1. Arango C. Reply to : Another Vision From the Coronavirus Health Crisis in Spain : The Perspective From the Plena inclusión Developmental Disabilities Associative Movement. Biol Psychiatry. 2021 ; 89(4) : e19-e20.

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2. Aye SZ, Ni H, Sein HH, Mon ST, Zheng Q, Wong YKY. The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder. Cochrane Database Syst Rev. 2021 ; 2 : Cd013457.

BACKGROUND : Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N-methyl-D-aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D-cycloserine – which is a partial agonist of the NMDA glutamate receptor – are potential treatment options for the core features of ASD. However, the potential effect of D-cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted. OBJECTIVES : To assess the efficacy and adverse effects of D-cycloserine compared with placebo for social and communication skills in individuals with ASD. SEARCH METHODS : In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers’ websites and sources of reports of adverse events. SELECTION CRITERIA : All randomised controlled trials (RCTs) of any duration and dose of D-cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS : Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review. MAIN RESULTS : We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA : Indiana University School of Medicine and Cincinnati Children’s Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D-cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D-cycloserine and placebo arms, and outcome measures were recorded at one-week post-treatment. The ‘risk of bias’ assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference between the two groups for all outcomes measured at one week post-treatment : social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82) ; social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18) ; restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95) ; serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31) ; non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93) ; and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68). AUTHORS’ CONCLUSIONS : We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

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3. Babb C, Brede J, Jones CRG, Elliott M, Zanker C, Tchanturia K, Serpell L, Mandy W, Fox JRE. ‘It’s not that they don’t want to access the support . . . it’s the impact of the autism’ : The experience of eating disorder services from the perspective of autistic women, parents and healthcare professionals. Autism. 2021 : 1362361321991257.

This study explores autistic women’s experiences of eating disorder services. About 20%-30% of people with anorexia nervosa are also autistic, and current treatments seem not to work as well for them. We interviewed 15 autistic women with experience of anorexia nervosa, 12 parents of autistic women with anorexia nervosa, and 11 healthcare professionals working in eating disorder services. We asked autistic women and parents about their experiences of eating disorder services, and we asked healthcare professionals about their experiences treating autistic women with anorexia nervosa. Participants’ views were represented by three overall themes : misunderstanding autism and autistic traits, one treatment does not fit all, and improving accessibility and engagement within services. We found that autistic women face many barriers when in treatment for anorexia nervosa, often because of a lack of autism understanding within eating disorder services. Future research should look at developing anorexia nervosa treatments that can specifically help autistic individuals.

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4. Cantin-Garside KD, Nussbaum MA, White SW, Kim S, Kim CD, Fortes DMG, Valdez RS. Understanding the experiences of self-injurious behavior in autism spectrum disorder : Implications for monitoring technology design. Journal of the American Medical Informatics Association : JAMIA. 2021 ; 28(2) : 303-10.

OBJECTIVE : Monitoring technology may assist in managing self-injurious behavior (SIB), a pervasive concern in autism spectrum disorder (ASD). Affiliated stakeholder perspectives should be considered to design effective and accepted SIB monitoring methods. We examined caregiver experiences to generate design guidance for SIB monitoring technology. MATERIALS AND METHODS : Twenty-three educators and 16 parents of individuals with ASD and SIB completed interviews or focus groups to discuss needs related to monitoring SIB and associated technology use. RESULTS : Qualitative content analysis of participant responses revealed 7 main themes associated with SIB and technology : triggers, emotional responses, SIB characteristics, management approaches, caregiver impact, child/student impact, and sensory/technology preferences. DISCUSSION : The derived themes indicated areas of emphasis for design at the intersection of monitoring and SIB. Systems design at this intersection should consider the range of manifestations of and management approaches for SIB. It should also attend to interactions among children with SIB, their caregivers, and the technology. Design should prioritize the transferability of physical technology and behavioral data as well as the safety, durability, and sensory implications of technology. CONCLUSIONS : The collected stakeholder perspectives provide preliminary groundwork for an SIB monitoring system responsive to needs as articulated by caregivers. Technology design based on this groundwork should follow an iterative process that meaningfully engages caregivers and individuals with SIB in naturalistic settings.

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5. Drill RB, Bellini S. Combining Readers Theater, Story Mapping and Video Self-Modeling Interventions to Improve Narrative Reading Comprehension in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2021.

