1. Borrmann D, Danzer A, Sadowski G. Predicting the Water Sorption in ASDs. Pharmaceutics;2022 (May 31);14(6)

Water decreases the stability of amorphous solid dispersions (ASDs) and water sorption is, therefore, unwanted during ASD storage. This work suggests a methodology to predict the water-sorption isotherms and the water-sorption kinetics in amorphous pharmaceutical formulations like ASDs. We verified the validity of the proposed methodology by measuring and predicting the water-sorption curves in ASD films of polyvinylpyrrolidone-based polymers and of indomethacin. This way, the extent and the rate of water sorption in ASDs were predicted for drug loads of 0.2 and 0.5 as well as in the humidity range from 0 to 0.9 RH at 25 °C. The water-sorption isotherms and the water-sorption kinetics in the ASDs were predicted only based on the water-sorption isotherms and water-sorption kinetics in the neat polymer on the one hand and in the neat active pharmaceutical ingredient (API) on the other hand. The accurate prediction of water-sorption isotherms was ensured by combining the Perturbed-Chain Statistical Association Theory (PC-SAFT) with the Non-Equilibrium Thermodynamics of Glassy Polymers (NET-GP) approach. Water-sorption kinetics were predicted using Maxwell-Stefan diffusion coefficients of water in the ASDs.

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2. Bruford E, On Behalf Of The Hugo Gene Nomenclature Committee H. Comment on Herring et al. The Use of « Retardation » in FRAXA, FMRP, FMR1 and Other Designations. Cells 2022, 11, 1044. Cells;2022 (Jun 16);11(12)

This commentary is written in response to the recent article from Herring et al., discussing the eradication of the offensive term « retardation » from gene nomenclature. We discuss the work of the HUGO (Human Genome Organisation) Gene Nomenclature Committee (HGNC) and outline the steps already taken to remove this term from our gene names. We also highlight the latest nomenclature changes made as a result of discussions with the authors and agreement with the European Fragile X Network.

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3. Cai C, Yin Z, Liu A, Wang H, Zeng S, Wang Z, Qiu H, Li S, Zhou J, Wang M. Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder. Genes (Basel);2022 (Jun 20);13(6)

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2-12 years old) and 107 healthy controls without ASD (20-78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis.

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4. Carpita B, Migli L, Chiarantini I, Battaglini S, Montalbano C, Carmassi C, Cremone IM, Dell’Osso L. Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder: A Literature Review. Brain Sci;2022 (Jun 16);12(6)

Fetal alcohol spectrum disorders (FASD) are a group of conditions associated with the effects of prenatal alcohol exposure and characterized by somatic and neuropsychological alterations. On the other hand, autism spectrum disorder (ASD) is characterized by a multifaceted neurobehavioral syndrome. Since alcohol can affect every stage of brain development, some authors hypothesized that in utero alcohol exposure might be linked to an increased risk of ASD in subjects with genetic vulnerability. The present review aimed to summarize the available literature on the possible association between FASD and ASD, also focusing on the reported clinical overlaps and on the possible shared pathogenic mechanisms. Studies in this field have stressed similarities and differences between the two conditions, leading to controversial results. The available literature also highlighted that both the disorders are often misdiagnosed or underdiagnosed, stressing the need to broaden the perspective, paying specific attention to milder presentations and sub-syndromic traits.

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5. Carta A, Manca MA, Scoppola C, Simula ER, Noli M, Ruberto S, Conti M, Zarbo IR, Antonucci R, Sechi LA, Sotgiu S. Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism. Biomedicines;2022 (Jun 9);10(6)

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.

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6. Caruso A, Ricceri L, Nicoletti F, Gaetano A, Scaccianoce S. Postweaning social isolation and autism-like phenotype: A biochemical and behavioral comparative analysis. Behav Brain Res;2022 (Jun 25);428:113891.

Adolescence is a critical period for brain development. In most mammalian species, disturbances experienced during adolescence constitute a risk factor for several neuropsychiatric disorders. In this study, we compared the biochemical and behavioral profile induced by postweaning social isolation (PWSI) in inbred C57BL/6 N mice with that of BTBR mice, a rodent model of autism spectrum disorders. Male C57BL/6 N mice were either housed in groups of four or isolated from weaning (postnatal day 21) for four weeks before experimental analyses. After weaning, male BTBR mice were housed four per cage and analyzed at 48 days of age. PWSI reduced hippocampal levels of type 2 metabotropic glutamate (mGlu2) receptors, and glucocorticoid and mineralocorticoid receptors. A similar reduction was seen in group-housed BTBR mice. Plasma corticosterone levels in basal conditions were not influenced by PWSI, but were increased in BTBR mice. Social investigation (total and head sniffing) and the number of ultrasonic vocalizations were reduced in both PWSI mice and age-matched group-housed BTBR mice, indicating a lower social responsiveness in both groups of mice. These results suggest that absence of social stimuli during adolescence induces an endophenotype with social deficit features, which mimics the phenotype of a mouse model of autism spectrum disorders.

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7. Cervin M. Developmental signs of ADHD and autism: a prospective investigation in 3623 children. Eur Child Adolesc Psychiatry;2022 (Jun 24)

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with an early onset. Guidelines recommend a careful evaluation of developmental history when assessing the disorders, but it is unclear how children with ADHD and ASD differ from their peers growing up. In this study, physical, family, psychological, social, and educational information were examined in 3623 ethnically diverse children that were prospectively followed from birth to age 15 as part of the Fragile Families and Child Wellbeing Study. Fifteen-thousand variables were screened, and 506 variables included in the final analyses. Accuracy of the most indicative information to predict ADHD and ASD diagnoses in adolescence was evaluated. Adolescents with ADHD (n = 627) and ASD (n = 91) differed from their peers on a plethora of developmental signs, with signs closely related to the core symptoms of the disorders after age 5 being most indicative of the disorders. Predictive models correctly identified 66% of individuals with ADHD and 81% of those with ASD, but 62-88% of identified cases were false positives. The mean proportion of developmental deviations was 18.7% in the ADHD group, 20.0% in the ASD group, and 15.6% in peers; youth with both ADHD and ASD (n = 50) deviated on 21.8% of all developmental signs and had more pronounced deviations than those with ADHD or ASD alone. ADHD and ASD are characterized by broad and non-specific developmental deviations. Developmental information alone cannot be used to accurately predict diagnostic status in adolescence and false positives are likely if the diagnostic process relies heavily on such information. Developmental deviations are part of normal development and common in children without ADHD and ASD. Etiological heterogeneity and considerable temporal fluctuation in the core characteristics of ADHD and ASD may explain the lack of distinct developmental patterns.

