1. Bahathiq RA, Banjar H, Bamaga AK, Jarraya SK. Machine learning for autism spectrum disorder diagnosis using structural magnetic resonance imaging: Promising but challenging. Frontiers in neuroinformatics. 2022; 16: 949926.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects approximately 1% of the population and causes significant burdens. ASD’s pathogenesis remains elusive; hence, diagnosis is based on a constellation of behaviors. Structural magnetic resonance imaging (sMRI) studies have shown several abnormalities in volumetric and geometric features of the autistic brain. However, inconsistent findings prevented most contributions from being translated into clinical practice. Establishing reliable biomarkers for ASD using sMRI is crucial for the correct diagnosis and treatment. In recent years, machine learning (ML) and specifically deep learning (DL) have quickly extended to almost every sector, notably in disease diagnosis. Thus, this has led to a shift and improvement in ASD diagnostic methods, fulfilling most clinical diagnostic requirements. However, ASD discovery remains difficult. This review examines the ML-based ASD diagnosis literature over the past 5 years. A literature-based taxonomy of the research landscape has been mapped, and the major aspects of this topic have been covered. First, we provide an overview of ML’s general classification pipeline and the features of sMRI. Next, representative studies are highlighted and discussed in detail with respect to methods, and biomarkers. Finally, we highlight many common challenges and make recommendations for future directions. In short, the limited sample size was the main obstacle; Thus, comprehensive data sets and rigorous methods are necessary to check the generalizability of the results. ML technologies are expected to advance significantly in the coming years, contributing to the diagnosis of ASD and helping clinicians soon.

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2. Barbaresi W, Cacia J, Friedman S, Fussell J, Hansen R, Hofer J, Roizen N, Stein REK, Vanderbilt D, Sideridis G. Clinician Diagnostic Certainty and the Role of the Autism Diagnostic Observation Schedule in Autism Spectrum Disorder Diagnosis in Young Children. JAMA pediatrics. 2022.

IMPORTANCE: Autism spectrum disorder (ASD) affects 1 in 44 children. The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured observation developed for use in research but is considered a component of gold standard clinical diagnosis. The ADOS adds time and cost to diagnostic assessments. OBJECTIVE: To evaluate consistency between clinical diagnosis (index ASD diagnosis) and diagnosis incorporating the ADOS (reference standard ASD diagnosis) and to examine clinician and child factors that predict consistency between index diagnoses and reference standard diagnoses. DESIGN, SETTING, AND PARTICIPANTS: This prospective diagnostic study was conducted between May 2019 and February 2020. Developmental-behavioral pediatricians (DBPs) made a diagnosis based on clinical assessment (index ASD diagnosis). The ADOS was then administered, after which the DBP made a second diagnosis (reference standard ASD diagnosis). DBPs self-reported diagnostic certainty at the time of the index diagnoses and reference standard diagnoses. The study took place at 8 sites (7 US and 1 European) that provided subspecialty assessments for children with concerns for ASD. Participants included children aged 18 months to 5 years, 11 months, without a prior ASD diagnosis, consecutively referred for possible ASD. Among 648 eligible children, 23 refused, 376 enrolled, and 349 completed the study. All 40 eligible DBPs participated. EXPOSURES: ADOS administered to all child participants. MAIN OUTCOMES AND MEASURES: Index diagnoses and reference standard diagnoses of ASD (yes/no). RESULTS: Among the 349 children (279 [79.7%] male; mean [SD] age, 39.9 [13.4] months), index diagnoses and reference standard diagnoses were consistent for 314 (90%) (ASD = 250; not ASD = 64) and changed for 35. Clinician diagnostic certainty was the most sensitive and specific predictor of diagnostic consistency (area under curve = 0.860; P < .001). In a multilevel logistic regression, no child or clinician factors improved prediction of diagnostic consistency based solely on clinician diagnostic certainty at time of index diagnosis. CONCLUSIONS AND RELEVANCE: In this prospective diagnostic study, clinical diagnoses of ASD by DBPs with vs without the ADOS were consistent in 90.0% of cases. Clinician diagnostic certainty predicted consistency of index diagnoses and reference standard diagnoses. This study suggests that the ADOS is generally not required for diagnosis of ASD in young children by DBPs and that DBPs can identify children for whom the ADOS may be needed.

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3. Calabretta BT, Schneider JL, Iverson JM. Bidding on the go: Links between walking, social actions, and caregiver responses in infant siblings of children with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2324-35.

The development of walking is associated with a shift in how neurotypical infants initiate social interactions. Walking infants are more likely to locate objects in distant places, carry them, and then share those objects by approaching caregivers and using gestures to show or offer their discoveries (i.e., moving bids). The simultaneous organization of the behaviors necessary to generate moving bids requires the coordination of multiple skills-walking, fine motor skills, and gesturing. Infants with an elevated likelihood (EL) for autism spectrum disorder (ASD) exhibit differences and delays in each of these behaviors. This study investigated interconnections between infant walking, social actions, and caregiver responses in 18-month-old EL infants with diverse developmental outcomes (ASD, non-ASD language delay, no diagnosis). We observed 85 infant-caregiver dyads at home during everyday activities for 45 minutes and identified all times when infants walked, instances of walking paired with social action (i.e., approaching the caregiver, approaching while carrying an object, producing a moving bid), and whether caregivers responded to their infants’ social actions. There were no group differences in infants’ production of social actions. Caregiver responses, however, were more clearly modulated by outcome group. While all caregivers were similarly and highly likely to respond to moving bids, caregivers of EL-ASD infants were substantially more likely to respond when their infants simply approached them (with or without an object in hand). Taken together, this research underscores the complexity of EL infant-caregiver interactions and highlights the role that each partner plays in shaping how they unfold.

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4. Camarata SM. Tensions Between Autistic Sociality, Communication, and Social Skills Research: Utilizing the Communication Bill of Rights to Support Autistic People. Journal of speech, language, and hearing research : JSLHR. 2022; 65(11): 4351-3.

