hippocampal neurons and behavioral disorders in WT mice; however, it did not reveal such effects in Fmr1 KO mice. Further, immunohistochemical staining and western blotting analyses after knocking down miR-125a revealed similar effects of castration and post-castration DHT supplementation on PSD95 protein expression. These findings clarified that FMRP mediated the effects of DHT through miR-125a in regulating the expression of hippocampal synaptic protein PSD95. This study provides evidence for the neuroprotective mechanism of androgen in PSD95 expression and dendritic spines density/morphology and suggests that treatment interventions with androgen could be helpful for the management of synaptic plasticity disorders.
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3. Cho AB, Otte K, Baskow I, Ehlen F, Maslahati T, Mansow-Model S, Schmitz-Hübsch T, Behnia B, Roepke S. Motor signature of autism spectrum disorder in adults without intellectual impairment. Sci Rep;2022 (May 10);12(1):7670.
Motor signs such as dyspraxia and abnormal gait are characteristic features of autism spectrum disorder (ASD). However, motor behavior in adults with ASD has scarcely been quantitatively characterized. In this pilot study, we aim to quantitatively examine motor signature of adults with ASD without intellectual impairment using marker-less visual-perceptive motion capture. 82 individuals (37 ASD and 45 healthy controls, HC) with an IQ > 85 and aged 18 to 65 years performed nine movement tasks and were filmed by a 3D-infrared camera. Anatomical models were quantified via custom-made software and resulting kinematic parameters were compared between individuals with ASD and HCs. Furthermore, the association between specific motor behaviour and severity of autistic symptoms (Autism Diagnostic Observation Schedule 2, Autism Spectrum Quotient) was explored. Adults with ASD showed a greater mediolateral deviation while walking, greater sway during normal, tandem and single leg stance, a reduced walking speed and cadence, a greater arrhythmicity during jumping jack tasks and an impaired manual dexterity during finger tapping tasks (p < 0.05 and |D|> 0.48) compared to HC. Furthermore, in the ASD group, some of these parameters correlated moderately to severity of ASD symptoms. Adults with ASD seem to display a specific motor signature in this disorder affecting movement timing and aspects of balance. The data appear to reinforce knowledge about motor signs reported in children and adolescents with ASD. Also, quantitative motor assessment via visual-perceptive computing may be a feasible instrument to detect subtle motor signs in ASD and perhaps suitable in the diagnosis of ASD in the future.
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4. Dell’Osso L, Massoni L, Battaglini S, Cremone IM, Carmassi C, Carpita B. Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder. Ann Gen Psychiatry;2022 (May 9);21(1):13.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex and multifaceted neurobehavioral syndrome. In the last decades, several studies highlighted an increased prevalence of sleep problems in ASD, which would be associated with autonomic system and circadian rhythm disruption. The present review aimed to summarize the available literature about sleep problems in ASD subjects and about the possible biological factors implicated in circadian rhythm and autonomic system deregulation in this population, as well as possible therapeutic approaches. Shared biological underpinnings between ASD symptoms and altered circadian rhythms/autonomic functions are also discussed. Studies on sleep showed how ASD subjects typically report more problems regarding insufficient sleep time, bedtime resistance and reduced sleep pressure. A link between sleep difficulties and irritability, deficits in social skills and behavioral problems was also highlighted. Among the mechanisms implicated, alteration in genes related to circadian rhythms, such as CLOCK genes, and in melatonin levels were reported. ASD subjects also showed altered hypothalamic pituitary adrenal (HPA) axis and autonomic functions, generally with a tendency towards hyperarousal and hyper sympathetic state. Intriguingly, some of these biological alterations in ASD individuals were not associated only with sleep problems but also with more autism-specific clusters of symptoms, such as communication impairment or repetitive behaviors Although among the available treatments melatonin showed promising results, pharmacological studies for sleep problems in ASD need to follow more standardized protocols to reach more repeatable and reliable results. Further research should investigate the issue of sleep problems in ASD in a broader perspective, taking into account shared pathophysiological mechanisms for core and associated symptoms of ASD.
