1. Beopoulos A, Gea M, Fasano A, Iris F. Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome-Host Interaction Mechanistic Hypothesis. Nutrients. 2021; 14(1).

Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro-immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro-anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut-brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome-host interactions that may contribute to the severity of ASD by maintaining the brain-gut axis pathways in a dysregulated state.

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2. Bulgarelli D, Testa S, Molina P. Theory of Mind Development in Italian Children with Specific Language Impairment and Autism Spectrum Disorder: Delay, Deficit, or Neither?. Journal of autism and developmental disorders. 2022.

Some studies report delayed theory of mind (ToM) development in children with specific language impairment (SLI), while others do not. A ToM delay is acknowledged in children with autism spectrum disorder (ASD), while whether these children also display a deficit is still under debate. In the current study, we drew on a developmental trajectory approach to assess whether children with SLI or ASD displayed delays or deficits in their ToM performance. Forty-three children with SLI (age 4-10 years), 44 children with ASD (age 5-12 years), and 227 typically developing children (age 3-11 years) completed the ToM Storybooks. Children with SLI were not found to display either a delay or a deficit in ToM, while children with ASD were found to display a deficit.

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3. Cabana-Domínguez J, Torrico B, Reif A, Fernàndez-Castillo N, Cormand B. Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders. Translational psychiatry. 2022; 12(1): 11.

Psychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to play an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), anorexia nervosa (ANO), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression (MD), obsessive-compulsive disorder (OCD), schizophrenia (SCZ) and Tourette’s syndrome (TS)) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium that include more than 160,000 cases and 275,000 controls. To do so, we elaborated four different gene sets: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT) using the Gene Ontology and KEGG pathways tools, and two’core’ selections for the same systems, manually curated. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with the core SERT set. Interestingly, interrogation of a cross-disorder GWAS meta-analysis of the eight psychiatric conditions displayed association with the wide DA gene set. To our knowledge, this is the first systematic examination of genes encoding proteins essential to the function of these two neurotransmitter systems in these disorders. Our results support a pleiotropic contribution of the dopaminergic and serotonergic systems in several psychiatric conditions.

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4. Cha JH, Lim JS, Jang YH, Hwang JK, Na JY, Lee JM, Lee HJ, Ahn JH. Altered microstructure of the splenium of corpus callosum is associated with neurodevelopmental impairment in preterm infants with necrotizing enterocolitis. Italian journal of pediatrics. 2022; 48(1): 6.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC. METHODS: We included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA). Regional brain volume analysis and white matter tractography were performed to study brain microstructure alterations. NDI was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 months of corrected age (CA). RESULTS: Preterm infants with NEC showed significantly high risk of motor impairment (odds ratio 58.26, 95% confidence interval 7.80-435.12, p < 0.001). We found significantly increased mean diffusivity (MD) in the splenium of corpus callosum (sCC) (p = 0.001) and the left corticospinal tract (p = 0.001) in preterm infants with NEC. The sCC with increased MD showed a negative association with the BSID-III language (p = 0.025) and motor scores (p = 0.002) at 18 months of CA, implying the relevance of sCC integrity with later NDI. CONCLUSION: The white matter microstructure differed between preterm infants with and without NEC. The prognostic value of network parameters of sCC at TEA may provide better information for the early detection of NDI in preterm infants.

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5. Christensen KE, Malysheva OV, Carlin S, Matias F, MacFarlane AJ, Jacobs RL, Caudill MA, Rozen R. Mild Choline Deficiency and MTHFD1 Synthetase Deficiency Interact to Increase Incidence of Developmental Delays and Defects in Mice. Nutrients. 2021; 14(1).

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80-90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S(+/+) and Mthfd1S(+/-) females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S(+/-) genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.

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6. Cola M, Yankowitz LD, Tena K, Russell A, Bateman L, Knox A, Plate S, Cubit LS, Zampella CJ, Pandey J, Schultz RT, Parish-Morris J. Friend matters: sex differences in social language during autism diagnostic interviews. Molecular autism. 2022; 13(1): 5.