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5. Cao H, Tang J, Liu Q, Huang J, Xu R. Autism-like behaviors regulated by the serotonin receptor 5-HT2B in the dorsal fan-shaped body neurons of Drosophila melanogaster. European journal of medical research. 2022; 27(1): 203.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and repetitive stereotyped behaviors. Previous studies have reported an association of serotonin or 5-hydroxytryptamine (5-HT) with ASD, but the specific receptors and neurons by which serotonin modulates autistic behaviors have not been fully elucidated. METHODS: RNAi-mediated knockdown was done to destroy the function of tryptophan hydroxylase (Trh) and all the five serotonin receptors. Given that ubiquitous knockdown of 5-HT2B showed significant defects in social behaviors, we applied the CRISPR/Cas9 system to knock out the 5-HT2B receptor gene. Social space assays and grooming assays were the major methods used to understand the role of serotonin and related specific receptors in autism-like behaviors of Drosophila melanogaster. RESULTS: A close relationship was identified between serotonin and autism-like behaviors reflected by increased social space distance and high-frequency repetitive behavior in Drosophila. We further utilized the binary expression system to knock down all the five 5-HT receptors, and observed the 5-HT2B receptor as the main receptor responsible for the normal social space and repetitive behavior in Drosophila for the specific serotonin receptors underlying the regulation of these two behaviors. Our data also showed that neurons in the dorsal fan-shaped body (dFB), which expressed 5-HT2B, were functionally essential for the social behaviors of Drosophila. CONCLUSIONS: Collectively, our data suggest that serotonin levels and the 5-HT2B receptor are closely related to the social interaction and repetitive behavior of Drosophila. Of all the 5 serotonin receptors, 5-HT2B receptor in dFB neurons is mainly responsible for serotonin-mediated regulation of autism-like behaviors.

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6. Chien YL, Chen YJ, Tseng WL, Hsu YC, Wu CS, Tseng WI, Gau SS. Differences in white matter segments in autistic males, non-autistic siblings, and non-autistic participants: An intermediate phenotype approach. Autism : the international journal of research and practice. 2022: 13623613221125620.

White matter is the neural pathway that connects neurons in different brain regions. Although research has shown white matter differences between autistic and non-autistic people, little is known about the properties of white matter in non-autistic siblings. In addition, past studies often focused on the whole neural tracts; it is unclear where differences exist in specific segments of the tracts. This study identified neural segments that differed between autistic people, their non-autistic siblings, and the age- and non-autistic people. We found altered segments within the tracts connected to anterior brain regions corresponding to several higher cognitive functions (e.g. executive functions) in autistic people and non-autistic siblings. Segments connecting to regions for social cognition and Theory of Mind were altered only in autistic people, explaining a large portion of autistic traits and may serve as neuroimaging markers. Segments within the tracts associated with fewer autistic traits or connecting brain regions for diverse highly integrated functions showed compensatory increases in the microstructural properties in non-autistic siblings. Our findings suggest that differential white matter segments that are shared between autistic people and non-autistic siblings may serve as potential « intermediate phenotypes »-biological or neuropsychological characteristics in the causal link between genetics and symptoms-of autism. These findings shed light on a promising neuroimaging model to refine the intermediate phenotype of autism which may facilitate further identification of the genetic and biological bases of autism. Future research exploring links between compensatory segments and neurocognitive strengths in non-autistic siblings may help understand brain adaptation to autism.

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7. Chien YL, Wu CS, Chang YC, Cheong ML, Yao TC, Tsai HJ. Associations between parental psychiatric disorders and autism spectrum disorder in the offspring. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2409-19.

Whether parental psychiatric disorders are associated with autism spectrum disorder (ASD) in offspring has remained inconclusive. We examined the associations of parental psychiatric disorders with ASD in offspring. This population-based case-control study used Taiwan’s National Health Insurance Research Database to identify a cohort of children born from 2004 to 2017 and their parents. A total of 24,279 children with ASD (diagnostic ICD-9-CM code: 299.x or ICD-10 code F84.x) and 97,715 matched controls were included. Parental psychiatric disorders, including depressive disorders, bipolar spectrum disorders, anxiety disorders, obsessive-compulsive disorder, schizophrenia, substance use disorders, autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and adjustment disorders were identified. Conditional logistic regressions with covariate adjustment were performed. The results suggest that parental diagnosis with any of the psychiatric disorders is associated with ASD in offspring (adjusted odds ratio [AOR] = 1.45, 95%CI: 1.40-1.51 for mothers; and AOR = 1.12, 95%CI: 1.08-1.17 for fathers). ASD in offspring was associated with schizophrenia, depressive disorders, obsessive-compulsive disorder, adjustment disorders, ADHD and ASD in both parents. The relationship between parental psychiatric disorders and the timing of the child’s birth and ASD diagnosis varied across the different psychiatric disorders. The present study provides supportive evidence that parental psychiatric disorders are associated with autistic children. Furthermore, because the associations between parental psychiatric disorders and the timing of child’s birth and ASD diagnosis varied across psychiatric disorders, the observed relationships may be affected by both genetic and environmental factors. Future studies are needed to disentangle the potential influence of genetic and environmental factors on the observed associations.

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8. Dai H, He X, Chen L, Yin C. Language impairments in children with developmental language disorder and children with high-functioning autism plus language impairment: Evidence from Chinese negative sentences. Frontiers in psychology. 2022; 13: 926897.

There is controversy as to whether children with developmental language disorder (DLD) and those with high-functioning autism plus language impairment (HFA-LI) share similar language profiles. This study investigated the similarities and differences in the production of Chinese negative sentences by children with DLD and children with HFA-LI to provide evidence relevant to this controversy. The results reflect a general resemblance between the two groups in their lower-than-TDA (typically developing age-matched) performance. Both groups encountered difficulties in using negative markers, which suggests that they might be impaired in feature agreement. Slight differences were detected between the two groups. Specifically, children with DLD experienced difficulties with the agreement on the feature [+telic] and that on the feature [+dynamic], while children with HFA-LI had difficulties with the agreement on the feature [+dynamic] and that on the feature [-dynamic]. This study supports the idea of a common symptomatology for the two disorders. More importantly, it suggests that these two disorders, DLD and HFA-LI, are not altogether the same in terms of language impairment. This paper concludes that general labels should not be simply attached to any children with language disorders. Instead, atypical language is very worthy of further analysis in the categorization of language disorders.

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9. Etyemez S, Esler A, Kini A, Tsai PC, DiRienzo M, Maenner M, Lee LC. The role of intellectual disability with autism spectrum disorder and the documented cooccurring conditions: A population-based study. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2399-408.

Previous research has identified that patterns of cooccurring conditions (CoCs) associated with autism spectrum disorder (ASD) differ based on the presence of intellectual disability (ID). This study explored the association of documented CoCs among 8-year-old children with ASD and ID (ASD+ID, n = 2416) and ASD without ID (ASD-ID, n = 5372) identified by the Autism and Developmental Disabilities Monitoring Network, surveillance years (SYs) 2012 and 2014. After adjusting for demographic variables, record source, surveillance site, and SY, children with ASD+ID, as compared with children with ASD-ID, were more likely to have histories of nonspecific developmental delays and neurological disorders documented in their records but were less likely to have behavioral and psychiatric disorders. ID plays a key role on how children with ASD would experience other CoCs. Our results emphasize how understanding the pattern of CoCs in ASD+ID and ASD-ID can inform comprehensive and multidisciplinary approaches in assessment and management of children in order to develop targeted interventions to reduce possible CoCs or CoCs-related impairments.

