1. Alhosaini K, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Ayadhi LY, Mahmood HM, Al-Mazroua HA, Ahmad SF. Dysregulation of Ki-67 Expression in T Cells of Children with Autism Spectrum Disorder. Children (Basel, Switzerland). 2021 ; 8(2).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT-PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.

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2. Au TC, Lau NS. Private music teachers’ knowledge of and attitudes toward students with autism spectrum disorder. J Autism Dev Disord. 2021.

Although extracurricular music activities are common in Hong Kong, private music teachers’ perceptions of children with autism spectrum disorder (ASD) are underexplored in research in this context. This study examined private music teachers’ knowledge of ASD and their attitudes toward students with ASD in Hong Kong, and the relationship between these two factors. The study collected data from a questionnaire survey (n = 200) and eleven individual interviews. Unexpectedly, the findings showed that the teachers had a good understanding and a marginally positive perception of ASD, despite some anxiety about teaching students with ASD. Furthermore, knowledge of and attitude toward ASD were positively correlated. Teachers with previous training in special education needs had a better understanding of ASD and a more positive attitude toward ASD than those without related training. These results imply that further formal and public education could promote acceptance of and equal learning opportunities for students with ASD.

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3. Bal VH, Wilkinson E, White LC, Law JK, Feliciano P, Chung WK. Early Pandemic Experiences of Autistic Adults : Predictors of Psychological Distress. Autism Res. 2021.

The COVID-19 pandemic has disrupted lives around the world. Autistic adults are at higher risk for co-occurring medical and psychiatric conditions and may be more prone to difficulties adapting to pandemic-related changes and social distancing mandates and coping with ongoing uncertainties. On the other hand, the pandemic may lead to greater understanding and acceptance of accommodations in the broader community that may facilitate supports for autistic adults beyond the pandemic. To learn more about their early pandemic experiences, online surveys were sent to independent adults enrolled in the Simons Powering Autism Research Knowledge (SPARK). The first survey was open from March 30 to April 19, 2020 ; a follow-up survey sent to original responders was open from May 27 to June 6, yielding 396 participants with data for both surveys. We found that adults who were female, younger, had prior diagnoses of a mental health condition, personal COVID-19 experience (i.e., knowing someone who had symptoms or tested positive) or less frequent hope for the future reported the greatest negative impacts. Decrease in feelings of hopefulness over time predicted greater psychological distress at T2, accounting for T1 impact and distress levels and increases in total COVID-19 impact. Less perceived benefit of online services also predicted later distress. Although there tends to be a focus on coping with negative effects of the pandemic, mental health providers may consider approaches that focus on positives, such as fostering hope and understanding factors that facilitate benefit from online services. LAY SUMMARY : Autistic adults may be at risk for psychological distress during the COVID-19 pandemic. The current study suggests that autistic adults who were younger, female, had a mental health diagnosis before the pandemic and knew someone who showed symptoms or tested positive for COVID-19 reported more areas negatively impacted by COVID-19 and greater difficulty coping with those effects. Decreases in hope over time were associated with greater psychological distress. Less perceived benefit from online services also predicted distress 2 months later. These results suggest important areas to further explore as we develop supports for autistic adults during the pandemic.

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4. Bemmer ER, Boulton KA, Thomas EE, Larke B, Lah S, Hickie IB, Guastella AJ. Modified CBT for social anxiety and social functioning in young adults with autism spectrum disorder. Mol Autism. 2021 ; 12(1) : 11.

BACKGROUND : There is a strong research imperative to investigate effective treatment options for adolescents and adults with autism spectrum disorder (ASD). Elevated social anxiety, difficulties with social functioning and poor mental health have all been identified as core treatment targets for this group. While theoretical models posit a strong bidirectionality between social anxiety and ASD social functioning deficits, few interventions have targeted both domains concurrently. Of the two group interventions previously conducted with adolescents and adults with ASD, significant results have only been observed in either social anxiety or social functioning, and have not generalised to changes in overall mood. The aim of this study was to evaluate the potential benefit, tolerability and acceptability of a group cognitive-behaviour therapy (CBT) intervention in young adults with ASD. Primary treatment outcomes were social anxiety symptoms and social functioning difficulties ; secondary outcomes were self-reported mood and overall distress. METHOD : Ten groups of participants completed an eight-week, modified group CBT intervention targeting both social anxiety and social functioning, that included social skills training, exposure tasks and behavioural experiment components. Seventy-eight adolescents and young adults with ASD, without intellectual impairment, aged between 16 and 38 (M = 22.77 ; SD = 5.31), were recruited from the community, Headspace centres and the Autism Clinic for Translational Research at the Brain and Mind Centre, University of Sydney. Outcomes (social anxiety, social functioning and mood) were measured pre- and post-intervention via self-report questionnaires (administered either online or through the return of hard-copy booklets), and participants were invited to provide anonymous feedback on the intervention (at the mid-point and end of the intervention). RESULTS : Participants demonstrated statistically significant improvements on all outcome measures in response to the intervention. Specifically, social anxiety symptoms decreased (p < .001), and specific subdomains of social functioning improved post-intervention, particularly in social motivation (p = .032) and restricted interests and repetitive behaviours (p = .025). Self-reported symptom improvements also generalised to mood (depression, anxiety and stress ; p < .05). All improvements demonstrated small effect sizes. Participant feedback was positive and indicated strong satisfaction with the program. LIMITATIONS : The absence of a control group and follow-up measures, reliance on self-report instruments as outcome measures and the exclusion of those with intellectual disability represent significant limitations to this study. CONCLUSIONS : These findings indicate that a group CBT intervention appears to be a beneficial intervention for self-reported social anxiety, social functioning and overall mental health in adolescents and young adults with ASD. The stand-alone nature of the intervention combined with positive participant feedback indicates it was well tolerated, has potential clinical utility and warrants further study in a randomised-controlled, follow-up design.