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8. Clothier JL, Grooms AN, Porter-Gill PA, Gill PS, Schaefer GB. Identification of DCAF1 by Clinical Exome Sequencing and Methylation Analysis as a Candidate Gene for Autism and Intellectual Disability: A Case Report. J Pers Med;2022 (May 27);12(6)

Autism spectrum disorder (ASD) comprises a heterogeneous group of neurodevelopmental disorders and occurs in all racial, ethnic, and socioeconomic groups. Cutting-edge technologies are contributing to understanding genetic underpinnings in ASD. The reported patient is a 32-year-old male and as an infant was noted to have microcephaly, hypospadias, pulmonary vascular anomaly, and small stature. He was diagnosed with Cornelia De Lange Syndrome (CDLS) at that time based on the clinical features. As a child, he had autistic features and intellectual disabilities and as diagnoses with autism and intellectual disability. He was referred as an adult to our neurodiversity clinic and a full exome trio sequencing with reflex to mitochondrial genes identified a de novo variant of uncertain significance in a candidate gene, DCAF1. The specific variant was c.137 C > T (p.Thr46Ile) in exon 4 in the DCAF1 gene. In silico analysis supports a deleterious effect on protein structure/function. DCAF1 participates with DDB1 and CUL4 as a part of the E3 ubiquitin ligase complex. The E3 ligase complex has been associated with a syndromic form of X-linked intellectual disability. The DDB1/CUL4 E3 ubiquitination complex plays a role in methylation-dependent ubiquitination. Next, a methylation study identified a signature similar to the methylation pattern found in X- linked intellectual disability type 93. This is associated with variants of the BRWD3 gene, which is linked with the functioning of the DDB1/CUL4 E3 ubiquitination complex. Taken together, this suggests that the de novo DCAF1 variant may be a newly identified molecular cause of autism and intellectual disability.

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9. Dey R, Chattarji S. The same stress elicits different effects on anxiety-like behavior in rat models of Fmr1(-/y) and Pten(+/). Behav Brain Res;2022 (Jun 25);428:113892.

Individuals affected by autism spectrum disorders (ASDs) exhibit affective symptoms such as enhanced anxiety, which has been seen in rodent models of ASDs as well. Exposure to stress is also known to be anxiogenic. However, the effects of stress on animal models of ASDs remains less explored. Hence, in the present study we examined the impact of acute foot shock stress on anxiety-like behavior in two monogenic rat models of ASDs, fragile X mental retardation 1 knockout (Fmr1(-/y)) and phosphatase and tensin homolog heterozygous (Pten(+/-)). Before exposure to stress, the basal levels of anxiety-like behavior in both Fmr1(-/y) and Pten(+/-) rats were comparable to that seen in wild-type (WT) control rats in an open-field arena. After exposure to the foot shock stress, however, Fmr1(-/y) rats showed the highest levels of anxiety-like behavior. WT animals also showed enhanced anxiety-like behavior but not as robustly as the Fmr1(-/y) animals. In Pten(+/-) animals, on the other hand, the same stressor did not elicit any anxiogenic effects. In a separate group of rats, the efficacy of the acute foot shock in triggering a stress response was confirmed wherein a comparable surge in circulating corticosterone was seen in all three experimental groups. Thus, the same acute stress led to different effects on anxiety-like behavior in different rodent models of ASDs, suggesting that vulnerability to stress-induced changes in anxiety may vary with the underlying genetic mutations.

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10. Dietz N, Hollis P, Fortuny E, Gruter B, Virojanapa J, Williams B, Spiessberger A. Systemic Risk Factors for Adult Spinal Deformity (ASD): A Retrospective Analysis of 48 Patients. Cureus;2022 (May);14(5):e25214.

INTRODUCTION: Adult spinal deformity (ASD) results in significant patient morbidity and burden to quality of life. The degree to which systemic risk factors and comorbidities that contribute to ASD affect specific spinopelvic parameters is not well-documented. We determine the extent to which preoperative risk factors may contribute to spinopelvic parameters associated with ASD. METHODS: Retrospective single-center study of 48 patients with ASD. Analysis of variance (ANOVA) linear regression analysis was performed to evaluate correlation between systemic comorbidities (obesity, arterial hypertension (HTN), hyperlipidemia (HLD), cardiomyopathy, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and asthma) and the following radiographic parameters: pelvic incidence (PI), lumbar lordosis (LL), C7 sagittal vertical axis (C7SVA), and the T10-L2 sagittal cobb angle. RESULTS: A total of 48 patients were included with mean C7SVA of 79.6 mm (SD: 63, range: 43-254), mean LL of 32.9° (SD: 15.9, range: -14 to 78), T10-L2 sagittal cobb angle of 3° (SD: 12.7, range: -24 to 30), and PI was 49° (SD: 10.7, range: 21 to 77). Only DM correlated with sagittal imbalance with high C7SVA and PI-LL mismatch. The beta coefficient for DM and preoperative C7SVA was 0.49, t=3.16, p=0.003, preoperative PI-LL mismatch standardized beta coefficient was -0.4, t=-2.38, p=0.022, and preoperative T10-L2 sagittal cobb standard beta coefficient was -0.07, t=-0.46, p=0.645. No significant correlations were found for asthma, COPD, HTN, HLD, or cardiomyopathy. CONCLUSIONS: Diagnosis of DM was found to correlate with pathologic C7SVA and significant PI-LL mismatch associated with ASD. HTN, HLD, cardiomyopathy, obesity, and pulmonary disease did not correlate with radiographic findings of sagittal imbalance.

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11. Engal E, Baker M, Salton M. The chromatin roots of abnormal splicing in autism. Trends Genet;2022 (Jun 21)

Spatiotemporal gene expression drives neurodevelopment. Therefore, abnormal expression during development results in atypical brain function. Alterations in gene expression have been described in autism spectrum disorder (ASD). Here, we focus on one aspect of gene expression, pre-mRNA splicing, specifically, the mechanism of its regulation by chromatin and how this is altered in ASD.

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12. Feng XW, Hadizadeh M, Cheong JPG. Global Trends in Physical-Activity Research of Autism: Bibliometric Analysis Based on the Web of Science Database (1980-2021). Int J Environ Res Public Health;2022 (Jun 14);19(12)

The World Health Organization has identified nervous system diseases as one of the biggest public health problems, including autism spectrum disorder (ASD). Considering the extensive benefits of physical activity (PA), the literature on the PA research of ASD has increased each year, but there is a lack of bibliometric analyses in this field. To investigate the research achievements worldwide, this paper adopts bibliometrics to analyze the trend in the academic literature on the PA research of ASD published from 1980 to 2021. The documents were retrieved from the Web of Science database, and the search strategy was to combine the keywords related to « physical activity » and « autism spectrum disorder » by using the Boolean operator tools « OR » and « AND » in the title. A total of 359 English documents were retrieved. Microsoft Excel, Data Wrapper, VOSviewer, and Biblioshiny were used for the visual analysis. We found that the number of published documents increased the fastest from 2017 to 2021, which may be due to the promulgation of the Global Action Plan for Physical Activity 2018-2030 and the influence of COVID-19 on the world. The United States and the University of California systems are in the leading position in this field. Cooperation among countries with different levels of development will help to jointly promote the PA research progress on ASD. The focus themes include « individual effect », « social support » and « activity dose ». The analysis of the frontier topic points out that researchers are paying increasing attention to how to improve the health and physical fitness of this group through PA. This research clearly puts forward a comprehensive overview, theme focus, and future trends in this field, which may be helpful to guide future research.