BACKGROUND: Autistic individuals frequently experience social communication challenges. Girls are diagnosed with autism less often than boys even when their symptoms are equally severe, which may be due to insufficient understanding of the way autism manifests in girls. Differences in the behavioral presentation of autism, including how people talk about social topics, could contribute to these persistent problems with identification. Despite a growing body of research suggesting that autistic girls and boys present distinct symptom profiles in a variety of domains, including social attention, friendships, social motivation, and language, differences in the way that autistic boys and girls communicate verbally are not yet well understood. Closely analyzing boys’ and girls’ socially-focused language during semi-structured clinical assessments could shed light on potential sex differences in the behavioral presentation of autistic individuals that may prove useful for identifying and effectively supporting autistic girls. Here, we compare social word use in verbally fluent autistic girls and boys during the interview sections of the ADOS-2 Module 3 and measure associations with clinical phenotype. METHODS: School-aged girls and boys with autism (N = 101, 25 females; aged 6-15) were matched on age, IQ, and parent/clinician ratings of autism symptom severity. Our primary analysis compared the number of social words produced by autistic boys and girls (normalized to account for differences in total word production). Social words are words that make reference to other people, including friends and family. RESULTS: There was a significant main effect of sex on social word production, such that autistic girls used more social words than autistic boys. To identify the specific types of words driving this effect, additional subcategories of friend and family words were analyzed. There was a significant effect of sex on friend words, with girls using significantly more friend words than boys. However, there was no significant main effect of sex on family words, suggesting that sex differences in social word production may be driven by girls talking more about friends compared to boys, not family. To assess relationships between word use and clinical phenotype, we modeled ADOS-2 Social Affect (SA) scores as a function of social word production. In the overall sample, social word use correlated significantly with ADOS-2 SA scores, indicating that participants who used more social words were rated as less socially impaired by clinicians. However, when examined in each sex separately, this result only held for boys. LIMITATIONS: This study cannot speak to the ways in which social word use may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects. CONCLUSIONS: Autistic girls used significantly more social words than boys during a diagnostic assessment-despite being matched on age, IQ, and both parent- and clinician-rated autism symptom severity. Sex differences in linguistic markers of social phenotype in autism are especially important in light of the late or missed diagnoses that disproportionately affect autistic girls. Specifically, heightened talk about social topics could complicate autism referral and diagnosis when non-clinician observers expect a male-typical pattern of reduced social focus, which autistic girls may not always exhibit.

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7. D’Urso G, Toscano E, Sanges V, Sauvaget A, Sheffer CE, Riccio MP, Ferrucci R, Iasevoli F, Priori A, Bravaccio C, de Bartolomeis A. Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy. Journal of clinical medicine. 2021; 11(1).

Patients with autism spectrum disorder (ASD) display distinctive neurophysiological characteristics associated with significant cognitive, emotional, and behavioral symptoms. Transcranial direct current stimulation (tDCS) applied to the frontal or temporoparietal lobes has demonstrated potential to reduce the severity of ASD-related symptoms. Recently, the cerebellum has been identified as a brain area involved in ASD pathophysiology. In this open-label pilot study, seven ASD patients aged between 9 and 13 years underwent 20 daily sessions of 20 min cathodal stimulation of the right cerebellar lobe. At the end of the treatment, the Aberrant Behavior Checklist (ABC) scores showed a 25% mean reduction in global severity of symptoms, with a more pronounced reduction in the « social withdrawal and lethargy » (-35%), « hyperactivity and noncompliance » (-26%), and « irritability, agitation, and crying » (-25%) subscales. Minor and no improvement were observed in the « stereotypic behavior » (-18%) and « inappropriate speech » (-0%) subscales, respectively. Improvements were not detected in the two patients who were taking psychotropic drugs during the study. Clinical response showed a symptom-specific time course. Quality of sleep and mood improved earlier than hyperactivity and social withdrawal. The treatment was generally accepted by patients and well tolerated. No serious adverse events were reported. Stimulation also appeared to markedly reduce the severity of tics in a patient with comorbid tic disorder and led to the disappearance of a frontal epileptogenic focus in another patient with a history of seizures. In conclusion, cerebellar tDCS is safe, feasible, and potentially effective in the treatment of ASD symptoms among children. Strategies to improve recruitment and retention are discussed.