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5. Beverly J, Giannouchos T, Callaghan T. Examining frequent emergency department use among children and adolescents with autism spectrum disorder. Autism. 2021 : 1362361321990925.

This study used data for 5.9 million individuals with 9.1 million emergency department visits from all hospitals in the state of New York to explore frequent emergency department use between children and adolescents with autism spectrum disorders and those without autism spectrum disorders. We found that children and adolescents with autism spectrum disorders had larger shares of comorbidities and diagnoses related to attention-deficit/hyperactivity disorder, intellectual disability, and epilepsy. Children and adolescents with autism spectrum disorders were also more likely to utilize emergency departments and to exhibit frequent use. These results emphasize the need for using family-centered care to improve the care experiences of children and youth with autism spectrum disorders and their families. In addition, the education of emergency department staff of processes and practices as it relates to delivery of care and the care experience.

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6. Camero R, Martínez V, Gallego C. Gaze Following and Pupil Dilation as Early Diagnostic Markers of Autism in Toddlers. Children (Basel, Switzerland). 2021 ; 8(2).

Background : Children with autism spectrum disorder (ASD) show certain characteristics in visual attention. These may generate differences with non-autistic children in the integration of relevant social information to set the basis of communication. Reliable and objective measurement of these characteristics in a language learning context could contribute to a more accurate early diagnosis of ASD. Gaze following and pupil dilation are being studied as possible reliable measures of visual attention for the early detection of ASD. The eye-tracking methodology allows objective measurement of these biomarkers. The aim of this study is to determine whether measurements of gaze following and pupillary dilation in a linguistic interaction task are potential objective biomarkers for the early diagnosis of ASD. Method : A group of 20 children between 17 and 24 months of age, made up of 10 neurotypical children (NT) and 10 children with an increased likelihood of developing ASD were paired together according to chronological age. A human face on a monitor pronounced pseudowords associated with pseudo-objects. Gaze following and pupil dilation were registered during the task These measurements were captured using eye-tracking methodology. Results : Significant statistical differences were found in the time of gaze fixation on the human face and on the object, as well as in the number of gazes. Children with an increased possibility of developing ASD showed a slightly higher pupil dilation than NT children. However, this difference was not statistically significant. Nevertheless, their pupil dilation was uniform throughout the different periods of the task while NT participants showed greater dilation on hearing the pseudoword. Conclusions : The fixing and the duration of gaze, objectively measured by a Tobii eye-tracking system, could be considered as potential biomarkers for early detection of ASD. Additionally, pupil dilation measurement could reflect differential activation patterns during word processing in possible ASD toddlers and NT toddlers.

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7. Campbell K, Carbone PS, Liu D, Stipelman CH. Improving Autism Screening and Referrals With Electronic Support and Evaluations in Primary Care. Pediatrics. 2021.

BACKGROUND : Universal screening for autism promotes early evidence-based treatment. However, many children are not screened, and screened children are often not referred for autism evaluation. METHODS : We implemented process changes in 3 phases : phase 1, changing the screening instrument and adding decision support ; phase 2, adding automatic reminders ; and phase 3, adding a referral option for autism evaluations in primary care. We analyzed the proportion of visits with autism screening at 2 intervention clinics before and after implementation of process changes versus 27 community clinics (which received only automatic reminders in phase 2) with χ(2) test and interrupted time series. We evaluated changes in referral for autism evaluation by calculating the rate ratio for referral. RESULTS : In 12 233 visits over 2 years (baseline and phased improvements), autism screening increased by 52% in intervention clinics (58.6%-88.8% ; P < .001) and 21% in community clinics (43.4%-52.4% ; P < .001). In phase 1, interrupted time series trend for screening in intervention clinics increased by 2% per week (95% confidence interval [CI] : 1.1% to 2.9%) and did not increase in community clinics. In phase 2, screening in the community clinics increased by 0.46% per week (95% CI : 0.03% to 0.89%). In phase 3, the intervention clinic providers referred patients for diagnostic evaluation 3.4 times more frequently (95% CI : 2.0 to 5.8) than at baseline. CONCLUSIONS : We improved autism screening and referrals by changing the screening instrument, adding decision support, using automatic reminders, and offering autism evaluation in primary care in intervention clinics. Automatic reminders alone improved screening in community clinics.