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10. Firestein MR, Romeo RD, Winstead H, Goldman DA, Grobman WA, Haas DM, Parry S, Reddy UM, Silver RM, Wapner RJ, Champagne FA. Hypertensive disorders during pregnancy and polycystic ovary syndrome are associated with child communication and social skills in a sex-specific and androgen-dependent manner. Frontiers in endocrinology. 2022; 13: 1000732.

Prenatal exposure to testosterone is implicated in the etiology of autism spectrum disorder (ASD). Hypertensive disorders of pregnancy and polycystic ovary syndrome are associated with both hyperandrogenism and increased risk for ASD. We examined whether increased maternal testosterone mediates the relationship between these hyperandrogenic disorders (HDs) during pregnancy and child communication and social skills. Maternal plasma was collected during the second trimester and parent-report measures of child communication and social skills were obtained at 4.5-6.5 years of age from 270 participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). Our retrospective frequency-matched cohort study design identified 58 mothers with one or both of the HDs and 58 matched controls. Women diagnosed with an HD who carried a female had higher testosterone levels compared to those carrying a male (t(56) = -2.70, p = 0.01). Compared to females controls, females born to women with an HD had significantly higher scores on the Social Communication Questionnaire (t(114) = -2.82, p =0.01). Maternal testosterone partially mediated the relationship between a diagnosis of an HD and SCQ scores among females. These findings point to sex-specific associations of two HDs – hypertensive disorders of pregnancy and polycystic ovary syndrome – on child communication and social skills and a mediating effect of maternal testosterone during pregnancy. Further research is needed to understand placental-mediated effects of maternal testosterone on child brain development and neurodevelopmental outcomes.

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11. Frontiers Production O. Erratum: The absence of caspase-8 in the dopaminergic system leads to mild autism-like behavior. Frontiers in cell and developmental biology. 2022; 10: 1040623.

[This corrects the article DOI: 10.3389/fcell.2022.839715.].

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12. Galvin J, Evans EH, Talbot CV, Wilson C, Richards G. The associations between autistic traits and disordered eating/drive for muscularity are independent of anxiety and depression in females but not males. PloS one. 2022; 17(10): e0276249.

Previous research has shown a positive correlation between autistic traits and eating disorder symptoms, and this relationship appears to be independent of co-occurring mental health status. The current study followed a pre-registered analysis plan with the aim to investigate a previously unconsidered factor in the relationship between autistic traits and disorders of eating and body image: the drive for muscularity. Participants (N = 1068) completed the Autism Spectrum Quotient (AQ), Hospital Anxiety and Depression Scale (HADS), Eating Attitudes Test-26 (EAT-26) and Drive for Muscularity Scale (DMS). Positive correlations between AQ and EAT-26 and AQ and DMS were observed. In females, AQ remained significantly correlated with EAT-26 and DMS when controlling for co-occurring anxiety and depression symptoms, but this was not the case in males. These findings demonstrate the moderating role of sex, and the need to consider autistic traits in individuals diagnosed with, or at a heightened risk for, disorders of eating and body image.

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13. Gitimoghaddam M, Chichkine N, McArthur L, Sangha SS, Symington V. Applied Behavior Analysis in Children and Youth with Autism Spectrum Disorders: A Scoping Review. Perspectives on behavior science. 2022; 45(3): 521-57.

This manuscript provides a comprehensive overview of the impact of applied behavior analysis (ABA) on children and youth with autism spectrum disorders (ASD). Seven online databases and identified systematic reviews were searched for published, peer-reviewed, English-language studies examining the impact of ABA on health outcomes. Measured outcomes were classified into eight categories: cognitive, language, social/communication, problem behavior, adaptive behavior, emotional, autism symptoms, and quality of life (QoL) outcomes. Improvements were observed across seven of the eight outcome measures. There were no included studies that measured subject QoL. Moreover, of 770 included study records, only 32 (4%) assessed ABA impact, had a comparison to a control or other intervention, and did not rely on mastery of specific skills to mark improvement. Results reinforce the need for large-scale prospective studies that compare ABA with other non-ABA interventions and include measurements of subject QoL to provide policy makers with valuable information on the impacts of ABA and other existing and emerging interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40614-022-00338-x.

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14. Hladik L, Meyer R, Allen S, Bonnici S, Froelke NA, Romaniak H, Ougayour Y, Nelson N, Alkhamees AK, Davis H, Ausderau KK. Accessibility and Inclusion for Families with Children with Autism Spectrum Disorders in Cultural Institutions. Curator : a quarterly publication of the American Museum of Natural History. 2022; 65(2): 435-49.

This project aimed to develop a comprehensive set of evaluation tools to assess the accessibility and inclusion of families with children on the autism spectrum in cultural institutions. A stakeholder team conducted interviews, reviewed museum artifacts, and observed museum programming. An evaluation toolkit was constructed by incorporating best practices from current literature and collected data. Tools were piloted and revised after being implemented in the museum context. The Toolkit to Increase Accessibility and Inclusion for Children on the Autism Spectrum and with Sensory Processing Differences in Cultural Institutions was developed with five unique tools, the Dimensions of Accessibility framework, and further resources to provide a self-assessment of cultural institutions. The toolkit can be used broadly across many types of institutions and self-assessment can lead to proactive development of public spaces, institutions, and programming that is accessible and inclusive of diverse groups of people, beyond families with children on the autism spectrum.

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15. Huang J, Liu J, Tian R, Liu K, Zhuang P, Sherman HT, Budjan C, Fong M, Jeong MS, Kong XJ. Correction: Huang et al. A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells 2022, 11, 10. Cells. 2022; 11(20).

In the original publication […].

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16. Hwang IS, Hong SB. Association between body mass index and subcortical volume in pre-adolescent children with autism spectrum disorder: An exploratory study. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2238-49.

