1. Absoud M. Social determinants, inequality, and autism. The Lancet Child & adolescent health. 2022; 6(12): 832-3.

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2. Ahumada D, Guzmán B, Rebolledo S, Opazo K, Marileo L, Parra-Soto S, Viscardi S. Eating Patterns in Children with Autism Spectrum Disorder. Healthcare (Basel, Switzerland). 2022; 10(10).

The purpose of this research was to analyze the eating patterns of preschool- and school-aged children with ASD, as provided by their families, in the La Araucanía Region of Chile. It involved a cross-sectional study with 72 families with children diagnosed with ASD aged between 2 and 12 years old. Food selectivity, appetite, body mass index (BMI) and frequency of food consumption were studied. The research determined that 97.67% present food selectivity, corresponding to alterations in the frequency of consumption of specific food groups. Moreover, 93.06%, 90.28%, 80.56% and 62.50% of children in the study do not meet the daily recommendations for fruit, fish, water and vegetable consumption, respectively. Therefore, it is important for these findings to be considered when designing and carrying out educational interventions regarding food in families with children with ASD for greater assertiveness and effectiveness in improving health.

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3. Araripe B, Montiel-Nava C, Bordini D, Cunha GR, Garrido G, Cukier S, Garcia R, Rosoli A, Valdez D, Caetano SC, Rattazzi A, Paula CS. Profile of Service Use and Barriers to Access to Care among Brazilian Children and Adolescents with Autism Spectrum Disorders. Brain sciences. 2022; 12(10).

Delayed diagnosis and a lack of adequate care for people with autism spectrum disorder (ASD) are related to worse outcomes and quality of life. This study aimed to identify the profile of service use, barriers to access care, and factors related to those barriers in Brazilian families with children with ASD. A total of 927 families with children with ASD (3-17 years) from five Brazilian regions completed an online version of the Caregivers Needs Survey. Results showed that the most used services were behavioral interventions and pharmacotherapy, while the most used professionals were neurologists, nutritionists, speech therapists, psychiatrists, psychologists, and pediatricians. The main barriers included waiting lists, costs, and the absence of services or treatment. Service use varied according to age, the region of residence, type of health care system used, and the parents/caregivers’ education. Access to behavioral interventions was more frequent among users of the private system/health insurance and families whose caregivers had higher education. The absence of specialized services/treatments was less frequent among residents of state capitals and families whose caregivers had higher levels of education. This study highlights how families with children/adolescents with ASD in Brazil face significant barriers to access care related to sociodemographic factors.

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4. Brister D, Rose S, Delhey L, Tippett M, Jin Y, Gu H, Frye RE. Metabolomic Signatures of Autism Spectrum Disorder. Journal of personalized medicine. 2022; 12(10).

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.

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5. Budimirovic DB, Protic DD. Fragile X Syndrome: Recent Research Updates toward Capturing Treatments’ Improvement in Clinical Trials. Brain sciences. 2022; 12(10).

This Brain Sciences 2020 Special Issue of nine manuscripts contribute novel data on treatment updates in fragile X syndrome (FXS) […].

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6. Campi E, Choi E, Chen YJ, Holland CM, Bristol S, Sideris J, Crais ER, Watson LR, Baranek GT. Sensory Reactivity of Infants at Elevated Likelihood of Autism and Associations with Caregiver Responsiveness. Journal of autism and developmental disorders. 2022: 1-10.

Infants at elevated likelihood of developing autism display differences in sensory reactivity, especially hyporeactivity, as early as 7 months of age, potentially contributing to a developmental cascade of autism symptoms. Caregiver responsiveness, which has been linked to positive social communication outcomes, has not been adequately examined with regard to infant sensory reactivity. This study examined the multiplicative impact of infant sensory hypo- and hyperreactivity on caregiver responsiveness to sensory reactivity and regulation cues in 43 infants at elevated likelihood of autism. Sensory hyperreactivity was found to moderate the association between sensory hyporeactivity and caregiver responsiveness, such that caregivers of infants with moderately high sensory hypo- and hyperreactivity demonstrated higher responsiveness.