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8. Dai L, Weiss RB, Dunn DM, Ramirez A, Paul S, Korenberg JR. Core Transcriptional Networks in Williams Syndrome : IGF1-PI3K-AKT-mTOR, MAPK and Actin Signaling at the Synapse Echo Autism. Hum Mol Genet. 2021.

Gene networks for disorders of social behavior provide the mechanisms critical for identifying therapeutic targets and biomarkers. Large behavioral phenotypic effects of small human deletions make the positive sociality of Williams syndrome (WS) ideal for determining transcriptional networks for social dysfunction currently based on DNA variations for disorders such as Autistic spectrum disorder (ASD). Consensus on WS networks has been elusive due to the need for larger cohort size, sensitive genome wide detection, and analytic tools. We report a core set of WS network perturbations in a cohort of 58 individuals (34 with typical, six atypical deletions and 18 controls). Genome-wide exon-level expression arrays robustly detected changes in differentially expressed gene (DEG) transcripts from WS deleted genes that ranked in the top 11 of 12 122 transcripts, validated by qRT-PCR, RNASeq and Western blots. WS DEG’s were strictly dosed in the full but not the atypical deletions that revealed a breakpoint position effect on non-deleted CLIP2, a caveat for current phenotypic mapping based on CNV. Network analyses tested the role of the top WS DEG’s in the dendritic spine, employing GeneMANIA to harmonize WS DEGs with comparable query gene-sets. The results indicate perturbed actin cytoskeletal signaling analogous to the excitatory dendritic spine. Independent Protein-Protein Interaction analyses of top WS DEGs generated a 100-node graph annotated topologically revealing three interacting pathways, MAPK, IGF1-PI3K-AKT-mTOR/insulin, and actin signaling at the synapse. The results indicate striking similarity of WS transcriptional networks to GWAS-based ASD risk suggesting common network dysfunction for these disorders of divergent sociality.

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9. Davis R, Crompton CJ. What Do New Findings About Social Interaction in Autistic Adults Mean for Neurodevelopmental Research ?. Perspectives on psychological science : a journal of the Association for Psychological Science. 2021 : 1745691620958010.

Deficit-based accounts of social and communication abilities continue to dominate autism research. However, emerging findings suggest that this view may be overly simplistic and discount the two-way nature of interaction. Here we discuss the reconceptualization of social cognition to consider such difficulties as examples of bidirectional, multifaceted misattunement between autistic and nonautistic individuals. Aligned with progressive theoretical frameworks, emerging empirical research indicates that mismatches in communication styles can contribute to autistic social difficulties and the important role that nonautistic difficulties play. We highlight two areas of future research with the aim of providing empirical support for the views that the autistic community has proposed over the past 2 decades. We discuss the impact of such a paradigm shift on a number of levels, including how bridging the gap between different interaction styles can reduce stigma and increase understanding. Adopting such a framework will provide radical opportunities for transformative societal changes and education around inclusion.

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10. de Korte MWP, van den Berk-Smeekens I, Buitelaar JK, Staal WG, van Dongen-Boomsma M. Pivotal Response Treatment for School-Aged Children and Adolescents with Autism Spectrum Disorder : A Randomized Controlled Trial. J Autism Dev Disord. 2021.

Pivotal Response Treatment (PRT) is promising for children with Autism Spectrum Disorder (ASD), but more methodologically robust designed studies are needed. In this randomized controlled trial, forty-four children with ASD, aged 9-15 years, were randomly allocated to PRT (n = 22) or treatment-as-usual (TAU ; n = 22). Measurements were obtained after 12- and 20-weeks treatment, and 2-month follow-up. PRT resulted in significant greater improvements on parent-rated social-communicative skills after 12 weeks treatment (p = .004, partial η(2) = 0.22), compared to TAU. Furthermore, larger gains in PRT compared to TAU were observed on blindly rated global functioning, and parent-rated adaptive socialization skills and attention problems. Implications for clinical practice and suggestions for future research are discussed.

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11. Fabio RA, Giannatiempo S, Semino M, Caprì T. Longitudinal cognitive rehabilitation applied with eye-tracker for patients with Rett Syndrome. Res Dev Disabil. 2021 ; 111 : 103891.

