1. Al-Ali Z, Yasseen AA, Al-Dujailli A, Al-Karaqully AJ, McAllister KA, Jumaah AS. The oxytocin receptor gene polymorphism rs2268491 and serum oxytocin alterations are indicative of autism spectrum disorder: A case-control paediatric study in Iraq with personalized medicine implications. PloS one. 2022; 17(3): e0265217.

BACKGROUND: Impairment of social functioning skills is a key hallmark of autism. The neuropeptide oxytocin (OXT) is a blood-based biomarker of social functioning, and a candidate for individualized treatment of ASD. The effects of OXT on the social brain are mediated by the OXT receptor (OXTR). This study assessed the clinical utility of blood OXT serum levels and the OXT receptor (OXTR) genotype as biomarkers of autism and its severity in a pediatric population in Iraq. METHODS: Blood samples were collected from patients with a clinical diagnosis of ASD (n = 60) and corresponding age and gender matched healthy controls (n = 60). All clinical samples were processed at the Department of Pathology and Forensic Medicine, Faculty of Medicine, University of Kufa in Iraq. Blood serum was assayed for OXT by sandwich ELISA. Receiver operator analysis (ROC) determined area under the curve (AUC), cutoff values, and sensitivity and specificity of OXT values for accuracy of diagnosis of ASD. Isolated genomic DNA was genotyped for the OXTR gene rs2268491(C/T) SNP using allele-specific PCR. The significance of genotype (CC, CT, and TT) and allele (C and T) distributions in different patient groups was assessed using odd ratios (OR) with 95% confidence intervals (CI) and the Chi-square test. All statistical analysis was performed used SPSS software. RESULTS: Study characteristics in the ASD population revealed a high level of consanguinity (36.66%), and ASD recurrence rate (11.66%) and family history (28.33%). OXT levels in patients with ASD (157.58±28.81 pg/ml) were significantly higher (p = 0.003) compared to controls (75.03±6.38 pg/ml). Within stratified ASD severity groups-OXT levels were significantly different (P = 0.032). ROC analysis determined similar AUC values for overall ASD (0.807), and stratified mild (0.793), moderate (0.889), and severe categories (0.795). The best cutoff for diagnosis of ASD was 83.8 pg/ml OXT with a sensitivity and specificity of 80% and 72.1% respectively. OXTR gene rs2268491(C/T) genotyping found that ASD patients have significantly lower (p = 0.021) genotype CC frequency and a significantly higher (p = 0.04) occurrence of the heterozygous CT genotype relative to controls. ASD subjects produced highest OXT levels with the TT genotype. T allele distribution was higher in ASD males. ASD males had significantly lower distribution of the CC genotype (48.89%) compared to females (80%) (Chi-square test: χ2 = 4.43, df = 1, p = 0.035). Whereas distribution of the CT genotype was significantly higher in autistic males (44.45%) compared to females (13.33%) (Chi-square test: χ2 = 4.68, df = 1, p = 0.03). CONCLUSION: Peripheral OXT levels and OXTR genetic alterations are potential biomarkers of social functioning in the ASD patient setting. The stratification of patients with ASD into severity categories shows significant differences both in OXT levels and OXTR (rs2268491, C/T) genotype and allele distributions, that can be sex dependent. OXT based therapies will require personalized medicine tactics to correctly identify patients with ASD who require neuropeptide boosting in social settings.

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2. Elnaiem W, Benmelouka AY, Elgendy AMN, Abdelgalil MS, Brimo Alsaman MZ, Mogheeth A, Ali MM, Yousof SM. Evaluation of memantine’s efficacy and safety in the treatment of children with autism spectrum disorder: A systematic review and meta-analysis. Human psychopharmacology. 2022: e2841.

BACKGROUND: The United States Food and Drug Administration has approved drugs that address only autism-related symptoms rather than the underlying impairments. N-Methyl-D-Aspartate receptor antagonists have recently emerged as a promising treatment option for a variety of neurologic and developmental problems, including autism. AIMS: To review (systematically), for the first time, the medical literature that explores the safety in and efficacy of memantine in autism. METHODS AND PROCEDURES: A comprehensive electronic search for relevant randomized controlled trials was conducted in four databases. Using RevMan software, we extracted and pooled data as a risk ratio (RR) or normalized mean differences in an inverse variance strategy. RESULTS: This systematic review and meta-analysis includes five trials. There was no difference in enhancing social responsiveness when compared to placebo, though memantine lowered the likelihood of anxiety (RR = 0.25; 95% Confidence interval: [0.07; 0.87], p = 0.03). However, memantine aggravated impulsive behaviors. Additionally, in another trial that compared memantine added to risperidone versus risperidone added to placebo, memantine was found to be effective and safe. CONCLUSION: Memantine showed safety in reducing acute symptoms of anxiety and other symptoms encountered in pediatric patients with autism spectrum disorders. However, memantine does not improve the core symptoms of autism. Nevertheless, further long-term trials are needed to explore its potential efficacy.