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5. Dolata JK, Suarez S, Calamé B, Fombonne E. Pragmatic Language Markers of Autism Diagnosis and Severity. Res Autism Spectr Disord;2022 (Jun);94
PURPOSE: Assessment of pragmatic language difficulties is limited with conventional tests but can be performed with informant reports. We evaluated the performance of a parent-completed language scale in differentiating autism from typical development (TD) and another neurodevelopmental disorder. Specifically, we aimed to gauge the respective values of structural and pragmatic language scores for diagnostic discrimination and for predicting severity of social impairment in autistic children. METHOD: 174 children aged 7 to 17 (101 with autism, 45 with ADHD, 28 with TD) were evaluated with the ADOS-2 and an abbreviated version of the WISC. Parents completed the Children’s Communication Checklist, 2nd Edition (CCC-2) and the Social Responsiveness Scale. CCC-2 mean differences across diagnostic groups were tested with analysis of variance and covariance. Multiple linear regression was used to compare the structural and pragmatic CCC-2 scores in predicting autism symptom severity. RESULTS: Both structural and pragmatic language scores discriminated between the three diagnostic groups, with stronger effects for the pragmatic scores. Pragmatic scores remained robust predictors of ADHD and ASD diagnoses even after accounting for cognitive and structural linguistic differences. Among autistic children, social impairment severity was associated with pragmatic, but not structural, language profiles. CONCLUSIONS: In order to characterize pragmatic language, easy to administer parent questionnaires such as the CCC-2 may support clinicians who are considering an autism diagnosis and needing to evaluate and monitor social communication.
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6. DuBay M. Cultural Adaptations to Parent-Mediated Autism Spectrum Disorder Interventions for Latin American Families: A Scoping Review. Am J Speech Lang Pathol;2022 (May 10);31(3):1517-1534.
PURPOSE: This scoping review maps research in parent-mediated autism spectrum disorder interventions culturally adapted for Latin American populations, to provide an overview of the available evidence across perspectives and disciplines and to identify gaps in the research knowledge base. METHOD: A systematic search for relevant articles was conducted using six databases and archival and forward hand searches of articles that met inclusion criteria. Titles and abstracts were reviewed by three authors, followed by full-text reviews of remaining articles. Twenty-one articles met inclusion criteria and were retained for data extraction. The ecological validity framework was used to frame data analysis and results. RESULTS: In total, 19 studies described unique implementations of 16 different interventions, which spanned 21 articles, representing a range of study designs and implementing a variety of adaptations. Most adaptations consisted of surface-structure changes, spanning the dimensions of language, concepts, methods, context, and persons. Few articles were identified that described international studies or studies examining direct parent-mediated strategies with large sample sizes and strong methodological designs. CONCLUSIONS: Several intervention adaptations that have potential for clinical utility are presented. Clinicians working with Latin American families are encouraged to discuss potential adaptations openly with families before choosing and implementing specific strategies.
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7. Federici S, Balboni G, Buracchi A, Barbanera F, Pierini A. WHODAS-Child: psychometric properties of the WHODAS 2.0 for children and youth among Italian children with autism spectrum disorder. Disabil Rehabil;2022 (May 8):1-7.
PURPOSE: A contribution to the Italian adaptation of the original English version of the World Health Organization Disability Assessment Schedule 2.0 for children and youth (WHODAS-Child), proxy-administered among children with autism spectrum disorder (ASD) without intellectual disability. MATERIALS AND METHODS: Observational and retrospective study with within-dependent variables by cross-sectional sampling on psychometric properties (internal consistency and construct/criterion validity) of the 36- and 7-item versions of the Italian WHODAS-Child. The original English version was translated into Italian, also considering the Italian version of the WHODAS 2.0 for adults. The Italian questionnaire was then translated back into English. All authors compared the original and back-translated English versions. The sample was collected among parents and clinicians of 100 children with ASD. To assess convergent/divergent validity, the Autism Diagnostic Observational Schedule (ADOS) was also administered. RESULTS: Cronbach’s α for both versions’ total scores was good. WHODAS-Child also showed a positive correlation with the three DSM-5 levels of impairment. A pattern of correlations with the ADOS was found for all domains of the WHODAS-Child except for the mobility and self-care domains. CONCLUSIONS: The WHODAS-Child Italian proxy-administered version has the potential to be a reliable and valid tool to measure functional impairment in children with ASD. Implications for rehabilitationWorld Health Organization Disability Assessment Schedule 2.0 for children and youth (WHODAS-Child) has shown to be sensitive in detecting children and youth functioning in the domains of activity and participation.WHODAS-Child Italian version seems to be a reliable and valid tool to measure the functional impairment in children with autism spectrum disorder.A critical issue for rehabilitation is that a single « minimal clinically important difference » score for the WHODAS-Child has not yet been established.