BACKGROUND : longitudinal effects of cognitive rehabilitation in Rett Syndrome (RTT) have been poorly investigated and the mechanisms do not appear to have been described in detail. AIMS : the aim of this study was to examine the effects of cognitive rehabilitation with eye-tracker technology on attention, choice behaviours and language over a 2-year period in patients with RTT. METHODS AND PROCEDURES : 28 participants with RTT, ranging from age 4-22 years old (M = 13.85 years, SD = 5.89), received 30 min of cognitive rehabilitation with eye-tracker for 3 days a week over a 1-month for 2 years. They then underwent cognitive assessment to evaluate attention, choice, language and global functioning in four specific times : before cognitive rehabilitation (T1), after six months of cognitive rehabilitation (T2), six months after the second cognitive rehabilitation phase (T3) and at the end of the third cognitive rehabilitation phase (T4). OUTCOME AND RESULTS : patients with RTT show long-term improvements in seconds of attention and number of choice behaviours, with barely any improvement in global functioning. No improvement in language was found. CONCLUSIONS AND IMPLICATIONS : this is the first study aimed at examining longitudinal effects of cognitive rehabilitation in patients with RTT, demonstrating a linear improvement across time in attention and choice.

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12. Ferahkaya H, Bilgiç A. Excessive Masturbation Successfully Treated With Methylphenidate in a 6-Year-Old Child With Autism Spectrum Disorder Accompanied by Attention Deficit Hyperactivity Disorder. Clinical neuropharmacology. 2021.

Children with autism spectrum disorder frequently exhibit inappropriate sexual behaviors, such as excessive masturbation. However, research on the control and management of excessive masturbation in these children is very limited. In this presentation, excessive masturbation that responded to treatment with methylphenidate is described in a young boy diagnosed with autism spectrum disorder and comorbid attention deficit hyperactivity disorder.

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13. Frazier TW, Klingemier EW, Anderson CJ, Gengoux GW, Youngstrom EA, Hardan AY. A Longitudinal Study of Language Trajectories and Treatment Outcomes of Early Intensive Behavioral Intervention for Autism. J Autism Dev Disord. 2021.

The present study examined language trajectories and placement outcomes for children with autism spectrum disorder (ASD) receiving early intensive behavioral intervention (EIBI). Language measures were collected at baseline and 6, 12, 18, 24, and 36 months or until exit from EIBI in 131 children with ASD. Growth models estimated overall and subgroup language trajectories. Overall, children receiving EIBI showed substantial increases in language relative to normative expectations. Earlier age at EIBI start, higher baseline cognitive function, and lower baseline ASD severity predicted better language trajectories. Although there was significant variability in language trajectories and educational outcomes, most children showed significant increases in language scores, relative to normative expectations. Additional research, in more representative samples, is needed to understand this variability.

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14. Goel A, Aschner M. The Effect of Lead Exposure on Autism Development. International journal of molecular sciences. 2021 ; 22(4).

Autism Spectrum Disorder (ASD) remains one of the most detrimental neurodevelopmental conditions in society today. Common symptoms include diminished social and communication ability. Investigations on autism etiology remain largely ambiguous. Previous studies have highlighted exposure to lead (Pb) may play a role in ASD. In addition, lead has been shown to be one of the most prevalent metal exposures associated with neurological deficits. A semi-systematic review was conducted using public databases in order to evaluate the extent of lead’s role in the etiology of autism. This review examines the relationship between autistic comorbid symptoms-such as deterioration in intelligence scores, memory, language ability, and social interaction-and lead exposure. Specifically, the mechanisms of action of lead exposure, including changes within the cholinergic, dopaminergic, glutamatergic, gamma aminobutyric acid (GABA)ergic systems, are discussed. The goal of this review is to help illustrate the connections between lead’s mechanistic interference and the possible furthering of the comorbidities of ASD. Considerations of the current data and trends suggest a potential strong role for lead in ASD.

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15. Gordon A, Krug MK, Wulff R, Elliott MV, Hogeveen J, Lesh T, Carter C, Solomon M. Components of Executive Control in Autism Spectrum Disorder : A Functional Magnetic Resonance Imaging Examination of Dual-Mechanism Accounts. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020.

BACKGROUND : It remains unclear whether executive control (EC) deficits in autism spectrum disorder (ASD) represent a failure in proactive EC (engaged and maintained before a cognitively demanding event) or in reactive EC (engaged transiently as the event occurs). We addressed this question by administering a paradigm investigating components of EC in a sample of individuals with ASD and typically developing individuals during functional magnetic resonance imaging. METHODS : During functional magnetic resonance imaging, 141 participants (64 ASD, 77 typically developing) completed a rapid preparing to overcome prepotency task that required participants to respond to an arrow probe based on the color of an initially presented cue. We examined functional recruitment and connectivity in the frontoparietal task control, cingulo-opercular task control, salience, and default mode networks during cue and probe phases of the task. RESULTS : ASD participants showed evidence of behavioral EC impairment. Analyses of functional recruitment and connectivity revealed that ASD participants showed significantly greater activity during the cue in networks associated with proactive control processes, but on the less cognitively demanding trials. On the more cognitively demanding trials, cue activity was similar across groups. During the probe, connectivity between regions associated with reactive control processes was uniquely enhanced on more-demanding (relative to less-demanding) trials in individuals with ASD but not in typically developing individuals. CONCLUSIONS : The current data suggest that rather than arising from a specific failure to engage proactive or reactive forms of EC, the deficits in EC commonly observed in ASD may be due to reduced proactive EC and a consequent overreliance on reactive EC on more cognitively demanding tasks.