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3. Li M, Lin Y, Bao T, Zhao Q, Wang Y, Li M, Chen Y, Qian Y, Chen L, Zhu D. Inclusive education of elementary students with autism spectrum disorders in Shanghai, China: From the teachers’ perspective. Bioscience trends. 2022.

Given an increasing number of children with ASD, the need for inclusive education has rapidly increased in China. Since 2011, children with ASD have been eligible for inclusive education. However, little is known of the implementation process by key personnel. The purpose of the current study was to qualitatively explore elementary school teachers’ experiences and perspectives on an inclusive education policy and practice for students with ASD. Participants were from 5 elementary schools in 2 districts in Shanghai. This study consisted of data collection in 2 phases. First, semi-structured, in-depth interviews were conducted with school psychologists and vice principals responsible for students’ mental health for implementation of general inclusive education at each school. Second, focus groups of frontline teachers were assembled to hear their firsthand experiences. A thematic analysis was performed. Findings indicated that although all 5 schools had some ASD-related support, training and resources varied depending on whether learning in regular classrooms (LRC) was implemented. Frontline teachers in particular faced challenges implementing LRC, including the limited extent of LRC, tedious implementation procedures, and parents’ misconceptions of LRC. Regardless of these challenges, frontline teachers tried to support students with ASD as much as they could. The current findings should help to advance the inclusive education policy in Shanghai, including increasing the availability of inclusive education resources and training for teachers, issuing specific LRC guidance, and reducing ASD-related stigma. This study is among the first to explore the implementation of inclusive education in urban China.

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4. Moroe N, Masuku K, Shirame L. Rehabilitation healthcare professionals’ competence and confidence in differentially diagnosing deafblindness from autism spectrum disorders: a cross-sectional survey in South Africa. BMC medical education. 2022; 22(1): 194.

BACKGROUND: Early diagnosis and management of children who are deafblind is important to alleviate the effects of deafblindness on the development of the child who is deafblind and their families. However, children who are deafblind are often misdiagnosed or diagnosed late. The misdiagnosis or late diagnosis has been attributed to many factors, one of which is the competence and confidence of healthcare professionals in differentially diagnosing deafblindness from other conditions, in most cases, autism spectrum disorder (ASD). The study therefore aimed to establish the competence and confidence of rehabilitation healthcare professionals in differentially diagnosing deafblindness from ASD in the South African context. METHODS: A cross-sectional survey design was employed for the study. An online questionnaire was distributed to rehabilitation healthcare professionals (N = 78) via Survey Monkey. Data were analyzed using descriptive and inferential statistics. Ethical clearance and permission were obtained from relevant stakeholders prior to the commencement of the study. RESULTS: Regarding the rehabilitation healthcare professionals in this study, 54% were competent in diagnosing ASD, while only 35% could correctly diagnose deafblindness. In some instances, symptoms were classified as associated with both ASD and deafblindness, when they were just those of deafblindness. Of all the rehabilitation healthcare professionals in this study, speech language therapists displayed the most knowledge of deafblindness. Furthermore, healthcare professionals who had between one and nine years of working experience had more knowledge of deafblindness than other professionals with more or less experience. CONCLUSION: Deafblindness is often underdiagnosed or misdiagnosed as ASD. This is due to the lack of competence and confidence of rehabilitation healthcare professionals in diagnosing it. The findings therefore highlight the need for training of rehabilitation healthcare professionals. Training on deafblindness could be included as part of the curriculum in the various undergraduate programs. Deafblindness could also form part of the Continuous Professional Development (CPD) training programs at various healthcare facilities. A team approach to the training would be ideal as it would facilitate peer learning and support. More research is required as it would inform evidence-based assessment, and management and support strategies for children who are deafblind and their families.

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5. Moseley RL, Gregory NJ, Smith P, Allison C, Cassidy S, Baron-Cohen S. The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults. Molecular autism. 2022; 13(1): 14.

BACKGROUND: While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explain why risk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk. METHODS: Autistic adults (n = 314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS. RESULTS: Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables. LIMITATIONS: Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities. CONCLUSIONS: Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs.

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6. Ning J, Qiao L. [Analysis of CASR gene variant in a child with idiopathic epilepsy and autism]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2022; 39(3): 309-11.

OBJECTIVE: To explore the genetic basis for a child featuring idiopathic epilepsy and autism. METHODS: Peripheral blood samples of the child and his parents were collected with informed consent for the extraction of genome DNA. Whole exome sequencing was carried out for the family trio. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband was found to harbor a heterozygous nonsense c.3025C>T (p.Arg1009Ter) variant in exon 7 of the CASR gene exon 7, which may produce a truncated protein. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be deleterious and classified as possibly pathogenic (PVS1+PM2). CONCLUSION: The c.3025C>T (p.Arg1009Ter) variant of the CASR gene probably underlay the disease in this child.

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7. Parmar KR, Porter CS, Dickinson CM, Baimbridge P, Pelham J, Gowen E. Autism-friendly eyecare: Developing recommendations for service providers based on the experiences of autistic adults. Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists). 2022.