Individuals with Autism Spectrum Disorder (ASD) demonstrate atypical development, resulting in significant deficits in perspective-taking and observational learning. Children with ASD tend to have challenges in social interactions and academic performance, such as comprehending narrative texts, which heavily rely on accurate understanding of the thoughts and feelings of others. However, the current literature provides limited information on effective interventions to address these areas. The present study expands the existing research base by combining Readers Theater, story mapping, and video self-modeling, three separate research-based interventions, into an intervention package for children with ASD. A multiple-baseline across participants design was utilized. Overall, the results indicate that the intervention package successfully improved reading comprehension. Implications and suggestions for future research are discussed.

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6. Droboniku MJ, Mychailyszyn MP. Animal Interaction Affecting Core Deficit Domains Among Children with Autism : A Meta-Analysis. J Autism Dev Disord. 2021.

Animal-assisted intervention (AAI) has garnered public interest and has been implemented for youth with autism spectrum disorders-a practice supported by anecdotal evidence. While investigations of AAI for children with autism have been conducted, the extant literature is characterized by significant variability in methodology and practice. The present meta-analysis examines the aggregated effects of equine AAI on adaptive functioning among children with autism. Results indicated that interacting with an equine specifically during AAI produced small-to-medium effects (g = 0.40) on the adaptive functioning of children with autism. Recommendations are made for future research on this topic.

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7. Feller C, Dubois C, Eliez S, Schneider M. Episodic Future Thinking in Autism Spectrum Disorder and 22q11.2 Deletion Syndrome : Association with Anticipatory Pleasure and Social Functioning. J Autism Dev Disord. 2021.

Episodic future thinking (EFT) has been suggested to underlie anticipatory pleasure (AP), itself known to play a crucial role in social functioning (SF). Both AP and SF are impaired in various clinical populations, including autism spectrum disorders (ASD) and 22q11.2 deletion syndrome (22q11DS). Therefore, the relationship between EFT, AP and SF was investigated, as well as the potential role of projecting oneself in a social vs. non-social context. Seventy-seven participants [24 with 22q11DS, 20 with ASD, 33 typically developing controls (TDs)] (aged 12-25) were included. They were assessed with a future thinking task in which they were asked to recall a memory and produce a likely event. Narratives were rated based of specificity, richness and imaginability. Participants completed questionnaires assessing AP and SF. Narratives from ASD and 22q11DS participants were rated as less vivid compared to TDs. However, the characteristics of the narratives differed between ASD and 22q11DS participants in terms of specificity and level of details, as well as in reaction to social condition. Moreover, correlations were found between AP and EFT in both ASD and 22q11DS participants, and between SF and EFT in ASD participants. These results point towards impairments in EFT in both ASD and 22q11DS participants but with a specific profile in each condition. The observed associations between EFT and AP suggest that decreased autonoetic consciousness might underlie AP impairments. In ASD individuals, the association between SF and EFT highlights the need to better characterize EFT since EFT could be another mechanism contributing to social difficulties.

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8. 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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9. Galván E. Another Vision From the Coronavirus Health Crisis in Spain : The Perspective From the Plena inclusión Developmental Disabilities Associative Movement. Biol Psychiatry. 2021 ; 89(4) : e17-e8.

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10. Jung J, Zbozinek TD, Cummings KK, Wilhelm FH, Dapretto M, Craske MG, Bookheimer SY, Green SA. Associations between physiological and neural measures of sensory reactivity in youth with autism. J Child Psychol Psychiatry. 2021.

BACKGROUND : Individuals with Autism Spectrum Disorder (ASD) commonly show sensory over-responsivity (SOR), an impairing condition related to over-reactive brain and behavioral responses to aversive stimuli. While individuals with ASD often show atypically high physiological arousal, it is unclear how this relates to sensory reactivity. We therefore investigated how physiological arousal relates to brain and behavioral indices of SOR, to inform understanding of the biological mechanisms underlying SOR and to determine whether physiological measures are associated with SOR-related brain responses. METHODS : Youth aged 8-18 (49 ASD ; 30 age- and performance-IQ-matched typically developing (TD)) experienced mildly aversive tactile and auditory stimuli first during functional magnetic resonance imaging (N = 41 ASD, 26 TD) and then during skin conductance (SCR) (N = 48 ASD, 28 TD) and heart rate (HR) measurements (N = 48 ASD, 30 TD). Parents reported on their children’s SOR severity. RESULTS : Autism Spectrum Disorder youth overall displayed greater SCR to aversive sensory stimulation than TD youth and greater baseline HR. Within ASD, higher SOR was associated with higher mean HR across all stimuli after controlling for baseline HR. Furthermore, the ASD group overall, and the ASD-high-SOR group in particular, showed reduced HR deceleration/greater acceleration to sensory stimulation compared to the TD group. Both SCR and HR were associated with brain responses to sensory stimulation in regions previously associated with SOR and sensory regulation. CONCLUSIONS : Autism Spectrum Disorder youth displayed heightened physiological arousal to mildly aversive sensory stimulation, with HR responses in particular showing associations with brain and behavioral measures of SOR. These results have implications for using psychophysiological measures to assess SOR, particularly in individuals with ASD who cannot undergo MRI.