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16. Kumazaki H, Muramatsu T, Yoshikawa Y, Kato TA, Ishiguro H, Kikuchi M, Mimura M. Use of a tele-operated robot to increase sociability in individuals with autism spectrum disorder who display Hikikomori. Asian J Psychiatr. 2021 ; 57 : 102588.

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17. Lee GT, Hu X, Jin N. Brief Report : Using Computer-Assisted Multiple Exemplar Instruction to Facilitate the Development of Bidirectional Naming for Children with Autism Spectrum Disorder. J Autism Dev Disord. 2021.

Bidirectional naming is an important ability which enables children to acquire listener and speaker behaviors through exposure to relevant word-object associations. Many children with autism spectrum disorder (ASD) or developmental delays do not demonstrate this ability and require systematic instruction. The purpose of the present study was to evaluate the efficacy of computer-assisted multiple exemplar instruction to facilitate bidirectional naming. Three 5-year-old Chinese boys with ASD participated in a multiple probe across three participants design. The results indicated that all three children’s naming performance increased from pretest to posttest, supporting the potential practicality of the instructional system for use in applied settings.

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18. Liu G, Wang S, Liao J, Ou P, Huang L, Xie N, He Y, Lin J, He HG, Hu R. The Efficacy of WeChat-Based Parenting Training on the Psychological Well-being of Mothers With Children With Autism During the COVID-19 Pandemic : Quasi-Experimental Study. JMIR mental health. 2021 ; 8(2) : e23917.

BACKGROUND : During the COVID-19 pandemic, special education schools for children in most areas of China were closed between the end of January and the beginning of June in 2020. The sudden interruption in schooling and the pandemic itself caused parents to be anxious and even to panic. Mobile-based parenting skills education has been demonstrated to be an effective method for improving the psychological well-being of mothers with children with autism. However, whether it can improve the psychological states of mothers in the context of the COVID-19 pandemic is a subject that should be urgently investigated. OBJECTIVE : The aim of this study is to evaluate the efficacy of WeChat-based parenting training on anxiety, depression, parenting stress, and hope in mothers with children with autism, as well as the feasibility of the program during the COVID-19 pandemic. METHODS : This was a quasi-experimental trial. A total of 125 mothers with preschool children with autism were recruited in January 2020. The participants were assigned to the control group (n=60), in which they received routine care, or the intervention group (n=65), in which they received the 12-week WeChat-based parenting training plus routine care, according to their preferences. Anxiety, depression, parenting stress, hope, satisfaction, and adherence to the intervention were measured at three timepoints : baseline (T0), postintervention (T1), and a 20-week follow-up (T2). RESULTS : In total, 109 mothers completed the T1 assessment and 104 mothers completed the T2 assessment. The results of the linear mixed model analysis showed statistically significant group × time interaction effects for the intervention on anxiety (F=14.219, P<.001), depression (F=26.563, P<.001), parenting stress (F=68.572, P<.001), and hope (F=197.608, P<.001). Of all mothers in the intervention group, 90.4% (48.8/54) reported that they were extremely satisfied with the WeChat-based parenting training. In total, 40.0% (26/65) logged their progress in home training each week and 61.5% (40/65) logged their progress more than 80% of the time for all 20 weeks. CONCLUSIONS : The WeChat-based parenting training is acceptable and appears to be an effective approach for reducing anxiety, depression, and parenting stress, as well as increasing hope in mothers with children with autism during the global COVID-19 pandemic. Future studies with rigorous designs and longer follow-up periods are needed to further detect the effectiveness of the WeChat-based parenting training. TRIAL REGISTRATION : Chinese Clinical Trial Registry ChiCTR2000031772 ; http://www.chictr.org.cn/showproj.aspx?proj=52165.

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19. Lopez-Espejo MA, Nuñez AC, Moscoso OC, Escobar RG. Brief Report : Health-Related Quality of Life in Preschoolers with Autism Spectrum Disorder is Related to Diagnostic Age and Autistic Symptom Severity. J Autism Dev Disord. 2021.

