1. Bao B, Zahiri J, Gazestani VH, Lopez L, Xiao Y, Kim R, Wen TH, Chiang AWT, Nalabolu S, Pierce K, Robasky K, Wang T, Hoekzema K, Eichler EE, Lewis NE, Courchesne E. A predictive ensemble classifier for the gene expression diagnosis of ASD at ages 1 to 4 years. Molecular psychiatry. 2022.

Autism Spectrum Disorder (ASD) diagnosis remains behavior-based and the median age of diagnosis is ~52 months, nearly 5 years after its first-trimester origin. Accurate and clinically-translatable early-age diagnostics do not exist due to ASD genetic and clinical heterogeneity. Here we collected clinical, diagnostic, and leukocyte RNA data from 240 ASD and typically developing (TD) toddlers (175 toddlers for training and 65 for test). To identify gene expression ASD diagnostic classifiers, we developed 42,840 models composed of 3570 gene expression feature selection sets and 12 classification methods. We found that 742 models had AUC-ROC ≥ 0.8 on both Training and Test sets. Weighted Bayesian model averaging of these 742 models yielded an ensemble classifier model with accurate performance in Training and Test gene expression datasets with ASD diagnostic classification AUC-ROC scores of 85-89% and AUC-PR scores of 84-92%. ASD toddlers with ensemble scores above and below the overall ASD ensemble mean of 0.723 (on a scale of 0 to 1) had similar diagnostic and psychometric scores, but those below this ASD ensemble mean had more prenatal risk events than TD toddlers. Ensemble model feature genes were involved in cell cycle, inflammation/immune response, transcriptional gene regulation, cytokine response, and PI3K-AKT, RAS and Wnt signaling pathways. We additionally collected targeted DNA sequencing smMIPs data on a subset of ASD risk genes from 217 of the 240 ASD and TD toddlers. This DNA sequencing found about the same percentage of SFARI Level 1 and 2 ASD risk gene mutations in TD (12 of 105) as in ASD (13 of 112) toddlers, and classification based only on the presence of mutation in these risk genes performed at a chance level of 49%. By contrast, the leukocyte ensemble gene expression classifier correctly diagnostically classified 88% of TD and ASD toddlers with ASD risk gene mutations. Our ensemble ASD gene expression classifier is diagnostically predictive and replicable across different toddler ages, races, and ethnicities; out-performs a risk gene mutation classifier; and has potential for clinical translation.

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2. Bhalla S, Mehan S. 4-hydroxyisoleucine mediated IGF-1/GLP-1 signalling activation prevents propionic acid-induced autism-like behavioural phenotypes and neurochemical defects in experimental rats. Neuropeptides. 2022; 96: 102296.

Autism is a neuropsychiatric disorder characterized by a neurotransmitter imbalance that impairs neurodevelopment processes. Autism development is marked by communication difficulties, poor socio-emotional health, and cognitive impairment. Insulin-like growth factor-1 (IGF-1) and glucagon-like growth factor-1 (GLP-1) are responsible for regular neuronal growth and homeostasis. Autism progression has been linked to dysregulation of IGF-1/GLP-1 signalling. 4-hydroxyisoleucine (HI), a pharmacologically active amino acid produced from Trigonella foenum graecum, works as an insulin mimic and has neuroprotective properties. The GLP-1 analogue liraglutide (LRG) was employed in our investigation to compare the efficacy of 4-HI in autism prevention. The current study explores the protective effects of 4-HI 50 and 100 mg/kg orally on IGF-1/GLP-1 signalling activation in a PPA-induced experimental model of autism. Propionic acid (PPA) injections to rats by intracerebroventricular (ICV) route for the first 11 days of the experiment resulted in autism-like neurobehavioral, neurochemical, gross morphological, and histopathological abnormalities. In addition, we investigated the dose-dependent neuroprotective effects of 4-HI on the levels of several neurotransmitters and neuroinflammatory cytokines in rat brain homogenate and blood plasma. Neuronal apoptotic and anti-oxidant cellular markers were also studied in blood plasma and brain homogenate samples. Furthermore, the luxol fast blue (LFB) staining results demonstrated significant demyelination in the brains of PPA-induced rats reversed by 4-HI treatment. Rats were assessed for spontaneous locomotor impairments, neuromuscular coordination, stress-like behaviour, learning, and memory to assess neurobehavioral abnormalities. The administration of 4-HI and LRG significantly reversed the behavioural, gross and histological abnormalities in the PPA-treated rat brains. After treatment with 4-HI and LRG, LFB-stained photomicrographs of PPA-treated rats’ brains demonstrated the recovery of white matter loss. Our findings indicate that 4-HI protects neurons in rats with autism by enhancing the IGF-1 and GLP-1 protein levels.