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13. Freitag CM, Persico AM, Vorstman JAS. Developing Gene-Based Personalised Interventions in Autism Spectrum Disorders. Genes (Basel);2022 (Jun 2);13(6)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in early childhood […].

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14. Gabellone A, Marzulli L, Matera E, Petruzzelli MG, Margari A, Giannico OV, Margari L. Expectations and Concerns about the Use of Telemedicine for Autism Spectrum Disorder: A Cross-Sectional Survey of Parents and Healthcare Professionals. J Clin Med;2022 (Jun 8);11(12)

Telemedicine has recently been used for diagnosis and interventions inpatients with autism spectrum disorder (ASD), traditionally performed in-person, but little attention has been paid to user expectations prior to its use. The aim of this study is to compare the expectations and concerns of 50 healthcare professionals and 45 parents of children with ASD regarding the use of telemedicine for diagnostic or treatment purposes. Parents have higher expectations for the use of telemedicine as an alternative (p = 0.0223) and supplement (p = 0.0061) to in-person diagnosis of ASD, as well as a supplement to traditional intervention (p ≤ 0.0001). In addition, while they also have greater hope for improvement in family routines (p = 0.0034) and parenting skills in child management (p = 0.0147), they express greater concern about the need for active parental involvement/supervision during telemedicine services (p = 0.015) and changes in the behaviour of the child with ASD during telemedicine services (p = 0.049). On the other hand, healthcare professionals are more concerned about barriers such as lack of devices (p = 0.000), unfamiliarity with the technology (p = 0.000), poor quality of internet connection (p = 0.006), and severity of ASD (p = 0.000). To achieve promising healthcare for ASD patients, the telemedicine service should try to meet the needs and preferences of both healthcare professionals and parents, as well as identify and, if possible, reduce perceived barriers.

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15. Gallardo-Montes CDP, Rodríguez Fuentes A, Caurcel Cara MJ, Capperucci D. Functionality of Apps for People with Autism: Comparison between Educators from Florence and Granada. Int J Environ Res Public Health;2022 (Jun 8);19(12)

BACKGROUND: Studies on the potential of smartphone apps for people with autism are currently increasing in number, given the large digital supply available and the benefits they offer. We analyzed the opinion of educators from Florence (Italy) and Granada (Spain) regarding the benefits and applicability of apps, frequency of their use, and the type of apps used for people with autism. METHODS: The study involved 1261 professionals, of whom 286 worked with apps, using a non-experimental quantitative design, descriptive and frequency statistics, parametric inferential analyses (Student’s t and one-factor ANOVA), and calculation of the effect size (Cohen’s d and eta squared) and intrafactorial correlations. RESULTS: Statistically significant differences were observed in respect of city, sex, age, years of experience, place of work, and type of teacher. The teachers from Granada found more benefits and applicability in apps, and revealed a slightly higher usage than those from Florence. CONCLUSIONS: It is an arduous but worthy task for professionals from schools and associations that work with people with autism to acquire the necessary knowledge to apply methodologies based on information and communication technology (ICT), as this will help achieve the integrated development of people with different capabilities.

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16. Gasser BA, Kurz J, Dick B, Mohaupt MG. How Is CYP17A1 Activity Altered in Autism? A Pilot Study to Identify Potential Pharmacological Targets. Life (Basel);2022 (Jun 10);12(6)

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m(2), age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m(2), 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m(2), age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m(2), age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11β-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism.

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17. Gill PS, Dweep H, Rose S, Wickramasinghe PJ, Vyas KK, McCullough S, Porter-Gill PA, Frye RE. Integrated microRNA-mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism. J Pers Med;2022 (Jun 1);12(6)

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with mutations in hundreds of genes contributing to its risk. Herein, we studied lymphoblastoid cell lines (LCLs) from children diagnosed with autistic disorder (n = 10) and controls (n = 7) using RNA and miRNA sequencing profiles. The sequencing analysis identified 1700 genes and 102 miRNAs differentially expressed between the ASD and control LCLs (p ≤ 0.05). The top upregulated genes were GABRA4, AUTS2, and IL27, and the top upregulated miRNAs were hsa-miR-6813-3p, hsa-miR-221-5p, and hsa-miR-21-5p. The RT-qPCR analysis confirmed the sequencing results for randomly selected candidates: AUTS2, FMR1, PTEN, hsa-miR-15a-5p, hsa-miR-92a-3p, and hsa-miR-125b-5p. The functional enrichment analysis showed pathways involved in ASD control proliferation of neuronal cells, cell death of immune cells, epilepsy or neurodevelopmental disorders, WNT and PTEN signaling, apoptosis, and cancer. The integration of mRNA and miRNA sequencing profiles by miRWalk2.0 identified correlated changes in miRNAs and their targets’ expression. The integration analysis found significantly dysregulated miRNA-gene pairs in ASD. Overall, these findings suggest that mRNA and miRNA expression profiles in ASD are greatly altered in LCLs and reveal numerous miRNA-gene interactions that regulate critical pathways involved in the proliferation of neuronal cells, cell death of immune cells, and neuronal development.

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18. Han GT, Trevisan DA, Foss-Feig J, Srihari V, McPartland JC. Distinct Symptom Network Structure and Shared Central Social Communication Symptomatology in Autism and Schizophrenia: A Bayesian Network Analysis. J Autism Dev Disord;2022 (Jun 25)

Autism (ASD) and schizophrenia spectrum disorders (SCZ) are neurodevelopmental conditions with overlapping and interrelated symptoms. A network analysis approach that represents clinical conditions as a set of « nodes » (symptoms) connected by « edges » (relations among symptoms) was used to compare symptom organization in the two conditions. Gaussian graphical models were estimated using Bayesian methods to model separate symptom networks for adults with confirmed ASD or SCZ diagnoses. Though overall symptom organization differed by diagnostic group, both symptom networks demonstrated high centrality of social communication difficulties. Autism-relevant restricted and repetitive behaviors and schizophrenia-related cognitive-perceptual symptoms were uniquely central to the ASD and SCZ networks, respectively. Results offer recommendations to improve differential diagnosis and highlight potential treatment targets in ASD and SCZ.

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19. Harshaw C, Kojima S, Wellman CL, Demas GE, Morrow AL, Taft DH, Kenkel WM, Leffel JK, Alberts JR. Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice. Dev Psychobiol;2022 (Sep);64(6):e22289.

Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as autism spectrum disorder (ASD). Studies in rodent models have found long-term neurobehavioral effects in offspring of ABx-treated dams, but ASD-relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD-relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory-guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx-treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early-life ABx exposure.