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8. Gatzia DE, Arnaud S. Loving Objects: Can Autism Explain Objectophilia?. Arch Sex Behav;2022 (May 10)
Objectophilia (also known as objectum-sexuality) involves romantic and sexual attraction to specific objects. Objectophiles often develop deep and enduring emotional, romantic, and sexual relations with specific inanimate (concrete or abstract) objects such as trains, bridges, cars, or words. The determinants of objectophilia are poorly understood. The aim of this paper is to examine the determining factors of objectophilia. We examine four hypotheses about the determinants of objectophilia (pertaining to fetishism, synesthesia, cross-modal mental imagery, and autism) and argue that the most likely determining factors of objectophilia are the social and non-social features of autism. Future studies on the determinants of objectophilia could enhance our understanding and potentially lessen the marginalization experienced by objectophiles.
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9. Geretsegger M, Fusar-Poli L, Elefant C, Mössler KA, Vitale G, Gold C. Music therapy for autistic people. Cochrane Database Syst Rev;2022 (May 9);5:CD004381.
BACKGROUND: Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of autistic people. Music therapy has been applied in autism since the early 1950s, but its availability to autistic individuals varies across countries and settings. The application of music therapy requires specialised academic and clinical training which enables therapists to tailor the intervention to the specific needs of the individual. The present version of this review on music therapy for autistic people is an update of the previous Cochrane review update published in 2014 (following the original Cochrane review published in 2006). OBJECTIVES: To review the effects of music therapy, or music therapy added to standard care, for autistic people. SEARCH METHODS: In August 2021, we searched CENTRAL, MEDLINE, Embase, eleven other databases and two trials registers. We also ran citation searches, checked reference lists, and contacted study authors to identify additional studies. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-randomised trials and controlled clinical trials comparing music therapy (or music therapy alongside standard care) to ‘placebo’ therapy, no treatment, or standard care for people with a diagnosis of autism spectrum disorder were considered for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Four authors independently selected studies and extracted data from all included studies. We synthesised the results of included studies in meta-analyses. Four authors independently assessed risk of bias (RoB) of each included study using the original RoB tool as well as the certainty of evidence using GRADE. MAIN RESULTS: We included 16 new studies in this update which brought the total number of included studies to 26 (1165 participants). These studies examined the short- and medium-term effect of music therapy (intervention duration: three days to eight months) for autistic people in individual or group settings. More than half of the studies were conducted in North America or Asia. Twenty-one studies included children aged from two to 12 years. Five studies included children and adolescents, and/or young adults. Severity levels, language skills, and cognition were widely variable across studies. Measured immediately post-intervention, music therapy compared with ‘placebo’ therapy or standard care was more likely to positively effect global improvement (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.06 to 1.40; 8 studies, 583 participants; moderate-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) = 11 for low-risk population, 95% CI 6 to 39; NNTB = 6 for high-risk population, 95% CI 3 to 21) and to slightly increase quality of life (SMD 0.28, 95% CI 0.06 to 0.49; 3 RCTs, 340 participants; moderate-certainty evidence, small to medium effect size). In addition, music therapy probably results in a large reduction in total autism symptom severity (SMD -0.83, 95% CI -1.41 to -0.24; 9 studies, 575 participants; moderate-certainty evidence). No clear evidence of a difference between music therapy and comparison groups at immediately post-intervention was found for social interaction (SMD 0.26, 95% CI -0.05 to 0.57, 12 studies, 603 participants; low-certainty evidence); non-verbal communication (SMD 0.26, 95% CI -0.03 to 0.55; 7 RCTs, 192 participants; low-certainty evidence); and verbal communication (SMD 0.30, 95% CI -0.18 to 0.78; 8 studies, 276 participants; very low-certainty evidence). Two studies investigated adverse events with one (36 participants) reporting no adverse events; the other study found no differences between music therapy and standard care immediately post-intervention (RR 1.52, 95% CI 0.39 to 5.94; 1 study, 290 participants; moderate-certainty evidence). AUTHORS’ CONCLUSIONS: The findings of this updated review provide evidence that music therapy is probably associated with an increased chance of global improvement for autistic people, likely helps them to improve total autism severity and quality of life, and probably does not increase adverse events immediately after the intervention. The certainty of the evidence was rated as ‘moderate’ for these four outcomes, meaning that we are moderately confident in the effect estimate. No clear evidence of a difference was found for social interaction, non-verbal communication, and verbal communication measured immediately post-intervention. For these outcomes, the certainty of the evidence was rated as ‘low’ or ‘very low’, meaning that the true effect may be substantially different from these results. Compared with earlier versions of this review, the new studies included in this update helped to increase the certainty and applicability of this review’s findings through larger sample sizes, extended age groups, longer periods of intervention and inclusion of follow-up assessments, and by predominantly using validated scales measuring generalised behaviour (i.e. behaviour outside of the therapy context). This new evidence is important for autistic individuals and their families as well as for policymakers, service providers and clinicians, to help in decisions around the types and amount of intervention that should be provided and in the planning of resources. The applicability of the findings is still limited to the age groups included in the studies, and no direct conclusions can be drawn about music therapy in autistic individuals above the young adult age. More research using rigorous designs, relevant outcome measures, and longer-term follow-up periods is needed to corroborate these findings and to examine whether the effects of music therapy are enduring.
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10. Ivashko-Pachima Y, Ganaiem M, Ben-Horin-Hazak I, Lobyntseva A, Bellaiche N, Fischer I, Levy G, Sragovich S, Karmon G, Giladi E, Shazman S, Barak B, Gozes I. SH3- and actin-binding domains connect ADNP and SHANK3, revealing a fundamental shared mechanism underlying autism. Mol Psychiatry;2022 (May 10)
De novo heterozygous mutations in activity-dependent neuroprotective protein (ADNP) cause autistic ADNP syndrome. ADNP mutations impair microtubule (MT) function, essential for synaptic activity. The ADNP MT-associating fragment NAPVSIPQ (called NAP) contains an MT end-binding protein interacting domain, SxIP (mimicking the active-peptide, SKIP). We hypothesized that not all ADNP mutations are similarly deleterious and that the NAPV portion of NAPVSIPQ is biologically active. Using the eukaryotic linear motif (ELM) resource, we identified a Src homology 3 (SH3) domain-ligand association site in NAP responsible for controlling signaling pathways regulating the cytoskeleton, namely NAPVSIP. Altogether, we mapped multiple SH3-binding sites in ADNP. Comparisons of the effects of ADNP mutations p.Glu830synfs*83, p.Lys408Valfs*31, p.Ser404* on MT dynamics and Tau interactions (live-cell fluorescence-microscopy) suggested spared toxic function in p.Lys408Valfs*31, with a regained SH3-binding motif due to the frameshift insertion. Site-directed-mutagenesis, abolishing the p.Lys408Valfs*31 SH3-binding motif, produced MT toxicity. NAP normalized MT activities in the face of all ADNP mutations, although, SKIP, missing the SH3-binding motif, showed reduced efficacy in terms of MT-Tau interactions, as compared with NAP. Lastly, SH3 and multiple ankyrin repeat domains protein 3 (SHANK3), a major autism gene product, interact with the cytoskeleton through an actin-binding motif to modify behavior. Similarly, ELM analysis identified an actin-binding site on ADNP, suggesting direct SH3 and indirect SHANK3/ADNP associations. Actin co-immunoprecipitations from mouse brain extracts showed NAP-mediated normalization of Shank3-Adnp-actin interactions. Furthermore, NAP treatment ameliorated aberrant behavior in mice homozygous for the Shank3 ASD-linked InsG3680 mutation, revealing a fundamental shared mechanism between ADNP and SHANK3.