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3. Bo J, Acluche F, Lasutschinkow PC, Augustiniak A, Ditchfield N, Lajiness-O’Neill R. Motor networks in children with autism spectrum disorder: a systematic review on EEG studies. Experimental brain research. 2022; 240(12): 3073-87.

Motor disturbance and altered motor networks are commonly reported in individuals with autism spectrum disorder (ASD). It has been suggested that electroencephalogram (EEG) can be used to provide exquisite temporal resolution for understanding motor control processes in ASD. However, the variability of study design and EEG approaches can impact our interpretation. Here, we conducted a systematic review on recent 11 EEG studies that involve motor observation and/or execution tasks and evaluated how these findings help us understand motor difficulties in ASD. Three behavior paradigms with different EEG analytic methods were demonstrated. The main findings were quite mixed: children with ASD did not always show disrupted neuronal activity during motor observation. Additionally, they might have intact ability for movement execution but have more difficulties in neuronal modulation during movement preparation. We would like to promote discussions on how methodological selections of behavioral tasks and data analytic approaches impact our interpretation of motor deficits in ASD. Future EEG research addressing the inconsistency across methodological approaches is necessary to help us understand neurophysiological mechanism of motor abnormalities in ASD.

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4. Caron J, Light J, McNaughton D. Effects of adapted Letter-Sound correspondence instruction with older learners with complex communication needs and autism spectrum disorder. Augmentative and alternative communication (Baltimore, Md : 1985). 2022: 1-15.

Individuals who use augmentative and alternative communication (AAC) are often excluded from learning literacy skills that use phonological approaches due to challenges with verbal production of speech sounds. This study was conducted to evaluate the effectiveness of systematic literacy instruction with materials modified to teach letter-sound correspondences (LSC) to pre-adolescent and adolescents with autism spectrum disorders (ASD) with minimal or no speech who use AAC. A single subject design across three letter-sound sets was used, with three individuals with ASD. A total of 12 LSC were targeted in the intervention. During the intervention, the participants were instructed using model, guided, and independent practice trials using low-tech letter tiles followed by two extension activities: letter sorting and initial letter-sound picture books. A functional relationship was established between the LSC intervention and the percent of correct responses on the LSC assessment probes. Very large and large effects sizes were calculated for all participants across the three LSC sets. The study adds to the very limited research base related to phonics instruction for older learners (ages 9 to 18) with ASD, demonstrating that LSC progress can still be made at an older age with systematic instruction.

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5. Daly G, Jackson J, Lynch H. Family life and autistic children with sensory processing differences: A qualitative evidence synthesis of occupational participation. Frontiers in psychology. 2022; 13: 940478.

Autistic children with sensory processing differences successfully navigate and engage in meaningful family daily occupations within home and community environments through the support of their family. To date however, much of the research on autistic children with sensory processing differences, has primarily been deficit focused, while much of the caregiver research has focused on issues of distress, burden, effort, and emotional trauma in coping with their child’s diagnosis. This study aimed to conduct a qualitative evidence synthesis, using a meta-ethnographic approach to explore the gap identified in understanding successful occupational experiences of family participation and daily family routines when supporting an autistic child with sensory processing differences and to offer an alternative strengths-based perspective. Inclusion criteria were studies which were peer-reviewed qualitative design, published from 2000 to 2021, and that concerned parents/caregivers’ perspectives of family occupations of children diagnosed with autism spectrum disorder. Studies were electronically searched in eight databases from October to December 2021 and 23 studies were identified which met the inclusion criteria. Noblit and Hare’s seven step approach for conducting analysis in meta-ethnography was used, and three themes identified: (1) sensory processing differences in daily life, (2) what is hard about hard, and (3) orchestrating family life. Results identified the centrality of sensory experiences in understanding family life. Living with unpredictability while orchestrating certainty through routines was core to successful participation. This review provides insights into how parents negotiate the complexities of constructing family life when living with an autistic child. The results can inform the design of future interventions that specifically address the relationship between meaningful participation in family occupations and daily routines and sensory processing in autistic children. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298938, identifier: CRD42022298938.