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11. Kern-Goldberger AR, Burris HH, Levine LD. Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder. JAMA Pediatr. 2021.

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12. Lee A, Guglielminotti J, Landau R. Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder. JAMA Pediatr. 2021.

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13. Lorah E, Holyfield C, Kucharczyk S. Typical preschoolers’ perceptions of augmentative and alternative communication modes of a preschooler with autism spectrum disorder. Augmentative and alternative communication (Baltimore, Md : 1985). 2021 : 1-20.

Understanding typical preschoolers’ perceptions of communication modes could help guide augmentative and alternative communication (AAC) intervention for preschoolers with autism spectrum disorder (ASD). This study explored the perceptions of 16 typically developing preschoolers toward an (a) AAC application (app) on a tablet, (b) picture exchange using a binder with printed Picture Communication Symbols(TM), and (c) prelinguistic communication used by a preschooler with ASD in a series of videos the preschoolers watched. Using a multi-method design, the study implemented both quantitative (rank ordering and preference selection) and qualitative (interview) methodologies. Quantitative results revealed the typical preschoolers had a clear overall preference for the AAC app, but variation in preference existed when selecting a communication mode to use in specific social scenarios. Qualitative data show the children more easily understood the child with ASD when he used the AAC app and associated tablets with fun, which may have accounted for positive perceptions of this AAC mode. The study is exploratory in nature and limited by its size and scope. However, it provides insights useful for clinicians’ understanding not just how typical preschoolers perceive various modes of communication, but also why they may perceive some more favorably than others, in order to tailor intervention accordingly.

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14. McParland A, Gallagher S, Keenan M. Investigating Gaze Behaviour of Children Diagnosed with Autism Spectrum Disorders in a Classroom Setting. J Autism Dev Disord. 2021.

A defining feature of ASD is atypical gaze behaviour, however, eye-tracking studies in ‘real-world’ settings are limited, and the possibility of improving gaze behaviour for ASD children is largely unexplored. This study investigated gaze behaviour of ASD and typically developing (TD) children in their classroom setting. Eye-tracking technology was used to develop and pilot an operant training tool to positively reinforce typical gaze behaviour towards faces. Visual and statistical analyses of eye-tracking data revealed different gaze behaviour patterns during live interactions for ASD and TD children depending on the interaction type. All children responded to operant training with longer looking times observed on face stimuli post training. The promising application of operant gaze training in ecologically valid settings is discussed.

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15. Nabil MA, Akram A, Fathalla KM. Applying machine learning on home videos for remote autism diagnosis : Further study and analysis. Health informatics journal. 2021 ; 27(1) : 1460458221991882.

Autism Spectrum Disorder (Autism) is a developmental disorder that impedes the social and communication capabilities of a person through out his life. Early detection of autism is critical in contributing to better prognosis. In this study, the use of home videos to provide accessible diagnosis is investigated. A machine learning approach is adopted to detect autism from home videos. Feature selection and state-of-the-art classification methods are applied to provide a sound diagnosis based on home video ratings obtained from non-clinicians feedback. Our models results indicate that home videos can effectively detect autistic group with True Positive Rate reaching 94.05% using Support Vector Machines and backwards feature selection. In this study, human-interpretable models are presented to elucidate the reasoning behind the classification process and its subsequent decision. In addition, the prime features that need to be monitored for early autism detection are revealed.

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16. Ohashi K, Fukuhara S, Miyachi T, Asai T, Imaeda M, Goto M, Kurokawa Y, Anzai T, Tsurusaki Y, Miyake N, Matsumoto N, Yamagata T, Saitoh S. Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings. J Autism Dev Disord. 2021.