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11. Latsko MS, Koboldt DC, Franklin SJ, Hickey SE, Williamson RK, Garner S, Ostendorf AP, Lee K, White P, Wilson RK. De novo missense mutation in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy. Cold Spring Harb Mol Case Stud;2022 (May 9)
De novo variants are increasingly recognized as a common cause of early infantile epileptic encephalopathies. We present a 4-year-old male with epileptic encephalopathy characterized by seizures, autism spectrum disorder, and global developmental delay. Whole genome sequencing of the proband and his unaffected parents revealed a novel de novo missense variant in GRIA2 (c.1589A>T; p.Lys530Met; ENST00000264426.14). Variants in the GRIA2 gene were recently reported to cause an autosomal dominant neurodevelopmental disorder with language impairments and behavioral abnormalities (OMIM; MIM #618917), a condition characterized by intellectual disability and developmental delay in which seizures are a common feature. The de novo variant identified in our patient maps to the edge of a key ligand binding domain of the AMPA receptor and has not been previously reported in gnomAD or other public databases, making it novel. Our findings provided a long-sought diagnosis for this patient and support the link between GRIA2 and a dominant neurodevelopmental disorder.
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12. Li Z, Yang L, Chen H, Fang Y, Zhang T, Yin X, Man J, Yang X, Lu M. Global, regional and national burden of autism spectrum disorder from 1990 to 2019: results from the Global Burden of Disease Study 2019. Epidemiol Psychiatr Sci;2022 (May 10);31:e33.
AIMS: Autism spectrum disorder (ASD) is a neurodevelopmental condition, with symptoms appearing in the early developmental period. Little is known about its current burden at the global, regional and national levels. This systematic analysis aims to summarise the latest magnitudes and temporal trends of ASD burden, which is essential to facilitate more detailed development of prevention and intervention strategies. METHODS: The data on ASD incidence, prevalence, disability-adjusted life years (DALYs) in 204 countries and territories between 1990 and 2019 came from the Global Burden of Disease Study 2019. The average annual percentage change was calculated to quantify the secular trends in age-standardised rates (ASRs) of ASD burden by region, sex and age. RESULTS: In 2019, there were an estimated 60.38 × 104 [95% uncertainty interval (UI) 50.17-72.01] incident cases of ASD, 283.25 × 105 (95% UI 235.01-338.11) prevalent cases and 43.07 × 105 (95% UI 28.22-62.32) DALYs globally. The ASR of incidence slightly increased by around 0.06% annually over the past three decades, while the ASRs of prevalence and DALYs both remained stable over the past three decades. In 2019, the highest burden of ASD was observed in high-income regions, especially in high-income North America, high-income Asia Pacific and Western Europe, where a significant growth in ASRs was also observed. The ASR of ASD burden in males was around three times that of females, but the gender difference was shrunk with the pronounced increase among females. Of note, among the population aged over 65 years, the burden of ASD presented increasing trends globally. CONCLUSIONS: The global burden of ASD continues to increase and remains a major mental health concern. These substantial heterogeneities in ASD burden worldwide highlight the need for making suitable mental-related policies and providing special social and health services.
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13. Liu J, Wang H, Sun W, Liu Y. Prioritizing Autism Risk Genes using Personalized Graphical Models Estimated from Single Cell RNA-seq Data. J Am Stat Assoc;2022;117(537):38-51.
Hundreds of autism risk genes have been reported recently, mainly based on genetic studies where these risk genes have more de novo mutations in autism subjects than healthy controls. However, as a complex disease, autism is likely associated with more risk genes and many of them may not be identifiable through de novo mutations. We hypothesize that more autism risk genes can be identified through their connections with known autism risk genes in personalized gene-gene interaction graphs. We estimate such personalized graphs using single cell RNA sequencing (scRNA-seq) while appropriately modeling the cell dependence and possible zero-inflation in the scRNA-seq data. The sample size, which is the number of cells per individual, ranges from 891 to 1,241 in our case study using scRNA-seq data in autism subjects and controls. We consider 1,500 genes in our analysis. Since the number of genes is larger or comparable to the sample size, we perform penalized estimation. We score each gene’s relevance by applying a simple graph kernel smoothing method to each personalized graph. The molecular functions of the top-scored genes are related to autism diseases. For example, a candidate gene RYR2 that encodes protein ryanodine receptor 2 is involved in neurotransmission, a process that is impaired in ASD patients. While our method provides a systemic and unbiased approach to prioritize autism risk genes, the relevance of these genes needs to be further validated in functional studies.