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20. Hayes KN, Rossetti KG, Zlomke K, Bcba D. Community support, family resilience, and mental health among caregivers of youth with autism spectrum disorder. Child Care Health Dev;2022 (Jun 25)

BACKGROUND: Caregivers of children with autism spectrum disorder (ASD) has been shown to have unique mental health vulnerabilities that community support may buffer. Positive caregiver mental health can stimulate family resilience behaviors, such as strong communication and problem-solving. Further, community support has been found to be related to caregiver mental health, as well as improved child functioning. The current study aimed to investigate caregiver mental health as a mediator between community support and family resilience in families of a child with an autism spectrum disorder. METHODS: Data obtained from caregivers of 654 children with a reported diagnosis of ASD were utilized from the 2016 National Survey of Children’s Health (NSCH) public database. RESULTS: Community support was positively correlated with family resilience and caregiver mental health. Bivariate correlations indicated significant positive associations between community support and family resilience. Caregiver mental health significantly partially mediated the relationship between community support and family resilience. CONCLUSIONS: The present study provided important insight into fostering caregiver health as a strategy to promote family resilience behaviors. Interventions designed to address family resilience behaviors among families of children with ASD should focus on ways in which to positively impact caregiver mental health.

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21. Hocking DR, Ardalan A, Abu-Rayya HM, Farhat H, Andoni A, Lenroot R, Kachnowski S. Correction to: Feasibility of a virtual reality-based exercise intervention and low-cost motion tracking method for estimation of motor proficiency in youth with autism spectrum disorder. J Neuroeng Rehabil;2022 (Jun 24);19(1):62.

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22. Hoekstra RA. Serving the underserved: How can we reach autism families who systemically miss out on support?. Autism;2022 (Jun 25):13623613221105389.

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23. Horgan F, Kenny N, Flynn P. A systematic review of the experiences of autistic young people enrolled in mainstream second-level (post-primary) schools. Autism;2022 (Jun 25):13623613221105089.

Internationally, more autistic pupils are being educated in mainstream schools. Some people have voiced concerns that this policy roll-out is happening before examining the effective outcomes for autistic students. Concerns have also been expressed regarding a lack of the voices of autistic pupils themselves within research and policy. This study was undertaken in order to gather literature that explores the views and experiences of autistic young people in relation to their mainstream school placement at the secondary level. This study aims to summarise the existing literature and provide a new, more complete account of the school experiences of this cohort. After an extensive search, 33 studies were identified by the authors as meeting a set of inclusion criteria. All of the studies included in this review elicited the views and perspectives of at least one autistic young person regarding their mainstream secondary school placement. Upon carefully analysing these studies, the authors developed three key themes as follows: ‘Demands of mainstream placements’, ‘Social participation’ and ‘Impacts on the student’. Our analysis revealed that for many autistic young people, mainstream school is a complex and demanding social environment. Further research that prioritises the voices and perspectives of this cohort is essential as inclusive policy and practice continues to develop.

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24. Hu C, He L, Li H, Ding Y, Zhang K, Li D, Zhu G, Wu B, Xu X, Xu Q. Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China. Genes (Basel);2022 (Jun 2);13(6)

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the SHANK3 gene has the greatest number of reportable variants, followed by gene MYT1L. Patients with MYT1L variants share common and specific clinical characteristics. We found a child with compound heterozygous SLC26A4 variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition.

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25. Huang YS, Fang TH, Kung B, Chen CH. Two Genetic Mechanisms in Two Siblings with Intellectual Disability, Autism Spectrum Disorder, and Psychosis. J Pers Med;2022 (Jun 20);12(6)

Intellectual disability (ID) and autism spectrum disorder (ASD) are complex neurodevelopmental disorders with high heritability. To search for the genetic deficits in two siblings affected with ID and ASD in a family, we first performed a genome-wide copy number variation (CNV) analysis using chromosomal microarray analysis (CMA). We found a 3.7 Mb microdeletion at 22q13.3 in the younger sister. This de novo microdeletion resulted in the haploinsufficiency of SHANK3 and several nearby genes involved in neurodevelopment disorders. Hence, she was diagnosed with Phelan-McDermid syndrome (PMS, OMIM#606232). We further performed whole-genome sequencing (WGS) analysis in this family. We did not detect pathogenic mutations with significant impacts on the phenotypes of the elder brother. Instead, we identified several rare, likely pathogenic variants in seven genes implicated in neurodevelopmental disorders: KLHL17, TDO2, TRRAP, EIF3F, ATP10A, DICER1, and CDH15. These variants were transmitted from his unaffected parents, indicating these variants have only moderate clinical effects. We propose that these variants worked together and led to the clinical phenotypes in the elder brother. We also suggest that the combination of multiple genes with moderate effects is part of the genetic mechanism of neurodevelopmental disorders.

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26. Kayser K, Monschke M, Wagner KG. ASD Formation Prior to Material Characterization as Key Parameter for Accurate Measurements and Subsequent Process Simulation for Hot-Melt Extrusion. AAPS PharmSciTech;2022 (Jun 25);23(6):176.

Process simulation facilitates scale-up of hot-melt extrusion (HME) and enhances proper understanding of the underlying critical process parameters. However, performing numeric simulations requires profound knowledge of the employed materials’ properties. For example, an accurate description of the compounds’ melt rheology is paramount for proper simulations. Hence, sample preparation needs to be optimized to yield results as predictive as possible. To identify the optimal preparation method for small amplitude oscillatory shear (SAOS) rheological measurements, binary mixtures of hydroxypropylmethylcellulose acetate succinate or methacrylic acid ethyl acrylate copolymer (Eudragit L100-55) together with the model drugs celecoxib and ketoconazole were prepared. The physical powder mixtures were introduced into the SAOS as a compressed tablet or a disk prepared via vacuum compression molding (VCM). Simulations with the derived parameters were conducted and compared to lab-scale extrusion trials. VCM was identified as the ideal preparation method resulting in the highest similarity between simulated and experimental values, while simulation based on conventional powder-based methods insufficiently described the HME process.

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27. Król JW, Stanirowski PJ, Mazanowska N, Majewska A, Wielgoś M, Bomba-Opoń D. Is There an Association between the Use of Epidural Analgesia during Labor and the Development of Autism Spectrum Disorder in the Offspring?-A Review of the Literature. Int J Environ Res Public Health;2022 (Jun 12);19(12)

Autism spectrum disorders (ASDs) are multifactorial and complex neurodevelopmental conditions usually diagnosed in the early childhood. The etiology of ASDs is commonly described as a genetic predisposition combined with an environmental impact. As a result of broadening of the diagnostic criteria the prevalence of ASDs has been increasing worldwide and the search for the modifiable factors is still on-going. Epidural analgesia (ELA) provides effective pain relief during labor and is currently the most preferred method of anesthesia during the delivery. The safety of the procedure is well-discussed and documented; nonetheless, in 2020 a single population-based study indicated an association between the use of ELA during labor and newborn risk of ASD development, which led to widespread concern. To explore the possible association between the ELA and ASD occurrence in the offspring several studies in different countries have been conducted to date. In this review we aimed to summarize the current state of knowledge concerning the association between the use of epidural analgesia during labor and risk of ASD. In conclusion, the literature review indicates that there is no significant association.