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7. Canitano R, Palumbi R, Scandurra V. Autism with Epilepsy: A Neuropsychopharmacology Update. Genes. 2022; 13(10).

The association between autism spectrum disorders (ASD) and epilepsy has been extensively documented, and the estimated prevalence varies depending upon the selected population and the clinical characteristics. Currently, there are a lack of studies assessing the patient care pathways in ASD, particularly for comorbidity with epilepsy, despite its personal, familial, and economic impacts. Genetic abnormalities are likely implicated in the association of ASD and epilepsy, although they are currently detectable in only a small percentage of patients, and some known genetic and medical conditions are associated with ASD and epilepsy. There is no specificity of seizure type to be expected in children and adolescents with ASD compared with other neurodevelopmental disorders or epileptic syndromes. Treatment options include antiepileptic drugs (AED) and developmentally-based early interventions for ASD. Carbamazepine and lamotrigine are the most used AED, but further studies are needed to more precisely define the most suitable medications for this specific group of children with ASD.

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8. Csillag A, Ádám Á, Zachar G. Avian models for brain mechanisms underlying altered social behavior in autism. Frontiers in physiology. 2022; 13: 1032046.

The current review is an update on experimental approaches in which birds serve as model species for the investigation of typical failure symptoms associated with autism spectrum disorder (ASD). The discussion is focused on deficiencies of social behavior, from social interactions of domestic chicks, based on visual and auditory cues, to vocal communication in songbirds. Two groups of pathogenetic/risk factors are discussed: 1) non-genetic (environmental/epigenetic) factors, exemplified by embryonic exposure to valproic acid (VPA), and 2) genetic factors, represented by a list of candidate genes and signaling pathways of diagnostic or predictive value in ASD patients. Given the similarities of birds as experimental models to humans (visual orientation, vocal learning, social cohesions), avian models usefully contribute toward the elucidation of the neural systems and developmental factors underlying ASD, improving the applicability of preclinical results obtained on laboratory rodents. Furthermore, they may predict potential susceptibility factors worthy of investigation (both by animal studies and by monitoring human babies at risk), with potential therapeutic consequence.

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9. Deutsch SI, Burket JA. From Mouse to Man: N-Methyl-d-Aspartic Acid Receptor Activation as a Promising Pharmacotherapeutic Strategy for Autism Spectrum Disorders. The Medical clinics of North America. 2023; 107(1): 101-17.

The BALB/c mouse displays hypersensitivity to behavioral effects of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor « open-channel » blocker, and shows both no preference for an enclosed stimulus mouse over an inanimate object and reduced social interaction with a freely behaving stimulus mouse. NMDA receptor agonist interventions improved measures of social preference and social interaction of the BALB/c mouse model of autism spectrum disorder (ASD). A « proof of principle/proof of concept » translational 10-week clinical trial with 8-week of active medication administration was conducted comparing 20 DSM-IV-TR-diagnosed older adolescent/young adult patients with ASD randomized to once-weekly pulsed administration (50 mg/d) versus daily administration of d-cycloserine (50 mg/d). The results showed that d-cycloserine, a partial glycine agonist, was well tolerated, the 2 dosing strategies did not differ, and improvement was noted on the « lethargy/social withdrawal » and « stereotypic behavior » subscales of the Aberrant Behavior Checklist. NMDA receptor activation contributes to the regulation of mTOR signaling, a pathologic point of convergence in several monogenic syndromic forms of ASD. Furthermore, both NMDA receptor hypofunction and imbalance between NMDA receptor activation mediated by GluN2B and GluN2A-containing NMDA receptors occur as « downstream » consequences of several genetically unrelated abnormalities associated with ASD. NMDA receptor-subtype selective « positive allosteric modulators (PAMs) » are particularly appealing medication candidates for future translational trials.