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6. Evers K, Gijbels E, Maljaars J, Rumball F, Spain D, Happé F, Noens I. Mental health of autistic adults during the COVID-19 pandemic: The impact of perceived stress, intolerance of uncertainty, and coping style. Autism : the international journal of research and practice. 2022: 13623613221119749.

More and more research shows us that autistic individuals are at risk of experiencing mental health problems in response to the COVID-19 pandemic. However, little is known about why this is the case. At two timepoints during the pandemic, we asked 149 autistic and 147 non-autistic adults about feelings of anxiety, depression, and stress, and about characteristics that may explain why some (autistic) people have a larger chance of developing anxiety and depression during this pandemic. In our study, autistic adults experienced more anxiety and depression than non-autistic adults. Across autistic and non-autistic individuals, the people who experienced more stress at timepoint 1 experienced more anxiety and depression 4 months later. This was especially the case for those individuals who use maladaptive coping styles, such as denial or venting, and for those who have difficulties dealing with uncertain situations. Our findings show the burden of the COVID-19 pandemic on the mental health of autistic adults. Interventions to support autistic adults during and after the pandemic are needed, and they may want to focus on the negative impact of stress and teach autistic (and non-autistic) adults more adaptive ways to cope with stressful circumstances.

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7. Ferron L, Zamponi GW. The road to the brain in Timothy syndrome is paved with enhanced CaV1.2 activation gating. The Journal of general physiology. 2022; 154(11).

Specific gating effects of Timothy syndrome Ca(V)1.2 channel mutations determine cardiovascular versus nervous system deficits.

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8. Hampton S, Allison C, Baron-Cohen S, Holt R. Autistic People’s Perinatal Experiences I: A Survey of Pregnancy Experiences. Journal of autism and developmental disorders. 2022.

Qualitative studies of autistic people’s pregnancy experiences have indicated sensory and communication related barriers to accessing adequate prenatal healthcare. However, quantitative work on the topic is scarce. This online survey study explored pregnancy experiences among 417 autistic and 524 non-autistic people. Compared with non-autistic people, autistic people reported heightened sensory and physical experiences during pregnancy and were more likely to experience prenatal depression and anxiety. Autistic people experienced lower satisfaction with prenatal healthcare, including having lower perceptions of their relationships with healthcare professionals and greater difficulties with antenatal classes. This study identifies key adjustments that can be made to prenatal healthcare, including sensory and communication adjustments. The findings highlight the need for greater autism understanding and awareness among professionals.

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9. Holyfield C, O’Neill Zimmerman T. A Scoping Review of Research Evaluating Physiological Information for Individuals With Developmental Disabilities: Augmentative and Alternative Communication Research Considerations. Journal of speech, language, and hearing research : JSLHR. 2022; 65(11): 4306-26.

PURPOSE: Today, an ever-increasing number of technological advancements are becoming mainstream. As the availability of technological innovations increases, so do opportunities for evaluating any benefits of those innovations in augmentative and alternative communication (AAC) research for individuals with developmental disabilities. One innovation that has become mainstream is the use of noninvasive wearable technology to provide physiological information (e.g., heart rate, skin conductance). Such information could be valuable in AAC research, but more information about its potential feasibility and utility is needed. METHOD: A scoping review was conducted to review and report on existing research that has evaluated (a) physiological information as a communication intervention tool for individuals with developmental disabilities and (b) the relationship between physiological information from individuals with developmental disabilities and behavioral and/or environmental information in real time. RESULTS: Results revealed that, while little communication intervention research has been completed, descriptive research demonstrates that physiological information from individuals with developmental disabilities gathered using wearable technology corresponds meaningfully to observable environmental and behavioral events. CONCLUSIONS: Future AAC research incorporating wearable technology to gather physiological information is warranted. Such research could evaluate potential benefits such as preempting challenging behavior with communication opportunities, signaling readiness for language learning, indicating AAC feature preferences, and expanding methodological approaches.