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28. Lee A, Choo H, Jeon B. Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment. Int J Mol Sci;2022 (Jun 10);23(12)

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. Although there are a couple of FDA (Food and Drug Administration)-approved drugs for ASD treatment such as aripiprazole and risperidone, they are efficient for alleviating aggression, hyperactivity, and self-injury but not the core symptoms. Serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter plays a crucial role in the early neurodevelopmental stage. In particular, 5-HT has been known to regulate a variety of neurobiological processes including neurite outgrowth, dendritic spine morphology, shaping neuronal circuits, synaptic transmission, and synaptic plasticity. Given the roles of serotonergic systems, the 5-HT receptors (5-HTRs) become emerging as potential therapeutic targets in the ASD. In this review, we will focus on the recent development of small molecule modulators of 5-HTRs as therapeutic targets for the ASD treatment.

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29. Lee J, Kaat AJ, Roberts MY. Involving Caregivers of Autistic Toddlers in Early Intervention: Common Practice or Exception to the Norm?. Am J Speech Lang Pathol;2022 (Jun 24):1-16.

PURPOSE: Family-centered practice (FCP) is a core component of early intervention (EI) associated with improved child and family outcomes, but little is known about community-based speech-language pathologists’ (SLPs’) inclusion of families in EI. Many caregivers of autistic children experience caregiving-related stress, making these intervention principles especially critical to the provision of optimal services. This study aimed to characterize EI SLPs’ use of FCP coaching strategies and the quality of caregiver-SLP relationships. METHOD: Participants included 25 families with an autistic toddler and their EI SLP. One intervention session for each SLP-family dyad was recorded and coded for the SLP’s use of FCP coaching strategies. Caregivers and SLPs completed surveys about their working alliance, caregiver perceptions of family-centered care, and SLPs’ approach to FCP. RESULTS: SLPs primarily use child-directed strategies without caregiver involvement. When involving caregivers, SLPs infrequently use coaching strategies that are important for caregiver learning and collaboration (e.g., joint planning and guided practice with feedback). However, caregivers perceived their child’s services to be highly family-centered, and caregivers and SLPs rated their working alliance to be of high quality. CONCLUSIONS: The presence of strong caregiver-SLP working alliances alongside infrequent usage of effective coaching strategies indicates that SLPs may engage caregivers in ways that are perceived to be highly collaborative but are not optimal for caregiver involvement in all aspects of their child’s services (goal setting and implementation of intervention). Consideration of family preferences and SLP beliefs about FCP will inform ways to disseminate FCPs needed to optimize families’ capacities to support their child’s development. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20113550.

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30. Lira Rodríguez EM, Pascual RC, Sanclemente MP, Martín-Hernández P, Gil-Lacruz M, Gil-Lacruz AI. The Influence of ASD Severity on Parental Overload: The Moderating Role of Parental Well-Being and the ASD Pragmatic Level. Children (Basel);2022 (May 24);9(6)

The aim of the present study is to analyze the relation between the severity of symptoms in people with ASD on their parents’ overload, moderated by parental well-being and the ASD pragmatic level. A sample consisted of 28 fathers and mothers whose children had ASD. The obtained results showed that the higher the ASD severity, the better the parental overload was perceived if parents had low well-being levels. However, this relation did not occur if the parental well-being level was high. Moreover, the relation between severity and parental overload moderated by parental well-being occurred regardless of the pragmatic language level. Therefore, the main results of this study are that the responsibility for parental overload depends more on parental well-being than on the symptom severity of the person with ASD. The relevance of carrying out interventions with not only people with ASD, but also with their parents or caregivers for their well-being is highlighted.

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31. Ma SY, Kwan KM. Size anomaly and alteration of GABAergic enzymes expressions in cerebellum of a valproic acid mouse model of autism. Behav Brain Res;2022 (Jun 25);428:113896.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficit and repetitive behaviour. In the past few years, increasing clinical evidence has shown that the cerebellum may contribute to the neuropathology of ASD. However, studies in the mechanism for the involvement of the cerebellum in autism remained speculative. Although some have suggested the possibility of a change of glutamate decarboxylases in the cerebellum of autistic patients, this remains controversial and is limited to the alteration in transcriptional level. This study aimed to investigate the cerebellar structure and determine the expression of rate-limiting GABAergic enzymes in GABA signalling of the autism cerebellum. Pregnant C57BL/6 J mice were intraperitoneally injected with a dosage of 500 mg/kg valproic acid (VPA) on embryonic day 10.5 for autistic behavioural induction. This study found that early prenatal exposure to VPA led to tail deformation and decreased cerebellar weight and size. Early adult mouse models with autistic behaviour showed reduced expression of both isoforms of glutamate decarboxylases (GAD) 65 and 67 in the cerebellum. Also, protein expressions of cerebellar type 1 GABA transporter (GAT-1) and GABA transaminase (GABAT) were reduced in VPA mice. It indicated that abnormal GABA production, recycling, and metabolism could alter the excitatory-inhibitory balance in the autistic cerebellum. Thus, our findings provide supporting evidence that cerebellum impairment could be an etiology of environmentally induced autism. Changes in cerebellar structure and the altered GABAergic enzymes in the cerebellum provide targets for future therapeutic studies in idiopathic autism.

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32. Miller HL, Thomi M, Patterson RM, Nandy K. Effects of Intersectionality Along the Pathway to Diagnosis for Autistic Children With and Without Co-occurring Attention Deficit Hyperactivity Disorder in a Nationally-Representative Sample. J Autism Dev Disord;2022 (Jun 24)

Children with complex behavioral profiles (e.g., ASD + ADHD) may experience delays in obtaining a final diagnosis. Low-resource or underrepresented groups may be at even greater risk for delayed diagnosis. We assessed the effect of sociodemographic factors, symptom complexity and co-occurring conditions, and identifier of first symptoms on diagnostic trajectories among children aged 3-17 years diagnosed with ASD (n = 52) or ASD + ADHD (n = 352) from a nationally-representative sample. Race/ethnicity and gender disparities were evident in both groups. Race, symptom complexity, and co-occuring conditions predicted age of final diagnosis and wait time between first concern and final diagnosis, both of which were staggeringly high. Results suggest a complex influence of sociodemographic factors on the diagnostic pathway, and risk of health disparities as a function of intersectionality.

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33. Moxon-Emre I, Croarkin PE, Daskalakis ZJ, Blumberger DM, Lyon RE, Tani H, Truong P, Lai MC, Desarkar P, Sailasuta N, Szatmari P, Ameis SH. NAA/Glu Ratio Associated with Suicidal Ideation in Pilot Sample of Autistic Youth and Young Adults. Brain Sci;2022 (Jun 15);12(6)

Suicidality is increased in autism spectrum disorder (ASD), yet effective interventions are lacking. Developing biologically based approaches for preventing and treating suicidality in ASD hinges on the identification of biomarkers of suicidal ideation (SI). Here, we assessed magnetic resonance spectroscopy (MRS) markers of glutamatergic neurotransmission in ASD youth and young adults. Twenty-eight ASD participants (16-33 years) underwent (1)H-MRS, and metabolites were quantified using LCModel. N-acetylaspartate (NAA), glutamate (Glu), and the NAA/Glu ratio from the left dorsolateral prefrontal cortex were compared between ASD SI+ (n = 13) and ASD SI- (n = 15) participants. We found that ASD SI+ participants had a higher NAA/Glu ratio compared ASD SI- participants. The NAA/Glu ratio also predicted SI and significantly discriminated between ASD SI+/SI- participants. All analyses including NAA and Glu alone were non-significant. Here, we provide preliminary evidence for the importance of NAA/Glu in ASD with SI, with implications for biomarker discovery. Further mechanistic research into risk and interventional approaches to address SI in ASD are needed.