Conflicting associations exist between autism spectrum disorder (ASD) and subcortical brain volumes. This study assessed whether obesity might have a confounding influence on associations between ASD and brain subcortical volumes. A comprehensive investigation evaluating the relationship between ASD, obesity, and subcortical structure volumes was conducted. Data obtained included body mass index (BMI) and T1-weighted structural magnetic resonance images for children with and without ASD diagnoses from the Autism Brain Imaging Data Exchange database. Brain subcortical volumes were calculated using vol2Brain software. Hierarchical linear regression analyses were performed to explore the subcortical volumes similarly or differentially associated with BMI in children with or without ASD and examine association and interaction effects regarding ASD and subcortical volume impact on the Social Responsiveness Scale and Vineland Adaptive Behavior Scale (VABS) scores. Bilateral caudate nuclei were smaller in children with ASD than in control participants. Significant interactions were observed between ASD diagnosis and BMI regarding the left caudate, right and left putamen, and right and left ventral diencephalon (DC) volumes (β = -0.384, p = 0.010; β = -0.336, p = 0.030; β = -0.317, p = 0.040; β = 0.322, p = 0.010; β = 0.295, p = 0.021, respectively) and between ASD diagnosis and right and left ventral DC volumes regarding the VABS scores (β = 0.434, p = 0.014; β = 0.495, p = 0.007, respectively). However, each subcortical structure volume included in the ventral DC area could not be measured separately. The results identified subcortical volumes differentially associated with obesity in children with ASD compared with typically developing peers. BMI may need to be considered an important confounder in future research examining brain subcortical volumes within ASD.

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17. Jang WE, Park JH, Park G, Bang G, Na CH, Kim JY, Kim KY, Kim KP, Shin CY, An JY, Lee YS, Kim MS. Cntnap2-dependent molecular networks in autism spectrum disorder revealed through an integrative multi-omics analysis. Molecular psychiatry. 2022.

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder in which patients present with core symptoms of social communication impairment, restricted interest, and repetitive behaviors. Although various studies have been performed to identify ASD-related mechanisms, ASD pathology is still poorly understood. CNTNAP2 genetic variants have been found that represent ASD genetic risk factors, and disruption of Cntnap2 expression has been associated with ASD phenotypes in mice. In this study, we performed an integrative multi-omics analysis by combining quantitative proteometabolomic data obtained with Cntnap2 knockout (KO) mice with multi-omics data obtained from ASD patients and forebrain organoids to elucidate Cntnap2-dependent molecular networks in ASD. To this end, a mass spectrometry-based proteometabolomic analysis of the medial prefrontal cortex in Cntnap2 KO mice led to the identification of Cntnap2-associated molecular features, and these features were assessed in combination with multi-omics data obtained on the prefrontal cortex in ASD patients to identify bona fide ASD cellular processes. Furthermore, a reanalysis of single-cell RNA sequencing data obtained from forebrain organoids derived from patients with CNTNAP2-associated ASD revealed that the aforementioned identified ASD processes were mainly linked to excitatory neurons. On the basis of these data, we constructed Cntnap2-associated ASD network models showing mitochondrial dysfunction, axonal impairment, and synaptic activity. Our results may shed light on the Cntnap2-dependent molecular networks in ASD.

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18. Jiao J, Tan L, Zhang Y, Li T, Tang X. Repetitive transcranial magnetic stimulation for insomnia in patients with autism spectrum disorder: Study protocol for a randomized, double-blind, and sham-controlled clinical trial. Frontiers in psychiatry. 2022; 13: 977341.

BACKGROUND: Insomnia is the most common comorbidity in children with autism spectrum disorder (ASD) and seriously affects their rehabilitation and prognosis. Thus, an intervention targeting insomnia in ASD seems warranted. Repetitive transcranial magnetic stimulation (rTMS), a potentially effective treatment for improving sleep quality and optimizing sleep structure, has already been demonstrated to alleviate insomnia symptoms and sleep disturbance in different neurological and neuropsychiatric conditions. This trial aims to investigate the effects of rTMS on insomnia in patients with ASD. METHOD: This study is designed to be a double-blind, randomized, and sham-controlled trial with a target sample size of 30 participants (aged 3-13 years) diagnosed with ASD comorbid with insomnia. The intervention phase will comprise 20 sessions of rTMS or sham rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) within four consecutive weeks. The effect of rTMS on insomnia and other symptoms of ASD will be investigated through home-PSG (two consecutive overnights), sleep diary, CSHQ, CARS, ABC, SRS, RBS-R, and metabolomics analysis at baseline and posttreatment. A follow-up assessment 1 month after the intervention will examine the long-term effects. DISCUSSION: The results of this study may address an important knowledge gap and may provide evidence for the use of rTMS to treat insomnia in ASD. Furthermore, it will elucidate the potential mechanism and link between sleep disorders and clinical symptoms. CLINICAL TRIAL REGISTRATION: The study is ongoing and has been registered at the Chinese Clinical Trial Registry (ChiCTR2100049266) on 28/07/2021.

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19. Kang HY, Lee DY, Hong JH, Kim JS, Kim SG, Seo YG, Yu JH. Effects of Augmented Reality-Based Dual-Task Program on Physical Ability by Cognitive Stage with Developmental Disabilities. Healthcare (Basel, Switzerland). 2022; 10(10).

People diagnosed with developmental disabilities are less likely to participate in physical activities even if they are provided opportunities. This study aimed to examine the effects of dual-task exercise-based augmented reality (AR) on muscle strength, muscle endurance, balance ability, and flexibility among people with developmental disabilities. Twenty-seven patients with developmental disabilities were included in the study. The intervention was based on an AR-based rehabilitation program and lasted for 8 weeks. The results showed a statistically significant improvement in muscle strength, muscle endurance, balance ability, and flexibility after the intervention (p < 0.05). The AR-based dual-task program increased interest and motivation in the high-cognitive-stage groups, while less interest and motivation were observed in the low-cognitive-stage groups. Our results suggest that an AR-based dual-task program can be an effective method to improve physical ability in patients with high cognitive levels.

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20. Keates N, Waldock KE, Dewar E. Tensions Between Autistic Sociality, Communication, and Social Skills Research: A Response to Bambara (2022) and Camarata (2022). Journal of speech, language, and hearing research : JSLHR. 2022; 65(11): 4346-50.

PURPOSE: The purpose of this letter to the editor is to further elucidate the arguments Keates (2022) and Beechey (2022) stated in their letters to the editor. Both Bambara (2022) and Camarata (2022) pose comments that require clarifying the original arguments, particularly regarding power and autistic sociality, which we feel will provide further clarity to this highly significant and growing topic within autism research. CONCLUSION: We recommend teaching not autistic people but rather non-autistic individuals about autistic sociality, in order to lower the burden on autistic interlocutors in cross-neurotype interactions and socialization (as per previous literature, Bottema-Beutel et al., 2018). We provide recommendations to address difficulties in cross-neurotype interactions-for example, bridging the neurotype gap through practice or psychosocial interventions for acceptance of autistic people and their system of interpretation, as per Jones et al. (2021).

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21. Knopp K, Ferguson JL, Piazza J, Weiss MJ, Lee M, Cihon JH, Leaf JB. A Comparison Between Direct Telehealth and In-Person Methods of Teaching Expressive Labels to Children Diagnosed With Autism Spectrum Disorder. Behavior modification. 2022: 1454455221130000.