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10. Doi H, Iijima N, Furui A, Soh Z, Yonei R, Shinohara K, Iriguchi M, Shimatani K, Tsuji T. Prediction of autistic tendencies at 18 months of age via markerless video analysis of spontaneous body movements in 4-month-old infants. Scientific reports. 2022; 12(1): 18045.

Early intervention is now considered the core treatment strategy for autism spectrum disorders (ASD). Thus, it is of significant clinical importance to establish a screening tool for the early detection of ASD in infants. To achieve this goal, in a longitudinal design, we analyzed spontaneous bodily movements of 4-month-old infants from general population and assessed their ASD-like behaviors at 18 months of age. A total of 26 movement features were calculated from video-recorded bodily movements of infants at 4 months of age. Their risk of ASD was assessed at 18 months of age with the Modified Checklist for Autism in Toddlerhood, a widely used screening questionnaire. Infants at high risk for ASD at 18 months of age exhibited less rhythmic and weaker bodily movement patterns at 4 months of age than low-risk infants. When the observed bodily movement patterns were submitted to a machine learning-based analysis, linear and non-linear classifiers successfully predicted ASD-like behavior at 18 months of age based on the bodily movement patterns at 4 months of age, at the level acceptable for practical use. This study analyzed the relationship between spontaneous bodily movements at 4 months of age and the ASD risk at 18 months of age. Experimental results suggested the utility of the proposed method for the early screening of infants at risk for ASD. We revealed that the signs of ASD risk could be detected as early as 4 months after birth, by focusing on the infant’s spontaneous bodily movements.

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11. Fabbri-Destro M, Maugeri F, Ianni C, Corsini S, Di Stefano E, Scatigna S, Crifaci G, Bruzzi G, Berloffa S, Fantozzi P, Prato A, Muccio R, Valente E, Pelagatti S, Pecchini E, Zulli F, Rizzo R, Milone A, Viglione V, Barone R, Masi G, Narzisi A. Early Sensory Profile in Autism Spectrum Disorders Predicts Emotional and Behavioral Issues. Journal of personalized medicine. 2022; 12(10).

BACKGROUND: Abnormal sensory reactivity is considered one of the diagnostic criteria for autism spectrum disorders (ASD) and has been associated with autism severity, poorer functional outcomes, and behavioral difficulties across the lifespan. Its early characterization could provide valuable insights into the processes favoring the instantiation of maladaptive behaviors. OBJECTIVES: The present study has two aims: (1) to describe the sensory profile of preschool children with ASD compared with an age-matched population of children with a diagnosis of language disorder (DLD) and typically developing (TD) control peers; (2) to explore within each group whether the sensory alterations play a predictive role in the instantiation of emotional and behavioral issues. METHODS: The parents of 42 ASD, 18 DLD, and 56 TD filled out the Sensory Processing Measure-Preschool (SPM-P). To gather information on competencies, behaviors, and emotional problems of children, the Child Behavior Checklist 1½-5 (CBCL 1½-5) was also administered. RESULTS: On the SPM-P, ASD and DLD samples generally had scores more compromised than control peers. The contrast between ASD and DLD was reflected in a higher (and highly significant) impairment on the social participation and hearing subscales, suggesting a greater sensitivity and a possible specificity of these scores for ASD. More importantly, linear regression analyses revealed a strong and predictive association for ASD children with SPM total scores explaining more than 50% of the variance of the CBCL 1½-5 total scores (p < 0.001). CONCLUSIONS: Our findings reinforce the need to detect the abnormal sensory profiles of ASD already at an early stage and during clinical evaluations. Due to the impact on the emotional and behavioral manifestations, such a procedure has significant clinical and social implications, potentially guiding the development of new interventions relying on multisensory strategies.

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12. Gasser B, Calin AE, Escher G, Kurz J, Emmenegger A, Buerki S, Schmidt-Trucksäss A, Mohaupt M. Light in the Rational Treatment of Autism? Effects of Metformin on Steroid Hormones in a Patient with Polycystic Ovarian Syndrome (PCOS). Life (Basel, Switzerland). 2022; 12(11).