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34. Northrup JB, Goodwin MS, Peura CB, Chen Q, Taylor BJ, Siegel MS, Mazefsky CA. Mapping the time course of overt emotion dysregulation, self-injurious behavior, and aggression in psychiatrically hospitalized autistic youth: A naturalistic study. Autism Res;2022 (Jun 25)

Challenges with emotion dysregulation, self-injurious behavior (SIB), and aggression are common in autistic individuals. Prior research on the relationships between these behaviors is limited mainly to cross-sectional correlations of parent-report data. Understanding how emotion dysregulation, SIB, and aggression present and relate to one another in real-time could add to our understanding of the context and function of these behaviors. The present study examined the real-time occurrence and temporal relationships between these behaviors in 53 psychiatrically hospitalized autistic youth. Over 500 hours of behavioral observation occurred during everyday activities in the hospital. Start and stop times for instances of overt emotion dysregulation, SIB, and aggression were coded live using a custom mobile phone app. Results indicated large individual variability in the frequency and duration of these behaviors and their co-occurrence. Both SIB and aggression co-occurred with overt emotion dysregulation at above-chance levels, suggesting a role for emotional distress in the occurrence of these behaviors. However, there was substantial variability within and between individuals in co-occurrence, and SIB and aggression often (and for some individuals, almost always) occurred without overt emotion dysregulation. Relatedly, cross-recurrence quantitative analysis revealed that SIB and aggression preceded emotion dysregulation more often than emotion dysregulation preceded SIB and aggression. Future research, perhaps using ambulatory psychophysiological measures, is needed to understand whether emotion dysregulation may sometimes be present but not easily observed during SIB and aggression.

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35. Philippe A. Alternatives to Gold Standard Diagnostic Tools for Distinguishing « Natural Kinds » on the Autism Spectrum. Front Psychiatry;2022;13:862410.

Next-generation sequencing techniques have accelerated the discovery of rare mutations responsible for autism spectrum disorder (ASD) in genes involved in a large number of physiological processes, including the control of gene expression, chromatin remodeling, signaling pathways, synaptic scaffolding, neurotransmitter receptors, and lipid metabolism. Genetic diagnosis provides subjects with an explanation of the cause of their disorder. However, it does not, or at least does not yet, shed light on the psychopathological phenomena specific to the individual. It could be hypothesized that each physiological impact of a mutation corresponds to a specific psychopathological phenomenon of ASD, i.e., « a psychopathological natural kind ». We discuss here the difficulties identifying this specificity of underlying psychopathology in individuals with ASD due to a rare mutation with a major effect. A comparison of Newson’s pathological demand avoidance and Wing’s Asperger’s syndrome with Asperger’s autistic psychopathy highlights different ways of approaching psychopathological descriptions and diagnosis, by focusing on either common or unusual features. Such a comparison calls into question the principles of clinical research recommended by Falret for characterizing « disease individuality » of ASD due to a rare mutation.

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36. Pochakom A, Mu C, Rho JM, Tompkins TA, Mayengbam S, Shearer J. Selective Probiotic Treatment Positively Modulates the Microbiota-Gut-Brain Axis in the BTBR Mouse Model of Autism. Brain Sci;2022 (Jun 14);12(6)

Recent studies have shown promise for the use of probiotics in modulating behaviour through the microbiota-gut-brain axis. In the present study, we assessed the impact of two probiotic strains in mitigating autism-related symptomology in the BTBR T(+) Itpr3(tf)/J mouse model of autism spectrum disorder (ASD). Male juvenile BTBR mice were randomized into: (1) control, (2) Lr probiotic (1 × 10(9) CFU/mL Lacticaseibacillus rhamnosus HA-114), and (3) Ls probiotic groups (1 × 10(9) CFU/mL Ligilactobacillus salivarius HA-118) (n = 18-21/group), receiving treatments in drinking water for 4 weeks. Gut microbiota profiling by 16S rRNA showed Lr, but not Ls supplementation, to increase microbial richness and phylogenetic diversity, with a rise in potential anti-inflammatory and butyrate-producing taxa. Assessing serum and brain metabolites, Lr and Ls supplementation produced distinct metabolic profiles, with Lr treatment elevating concentrations of potentially beneficial neuroactive compounds, such as 5-aminovaleric acid and choline. As mitochondrial dysfunction is often observed in ASD, we assessed mitochondrial oxygen consumption rates in the prefrontal cortex and hippocampus. No differences were observed for either treatment. Both Lr and Ls treatment reduced behavioural deficits in social novelty preference. However, no changes in hyperactivity, repetitive behaviour, and sociability were observed. Results show Lr to impart positive changes along the microbiota-gut-brain axis, exhibiting beneficial effects on selected behaviour, gut microbial diversity, and metabolism in BTBR mice.

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37. Porter K, Foli KJ. Egocentric norm in health-based decision making of patients on the autistic spectrum. Nurs Forum;2022 (Jun 25)

BACKGROUND: Individuals diagnosed with autism spectrum disorder (ASD) without intellectual disability (ID) may have advanced mental reasoning; however, symptomology may vary within the population. Possible symptomology includes communication problems, difficulty relating to people, things, and events, and sensory sensitivity. Current concepts in determining health behavior are not applicable to the ASD without ID population. AIM: The aim of this analysis is to define the concept of egocentric norm in the context of health-based decisions of adults diagnosed with ASD without ID and to support improved nursing practice with this population. DESIGN: The Walker and Avant approach was used. Model, borderline, and contrary cases are offered. DATA SOURCE: Literature search yielded 47 peer reviewed papers that were included in the analysis. REVIEW METHODS: Uses of the concept were reviewed, following the Walker and Avant approach. RESULTS: Egocentric norm is defined as an individual’s ability to perceive, adapt, and respond to information and potential consequences of personal health behavior based on self-evaluation and the immediate environment with limited regard to peer and family influence. CONCLUSIONS: The new concept of egocentric norm may account for the unique dynamics presented by adults with ASD without ID, which may impact health behaviors and actions.