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8. Fabio RA, Semino M, Giannatiempo S, Caprì T, Iannizzotto G, Nucita A. Comparing Advanced with Basic Telerehabilitation Technologies for Patients with Rett Syndrome-A Pilot Study on Behavioral Parameters. International journal of environmental research and public health. 2022; 19(1).

The aim of this study is to compare the performances of patients with Rett syndrome that were undergoing advanced telerehabilitation (ATR) and patients that were undergoing basic telerehabilitation (BTR). It was hypothesized that patients that were undergoing ATR training would have better improvement in nearly all the motor and cognitive scale scoring activities that were administered, thus showing reduced disability. A total of 20 young girls and women with a diagnosis of RTT, ranging from age 4 to 31 years old (Median: 12.50; IQR: 9.50-17.25) underwent a pre-test, treatment post-test 1, treatment, and post-test 2 procedure. The treatment consisted of either ATR or BTR, lasting 10 weeks with three sessions a week of about an hour. The results showed that the group with advanced telerehabilitation improved their performance better than the control group only in some neuropsychological measurements. The results are discussed in the light of critical factors of telerehabilitation.

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9. Hegde R, Hegde S, Kulkarni SS, Pandurangi A, Gai PB, Das KK. Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism. Genomics & informatics. 2021; 19(4): e44.

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5′-untranslated region [UTR] variants and two 3′-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

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10. Huang J, Liu J, Tian R, Liu K, Zhuang P, Sherman HT, Budjan C, Fong M, Jeong MS, Kong XJ. A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells. 2021; 11(1).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients’ clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD.

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11. Huang S, Wang X, Sun T, Yu H, Liao Y, Cao M, Cai L, Li X, Lin L, Su X, Jing J. Association of Breastfeeding for the First Six Months of Life and Autism Spectrum Disorders: A National Multi-Center Study in China. Nutrients. 2021; 14(1).

Previous studies have shown that exclusive breastfeeding is associated with lower odds of having autism spectrum disorders (ASD) in children, but data are lacking in Asian countries, especially China. This cross-sectional study of seven cities in China collected data from August 2016 to March 2017 from 6049 toddlers aged 16-30 months and their parents who responded to questionnaires. The breastfeeding status was collected via questionnaires based on recommendations from the World Health Organization. The standard procedure for screening and diagnosis was applied to identify toddlers with ASD. Among the 6049 toddlers (3364 boys [55.6%]; mean [SD] age, 22.7 [4.1] months), 71 toddlers (1.2%) were identified as ASD. The prevalence of exclusive breastfeeding, partial breastfeeding, and not breastfeeding was 48.8%, 42.2%, and 9.1%, respectively. Compared to toddlers with exclusive breastfeeding, toddlers with partial breastfeeding or without breastfeeding had higher odds of having ASD (odd ratios [OR]: 1.55, 95% confidence interval [CI]: 0.90-2.74; OR: 2.34, 95% CI: 1.10-4.82). We did not find significant modification of demographic characteristics on the associations. The results remained robust in multiple sensitivity analyses. Toddlers without breastfeeding for the first six months of life had higher odds of having ASD, and our findings shed light on the necessity of strengthening public health efforts to increase exclusive breastfeeding in China.

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12. Hunt JFV, Li M, Risgaard R, Ananiev GE, Wildman S, Zhang F, Bugni TS, Zhao X, Bhattacharyya A. High Throughput Small Molecule Screen for Reactivation of FMR1 in Fragile X Syndrome Human Neural Cells. Cells. 2021; 11(1).