Recent behavior analytic research has demonstrated that the provision of applied behavior analytic services via direct telehealth can be an effective teaching modality for some learners with autism spectrum disorder (ASD). Historically, teaching procedures based on applied behavior analysis (ABA), including discrete trial teaching (DTT), have been provided and evaluated via in-person delivery. This study sought to compare the implementation of DTT via direct telehealth to DTT implemented in-person within and across participants. Specifically, this study evaluated the two delivery modalities in terms of skill acquisition, maintenance, efficiency, and learner responding during teaching sessions. Results of an adapted alternating treatments design nested into a multiple baseline design demonstrated that all three participants diagnosed with ASD met the mastery criteria for the expressive labels taught. Areas of future research, participant prerequisite skills, and clinical implications will be discussed in the context of these results.

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22. Li LG, Fu HG, Zhao YH, Zhao PJ, Meng QK, Zheng RJ, Li EY. A Meta-Analysis on the Impact of Prenatal and Early Childhood Antimicrobial Use on Autism Spectrum Disorders. The Annals of pharmacotherapy. 2022: 10600280221130280.

OBJECTIVE: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). DATA SOURCES: We searched PubMed and Embase databases for relevant studies from inception to August 2022. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD (P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal (P = 0.47 > 0.05) nor early childhood (P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. CONCLUSIONS: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.

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23. Martorell L, Macaya A, Pérez-Dueñas B, Ortigoza-Escobar JD. Acetazolamide Improves Episodic Ataxia in a Patient with Non-Verbal Autism and Paroxysmal Dyskinesia Due To PRRT2 Biallelic Variants. Movement disorders clinical practice. 2022; 9(7): 979-82.

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24. Meng F, Qi Y, Wu Y, He F. Association between acrylamide exposure and the odds of developmental disabilities in children: A cross-sectional study. Frontiers in public health. 2022; 10: 972368.

BACKGROUND: The association between acrylamide exposure and the odds of developmental disabilities (DDs) is unclear. We conducted this analysis to explore whether acrylamide exposure is related to DDs. METHODS: We analyzed a sample of 1,140 children aged 6-17 years old from the US National Health and Nutrition Examination Survey 2013-2014 to 2015-2016. DDs were determined by reports of parents. Acrylamide exposure was evaluated by the hemoglobin adducts of acrylamide (HbAA) and its major metabolite glycidamide (HbGA). We investigated the association using binomial logistic regression analysis by taking HbAA and HbGA as continuous or quartile variables. Restricted cubic splines (RCS) were used to explore the non-linear relationship between HbAA or HbGA and the odds of DDs. Interaction analysis and propensity score matching (PSM) were used to validate the results. RESULTS: A total of 134 participants were reported to have DDs. The median level of HbAA and HbGA was 41.6 and 40.5 pmol/g Hb, respectively. HbAA and HbGA were not associated with the odds of DDs when taken as continuous variables. When divided into quartiles, there was no evidence for a linear trend for HbAA and HbGA. RCS showed that there was a J-shaped association between HbGA and the odds of DDs (P for non-linearity, 0.023). The results were consistent in interaction analysis by age, gender, and race, and after PSM. CONCLUSION: HbGA level was associated with the odds of DDs in a J-shaped manner among children. Further investigation is warranted to determine the causality and underlying mechanisms.

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25. Mok RSF, Zhang W, Sheikh TI, Pradeepan K, Fernandes IR, DeJong LC, Benigno G, Hildebrandt MR, Mufteev M, Rodrigues DC, Wei W, Piekna A, Liu J, Muotri AR, Vincent JB, Muller L, Martinez-Trujillo J, Salter MW, Ellis J. Wide spectrum of neuronal and network phenotypes in human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations. Translational psychiatry. 2022; 12(1): 450.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by heterozygous loss-of-function mutations in the X-linked gene MECP2 that is a global transcriptional regulator. Mutations in the methyl-CpG binding domain (MBD) of MECP2 disrupt its interaction with methylated DNA. Here, we investigate the effect of a novel MECP2 L124W missense mutation in the MBD of an atypical RTT patient with preserved speech in comparison to severe MECP2 null mutations. L124W protein had a limited ability to disrupt heterochromatic chromocenters due to decreased binding dynamics. We isolated two pairs of isogenic WT and L124W induced pluripotent stem cells. L124W induced excitatory neurons expressed stable protein, exhibited increased input resistance and decreased voltage-gated Na(+) and K(+) currents, and their neuronal dysmorphology was limited to decreased dendritic complexity. Three isogenic pairs of MECP2 null neurons had the expected more extreme morphological and electrophysiological phenotypes. We examined development and maturation of L124W and MECP2 null excitatory neural network activity using micro-electrode arrays. Relative to isogenic controls, L124W neurons had an increase in synchronous network burst frequency, in contrast to MECP2 null neurons that suffered a significant decrease in synchronous network burst frequency and a transient extension of network burst duration. A biologically motivated computational neural network model shows the observed changes in network dynamics are explained by changes in intrinsic Na(+) and K(+) currents in individual neurons. Our multilevel results demonstrate that RTT excitatory neurons show a wide spectrum of morphological, electrophysiological and circuitry phenotypes that are dependent on the severity of the MECP2 mutation.

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26. Muldoon DM, Murphy TM, DeBonis DA. « Tan and Crunchy Is Where We Live »: An Interpretative Phenomenological Analysis of Caregivers’ Perspectives of Pediatric Feeding Disorder in Children With Developmental Disability. American journal of speech-language pathology. 2022; 31(6): 2675-87.

PURPOSE: The purpose of this study was to examine caregivers’ perceptions of feeding disorders in their young child who also had a co-occurring developmental disability (DD). METHOD: Using interpretative phenomenological analysis, eight caregivers of children with DD and pediatric feeding disorder (PFD) were interviewed. Interviews were recorded, transcribed, and analyzed for the lived experiences of caregivers. Thematic analysis, member checking, and an audit were completed by three researchers. RESULTS: Three themes emerged: Parenting Journey, Emotions and Repercussions, and Winging It. Results indicated caregivers struggled to find appropriate professional help, referenced lack of confidence in the professionals designated to help, and were often ambivalent in approach to the PFD. Indications were that parents were frequently retelling past experiences as they presented the narrative of the feeding disorder and, as such, created narratives that became part of their present and the future experiences when feeding their child. CONCLUSIONS: Implications for speech-language pathologists are considered. Particularly, interventions that go beyond the immediate environmental variables of the feeding or mealtime environment are considered, including the application of this analysis to necessary psychological flexibility for caregivers of children with PFD.