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14. Lyons-Warren AM, Hirtz D. More Than a Brain Injury: A Novel Link Between Pediatric Stroke and Autism. Neurology;2022 (May 10);98(19):784-785.
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15. Ma L, Liu M, Xue K, Ye C, Man W, Cheng M, Liu Z, Zhu D, Liu F, Wang J. Abnormal Regional Spontaneous Brain Activities in White Matter in Patients with Autism Spectrum Disorder. Neuroscience;2022 (May 10);490:1-10.
Previous studies have demonstrated patients with autism spectrum disorder (ASD) are accompanied by alterations of spontaneous brain activity in gray matter. However, whether the alterations of spontaneous brain activity exist in white matter remains largely unclear. In this study, 88 ASD patients and 87 typical controls (TCs) were included and regional homogeneity (ReHo) was calculated to characterize spontaneous brain activity in white matter. Voxel-wise two-sample t-tests were performed to investigate ReHo alterations, and cluster-level analyses were conducted to examine structural-functional coupling changes. Compared with TCs, the ASD group showed significantly decreased ReHo in the left superior corona radiata and left posterior limb of internal capsule, and decreased ReHo in the left anterior corona radiata with a trend level of significance. In addition, significantly weaker structural-functional coupling was observed in the left superior corona radiata and left posterior limb of internal capsule in ASD patients. Taken together, these findings highlighted abnormalities of white matter’s regional spontaneous brain activity in ASD, which may provide new insights into the pathophysiological mechanisms of this disorder.
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16. McIntyre CL, Boucher TQ, Scheerer NE, Gurm M, Iarocci G. Correction to: Brief Report: Alexithymia Trait Severity, Not Autistic Trait Severity, Relates to Caregiver Reactions to Autistic Children’s Negative Emotions. J Autism Dev Disord;2022 (May 10)
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17. Nawaz W, Naveed M, Zhang J, Noreen S, Saeed M, Sembatya KR, Ihsan AU, Mohammad IS, Wang G, Zhou X. Cardioprotective effect of silicon-built restraint device (ASD), for left ventricular remodeling in rat heart failure model. J Mater Sci Mater Med;2022 (May 10);33(5):42.
This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat’s heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD’s functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).
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18. Pompa-Craven P, Tierman E, Martino J, Lotfizadeh AD. Caregiver Satisfaction with Delivery of Telehealth Autism Services. Adv Neurodev Disord;2022 (May 2):1-10.
OBJECTIVE: The purpose of this study was to assess satisfaction with telehealth interventions for a large nonprofit organization that transitioned interventions for individuals with autism spectrum disorder (ASD) to telehealth during a pandemic. Services provided via telehealth included applied behavior analysis (ABA), speech and language, and occupational therapies. A secondary survey evaluated reasons for declining telehealth services. METHODS: A survey was administered to 10,567 families who were receiving autism interventions. A total of 440 respondents answered all the questions on the survey, and their results were included in this study. A secondary survey was administered to 223 individuals who declined to have telehealth autism interventions. RESULTS: There was not a clinically meaningful difference in satisfaction across service types. Although all ratings were in the high range, caregivers ranked speech therapists as more dependable than ABA therapists, and this difference was statistically significant. The findings suggested that the majority of caregivers were generally satisfied with services provided in a telehealth format. For those who declined services, the majority indicated a discomfort with the use of technology. CONCLUSIONS: The participants of telehealth autism interventions reported high general satisfaction and indicated an improvement in their quality of life. Results provide suggestive evidence that increased satisfaction of telehealth services may allow for further acceptability and access for participants. Future research should evaluate participant and clinician satisfaction with telehealth versus in-person interventions.