Fragile X syndrome (FXS) is the most common inherited cause of autism and intellectual disability. The majority of FXS cases are caused by transcriptional repression of the FMR1 gene due to epigenetic changes that are not recapitulated in current animal disease models. FXS patient induced pluripotent stem cell (iPSC)-derived gene edited reporter cell lines enable novel strategies to discover reactivators of FMR1 expression in human cells on a much larger scale than previously possible. Here, we describe the workflow using FXS iPSC-derived neural cell lines to conduct a massive, unbiased screen for small molecule activators of the FMR1 gene. The proof-of-principle methodology demonstrates the utility of human stem-cell-based methodology for the untargeted discovery of reactivators of the human FMR1 gene that can be applied to other diseases.

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13. Johnson NL, Bekhet AK, Sawdy R, Zint E, Wang J, Pena S, Zurcher H, Enea N. Parent Physical Activity: A Systematic Review of the Literature and Recommendations for Parents of Children With Autism Spectrum Disorder. Journal of physical activity & health. 2022; 19(2): 132-47.

BACKGROUND: The aims of this review were to describe exercise interventions, facilitators, and barriers to physical activity for parents of children with autism spectrum disorder. METHODS: A systematic review of the literature, appraising the validity of each article with Melnyk and Fineout-Overholt’s level of evidence, from different databases CINAHL, Cochrane, PsycINFO, PubMed, ProQuest, and Web of Science between 2000 and 2020 was conducted. As the initial search revealed no articles on exercise interventions and only 2 articles with children with autism spectrum disorder, the aim was widened to all parents of children. RESULTS: Forty-five articles were identified on barriers to physical activity including being the primary caregiving parent, perception of guilt and selfishness, and adhering to exercise programs they do as part of research, once research ends. Facilitators for physical activity including parents being more likely to exercise if they can bring their child with them and parents preferring exercise that is a lifelong habit, such as walking. CONCLUSIONS: Due to the lack of research on parents of children with autism spectrum disorder, recommendations include development and testing of interventions for parents of children with this condition including family-based exercise interventions where children and parents have a choice to exercise together.

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14. Kaplan E, Shifeldrim A, Kraus D, Weissbach A, Kadmon G, Milkh R, Nahum E. Intranasal dexmedetomidine vs oral triclofos sodium for sedation of children with autism undergoing electroencephalograms. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2022; 37: 19-24.

BACKGROUND: Sedation may be necessary for performing electroencephalograms in children with autistic spectrum disorder, however, our sedation success rate using triclofos sodium (TFS) is limited. Intra-nasal dexmedetomidine (IN-DEX) may be a superior sedative for these children. OBJECTIVE: Compare IN-DEX with TFS for sedation efficacy, resistance to drug delivery and adverse events in children with autism undergoing an electroencephalogram. STUDY DESIGN: A single center, prospective observational study of children with autism sedated for electroencephalograms using IN-DEX compared to an age matched, historic group of children with autism, sedated for electroencephalograms using TFS. RESULTS: Characteristics of 41 IN-DEX sedations were compared to 41 TFS sedations in 82 ASD children. Epileptiform discharges were demonstrated in 23/82 (28%) of children in the cohort. Sedation depth by UMSS was significantly deeper in the IN-DEX group (2.49 ± 0.78 vs. 1.41 ± 0.89, p < 0.001). Electroencephalogram quality demonstrated less motion artifact in the IN-DEX group (1.75 ± 0.76 vs. 2.18 ± 0.88, p < 0.001). The rate of very poor or sedation failure was significantly lower in the IN-DEX group (17% vs 56.1%, p < 0.001), RR = 0.3 (95% CI 0.15 to 0.63, p < 0.001). No major adverse events were documented in either group. Bradycardia occurred in 8/41(19.5%) of children in IN-DEX group and none in TFS group (p = 0.003). Hypotension or poor perfusion were not demonstrated in either group. CONCLUSION: In children with autism undergoing electroencephalograms, IN-DEX was more tolerable than TFS, induced deeper sedation with a greater success rate, and improved electroencephalogram quality. Both sedatives were equally safe in this population.