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10. Huang R, Potla S, Bhalla S, Al Qabandi Y, Nandula SA, Boddepalli CS, Gutlapalli SD, Lavu VK, Abdelwahab R, Hamid P. The Clinical Implications of the Academic Performance of the Siblings of Individuals With Autism Spectrum Disorder. Cureus. 2022; 14(9): e29116.

We all know that autism spectrum disorder (ASD) can affect academic performance. Many children with autism face different challenges at school. However, less attention is paid to the siblings of autistic children, who are at a high risk of ASD or the broad autism phenotype (BAP). Recent data also shows that many siblings of ASD children suffer from neurodevelopmental disorders, mental health problems as well as poor academic performance. This review will look at the possible etiologies of the poor school performance of autistic children’s siblings, with an emphasis on the challenges they face. We will also highlight the clinical implications of these findings, and the possible solutions that can help this vulnerable group.

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11. Jarrige D, Haridas S, Bleykasten-Grosshans C, Joly M, Nadalig T, Sancelme M, Vuilleumier S, Grigoriev IV, Amato P, Bringel F. High-quality genome of the basidiomycete yeast Dioszegia hungarica PDD-24b-2 isolated from cloud water. G3 (Bethesda, Md). 2022; 12(12).

The genome of the basidiomycete yeast Dioszegia hungarica strain PDD-24b-2 isolated from cloud water at the summit of puy de Dôme (France) was sequenced using a hybrid PacBio and Illumina sequencing strategy. The obtained assembled genome of 20.98 Mb and a GC content of 57% is structured in 16 large-scale contigs ranging from 90 kb to 5.56 Mb, and another 27.2 kb contig representing the complete circular mitochondrial genome. In total, 8,234 proteins were predicted from the genome sequence. The mitochondrial genome shows 16.2% cgu codon usage for arginine but has no canonical cognate tRNA to translate this codon. Detected transposable element (TE)-related sequences account for about 0.63% of the assembled genome. A dataset of 2,068 hand-picked public environmental metagenomes, representing over 20 Tbp of raw reads, was probed for D. hungarica related ITS sequences, and revealed worldwide distribution of this species, particularly in aerial habitats. Growth experiments suggested a psychrophilic phenotype and the ability to disperse by producing ballistospores. The high-quality assembled genome obtained for this D. hungarica strain will help investigate the behavior and ecological functions of this species in the environment.

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12. Jarrige D, Nadalig T, Joly M, Sancelme M, Vuilleumier S, Amato P, Bringel F. Complete Genome of Sphingomonas aerolata PDD-32b-11, Isolated from Cloud Water at the Summit of Puy de Dôme, France. Microbiology resource announcements. 2022; 11(10): e0068422.

The complete genome of Sphingomonas aerolata PDD-32b-11, a bacterium isolated from cloud water, was sequenced. It features four circular replicons, a chromosome of 3.99 Mbp, and three plasmids. Two putative rhodopsin-encoding genes were detected which might act as proton pumps to harvest light energy.

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13. 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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14. Milton D, Gurbuz E, Lopez B. The ‘double empathy problem’: Ten years on. Autism : the international journal of research and practice. 2022; 26(8): 1901-3.

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15. Mungmunpuntipantip R, Wiwanitkit V. COVID-19 Vaccines for Children with Developmental Disabilities: Correspondence. Journal of developmental and behavioral pediatrics : JDBP. 2022.

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16. Sakamornchai W, Dumrongwongsiri O, Siwarom S. Case Report: Vitamin C combined with multiple micronutrient deficiencies is associated with pulmonary arterial hypertension in children with autistic spectrum disorder. Frontiers in nutrition. 2022; 9: 928026.