Although genetic factors are involved in the etiology of autism spectrum disorder (ASD), the significance of genetic analysis in clinical settings is unclear. Forty-nine subjects diagnosed with non-syndromic ASD were analyzed by microarray comparative genomic hybridization (CGH) analysis, whole-exome sequencing (WES) analysis, and panel sequencing analysis for 52 common causative genes of ASD to detect inherited rare variants. Genetic analysis by microarray CGH and WES analyses showed conclusive results in about 10% of patients, however, many inherited variants detected by panel sequencing analysis were difficult to interpret and apply in clinical practice in the majority of patients. Further improvement of interpretation of many variants detected would be necessary for combined genetic tests to be used in clinical settings.

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17. Qiu C, Desai V, Xiang AH. Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder-Reply. JAMA Pediatr. 2021.

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18. Roberta B, Riva V, Cantiani C, Riboldi EM, Molteni M, Macchi Cassia V, Bulf H. Dysfunctions in Infants’ Statistical Learning are Related to Parental Autistic Traits. J Autism Dev Disord. 2021.

Statistical learning refers to the ability to extract the statistical relations embedded in a sequence, and it plays a crucial role in the development of communicative and social skills that are impacted in the Autism Spectrum Disorder (ASD). Here, we investigated the relationship between infants’ SL ability and autistic traits in their parents. Using a visual habituation task, we tested infant offspring of adults (non-diagnosed) who show high (HAT infants) versus low (LAT infants) autistic traits. Results demonstrated that LAT infants learned the statistical structure embedded in a visual sequence, while HAT infants failed. Moreover, infants’ SL ability was related to autistic traits in their parents, further suggesting that early dysfunctions in SL might contribute to variabilities in ASD symptoms.

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19. Tamizkar KH, Ghafouri-Fard S, Omrani MD, Pouresmaeili F, Arsang-Jang S, Taheri M. Altered expression of lncRNAs in autism spectrum disorder. Metabolic brain disease. 2021.

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001 ; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = -3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = -0.982, P value<0.0001 and Posterior Beta = -0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = -0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs : DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.

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20. Yakubova G, Chen BB. Examining the Effects of Parent-Created and Parent-Implemented Video Prompting to Teach Daily Living Skills to an Adolescent with Autism. J Autism Dev Disord. 2021 : 1-13.

Teaching parents how to create their own video-prompting (VP) and implement it to help their children learn daily living tasks at home can be empowering for parents. Using a multiple probe across three tasks design, we examined the effects of parent-created and parent-implemented VP and error correction strategy on teaching three daily living tasks to a 14-year-old child with autism spectrum disorder (ASD). Following a one-time training and continuous coaching, a parent successfully created a VP intervention for all three tasks and implemented VP with error correction with high fidelity. Following the intervention implementation, the child with ASD learned to complete daily living tasks with high levels of accuracy and maintained task completion at a 1-week follow-up.

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21. Zheng W, Zhao Z, Zhang Z, Liu T, Zhang Y, Fan J, Wu D. Developmental pattern of the cortical topology in high-functioning individuals with autism spectrum disorder. Hum Brain Mapp. 2021 ; 42(3) : 660-75.

A number of studies have indicated alterations of brain morphology in individuals with autism spectrum disorder (ASD) ; however, how ASD influences the topological organization of the brain cortex at different developmental stages is not yet well characterized. In this study, we used structural images of 492 high-functioning participants in the Autism Brain Imaging Data Exchange database acquired from 17 international imaging centers, including 75 autistic children (age 7-11 years), 91 adolescents with ASD (age 12-17 years), and 80 young adults with ASD (age 18-29 years), and 246 typically developing controls (TDCs) that were age, gender, handedness, and full-scale IQ matched. Cortical thickness (CT) and surface area (SA) were extracted and the covariance between cortical regions across participants were treated as a network to examine developmental patterns of the cortical topological organization at different stages. A center-paired resampling strategy was developed to control the center bias during the permutation test. Compared with the TDCs, network of SA (but not CT) of individuals with ASD showed reduced small-worldness in childhood, and the network hubs were reorganized in the adulthood such that hubs inclined to connect with nonhub nodes and demonstrated more dispersed spatial distribution. Furthermore, the SA network of the ASD cohort exhibited increased segregation of the inferior parietal lobule and prefrontal cortex, and insular-opercular cortex in all three age groups, resulting in the emergence of two unique modules in the autistic brain. Our findings suggested that individuals with ASD may undergo remarkable remodeling of the cortical topology from childhood to adulthood, which may be associated with the altered social and cognitive functions in ASD.

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