Background: Metformin is an effective treatment option for type 2 diabetes mellitus, and it is, to this day, the most prescribed oral antiglycaemic drug. Besides its effects mainly on mitochondrial activity, an off-label use came up as a pharmaceutical for subjects with a diagnosis of polycystic ovarian syndrome (PCOS) along with altered steroid hormone homeostasis. Besides these effects, even an influence on mood and social behavior was described, leading to the aim of this case report to elucidate the effects before versus after treatment with metformin on steroid hormones and social behavior. Methods: A female patient with diagnosed PCOS was analyzed three times for steroid hormone levels. The first analysis was performed before treatment; the second, after a period of 71 days with metformin at 2 × 500 mg; and the third, after a total of 144 days with metformin at 2 × 500 mg. Spot urine probes were taken in the morning for a combined gas chromatography-mass spectrometry (GC-MS), and the steroid levels were adjusted for creatinine excretion. A questionnaire on social behavior (Autism Spectrum Questionnaire) was administered before treatment and after 71 days. Results: A decrease in all the steroid hormones measured was detected after 71 and 144 days of treatment with metformin, being more pronounced after 144 days of treatment and highly significant (p < 0.001). Furthermore, in the untreated state, the class of corticosterone metabolites showed increased values compared to the female reference values for TH-11-DH-corticosterone, TH-corticosterone, and 5a-TH-corticosterone. In the class of estrogen metabolites, increased values compared to the reference values were detected for 17b-estradiol; in the class of 11-deoxycortisol metabolites, an increase in TH-11-deoxycortisol was detected. For the class of cortisol metabolites, increased values compared to the reference values were detected for cortisone, TH-cortisone, a-cortolone, b-cortolone, 20b-dihydrocortisone, cortisol, TH-cortisol, 5a-TH-cortisol, a-cortol, 20b-dihydrocortisol, and 6b-OH-cortisol. No increases in androgen metabolites were detected. Interestingly, weight decreased from 93.4 kg to 91.3 kg after 71 days and fell to 82.7 kg after 144 days of treatment. The skeletal muscle mass was 30.1 kg at the first visit, decreasing to 29.9 kg and to 27.5 kg. No significant difference in the social behavior score from baseline to after 71 days of treatment was detected. Discussion: Metformin improved the steroid hormone profiles from levels above the upper reference values to the middle of the reference values after 71 days and to the lower ends of the reference values after 144 days of treatment. This implies not only that metformin has an effect on steroid hormone levels, but in addition that the efficacy of the pharmaceutical seems to depend on the time interval from intake. To summarize, in this patient, steroid hormones were affected but social behavior was not. If no effect of metformin on social behavior exists, this must be supported by further cases.

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13. Greene RK, Rich-Wimmer N, Williams CN, Hall TA. Social Functioning and Autistic Behaviors in Youth Following Acquired Brain Injury. Children (Basel, Switzerland). 2022; 9(11).

Children and adolescents who survive the pediatric intensive care unit (PICU) with an acquired brain injury (ABI) often demonstrate a variety of physical, cognitive, emotional/behavioral, and social sequelae termed post-intensive care syndrome (PICS). Social communication and interaction challenges have also been observed clinically, and there is growing literature documenting these occurrences in youth following ABI. The extent of these social changes varies among patients, and a subset of patients go on to exhibit social and behavioral profiles closely resembling those of autistic youth. We reviewed empirical research regarding social functioning in youth following ABI, as well as the overlap between individuals with ABI and autistic youth, published from January 2009 to August 2022 on PubMed and Scopus databases. Clinical case examples from a well-established post-PICU follow-up program are also provided to exemplify the complexity of this phenomenon.

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14. Guastella AJ, Boulton KA, Whitehouse AJO, Song YJ, Thapa R, Gregory SG, Pokorski I, Granich J, DeMayo MM, Ambarchi Z, Wray J, Thomas EE, Hickie IB. The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial. Molecular psychiatry. 2022: 1-9.