Children with developmental and behavioral problems including autistic spectrum disorders (ASDs) may have inappropriate feeding behaviors, which leads to an increased risk of multiple nutrient deficiencies. Vitamin C deficiency is one of the common nutrient deficiencies reported in children with inappropriate feeding. This case report illustrates two cases of ASD children with a clinical presentation of pulmonary arterial hypertension, a rare presentation of vitamin C deficiency. Vitamin C supplementation, pulmonary vasodilator, and supportive treatment were provided. Patients could recover from the illness and could be discharged from the hospital in a short time. In addition to vitamin C, the patients also had multiple micronutrient deficiencies. Nutrition counseling was given and micronutrient supplement was continued until follow-up. Regular nutrition assessment and counseling among children with ASD are needed to prevent nutrient deficiencies which may lead to life-threatening complications.

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17. Schuchard J, Kaplan-Kahn EA, Carle AC, Holmes LG, Law K, Miller JS, Parish-Morris J, Forrest CB. Using percentiles in the interpretation of Patient-Reported Outcomes Measurement Information System scores: Guidelines for autism. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2336-45.

The objectives of this study were to (1) demonstrate the application of percentiles to advance the interpretation of patient-reported outcomes and (2) establish autism-specific percentiles for four Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROMIS measures were completed by parents of autistic children and adolescents ages 5-17 years as part of two studies (n = 939 parents in the first study and n = 406 parents in the second study). Data from the first study were used to develop autism-specific percentiles for PROMIS parent-proxy sleep disturbance, sleep-related impairment, fatigue, and anxiety. Previously established United States general population percentiles were applied to interpret PROMIS scores in both studies. Results of logistic regression models showed that parent-reported material hardship was associated with scoring in the moderate-severe range (defined as ≥75th percentile in the general population) on all four PROMIS measures (odds ratios 1.7-2.2). In the second study, the percentage of children with severe scores (defined as ≥95th percentile in the general population) was 30% for anxiety, 25% for sleep disturbance, and 17% for sleep-related impairment, indicating a high burden of these problems among autistic children. Few children had scores at or above the autism-specific 95th percentile on these measures (3%-4%), indicating that their scores were similar to other autistic children. The general population and condition-specific percentiles provide two complementary reference points to aid interpretation of PROMIS scores, including corresponding severity categories that are comparable across different PROMIS measures.

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18. Simhal AK, Carpenter KLH, Kurtzberg J, Song A, Tannenbaum A, Zhang L, Sapiro G, Dawson G. Changes in the geometry and robustness of diffusion tensor imaging networks: Secondary analysis from a randomized controlled trial of young autistic children receiving an umbilical cord blood infusion. Frontiers in psychiatry. 2022; 13: 1026279.

Diffusion tensor imaging (DTI) has been used as an outcome measure in clinical trials for several psychiatric disorders but has rarely been explored in autism clinical trials. This is despite a large body of research suggesting altered white matter structure in autistic individuals. The current study is a secondary analysis of changes in white matter connectivity from a double-blind placebo-control trial of a single intravenous cord blood infusion in 2-7-year-old autistic children (1). Both clinical assessments and DTI were collected at baseline and 6 months after infusion. This study used two measures of white matter connectivity: change in node-to-node connectivity as measured through DTI streamlines and a novel measure of feedback network connectivity, Ollivier-Ricci curvature (ORC). ORC is a network measure which considers both local and global connectivity to assess the robustness of any given pathway. Using both the streamline and ORC analyses, we found reorganization of white matter pathways in predominantly frontal and temporal brain networks in autistic children who received umbilical cord blood treatment versus those who received a placebo. By looking at changes in network robustness, this study examined not only the direct, physical changes in connectivity, but changes with respect to the whole brain network. Together, these results suggest the use of DTI and ORC should be further explored as a potential biomarker in future autism clinical trials. These results, however, should not be interpreted as evidence for the efficacy of cord blood for improving clinical outcomes in autism. This paper presents a secondary analysis using data from a clinical trial that was prospectively registered with ClinicalTrials.gov(NCT02847182).