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27. Ong JH, Liu F. EXPRESS: Frequent experience with face coverings for 10 months improves emotion perception among individuals with high autistic traits: A repeated cross-sectional study. Quarterly journal of experimental psychology (2006). 2022: 17470218221135585.

Face coverings pose difficulties for emotion recognition, but it is unclear whether improvement in recognising emotions from the eyes is possible with experience and whether this might be dependent on one’s autistic traits, given the associations between high autistic traits and poorer emotion perception and reduced gaze to the eye region. In this preregistered study, participants completed a forced-choice emotion recognition task with photographs of eyes and demographic questionnaires that measure their autistic traits and their interaction frequency with others wearing face coverings at two time points: once at the start of the face covering mandate and again 10 months later. We found that after 10 months, individuals with high autistic traits as a cohort recognise emotions from just the eyes better as a function of their experience with others wearing face coverings, suggesting that emotion perception is malleable even for those who have difficulties with emotion perception.

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28. Pan EJ, Weleff J, Anand A, Barnett BS. Treatment of Misophonia with Risperidone in a Patient with Autism Spectrum Disorder. Case reports in psychiatry. 2022; 2022: 3169834.

We report the case of a 32-year-old male with autism spectrum disorder (ASD) suffering from severe misophonia. After titrating risperidone to 2 mg twice a day, the patient reported a significant reduction in his symptoms and his Amsterdam misophonia scale-revised (AMISOS-R) score dropped by from 31 to 5. Upon discharge, the patient was noted to have decreased irritability and overall improved behavior and effect. This significant symptomatic improvement was likely not explained by inpatient admission alone or other simultaneous pharmacologic treatments, as the effect was seen during an isolated titration of risperidone with other treatments remaining constant. Although, unfortunately, follow-up findings indicated that the treatment was not curative for the patient, risperidone’s potential for treating misophonia may warrant systematic investigation.

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29. Pavlova MA, Romagnano V, Kubon J, Isernia S, Fallgatter AJ, Sokolov AN. Ties between reading faces, bodies, eyes, and autistic traits. Frontiers in neuroscience. 2022; 16: 997263.

While reading covered with masks faces during the COVID-19 pandemic, for efficient social interaction, we need to combine information from different sources such as the eyes (without faces hidden by masks) and bodies. This may be challenging for individuals with neuropsychiatric conditions, in particular, autism spectrum disorders. Here we examined whether reading of dynamic faces, bodies, and eyes are tied in a gender-specific way, and how these capabilities are related to autistic traits expression. Females and males accomplished a task with point-light faces along with a task with point-light body locomotion portraying different emotional expressions. They had to infer emotional content of displays. In addition, participants were administered the Reading the Mind in the Eyes Test, modified and Autism Spectrum Quotient questionnaire. The findings show that only in females, inferring emotions from dynamic bodies and faces are firmly linked, whereas in males, reading in the eyes is knotted with face reading. Strikingly, in neurotypical males only, accuracy of face, body, and eyes reading was negatively tied with autistic traits. The outcome points to gender-specific modes in social cognition: females rely upon merely dynamic cues while reading faces and bodies, whereas males most likely trust configural information. The findings are of value for examination of face and body language reading in neuropsychiatric conditions, in particular, autism, most of which are gender/sex-specific. This work suggests that if male individuals with autistic traits experience difficulties in reading covered with masks faces, these deficits may be unlikely compensated by reading (even dynamic) bodies and faces. By contrast, in females, reading covered faces as well as reading language of dynamic bodies and faces are not compulsorily connected to autistic traits preventing them from paying high costs for maladaptive social interaction.

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30. Persichetti AS, Shao J, Gotts SJ, Martin A. Maladaptive Laterality in Cortical Networks Related to Social Communication in Autism Spectrum Disorder. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42(48): 9045-52.

Neuroimaging studies of individuals with autism spectrum disorders (ASDs) consistently find an aberrant pattern of reduced laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of reduced laterality in a social communication network in 70 ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high-quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social communication network exhibited the typical pattern of left laterality in both groups, whereas there was a significant increase in within- relative to across-hemisphere connectivity of homotopic regions in the right hemisphere in ASD individuals. Furthermore, greater within- relative to across-hemisphere connectivity in the left hemisphere was positively correlated with a measure of verbal ability in both groups, whereas greater within- relative to across-hemisphere connectivity in the right hemisphere in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal ability but not metrics of other core components of the ASD phenotype. These results suggest that previous reports of reduced laterality in social communication regions in ASD is because of the two hemispheres functioning more independently than seen in TD individuals, with the atypical right-hemisphere network component being maladaptive.SIGNIFICANCE STATEMENT A consistent neuroimaging finding in individuals with ASD is an aberrant pattern of reduced laterality of the brain networks that support functions related to social communication and language. We tested four models of reduced laterality in a social communication network in ASD individuals and a TD control group using high-quality resting-state fMRI data. Our results suggest that reduced laterality of social communication regions in ASD may be because of the two hemispheres functioning more independently than seen in TD individuals, with atypically greater within- than across-hemisphere connectivity in the right hemisphere being maladaptive.

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31. Rabia A, Mahmood S, Maqbool S. Prevalence of minor physical anomalies in children with autism spectrum disorder reporting to a tertiary care hospital Lahore-Pakistan. Pakistan journal of medical sciences. 2022; 38(7): 1918-23.

OBJECTIVE: To assess the frequency and type of minor physical anomalies (MPAs) in subjects with autism spectrum disorder (ASD). METHODS: This descriptive cross-sectional study was conducted from September, 2016 to October, 2020. Using purposive sampling technique, 147 subjects with ASD were recruited from Children’s Hospital and Institute of Child Health (CH & ICH) Lahore, with a confirmed clinical diagnosis by developmental pediatrician, using Diagnostic and Statistical Manual of Mental Disorders (DSM-V). For morphology assessment, 12 body regions of ASD subjects were examined using Autism Dysmorphology Measure (ADM) manual after taking informed consent. Physical measurements (height, weight, head circumference, ear length, philtrum, hand, finger and foot length) were also taken and were compared with the available standard charts. RESULTS: A total of 381 dysmorphologies were identified in 131 (89.1%) ASD subjects whereas 16 subjects had no dysmorphology at all. Microcephaly was exhibited by 14 (9.5%) subjects, out of which 13 had variable number of dysmorphologies while one had no dysmorphology in other body regions. Out of 131 subjects exhibiting dysmorphologies, there were 108 male and 23 female subjects, with a M:F ratio 4.7:1 whereas microcephaly was observed in 12 male and two female subjects, with a M:F ratio 6:1. The highest number of dysmorphic features were noted in the ears, followed by feet and hair growth pattern. CONCLUSIONS: MPAs associated with ASD are frequently found in, but are clearly not limited to, the head or facial region.