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8. Shic F, Naples AJ, Barney EC, Chang SA, Li B, McAllister T, Kim M, Dommer KJ, Hasselmo S, Atyabi A, Wang Q, Helleman G, Levin AR, Seow H, Bernier R, Charwaska K, Dawson G, Dziura J, Faja S, Jeste SS, Johnson SP, Murias M, Nelson CA, Sabatos-DeVito M, Senturk D, Sugar CA, Webb SJ, McPartland JC. The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials. Molecular autism. 2022; 13(1): 15.

BACKGROUND: Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). METHODS: The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. RESULTS: All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. LIMITATIONS: No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. CONCLUSIONS: All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

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9. Sundelin H, Söderling J, Bang P, Bolk J. Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study. Neurology. 2022.

BACKGROUND AND OBJECTIVES: Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. We aimed to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke as well as in their first-degree relatives. METHODS: In this cohort study individuals with ischemic stroke 1969 – 2016, <18 years of age, alive 1 week after stroke and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyse sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke. RESULTS: Of the 1322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls: adjusted hazard ratio (aHR)=3.02, 95% CI=2.15-4.25. There was no significant difference in risk of autism according to age at stroke: perinatal (aHR=2.69 95%CI=1.44-5.03) and childhood stroke (aHR=3.18 95%CI=2.12-4.78). The increased risk remained after excluding children born preterm or small for gestational age (aHR=3.78 95%CI=2.55-5.60) as well as when analysing children with stroke diagnosed from 1997-2014 (aHR=2.91, 95% CI=1.95-4.35). Compared to controls the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR=7.05, 95%CI=3.74-13.30) as well as adverse motor outcome (aHR=4.28, 95%CI=2.44-7.51). When individuals with adverse motor outcome and epilepsy were censored the risk of autism was still increased (aHR=2.37 1.45-3.85). Sex, gestational age or having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke. DISCUSSION: An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome implying that all children suffering ischemic stroke should be readily screened for autism if the disorder is suspected.

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10. Ta D, Downs J, Baynam G, Wilson A, Richmond P, Leonard H. A brief history of MECP2 duplication syndrome: 20-years of clinical understanding. Orphanet journal of rare diseases. 2022; 17(1): 131.

MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene-a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000. The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features-although these comorbidities are not yet understood with sufficient granularity. This review has covered the past two decades of MDS case studies and series since the discovery of the disorder in 1999. After comprehensively reviewing the reported characteristics, this review has identified areas of limited knowledge that we recommend may be addressed by better phenotyping this disorder through an international data collection. This endeavour would also serve to delineate the clinical overlap between MDS and RTT.

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11. Yuan D, Jiao J, Zhang M, Li S, Wang Z, Yang Y, Situ M, Wang M, Luo T, Huang Y. [Whole exome sequencing analysis of a patient with 45,X/46,XY mosaicism and autism spectrum disorder]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2022; 39(3): 297-300.

OBJECTIVE: To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter. RESULTS: The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. CONCLUSION: Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.

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12. Zerbo O, Modaressi S, Goddard K, Lewis E, Fireman B, Daley MF, Irving SA, Jackson LA, Donahue JG, Qian L, Getahun D, DeStefano F, McNeil MM, Klein NP. Safety of measles and pertussis-containing vaccines in children with autism spectrum disorders. Vaccine. 2022; 40(18): 2568-73.

OBJECTIVES: To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. METHODS: The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. RESULTS: The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. CONCLUSION: Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

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13. Zhang M, Chen Y, Lin Y, Ding H, Zhang Y. Multichannel Perception of Emotion in Speech, Voice, Facial Expression, and Gesture in Individuals With Autism: A Scoping Review. Journal of speech, language, and hearing research : JSLHR. 2022; 65(4): 1435-49.

PURPOSE: Numerous studies have identified individuals with autism spectrum disorder (ASD) with deficits in unichannel emotion perception and multisensory integration. However, only limited research is available on multichannel emotion perception in ASD. The purpose of this review was to seek conceptual clarification, identify knowledge gaps, and suggest directions for future research. METHOD: We conducted a scoping review of the literature published between 1989 and 2021, following the 2005 framework of Arksey and O’Malley. Data relating to study characteristics, task characteristics, participant information, and key findings on multichannel processing of emotion in ASD were extracted for the review. RESULTS: Discrepancies were identified regarding multichannel emotion perception deficits, which are related to participant age, developmental level, and task demand. Findings are largely consistent regarding the facilitation and compensation of congruent multichannel emotional cues and the interference and disruption of incongruent signals. Unlike controls, ASD individuals demonstrate an overreliance on semantics rather than prosody to decode multichannel emotion. CONCLUSIONS: The existing literature on multichannel emotion perception in ASD is limited, dispersed, and disassociated, focusing on a variety of topics with a wide range of methodologies. Further research is necessary to quantitatively examine the impact of methodological choice on performance outcomes. An integrated framework of emotion, language, and cognition is needed to examine the mutual influences between emotion and language as well as the cross-linguistic and cross-cultural differences. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19386176.

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