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19. Smith J, Rabba AS, Cong L, Datta P, Dresens E, Hall G, Heyworth M, Lawson W, Lee P, Lilley R, Syeda N, Ma E, Wang J, Wang R, Yeow CT, Pellicano E. Correction: « They Were Saying That I Was a Typical Chinese Mum »: Chinese Parents’ Experiences of Parent-Teacher Partnerships for Their Autistic Children. Journal of autism and developmental disorders. 2022.

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20. Stabile M, Eigsti IM. Lexical Alignment and Communicative Success in Autism Spectrum Disorder. Journal of speech, language, and hearing research : JSLHR. 2022; 65(11): 4300-5.

PURPOSE: Typical speakers tend to adopt words used by their conversational partners. This « lexical alignment » enhances communication by reducing ambiguity and promoting a shared understanding of the topic under discussion. Lexical alignment has been little studied to date in autism spectrum disorder (ASD); furthermore, it has been studied primarily via structured laboratory tasks that may overestimate performance. This study examined lexical alignment in ASD during discourse and explored associations with communicative success and executive function. METHOD: Thirty-one autistic and nonautistic adolescents were paired with a study-naïve research assistant (RA) to complete a social communication task that involved taking turns verbally instructing (guiding) the partner to navigate on a map. Lexical alignment was operationalized as the proportion of shared vocabulary produced by guides on successive maps. Task accuracy was operationalized as the pixels contained within the intended and drawn routes. RESULTS: Results indicated that autistic adolescents had greater difficulty describing navigational routes to RAs, yielding paths that were less accurate. Alignment was reduced in autistic participants, and it was associated with path accuracy for nonautistic, but not autistic, adolescents. The association between lexical alignment and executive function missed significance (p = .05); if significant, the association would indicate that greater executive function difficulty was associated with reduced lexical alignment. CONCLUSIONS: These findings provide preliminary evidence of reduced lexical alignment in ASD in an unstructured discourse context. Moreover, positive associations between lexical alignment and task performance in the neurotypical group raise the possibility that interventions to promote the use of shared vocabulary might support better communication. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21313719.

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21. Sterrett K, Holbrook A, Landa R, Kaiser A, Kasari C. The effect of responsiveness to speech-generating device input on spoken language in children with autism spectrum disorder who are minimally verbal(†). Augmentative and alternative communication (Baltimore, Md : 1985). 2022: 1-10.

The use of speech-generating devices (SGD) in early interventions for children with autism spectrum disorder (ASD) can improve communication and spoken language outcomes. The purpose of this study was to describe children’s responsiveness to SGD input modeled by a social partner during adult-child play interactions over a 24-week intervention trial and explore the effect of that responsiveness on spoken language growth. This secondary analysis consisted of 31 children with less than 20 functional words at study entry who received a blended behavioral intervention (JASPER + EMT) as part of a randomized controlled trial. Significant improvements were seen in rate of responsiveness to both adult SGD models and adult natural speech models; only rate of responsiveness to SGD models at entry was a significant predictor of frequency of commenting and was a more robust predictor of number of different words post-intervention. Lastly, at entry, children with more joint attention and language responded to SGD models at significantly higher rates. Attention and responsiveness to SGD output may be important mechanisms of language growth and children who have more joint attention skills may particularly benefit from use of an SGD.

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22. Vakilzadeh G, Falcone C, Dufour B, Hong T, Noctor SC, Martínez-Cerdeño V. Decreased number and increased activation state of astrocytes in gray and white matter of the prefrontal cortex in autism. Cerebral cortex (New York, NY : 1991). 2022; 32(21): 4902-12.