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15. Keim SA, Jude A, Smith K, Khan AQ, Coury DL, Rausch J, Udaipuria S, Norris M, Bartram LR, Narayanan AR, Rogers LK. Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2022.

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1β, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.

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16. Kittana M, Ahmadani A, Stojanovska L, Attlee A. The Role of Vitamin D Supplementation in Children with Autism Spectrum Disorder: A Narrative Review. Nutrients. 2021; 14(1).

Children with autism spectrum disorder (ASD) present with persistent deficits in both social communication and interactions, along with the presence of restricted and repetitive behaviors, resulting in significant impairment in significant areas of functioning. Children with ASD consistently reported significantly lower vitamin D levels than typically developing children. Moreover, vitamin D deficiency was found to be strongly correlated with ASD severity. Theoretically, vitamin D can affect neurodevelopment in children with ASD through its anti-inflammatory properties, stimulating the production of neurotrophins, decreasing the risk of seizures, and regulating glutathione and serotonin levels. A Title/Abstract specific search for publications on Vitamin D supplementation trials up to June 2021 was performed using two databases: PubMed and Cochrane Library. Twelve experimental studies were included in the synthesis of this review. Children with ASD reported a high prevalence of vitamin D deficiency or insufficiency. In general, it was observed that improved vitamin D status significantly reduced the ASD severity, however, this effect was not consistently different between the treatment and control groups. The variations in vitamin D dose protocols and the presence of concurrent interventions might provide an explanation for the variability of results. The age of the child for introducing vitamin D intervention was identified as a possible factor determining the effectiveness of the treatment. Common limitations included a small number of participants and a short duration of follow-ups in the selected studies. Long-term, well-designed randomized controlled trials are warranted to confirm the effect of vitamin D on severity in children with ASD.

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17. Maurizio B, Cartabia M, Clavenna A. Still too much delay in recognition of autism spectrum disorder. Epidemiology and psychiatric sciences. 2022; 31: e1.

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18. Mukhamedshina YO, Fayzullina RA, Nigmatullina IA, Rutland CS, Vasina VV. Health care providers’ awareness on medical management of children with autism spectrum disorder: cross-sectional study in Russia. BMC medical education. 2022; 22(1): 29.

BACKGROUND: Autism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD, and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD. METHODS: This online survey research study evaluated the awareness and experience of students/residents (n = 247) and physicians (n = 100) in the medical management of children with ASD. It also gathered the views and experiences of caregivers to children with ASD (n = 158), all based in Russia. RESULTS: We have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on results from online surveys completed by students/residents, non-psychiatric physicians, and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified. Possible problem solving solutions within medical practice were proposed. CONCLUSIONS: The results from this study should be considered when implementing measures to improve healthcare practices, and when developing models for effective medical management, due to start not only in Russia but also in a number of other countries.

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19. Perry V, Ellis K, Moss J, Beck SR, Singla G, Crawford H, Waite J, Richards C, Oliver C. Executive function, repetitive behaviour and restricted interests in neurodevelopmental disorders. Research in developmental disabilities. 2022; 122: 104166.

BACKGROUND: Individuals with genetic syndromes show unique profiles of repetitive behaviours and restricted interests (RRBs). The executive dysfunction account of RRBs suggests that in autistic (AUT) individuals executive function impairments underpin RRBs, but not communication and social interaction autistic characteristics. AIMS: To 1) describe profiles of behavioural manifestations of executive function (EF behaviours) and 2) explore the relationship between EF behaviours and autistic traits across individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and AUT individuals. METHOD: Carers completed the Behavior Rating Inventory of Executive Function – Preschool Version and the Social Communication Questionnaire. Data reporting on 25 individuals with CdLS (Mage = 18.60, SD = 8.94), 25 with FXS (Mage = 18.48, SD = 8.80), 25 with RTS (Mage = 18.60, SD = 8.65) and 25 AUT individuals (Mage = 18.52, SD = 8.65) matched on chronological age and adaptive ability were included in analyses. RESULTS: All groups showed impairments across EF behaviours compared to two-to-three-year-old typically developing normative samples with no differences between groups. Different EF behaviours predicted RRBs in the syndrome groups with no associations found in the AUT group. CONCLUSIONS: Syndrome related differences should be considered when developing targeted interventions that focus on EF behaviours and/or RRBs in these groups.