We conducted a cross-sectional study to explore whether clinical characteristics and autism diagnostic-traits severity are associated with caregiver-reported impairment of health-related quality of life (Pediatric Quality of Life Inventory Generic Core Scales, Fourth Edition) in 93 Chilean toddlers (age : 2-4 years) with autism spectrum disorder. Median total scale, physical health, and psychosocial health scores were 76 (IQR 70-81), 88 (IQR 81-94), and 71 (IQR 62-79), respectively. In multiple-regression analysis, diagnostic age (β = 0.219 ; p 0.021) and Calibrated Severity Score of Autism Diagnostic Observation Schedule, second edition (β = – 0.434 ; p < 0.001) were independently correlated to the total scale score. Lower age and higher autistic traits severity at diagnosis are correlated with worse well-being perception by caregivers.

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20. Muharib R, Lang R, Walker VL, Phinney A, Rodriguez M. An Evaluation of Reinforcer Magnitude and Echoic Prompts on Vocal Requesting of Individuals with Autism Spectrum Disorder. Journal of developmental and physical disabilities. 2021 : 1-15.

Individuals with autism spectrum disorder (ASD) often have communication support needs and many rely on augmentative and alternative communication (AAC) systems to communicate. Previous research suggests that AAC use does not preclude the acquisition of spoken language and, in some cases, may facilitate improvements in spoken communication in children with ASD. This study systematically applied echoic prompting and manipulated reinforcer magnitude in an effort to increase the spoken requests of 3 children with ASD, ages 10-12 years, who used iPad-based speech generating devices (SGDs). The spoken language (vocal requests) of all 3 participants increased in frequency and 1 participant began using spoken language exclusively, even when the SGD was an option. Implications for practitioners and directions for future research in this area are discussed.

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21. Parma V, Cellini N, Guy L, McVey AJ, Rump K, Worley J, Maddox BB, Bush J, Bennett A, Franklin M, Miller JS, Herrington J. Profiles of Autonomic Activity in Autism Spectrum Disorder with and without Anxiety. J Autism Dev Disord. 2021.

Both anxiety and autism spectrum disorder (ASD) are associated with atypical physiological activity. Few studies have systematically assessed the resting physiological activity in ASD with co-occurring anxiety disorders. We tested 75 participants divided in four groups : youth with ASD, with (ASD + Anxiety = 22, 6F, 12.29 ± 2.83 years old) and without co-occurring anxiety (ASD Alone = 15, 6F, 11.59 ± 2.85 years old) and compared their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F, 11.24 ± 3.36 years old) and without co-occurring anxiety disorders (TDC = 22, 8F, 11.88 ± 2.88 years old). Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth. ASD + Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic activity. These findings suggest that autonomic profile-based approaches may advance research, diagnosis, and treatment of ASD and anxiety.

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22. Parry JA, Brosnan S, Newton JT, Linehan C, Ryan C. Brief Report : Analysis of Dental Treatment Provided Under General Anaesthesia for Children and Young Adults with Autistic Spectrum Disorder and Identification of Challenges for Dental Services. J Autism Dev Disord. 2021.

Dental treatment provided under general anaesthesia (DGA) is an expectation for many children and young adults (CYA) diagnosed with Autistic Spectrum Disorder (ASD). Planning and delivery of DGA requires consideration of morbidity and mortality risks and implications for families and healthcare services. One hundred patient records of CYA with special healthcare needs were analysed to examine characteristics and experience of DGA revealing that 79% of CYA had a diagnosis of ASD. Forty-seven percent of CYA diagnosed with ASD had at least one previous hospital admission for DGA. For 24% of this repeat DGA group, the previous DGA was within a two-year period. Results highlight a high rate of DGA and need to investigate more effective primary dental care strategies.

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23. Ramezani M, Lotfi Y, Moossavi A, Bakhshi E. Effects of auditory processing training on speech perception and brainstem plastisity in adolescents with autism spectrum disorders. Iranian journal of child neurology. 2021 ; 15(1) : 69-77.

OBJECTIVE : Autism spectrum disorder (ASD) is a neurodevelopmental disorder. A major problem of ASD is speech perception impairment in the presence of background noise. Additionally, researchers have reported temporal auditory processing impairment in patients with ASD. In the present study, we evaluated the effects of a temporal-based training program on improvement of speech perception in the presence of noise using the speech auditory brainstem response (sABR). MATERIALS & METHODS : Twenty-eight adolescents with high functional ASD with the mean age of 14.35±1.86 years were randomly selected and divided into an ASD group (11 males and three females) and a control group (13 males and one female). All the subjects had a normal hearing and intelligence threshold and had no history of neurological disorder.A speech perception test was performed in signal-to-noise ratios of 0 and +10. The intervention group received a temporal processingbased auditory training program, and the control group received a conventional training program. A P-value of <0.05 was considered significant. RESULTS : After training, speech perception in the presence of noise was significantly higher (P <0.001) and the latency of all sABR waves was lower in the intervention group compared to the control group. CONCLUSION : Improvement of speech perception in noisy environments and the reduced latency of sABR waves following a temporal processingbased training program highlight the role of brainstem neural plasticity in speech processing.