The cerebral cortex presents with alterations in the number of specific cell types in autism spectrum disorder (ASD). Astrocytes have many functions in the brain including a role in higher cognitive functions and in inflammatory brain processes. Therefore, an alteration in number, function, and/or activation state of astrocytes, could be present in ASD. We quantified astrocyte number in the gray and white matter of the prefrontal cortex-BA9, BA46, and BA47-in 15 ASD and 15 age- and sex-matched control cases. We labeled astrocytes with antibodies against the protein GFAP and S100β, markers of astrocytes. We found a significant decrease in the number of astrocytes in the gray and white matter of all prefrontal areas of interest with both markers. We also found an increased state of activation of GFAP+ astrocytes in all areas. A reduced number of astrocytes in the cerebral cortex in ASD could lead to impaired synaptic function and disrupted connectivity. An increased astrocyte activation may indicate a chronic mild inflammatory state of the cerebral cortex in ASD. Overall, we found that astrocytes are disrupted in ASD.

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23. Valori I, Carnevali L, Mantovani G, Farroni T. Motivation from Agency and Reward in Typical Development and Autism: Narrative Review of Behavioral and Neural Evidence. Brain sciences. 2022; 12(10).

Our ability to perform voluntary actions and make choices is shaped by the motivation from having control over the resulting effects (agency) and positive outcomes (reward). We offer an overview of distinct and common behavioral and neural signatures of agency and reward. We discuss their typical and atypical developmental trajectories, focusing on autism spectrum disorder (ASD), which is characterized by neurodiverse processes underlying action selection. We propose that reduced sensitivity to agency and reward in ASD may be related to atypical multisensory processes and motor planning, with potential for understanding restricted and repetitive behaviors. We emphasize the limitations of the existing literature, and prospects for future research. Understanding the neurocognitive processes that shape the way people with ASD select actions and perceive outcomes is essential to support not only learning, but also volition and self-determination.

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24. Wang L, Zhang H, Shang C, Liang H, Liu W, Han B, Xia W, Zou M, Sun C. Mental health issues in parents of children with autism spectrum disorder: A multi-time-point study related to COVID-19 pandemic. Autism research : official journal of the International Society for Autism Research. 2022; 15(12): 2346-58.

Given the unpredictability and challenges brought about by the 2019 novel coronavirus (COVID-19) pandemic, this study aimed to investigate the impact trend of the prolonged pandemic on the mental health of parents of children with autism spectrum disorder (ASD). The 8112 participants included parents of children with ASD and parents of typically developing (TD) children at two sites (Heilongjiang and Fujian province, China). The parents completed a set of self-report questionnaires covering demographic characteristics, influences related to COVID-19, COVID-19 concerns and perceived behaviors, as well as the Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) by means of an online survey platform. Data were collected by three cross-sectional surveys carried out in April 2020 (Time 1), October 2020 (Time 2), and October 2021 (Time 3). The results of quantitative and qualitative comparisons showed that: (i) parents of children with ASD had lower levels of resilience, and more symptoms of anxiety and depression than parents of TD children at each time point (all P < 0.05); and (ii) there were significant time-cumulative changes in resilience, anxiety, and depression among all participants (all P < 0.05). The logistic regression analyzes after adjusting for demographic characteristics revealed that the following factors were significantly associated with poor resilience and a higher rate of anxiety and depression in parents of children with ASD: time-point, the effect of COVID-19 on children's emotions and parents' emotions, changes in relationships, changes in physical exercise, changes in daily diet during the COVID-19 pandemic, and COVID-19-related psychological distress. In conclusions, the parents did not report improvements in resilience, anxiety, or depression symptoms from Time 1 to Time 2 or 3, indicating that cumulative mental health issues increased when, surprisingly, the COVID-19 restrictions were eased. The psychological harm resulting from the COVID-19 pandemic is far-reaching, especially among parents of children with ASD.

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25. Wu Q, Yang T, Chen L, Dai Y, Wei H, Jia F, Hao Y, Li L, Zhang J, Wu L, Ke X, Yi M, Hong Q, Chen J, Fang S, Wang Y, Wang Q, Jin C, Hu R, Chen J, Li T. Early life exposure to triclosan from antimicrobial daily necessities may increase the potential risk of autism spectrum disorder: A multicenter study in China. Ecotoxicology and environmental safety. 2022; 247: 114197.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. OBJECTIVE: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. METHODS: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. RESULTS: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted β = 0.277, P < 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls. CONCLUSION: To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

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