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20. Pham C, Symeonides C, O’Hely M, Sly PD, Knibbs LD, Thomson S, Vuillermin P, Saffery R, Ponsonby AL. Early life environmental factors associated with autism spectrum disorder symptoms in children at age 2 years: A birth cohort study. Autism : the international journal of research and practice. 2022: 13623613211068223.

Mounting evidence indicates the contribution of early life environmental factors in autism spectrum disorder. We aim to report the prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; maternal lifestyle factors, such as prenatal alcohol and environmental air pollutant exposures, including particulate matter < 2.5 μm at birth, child secondhand tobacco smoke at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways.

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21. Sengupta K, Lobo L, Krishnamurthy V. Physician Voices on ECHO Autism India-Evaluation of a Telementoring Model for Autism in a Low-Middle Income Country. Journal of developmental and behavioral pediatrics : JDBP. 2022.

OBJECTIVES: Training pediatricians in low- and middle-income countries (LMICs) in early diagnosis and comprehensive management of autism spectrum disorder (ASD) is crucial to ensure optimal developmental outcomes for a substantial number of children with ASD in this region. This study evaluates the relevance and effectiveness of an evidence-based telementoring model Extension for Community Healthcare Outcomes (ECHO) Autism in increasing pediatricians’ access to best-practice care for children with ASD in LMIC contexts. METHODS: ECHO Autism was launched by a [DOUBLE HIGH-REVERSED-9 QUOTATION MARK]hub » team of multidisciplinary ASD experts at a child development center in Mumbai, India. The culturally modified model included 13 biweekly sessions conducted annually using video-conferencing technology. Sessions combined expert-delivered didactics and facilitated case-based discussions on best-practice methods in screening, diagnosing, and managing autism and its comorbidities. Sixty-two physicians, including 59 pediatricians across 2 cohorts (2019-2020), participated in the mixed-methods study to evaluate participants’ reactions, knowledge, behaviors, and impact on children and families. RESULTS: Participants represented a broad geographic reach across India (n = 47) and other LMICs (n = 15). Both quantitative and qualitative data revealed high levels of participant satisfaction and improved knowledge and self-efficacy in ASD diagnosis and management. Qualitative themes highlighted the adult-learning processes of ECHO Autism that participants considered novel and beneficial, such as reflective discussions, respectful mentoring, having a parent as [DOUBLE HIGH-REVERSED-9 QUOTATION MARK]expert, » and cultural relevance, alongside changes in practice behaviors. CONCLUSION: ECHO Autism clinics facilitated by local experts in LMICs can improve access to early diagnosis and evidence-based, comprehensive management for children with ASD and their families by positively influencing pediatricians’ knowledge, attitudes, and practice behaviors.

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22. Shi CL, Xin XW, Zhang JC. Domain adaptation based on rough adjoint inconsistency and optimal transport for identifying autistic patients. Computer methods and programs in biomedicine. 2022; 215: 106615.