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19. Qin Y, Du Y, Chen L, Liu Y, Xu W, Li Y, Leng J, Wang Y, Zhang XY, Feng J, Zhang F, Jin L, Qiu Z, Gong X, Wang H. Correction: A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling. Mol Psychiatry;2022 (May 10)
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20. Slama S, Bahia W, Soltani I, Gaddour N, Ferchichi S. Risk factors in autism spectrum disorder: A Tunisian case-control study. Saudi J Biol Sci;2022 (Apr);29(4):2749-2755.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition that causes disability in social interaction, communication, and restrictive and repetitive behaviors. Common environmental factors like prenatal, perinatal, and/or postnatal factors play a key role in ASD etiologies. Moreover, specific metabolic disorders can be associated with ASD. SUBJECTS AND METHODS: We performed a retrospective case-control study in child psychiatry clinics, involving 51 children with ASD and 40 typical development controls (TDC). RESULTS: We found a correlation between children being breastfed for less than 6 months, having fathers more than 40 years old at childbirth in ASD compared to TDC group. Our study also associated low blood cholesterol and low erythrocyte magnesium levels with increased risk for ASD. CONCLUSION: Findings support the implication of total cholesterol (TC) and erythrocyte magnesium level in defining autism outcome.
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21. Sturman M, Peffers K, Johnson JR, Venker CE. Association Between Toy Type and Parent Language Input Provided to Children With Autism Spectrum Disorder and Age-Matched Children With Typical Development. JAMA Pediatr;2022 (May 9)
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22. Sundelin H, Söderling J, Bang P, Bolk J. Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study. Neurology;2022 (May 10);98(19):e1953-e1963.
BACKGROUND AND OBJECTIVES: Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives. METHODS: In this cohort study, individuals with ischemic stroke from 1969 to 2016, <18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke. RESULTS: Of the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15-4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44-5.03) and childhood stroke (aHR 3.18, 95% CI 2.12-4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55-5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95-4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74-13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44-7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45-3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke. DISCUSSION: An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.
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23. Tantucci V, Wang A. Correction to: Dialogic Priming and Dynamic Resonance in Autism: Creativity Competing with Engagement in Chinese Children with ASD. J Autism Dev Disord;2022 (May 9)
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24. Wan G, Deng F, Jiang Z, Song S, Hu D, Chen L, Wang H, Li M, Chen G, Yan T, Su J, Zhang J. FECTS: A Facial Emotion Cognition and Training System for Chinese Children with Autism Spectrum Disorder. Comput Intell Neurosci;2022;2022:9213526.
Traditional training methods such as card teaching, assistive technologies (e.g., augmented reality/virtual reality games and smartphone apps), DVDs, human-computer interactions, and human-robot interactions are widely applied in autistic rehabilitation training in recent years. In this article, we propose a novel framework for human-computer/robot interaction and introduce a preliminary intervention study for improving the emotion recognition of Chinese children with an autism spectrum disorder. The core of the framework is the Facial Emotion Cognition and Training System (FECTS, including six tasks to train children with ASD to match, infer, and imitate the facial expressions of happiness, sadness, fear, and anger) based on Simon Baron-Cohen’s E-S (empathizing-systemizing) theory. Our system may be implemented on PCs, smartphones, mobile devices such as PADs, and robots. The training record (e.g., a tracked record of emotion imitation) of the Chinese autistic children interacting with the device implemented using our FECTS will be uploaded and stored in the database of a cloud-based evaluation system. Therapists and parents can access the analysis of the emotion learning progress of these autistic children using the cloud-based evaluation system. Deep-learning algorithms of facial expressions recognition and attention analysis will be deployed in the back end (e.g., devices such as a PC, a robotic system, or a cloud system) implementing our FECTS, which can perform real-time tracking of the imitation quality and attention of the autistic children during the expression imitation phase. In this preliminary clinical study, a total of 10 Chinese autistic children aged 3-8 are recruited, and each of them received a single 20-minute training session every day for four consecutive days. Our preliminary results validated the feasibility of the developed FECTS and the effectiveness of our algorithms based on Chinese children with an autism spectrum disorder. To verify that our FECTS can be further adapted to children from other countries, children with different cultural/sociological/linguistic contexts should be recruited in future studies.