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38. Qureshi F, Adams JB, Audhya T, Hahn J. Multivariate Analysis of Metabolomic and Nutritional Profiles among Children with Autism Spectrum Disorder. J Pers Med;2022 (Jun 1);12(6)

There have been promising results regarding the capability of statistical and machine-learning techniques to offer insight into unique metabolomic patterns observed in ASD. This work re-examines a comparative study contrasting metabolomic and nutrient measurements of children with ASD (n = 55) against their typically developing (TD) peers (n = 44) through a multivariate statistical lens. Hypothesis testing, receiver characteristic curve assessment, and correlation analysis were consistent with prior work and served to underscore prominent areas where metabolomic and nutritional profiles between the groups diverged. Improved univariate analysis revealed 46 nutritional/metabolic differences that were significantly different between ASD and TD groups, with individual areas under the receiver operator curve (AUROC) scores of 0.6-0.9. Many of the significant measurements had correlations with many others, forming two integrated networks of interrelated metabolic differences in ASD. The TD group had 189 significant correlation pairs between metabolites, vs. only 106 for the ASD group, calling attention to underlying differences in metabolic processes. Furthermore, multivariate techniques identified potential biomarker panels with up to six metabolites that were able to attain a predictive accuracy of up to 98% for discriminating between ASD and TD, following cross-validation. Assessing all optimized multivariate models demonstrated concordance with prior physiological pathways identified in the literature, with some of the most important metabolites for discriminating ASD and TD being sulfate, the transsulfuration pathway, uridine (methylation biomarker), and beta-amino isobutyrate (regulator of carbohydrate and lipid metabolism).

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39. Rahbar MH, Samms-Vaughan M, Kim S, Saroukhani S, Bressler J, Hessabi M, Grove ML, Shakspeare-Pellington S, Loveland KA. Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder. Genes (Basel);2022 (May 29);13(6)

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2-8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

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40. Ramirez-Melendez R, Matamoros E, Hernandez D, Mirabel J, Sanchez E, Escude N. Music-Enhanced Emotion Identification of Facial Emotions in Autistic Spectrum Disorder Children: A Pilot EEG Study. Brain Sci;2022 (May 30);12(6)

The Autistic Spectrum Disorder (ASD) is characterized by a difficulty in expressing and interpreting others’ emotions. In particular, people with ASD have difficulties when interpreting emotions encoded in facial expressions. In the past, music interventions have been shown to improve autistic individuals’ emotional and social skills. The present study describes a pilot study to explore the usefulness of music as a tool for improving autistic children’s emotion recognition in facial expressions. Twenty-five children (mean age = 8.8 y, SD = 1.24) with high-functioning ASD and normal hearing participated in the study consisting of four weekly sessions of 15 min each. Twenty-five participants were randomly divided into an experimental group (N = 14) and a control group (N = 11). During each session, participants in the experimental group were exposed to images of facial expressions for four emotions (happy, sad, angry, and fear). Images were shown in three conditions, with the second condition consisting of music of congruent emotion with the shown images. Participants in the control group were shown only images in all three conditions. For six participants in each group, EEG data were acquired during the sessions, and instantaneous emotional responses (arousal and valence values) were extracted from the EEG data. Inter- and intra-session emotion identification improvement was measured in terms of verbal response accuracy, and EEG response differences were analyzed. A comparison of the verbal responses of the experimental group pre- and post-intervention showed a significant (p = 0.001) average improvement in emotion identification accuracy responses of 26% (SD = 3.4). Furthermore, emotional responses of the experimental group at the end of the study showed a higher correlation with the emotional stimuli being presented, compared with their emotional responses at the beginning of the study. No similar verbal responses improvement or EEG-stimuli correlation was found in the control group. These results seem to indicate that music can be used to improve both emotion identification in facial expressions and emotion induction through facial stimuli in children with high-functioning ASD.

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41. Romaniello R, Pasca L, Panzeri E, D’Abrusco F, Travaglini L, Serpieri V, Signorini S, Aiello C, Bertini E, Bassi MT, Valente EM, Zanni G, Borgatti R, Arrigoni F. Superior Cerebellar Atrophy: An Imaging Clue to Diagnose ITPR1-Related Disorders. Int J Mol Sci;2022 (Jun 16);23(12)

The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene encodes an InsP(3)-gated calcium channel that modulates intracellular Ca(2+) release and is particularly expressed in cerebellar Purkinje cells. Pathogenic variants in the ITPR1 gene are associated with different types of autosomal dominant spinocerebellar ataxia: SCA15 (adult onset), SCA29 (early-onset), and Gillespie syndrome. Cerebellar atrophy/hypoplasia is invariably detected, but a recognizable neuroradiological pattern has not been identified yet. With the aim of describing ITPR1-related neuroimaging findings, the brain MRI of 14 patients with ITPR1 variants (11 SCA29, 1 SCA15, and 2 Gillespie) were reviewed by expert neuroradiologists. To further evaluate the role of superior vermian and hemispheric cerebellar atrophy as a clue for the diagnosis of ITPR1-related conditions, the ITPR1 gene was sequenced in 5 patients with similar MRI pattern, detecting pathogenic variants in 4 of them. Considering the whole cohort, a distinctive neuroradiological pattern consisting in superior vermian and hemispheric cerebellar atrophy was identified in 83% patients with causative ITPR1 variants, suggesting this MRI finding could represent a hallmark for ITPR1-related disorders.

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42. Stone B, Cameron A, Dowling S. The autistic experience of homelessness: Implications from a narrative enquiry. Autism;2022 (Jun 25):13623613221105091.

Recent research suggests many autistic people experience homelessness. However, little is known about the types of homelessness autistic people experience and what barriers autistic people face when trying to exit homelessness. This study involved gathering life stories of autistic people who had experienced homelessness. Ten autistic participants talked about their pathways through homelessness and the difficulties they had in accessing support. After first becoming homeless, participants tended to experience rough sleeping and sofa surfing. When participants approached housing and homelessness services, they were often told they were not eligible for support. This could happen when support workers were not aware of autism, or when autism was not considered ‘severe’ enough. Overcrowding, confrontation and lack of control over routine and environment were particular issues for participants when they entered homelessness hostels. Some participants chose to sleep on the streets rather than stay in environments which increased social anxiety and sensory difficulties. This study discusses ways in which homelessness and housing services can increase accessibility and improve engagement for autistic people. It is important to increase awareness of autism while understanding that autistic people who experience homelessness may have complex needs. In addition, services need to listen to autistic people with lived experience of homelessness to decide what changes will have the most impact.

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43. Tekola B, Kinfe M, Girma Bayouh F, Hanlon C, Hoekstra RA. The experiences of parents raising children with developmental disabilities in Ethiopia. Autism;2022 (Jun 25):13623613221105085.

The experiences of parents raising children with developmental disabilities have been widely researched, although most of this research comes from Western, high-income countries. In comparison, little is known about the lived experiences of parents of children with developmental disabilities in low- and middle-income countries and in Africa in particular. We interviewed 14 mothers and 4 fathers in Addis Ababa and the rural town of Butajira to explore what life is like for parents caring for children with developmental disabilities in Ethiopia. Cultural and religious beliefs played a role in the types of delays or differences in their child’s development that parents noticed early and the kinds of support they sought. Parents experienced stigma and lack of understanding from others. Their experiences regarding some of the challenges they faced such as lack of appropriate services varied based on where they lived (urban or rural). Single mothers especially were faced with multiple struggles including poverty, stigma, and lack of social support. Implications for future research and interventions that aim to increase knowledge about developmental disabilities, tackle stigma and improve the lives of children and their families are discussed.