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24. Sakamoto Y, Shimoyama S, Furukawa T, Adachi M, Takahashi M, Mikami T, Kuribayashi M, Osato A, Tsushima D, Saito M, Ueno S, Nakamura K. Copy number variations in Japanese children with autism spectrum disorder. Psychiatric genetics. 2021.

OBJECTIVE : Although autism spectrum disorder (ASD) occurs worldwide, most genomic studies on ASD were performed on those of Western ancestry. We hypothesized ASD-related copy number variations (CNVs) of Japanese individuals might be different from those of Western individuals. METHODS : Subjects were recruited from the Hirosaki 5-year-old children’s developmental health check-up (HFC) between 2013 and 2016 (ASD group ; n = 68, control group ; n = 124). This study conducted CNV analysis using genomic DNA from peripheral blood of 5-year-old Japanese children. Fisher’s exact test was applied for profiling subjects and CNV loci. RESULTS : Four ASD-related CNVs : deletion at 12p11.1, duplications at 4q13.2, 8p23.1 and 18q12.3 were detected (P = 0.015, 0.024, 0.009, 0.004, respectively). Specifically, the odds ratio of duplication at 18q12.3 was highest among the 4 CNVs (odds ratio, 8.13). CONCLUSIONS : Four CNVs : microdeletion at 12p11.1, microduplications at 4q13.2, 8p23.1 and 18q12.3 were detected as ASD-related CNVs in Japanese children in this study. Although these CNVs were consistent with several reports by Western countries at cytoband levels, these did not consistent at detailed genomic positions and sizes. Our data indicate the possibility that these CNVs are characteristic of Japanese children with ASD. We conclude that Japanese individuals with ASD may harbor CNVs different from those of Western individuals with ASD.

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25. Shirama A, Stickley A, Kamio Y, Nakai A, Takahashi H, Saito A, Haraguchi H, Kumazaki H, Sumiyoshi T. Emotional and behavioral problems in Japanese preschool children with motor coordination difficulties : the role of autistic traits. Eur Child Adolesc Psychiatry. 2021.

There has been little research on whether younger children with developmental coordination disorder (DCD) symptoms have an increased risk for emotional and behavioral problems. This study examined whether coordination difficulties are associated with emotional and behavioral problems (emotional symptoms, conduct problems, hyperactivity/inattention, peer problems, reduced prosocial behavior) in preschool children and the role of autistic traits in this association. Data (N = 1042, age 58-71 months) were analyzed from the Tama Children’s Survey (TCS). The Little Developmental Coordination Disorder Questionnaire (LDCDQ) was used to measure coordination difficulty symptoms. Information was obtained on emotional/behavioral problems using the Strengths and Difficulties Questionnaire (SDQ) and on autistic traits with the Social Responsiveness Scale (SRS). Higher autistic traits were based on SRS cutoff scores (53.5 for boys and 52.5 for girls). Logistic regression analysis was used to assess associations between the variables. In adjusted models, children with probable DCD (pDCD) were significantly more likely to score above the clinical thresholds on all SDQ emotional/behavioral domains. However, nearly all of these associations became nonsignificant after including autistic traits in the analysis. Additional analyses showed that children with pDCD with higher autistic traits had significantly increased odds for emotional problems (odds ratio [OR] : 4.47, 95% confidence interval [CI] : 1.52-13.19), hyperactivity/inattention (OR : 3.74, 95% CI : 1.45-9.64), peer problems (OR : 15.81, 95% CI : 5.96-41.99), and total difficulties (OR : 28.78, 95% CI : 7.23-114.57), compared to children with pDCD alone. These results indicate that the increased risk of emotional/behavioral difficulties in preschool children with pDCD might be mediated by autistic traits.

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26. Smith MJ, Sherwood K, Ross B, Smith JD, DaWalt L, Bishop L, Humm L, Elkins J, Steacy C. Virtual interview training for autistic transition age youth : A randomized controlled feasibility and effectiveness trial. Autism. 2021 : 1362361321989928.