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25. Yamamoto SH, Alverson CY. Post-high school outcomes of students with autism spectrum disorder and students with intellectual disability: Utilizing predictive analytics and state data for decision making. J Intellect Disabil;2022 (May 9):17446295221100039.
This study analyzed the post-high school outcomes of exited high-school students with intellectual disability and autism spectrum disorder from a southwestern U.S. state. A predictive analytics approach was used to analyze these students’ post-high school outcomes data, which every state is required to collect each year under U.S. special-education law. Data modeling was conducted with machine learning and logistic regression, which produced two main findings. One, the strongest significant predictors were (a) students spending at least 80% of their instructional days in general education settings and (b) graduating from high school. Two, machine learning models were consistently more accurate in predicting post-high school education or employment than were multilevel logistic regression models. This study concluded with the limitations of the data and predictive-analytic models, and the implications for researchers and state and local education professionals to utilize predictive analytics and state-level post-high school outcomes data for decision making.
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26. Yang G, Geng H, Hu C. Targeting 5-HT as a Potential Treatment for Social Deficits in Autism. Neurosci Bull;2022 (May 10)
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27. Zahra A, Wang Y, Wang Q, Wu J. Shared Etiology in Autism Spectrum Disorder and Epilepsy with Functional Disability. Behav Neurol;2022;2022:5893519.
Autism spectrum disorders and epilepsies are heterogeneous human disorders that have miscellaneous etiologies and pathophysiology. There is considerable risk of frequent epilepsy in autism that facilitates amplified morbidity and mortality. Several biological pathways appear to be involved in disease progression, including gene transcription regulation, cellular growth, synaptic channel function, and maintenance of synaptic structure. Here, abnormalities in excitatory/inhibitory (E/I) balance ratio are reviewed along with part of an epileptiform activity that may drive both overconnectivity and genetic disorders where autism spectrum disorders and epilepsy frequently co-occur. The most current ideas concerning common etiological and molecular mechanisms for co-occurrence of both autism spectrum disorders and epilepsy are discussed along with the powerful pharmacological therapies that protect the cognition and behavior of patients. Better understanding is necessary to identify a biological mechanism that might lead to possible treatments for these neurological disorders.
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28. Zhao M, Chang Q, Yang H, Wang M, Liu Y, Lv N, Lei Q, Wei H. Epothilone D Modulates Autism-like Behaviors in the BTBR Mouse Model of Autism Spectrum Disorder. Neuroscience;2022 (May 10);490:171-181.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by impaired social communication, abnormal repetitive behaviors and restricted interests and/or sensory behaviors. It has been widely accepted that ASD involves a complex interplay of both genetic and environmental risk factors. Existing medications are only symptomatic treatments, there are no effective treatments that can improve these core social behavior deficits. Recent studies indicated that synaptic development and abnormal myelination are linked to the pathogenesis of ASD. The stable tubule only polypeptide (STOP) protein, also known as microtubule-associated protein 6, plays an important role in neuronal development and synaptic plasticity. Our previous studies showed that STOP protein was significantly reduced in the plasma of autistic subjects and in the cortex of BTBR T(+) Itpr3(tf) (BTBR) mouse model of ASD. Furthermore, studies have shown that Epothilone D, a taxol-like microtubule-stabilizing agent, could alleviate behavioral and synaptic deficits in STOP-null mice. Here, we further evaluate whether Epothilone D treatment is sufficient to modulate the autism-like behaviors in the BTBR mice, and explore the underlying mechanism. BTBR mice were treated either with Epothilone D dissolved in 99% dimethyl sulfoxide (DMSO) or with 99% DMSO vehicle. Our studies demonstrated that the restricted and repetitive behaviors of BTBR mice were improved after Epothilone D treatment, which could be achieved by improving microtubule stability and further regulating the expression of excitatory synapse-related and myelin-related proteins. These results indicate that microtubule stability may be a new and promising therapeutic target for treating patients with ASD.