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44. Torres EB. Special Issue « Precision Medicine in Neurodevelopmental Disorders: Personalized Characterization of Autism from Molecules to Behavior ». J Pers Med;2022 (Jun 1);12(6)

The Precision Medicine (PM) platform […].

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45. Veatch OJ, Mazzotti DR, Schultz RT, Abel T, Michaelson JJ, Brodkin ES, Tunc B, Assouline SG, Nickl-Jockschat T, Malow BA, Sutcliffe JS, Pack AI. Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data. J Neurodev Disord;2022 (Jun 24);14(1):39.

BACKGROUND: Numerous genes are implicated in autism spectrum disorder (ASD). ASD encompasses a wide-range and severity of symptoms and co-occurring conditions; however, the details of how genetic variation contributes to phenotypic differences are unclear. This creates a challenge for translating genetic evidence into clinically useful knowledge. Sleep disturbances are particularly prevalent co-occurring conditions in ASD, and genetics may inform treatment. Identifying convergent mechanisms with evidence for dysfunction that connect ASD and sleep biology could help identify better treatments for sleep disturbances in these individuals. METHODS: To identify mechanisms that influence risk for ASD and co-occurring sleep disturbances, we analyzed whole exome sequence data from individuals in the Simons Simplex Collection (n = 2380). We predicted protein damaging variants (PDVs) in genes currently implicated in either ASD or sleep duration in typically developing children. We predicted a network of ASD-related proteins with direct evidence for interaction with sleep duration-related proteins encoded by genes with PDVs. Overrepresentation analyses of Gene Ontology-defined biological processes were conducted on the resulting gene set. We calculated the likelihood of dysfunction in the top overrepresented biological process. We then tested if scores reflecting genetic dysfunction in the process were associated with parent-reported sleep duration. RESULTS: There were 29 genes with PDVs in the ASD dataset where variation was reported in the literature to be associated with both ASD and sleep duration. A network of 108 proteins encoded by ASD and sleep duration candidate genes with PDVs was identified. The mechanism overrepresented in PDV-containing genes that encode proteins in the interaction network with the most evidence for dysfunction was cerebral cortex development (GO:0,021,987). Scores reflecting dysfunction in this process were associated with sleep durations; the largest effects were observed in adolescents (p = 4.65 × 10(-3)). CONCLUSIONS: Our bioinformatic-driven approach detected a biological process enriched for genes encoding a protein-protein interaction network linking ASD gene products with sleep duration gene products where accumulation of potentially damaging variants in individuals with ASD was associated with sleep duration as reported by the parents. Specifically, genetic dysfunction impacting development of the cerebral cortex may affect sleep by disrupting sleep homeostasis which is evidenced to be regulated by this brain region. Future functional assessments and objective measurements of sleep in adolescents with ASD could provide the basis for more informed treatment of sleep problems in these individuals.

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46. Vitale SR, Schneider H, Gardner L, Alessandri M, Marker C. Challenging Behavior and Parental Depression: The Effects of Everyday Stressors and Benefit Finding for Parents of Children with Autism Spectrum Disorder. J Autism Dev Disord;2022 (Jun 24)

Children with autism spectrum disorder present with challenging behaviors that can impact caregivers by increasing parental perceived stress and risk for depression. However, positive coping strategies have also been identified as protective factors for parents of children with ASD. The present study examined parental perceived daily stressors and positive coping strategies (i.e., benefit finding) as mediators to depression for parents of children with ASD. A latent profile analysis identified three classes of behavior severity for children with ASD. Across all classes, higher levels of perceived daily stressors predicted increased parental depression, while benefit finding predicted lower parental depression. Results support interventions that increase positive coping strategies to decrease levels of depression in parents of children with ASD.

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47. Yang J, Gu W, Feng C. Evaluating Interactive Language for Children with Autism Spectrum Disorder (ASD) in Different Contexts. Children (Basel);2022 (May 27);9(6)

Autism spectrum disorder (ASD) is characterized by impairments in the use of appropriate interactive language (including structural language and pragmatic skills) in social contexts. However, the phenotype and causes of interactive language deficits in children with ASD, in different contexts, are still unclear. In this study, we examined the structural language and pragmatic skills of children with ASD in four contexts: playing, drawing, reading, and free talking. We found that while children with ASD did not exhibit deficits in structural language (e.g., vocabulary and utterance), they clearly exhibit deficits in pragmatic skills. We, also, found that contexts played a key role in the use of interactive language by children with ASD. For example, the reading context had a significant impact on the diversity of vocabulary, while the playing and drawing contexts made an important contribution to the formation of complex utterances. The free talking context, on the other hand, contributed to producing more turns. Furthermore, Spearman’s rank correlation analysis was used to examine the relationships between maternal input and children’s language output. We found that the correlations between structural language and maternal input in children with ASD were not as high as revealed in previous studies, while a, relatively, obvious relationship was found between pragmatic skills and maternal input. Specifically, the total number of turns (TNT) for a child with ASD is related to their mother’s TNT, as are the total number of words (TNW) and number of different words (NDW). These results suggest that (1) assessment of pragmatic skills should be included in the evaluation of children with suspected ASD (2) the influence of context on pragmatic skills needs to be taken into account, when assessing the pragmatic development of children with ASD; and (3) the impact of maternal language on children’s language use is of great importance, for children with ASD.

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48. Zhou Y, Liu Y, Peng Q, Li F, Chen F. β-arrestin2 mediates the hippocampal dopaminergic system in autistic mouse through the ERK signaling pathway. Behav Brain Res;2022 (Jun 25);428:113888.

Autism is a complex neurodevelopmental disease that may be caused by genetic and environmental factors, that are incompletely understood. Overactivation of dopaminergic receptors can lead to autistic-like behavior. β-arrestin2 (Arrb2) is a scaffolding protein of the arrestin family, which function as cytosolic multifunctional adapter proteins that activate cell signal transduction and mediate the signal termination and endocytosis of G-protein-coupled receptors (GPCRs) complexes. In this study, we established an Arrb2 knockout (Arrb2(-/-)) mouse to explore the biological function of Arrb2 in autistic-like behavior caused by abnormality in the dopaminergic system. We found that Arrb2(-/-) mice did not exhibit the autistic-like behavior normally induced by SKF38393, an agonist of the dopamine receptor 1 (D1R). Compared with wild-type (WT) untreated mice, the SKF38393-treated WT mice and Arrb2(-/-) mice, with or without SKF38393 treatment, showed abnormalities on electroencephalography (EEG) and increased stimulation of the phosphorylated form of extracellular signal-regulated kinase (p-ERK) via the PKA/Rap1/B-Raf/MEK pathway. These results demonstrated that Arrb2 regulated the dopaminergic system through the ERK signaling pathway in the occurrence and development of autism, and that targeted deletion of Arrb2 impeded the development of autistic-like behavior.

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