Autistic transition age youth struggle with obtaining employment, and interviewing is a critical barrier to getting a job. We adapted an efficacious virtual reality job interview intervention to meet the needs of autistic transition age youth, called the Virtual Interview Training for Transition Age Youth. This study evaluated whether Virtual Interview Training for Transition Age Youth can be feasibly delivered in high school special education settings and whether Virtual Interview Training for Transition Age Youth improves job interview skills, job interview self-efficacy, job interview anxiety, and access to employment. Forty-eight autistic transition age youth received school-based pre-employment services as usual with Virtual Interview Training for Transition Age Youth, while 23 autistic transition age youth received services as usual only. Local teachers trained and supervised autistic transition age youth using Virtual Interview Training for Transition Age Youth. Participants reported Virtual Interview Training for Transition Age Youth was highly acceptable. Participants receiving services as usual and Virtual Interview Training for Transition Age Youth, compared to participants receiving services as usual only, had better job interview skills and lower job interview anxiety as well as greater access to jobs. Overall, Virtual Interview Training for Transition Age Youth appears to be effective at teaching job interview skills that are associated with accessing competitive jobs. Moreover, youth enjoyed Virtual Interview Training for Transition Age Youth and teachers feasibly implemented the tool within special education pre-employment transition services. Future research needs to better understand how autistic transition age youth from culturally diverse backgrounds and different social, behavioral, or mental health challenges may respond to Virtual Interview Training for Transition Age Youth.

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27. Straiton D, Groom B, Ingersoll B. A mixed methods exploration of community providers’ perceived barriers and facilitators to the use of parent training with Medicaid-enrolled clients with autism. Autism. 2021 : 1362361321989911.

Using quantitative data from an online survey and qualitative data from follow-up interviews with applied behavior analysis providers, researchers examined barriers and facilitators to providing parent training to Medicaid-enrolled youth with autism spectrum disorder. Barriers and facilitators were identified at the family-, provider-, and organization-levels. Family-level barriers were significantly related to less frequent parent training use and poorer quality of use. Two recommendations are provided to increase the use of parent training in low-resourced community settings : (1) provide professional training opportunities to providers about best practices in parent training and (2) increase agency support for parent training, particularly in reducing logistical barriers.

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28. Tayyar Iravanlou F, Soltani M, Alsadat Rahnemaei F, Abdi F, Ilkhani M. Non- Pharmacological Approaches on the Improvement of Sleep Disturbances in Patients with Autism Spectrum Disorder (ASD). Iranian journal of child neurology. 2021 ; 15(1) : 79-91.

ABSTRACT : Autism is a type of neurodegenerative disorder, caused by genetic and environmental factors. Children with autism spectrum disorder (ASD) have symptoms of attention deficit and behavioral problems. Child’s sleep pattern has a significant effect on mood. Sleep problems are more common in children with ASD. The current study aimed to investigate the effect of non-pharmacological approaches on the improvement of sleep disturbances in patients with ASD. MATERIALS & METHODS : We systematically searched PubMed, EMBASE, Web of Science, Scopus, and Science Direct to identify relevant articles published from January 2009 to May 2019. All original articles from observational and interventional studies were reviewed. The CONSORT Statement and Strengthening the Reporting of Observational Studies in Epidemiology(STROBE) checklist were used to assess the quality of selected papers. RESULTS : Reviewing 18 eligible articles according to the CONSORT checklist(for interventional studies) and STROBE (for descriptive studies) demonstrated that behavioral interventions, such as cognitivebehavioral therapy, bedtime fading with response cost, and functional behavioral assessment, physical activity such as aerobic exercise, swimming, and aquatic exercise and weighted blankets can improve sleep disturbances. CONCLUSION : Restlessness, tantrums, increased stereotypic activities, and reducedlearning level and speaking power in children with autism were. caused by poor sleep quality and sleep deficiency, which may affect other dimensions of life. Non- pharmacological approaches to sleep disturbances could improve both sleep quality and quality of life of children with ASD with no adverse effect.

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29. Weber S, Falter-Wagner C, Stöttinger E. Brief Report : Typical Visual Updating in Autism. J Autism Dev Disord. 2021.

Individuals with Autism Spectrum Disorder (ASD) can struggle with visual updating. In a previous picture morphing study (Burnett and Jellema 2012) adults with ASD recognized the second picture significantly later when seeing one picture gradually changing into another. The aim of the current study was to test whether this previously reported perceptual atypicality may be due to general perceptual deficits. We therefore employed a modified picture morphing task. Against expectations, people with ASD showed typical performance in the task and no general perceptual deficits in relation to the picture morphing paradigm. Our results suggest that reported difficulties with visual updating in ASD may be due to temporal task restrictions and do not reflect a genuine problem with visual updating.

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30. Yap CX, Alvares GA, Henders AK, Lin T, Wallace L, Farrelly A, McLaren T, Berry J, Vinkhuyzen AAE, Trzaskowski M, Zeng J, Yang Y, Cleary D, Grove R, Hafekost C, Harun A, Holdsworth H, Jellett R, Khan F, Lawson L, Leslie J, Levis Frenk M, Masi A, Mathew NE, Muniandy M, Nothard M, Visscher PM, Dawson PA, Dissanayake C, Eapen V, Heussler HS, Whitehouse AJO, Wray NR, Gratten J. Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank. Mol Autism. 2021 ; 12(1) : 12.

BACKGROUND : Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. METHODS : Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. RESULTS : The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7 ; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3 ; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. LIMITATIONS : This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. CONCLUSIONS : We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).

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