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32. Rosario R, Stewart HL, Choudhury NR, Michlewski G, Charlet-Berguerand N, Anderson RA. Evidence for a fragile X messenger ribonucleoprotein 1 (FMR1) mRNA gain-of-function toxicity mechanism contributing to the pathogenesis of fragile X-associated premature ovarian insufficiency. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022; 36(11): e22612.

Fragile X-associated premature ovarian insufficiency (FXPOI) is among a family of disorders caused by expansion of a CGG trinucleotide repeat sequence located in the 5′ untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene on the X chromosome. Women with FXPOI have a depleted ovarian follicle population, resulting in amenorrhea, hypoestrogenism, and loss of fertility before the age of 40. FXPOI is caused by expansions of the CGG sequence to lengths between 55 and 200 repeats, known as a FMRI premutation, however the mechanism by which the premutation drives disease pathogenesis remains unclear. Two main hypotheses exist, which describe an mRNA toxic gain-of-function mechanism or a protein-based mechanism, where repeat-associated non-AUG (RAN) translation results in the production of an abnormal protein, called FMRpolyG. Here, we have developed an in vitro granulosa cell model of the FMR1 premutation by ectopically expressing CGG-repeat RNA and FMRpolyG protein. We show that expanded CGG-repeat RNA accumulated in intranuclear RNA structures, and these aggregates were able to cause significant granulosa cell death independent of FMRpolyG expression. Using an innovative RNA pulldown, mass spectrometry-based approach we have identified proteins that are specifically sequestered by CGG RNA aggregates in granulosa cells in vitro, and thus may be deregulated as consequence of this interaction. Furthermore, we have demonstrated reduced expression of three proteins identified via our RNA pulldown (FUS, PA2G4 and TRA2β) in ovarian follicles in a FMR1 premutation mouse model. Collectively, these data provide evidence for the contribution of an mRNA gain-of-function mechanism to FXPOI disease biology.

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33. Shirayama Y, Matsumoto K, Osone F, Hara A, Guan S, Hamatani S, Muneoka K, Sato K, Okada A, Yokokawa T. The Lack of Alterations in Metabolites in the Medial Prefrontal Cortex and Amygdala, but Their Associations with Autistic Traits, Empathy, and Personality Traits in Adults with Autism Spectrum Disorder: A Preliminary Study. Journal of autism and developmental disorders. 2022.

Proton magnetic resonance spectroscopy ((1)H-MRS) has shown inconsistent alterations in brain metabolites of adults with autism spectrum disorder (ASD). We investigated brain metabolites in the medial prefrontal cortex and amygdala of 24 drug-naive adults with ASD and no intellectual disability and 24 non-ASD control subjects, using 3 T (1)H-MRS. Adults with ASD showed no significant differences from control in glutamate, glutamate plus glutamine, N-acetylaspartate, glycerophosphorylcholine plus phosphorylcholine, creatine plus phosphocreatine, or myo-inositol in either region. However, ASD subjects did show significant correlations of localized brain metabolites with autistic traits, empathy deficits, and personality traits using the Autism-Spectrum Quotient, Questionnaire of Cognitive and Affective Empathy, Interpersonal Reactivity Index, and NEO Personality Inventory-Revised. These findings should be taken as preliminary or exploratory.

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34. Singhi P, Malhi P. Early Diagnosis of Autism Spectrum Disorder: What the Pediatricians Should Know. Indian journal of pediatrics. 2022.

Autism is a spectrum disorder marked by considerable heterogeneity and characterized by impairments in the social communication domain along with the presence of restricted and repetitive behaviors or interests. Comprehensive autism evaluation generally consists of assessments by a multidisciplinary team. Having multiple specialists in the evaluation team aids in diagnosis and in chalking out a comprehensive management plan. Diagnosis is generally based on detailed developmental history, clinical judgment, and the use of standardized diagnostic instruments. Differential diagnosis is complicated as many of the mental health and neurodevelopmental conditions that routinely coexist with autism also have some symptoms that overlap with autism. Several barriers are linked to delay in diagnosis including lack of comfort in diagnosing autism by primary care providers, delayed referrals, the inability of parents to raise critical developmental concerns, confusion of autism with other conditions, and health system that is not responsive to the needs of the underserved communities. The etiology of autism spectrum disorder (ASD) is complex and still not completely understood; it involves genetics, neurobiology, and environmental exposures, leading to a diverse presentation of behaviors and symptoms. There is an imperative need to start therapeutic interventions as soon as a diagnosis of autism is suspected rather than wait for a definitive diagnosis. Early diagnosis is vital as timely intervention can lead to better outcomes for children and their families.

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35. Stolar O, Hazan A, Vissoker RE, Kishk IA, Barchel D, Lezinger M, Dagan A, Treves N, Meiri D, Berkovitch M, Kohn E, Heyman E. Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety. Frontiers in pharmacology. 2022; 13: 977484.

Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities. Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD. Methods: Data from 59 children and young adults (ages 5-25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment. Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile-14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance. Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.

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36. Timms S, Lodhi S, Bruce J, Stapleton E. Auditory symptoms and autistic spectrum disorder: A scoping review and recommendations for future research. Journal of otology. 2022; 17(4): 239-46.

INTRODUCTION: Auditory symptoms in individuals with Autistic Spectrum Disorder (ASD) are well described within the neurodevelopmental literature, yet there is minimal mention of ASD in Otolaryngology literature. This is surprising considering the potential clinical and diagnostic implications of this link, and the potential for ASD to present to Otolaryngologists in the form of unexplained auditory symptoms. The aims of this literature review were to explore the intersection of auditory symptoms and ASD from the perspective of clinical Otolaryngology, and to outline a clinically focused research agenda based on emerging themes relevant to Otolaryngology. METHODS: We searched Pubmed, Embase, Ovid and Cochrane library for studies until November 2021. Four authors independently reviewed 227 publications identified. 39 were filtered into the final analysis. The PRISMA 2020 guidelines were followed. The heterogeneity of literature meant that a Systematic Review was not feasible. Included studies were therefore classified thematically, forming the basis of the scoping review. RESULTS: Diagnostic theories for auditory symptoms in ASD include the entire auditory pathway and brain. There is a growing body of literature on auditory symptoms in ASD, suggesting that a primary diagnosis of ASD should be considered in patients presenting with otherwise unexplained auditory symptoms, and indicating a learning need for Otolaryngologists and audiologists, to whom these patients may present. CONCLUSION: We recommend a research agenda focusing on multidisciplinary collaboration, stakeholder engagement, responsible clinical screening, and clarification of pathophysiological mechanisms and terminology.