BACKGROUND AND OBJECTIVE: Computer aided diagnosis technology has been widely used to diagnose autism spectrum disorder (ASD) from neural images. The performance of the model usually depends largely on a sufficient number of training samples that reflect the real sample distribution. Due to the lack of labelled neural images data, multisite data are often pooled together to expand the sample size. However, the heterogeneity among sites will inevitably lead to a decline in the generalization of models. To solve this problem, we propose a multisource unsupervised domain adaptation method using rough adjoint inconsistency and optimal transport. METHODS: First, we define the concept of rough adjoint inconsistency and propose a double quantization method based on rough adjoint inconsistency and Dempster-Shafer (D-S) evidence theory to estimate the weight coefficient of each source domain to accurately describe the importance of each source domain to the target domain. Second, using optimal transport theory, we weaken the data distribution differences between domains and solve the problem of class imbalance by adjusting the sampling weights among classes. RESULTS: The ASD recognition accuracy of the proposed method is improved on all eight tasks, which are 70.67%, 64.86%, 62.50%, 70.80%, 73.08%, 71.19%, 75.41% and 75.76%, respectively. Our proposed model achieves superior performance compared to traditional machine learning methods and other recently proposed deep learning model. CONCLUSIONS: Our method demonstrates that the fusion of rough adjoint inconsistency and optimal transport can be a powerful tool for identifying ASD and quantifying the correlations between domains.

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23. Zhang Z, Kramer J, Wang H, Chen WJ, Huang TY, Chen YJ, Tseng TS, Chen LS. Attitudes toward Pursuing Genetic Testing among Parents of Children with Autism Spectrum Disorder in Taiwan: A Qualitative Investigation. International journal of environmental research and public health. 2021; 19(1).

BACKGROUND: The diagnosis of autism spectrum disorder (ASD) cases is increasing in Taiwan. Genetic testing for children with ASD offers several potential benefits and is available with out-of-pocket expenses. Parents play a pivotal role in having their children with ASD tested; therefore, understanding their perceptions of, and perceived barriers to genetic testing is vital. METHODS: Semi-structured interviews were conducted with 39 parents of children with ASD in Taiwan. Interviews were recorded and transcribed verbatim. NVivo 12 software (QSR International, Doncaster, Australia) was used to facilitate an inductive coding methodology. RESULTS: The majority of participants (74.4%) supported ASD genetic testing for their children with ASD, citing reasons such as clarifying ASD etiology, well-informed family planning, contributing to ASD research, and early ASD detection and intervention. Others indicated that they were either against such testing (17.9%), or unsure (7.7%) about whether to take their children with ASD for genetic testing. Those who were opposed reported that their main concerns related to perceptions of no value of genetic testing, potential for family conflict, and financial difficulties. CONCLUSIONS: Most of the parents of children with ASD that we interviewed expressed favorable views of ASD genetic testing. There exists a need to increase parental access to education and counseling, and to include testing coverage in Taiwanese national health insurance.

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24. Zhao P, Fu H, Cheng H, Zheng R, Yuan D, Yang J, Li S, Li E, Li L. Acupuncture at ST36 Alleviates the Behavioral Disorder of Autistic Rats by Inhibiting TXNIP-Mediated Activation of NLRP3. Journal of neuropathology and experimental neurology. 2022; 81(2): 127-34.

Autism is a common neurodevelopmental disorder that severely affects patients’ quality of life. We aimed to investigate whether acupuncture at Zusanli (ST36) could alleviate the behavior disorder of autistic rats by inhibiting thioredoxin-interacting protein (TXNIP)-mediated activation of NLRP3. An autism model was induced by intraperitoneal injection of pregnant rats with valproic acid (VPA). The pups’ behaviors were analyzed using hot plate, open field, Morris water maze, and 3-chamber social interaction tests. Nissl staining was used to visualize neurons in prefrontal cortex. Levels of TXNIP, NLRP3, interleukin (IL)-1β, and caspase were determined by Western blot or quantitative real-time PCR. After ST36 acupuncture, pain sensitivity, autonomous activity, sociability index, sociability preference index, and learning and memory were improved in the autism model rats. Levels of TXNIP, NLRP3, IL-1β, and caspase 1 were decreased after acupuncture. Interference with TXNIP alleviated the behavior disorders and inhibited NLRP3, caspase 1, and IL-1β levels. In summary, ST36 acupuncture reduced TXNIP expression, inhibited the activation of the NLRP3 inflammasome, and alleviated the behavior disorder related to the prefrontal cortex of the autistic rats. These results point to a potential mechanism for acupuncture-induced improvement of autistic behavioral disorders.

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