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37. Wandin H, Lindberg P, Sonnander K. A trained communication partner’s use of responsive strategies in aided communication with three adults with Rett syndrome: A case report. Frontiers in psychology. 2022; 13: 989319.

PURPOSE: To explore and describe a trained communication partner’s use of responsive strategies in dyadic interaction with adults with Rett syndrome. INTRODUCTION: Responsive partner strategies facilitate social, communicative, and linguistic development. The common feature is that the communication partner responds contingently to the other’s focus of attention and interprets their acts as communicative. Research on responsive partner strategies that involves individuals with significant communication and motor disabilities remains sparse. The same applies to if, and how, the use of communication aids impacts on the partner’s use of responsive strategies. MATERIALS AND METHODS: A therapist, trained in responsive partner strategies and aided communication interacted during 14 sessions with each of three participants. The participants were adults with Rett syndrome. A gaze-controlled device and responsive strategies were used during all sessions. The Responsive Augmentative and Alternative Communication Style scale (RAACS) was used to assess the partner’s responsiveness. RAACS consists of 11 items including ratings of to what extent the partner is being attentive to, confirms, and expands the individual’s communication. During eight of the 14 sessions, aided AAC Modelling was also used, i.e., the communication partner pointed at symbols on the gaze-controlled device while interacting. In addition to RAACS, each time the communication partner confirmed or expanded on communication when (a) the participants used the gaze-controlled device and (b) the participants did not use the gaze-controlled device was counted. Descriptive statistics were used to present the results. Non-parametric tests were used to compare means between the two conditions and between participants. RESULTS: Inter-rater agreement for the different RAACS items ranged from 0.73 to 0.96 and was thus found to be fair to excellent. The communication partner’s use of responsive strategies varied when communicating with different participants and the scores were higher when aided AAC modeling was used. The communication partner’s number of responses and use of responsive strategies were higher when the participants communicated through a gaze-controlled device. CONCLUSION: The communication partner’s use of responsive and scaffolding strategies is not a fixed construct but varies in interactions with different non-speaking persons. The same is true whether the non-speaking person uses a gaze-controlled device with digitized speech or not.

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38. Wang F, Lao UC, Xing YP, Zhou P, Deng WL, Wang Y, Ji Y, Chen MY, Li H, Zou XB. Parents’ knowledge and attitude and behavior toward autism: a survey of Chinese families having children with autism spectrum disorder. Translational pediatrics. 2022; 11(9): 1445-57.

BACKGROUND: In recent years, parent-mediated intervention for children with autism spectrum disorder (ASD) has increased. Therefore, implementing effective parent training programs for parents of children with autism is of paramount importance, particularly in low- and middle-income countries. However, little is known about the status of and gaps in parents’ knowledge on ASD, which may hinder the development of valid parental training programs. Herein, we aimed at exploring the status of Chinese parents’ knowledge, attitude and behavior toward ASD, and potential factors affecting the acquisition of correct knowledge. METHODS: This study used a self-designed parental knowledge questionnaire of autism (PKQA) comprising 20 questions alongside another questionnaire comprising additional 17 questions covering the aspects of family demographics, attitudes, and behaviors of parents. In total, we included 394 parents who visited the outpatient department of the Child’s Development and Behavior Center of the Third Affiliated Hospital of Sun Yat-Sen University between December 2018 and May 2019, with their children meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for ASD. RESULTS: The median knowledge score in the PKQA was 15 [interquartile range (IQR), 13-17]. Advanced paternal age and longer time interval from diagnosis to enrolling into the parent training program were associated with a lower total knowledge score (all P<0.001). Higher maternal education attainment, higher family income, child being currently under intervention, and family members sharing a common perception of the diagnosis were associated with a higher total knowledge score (all P<0.01). Reading autism-related books (P<0.001) or attending professional lectures (P=0.019) were also associated with a higher total knowledge score. CONCLUSIONS: Taken together, this study revealed that family demographics and parents' attitudes and behaviors toward ASD may significantly influence their knowledge about autism, suggesting the need for promoting more targeted parental skills training programs.

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39. Yang Y, Shen Y, Lin J, Dai S, Lu X, Xun G, Li Y, Wu R, Xia K, Luo X, Zhao J, Ou J. Association between history of miscarriage and autism spectrum disorder. European archives of psychiatry and clinical neuroscience. 2022.

This case-control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327-3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259-3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939-4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153-4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978-3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534-4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252-2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894-4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.

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40. Zhou A, Cao X, Mahaganapathy V, Azaro M, Gwin C, Wilson S, Buyske S, Bartlett CW, Flax JF, Brzustowicz LM, Xing J. Common genetic risk factors in ASD and ADHD co-occurring families. Human genetics. 2022.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two major neurodevelopmental disorders that frequently co-occur. However, the genetic mechanism of the co-occurrence remains unclear. The New Jersey Language and Autism Genetics Study (NJLAGS) collected more than 100 families with at least one member affected by ASD. NJLAGS families show a high prevalence of ADHD and provide a good opportunity to study shared genetic risk factors for ASD and ADHD. The linkage study of the NJLAGS families revealed regions on chromosomes 12 and 17 that are significantly associated with ADHD. Using whole-genome sequencing data on 272 samples from 73 NJLAGS families, we identified potential risk genes for ASD and ADHD. Within the linkage regions, we identified 36 genes that are associated with ADHD using a pedigree-based gene prioritization approach. KDM6B (Lysine Demethylase 6B) is the highest-ranking gene, which is a known risk gene for neurodevelopmental disorders, including ASD and ADHD. At the whole-genome level, we identified 207 candidate genes from the analysis of both small variants and structure variants, including both known and novel genes. Using enrichment and protein-protein interaction network analyses, we identified gene ontology terms and pathways enriched for ASD and ADHD candidate genes, such as cilia function and cation channel activity. Candidate genes and pathways identified in our study improve the understanding of the genetic etiology of ASD and ADHD and will lead to new diagnostic or therapeutic interventions for ASD and ADHD in the future.

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41. Zhu XW, Zhang LL, Zhu ZM, Wang LY, Ding ZX, Fang XM. Altered intrinsic brain activity and connectivity in unaffected parents of individuals with autism spectrum disorder: a resting-state fMRI study. Frontiers in human neuroscience. 2022; 16: 997150.

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state. Methods: A total of 42 unaffected parents of ASD children (pASD) and 39 age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well. Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (ρ (1) = 0.298, P (1) = 0.007; ρ (2) = 0.220, P (2) = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ(3) = -0.334, P (3) = 0.002). Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents.

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