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n = 45) or placebo (n = 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p = 0.686). However, a significant interaction with age (p = 0.028) showed that for younger children, aged 3-5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.Trial registration www.anzctr.org.au (ACTRN12617000441314).

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15. Hayden-Evans M, Milbourn B, D’Arcy E, Chamberlain A, Afsharnejad B, Evans K, Whitehouse AJO, Bölte S, Girdler S. An Evaluation of the Overall Utility of Measures of Functioning Suitable for School-Aged Children on the Autism Spectrum: A Scoping Review. International journal of environmental research and public health. 2022; 19(21).

A diagnosis of an autism spectrum condition (autism) provides limited information regarding an individual’s level of functioning, information key in determining support and funding needs. Using the framework introduced by Arksey and O’Malley, this scoping review aimed to identify measures of functioning suitable for school-aged children on the autism spectrum and evaluate their overall utility, including content validity against the International Classification of Functioning, Disability and Health (ICF) and the ICF Core Sets for Autism. The overall utility of the 13 included tools was determined using the Outcome Measures Rating Form (OMRF), with the Adaptive Behavior Assessment System (ABAS-3) receiving the highest overall utility rating. Content validity of the tools in relation to the ICF and ICF Core Sets for Autism varied, with few assessment tools including any items linking to Environmental Factors of the ICF. The ABAS-3 had the greatest total number of codes linking to the Comprehensive ICF Core Set for Autism while the Vineland Adaptive Behavior Scales (Vineland-3) had the greatest number of unique codes linking to both the Comprehensive ICF Core Set for Autism and the Brief ICF Core Set for Autism (6-16 years). Measuring functioning of school-aged children on the spectrum can be challenging, however, it is important to accurately capture their abilities to ensure equitable and individualised access to funding and supports.

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16. Hill AT, Van Der Elst J, Bigelow FJ, Lum JAG, Enticott PG. Right anterior theta connectivity predicts autistic social traits in typically developing children. Biological psychology. 2022; 175: 108448.

Growing evidence supports functional network alterations in autism spectrum disorder, however much less is known about the neural mechanisms underlying autistic traits in typically developing children. Using resting-state electroencephalographic (EEG) recordings, we examined whether functional connectivity could predict autistic trait expression in 127 children aged between 4 and 12 years. Regression models showed that right anterior theta connectivity was a significant predictor of autistic traits (p = 0.013), with increased connectivity in this region associated with greater autistic trait expression. These results corroborate similar recent findings in adults, extending this observation to a cohort of children spanning early-to-middle childhood. These findings further highlight EEG-derived functional connectivity as a sensitive physiological correlate of autistic trait expression in typically developing children.

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

In the original publication […].

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18. Janz P, Bainier M, Marashli S, Schoenenberger P, Valencia M, Redondo RL. Neurexin1α knockout rats display oscillatory abnormalities and sensory processing deficits back-translating key endophenotypes of psychiatric disorders. Translational psychiatry. 2022; 12(1): 455.

Neurexins are presynaptic transmembrane proteins crucial for synapse development and organization. Deletion and missense mutations in all three Neurexin genes have been identified in psychiatric disorders, with mutations in the NRXN1 gene most strongly linked to schizophrenia (SZ) and autism spectrum disorder (ASD). While the consequences of NRXN1 deletion have been extensively studied on the synaptic and behavioral levels, circuit endophenotypes that translate to the human condition have not been characterized yet. Therefore, we investigated the electrophysiology of cortico-striatal-thalamic circuits in Nrxn1α^-/- rats and wildtype littermates focusing on a set of translational readouts, including spontaneous oscillatory activity, auditory-evoked oscillations and potentials, as well as mismatch negativity-like (MMN) responses and responses to social stimuli. On the behavioral level Nrxn1α^-/- rats showed locomotor hyperactivity. In vivo freely moving electrophysiology revealed pronounced increases of spontaneous oscillatory power within the gamma band in all studied brain areas and elevation of gamma coherence in cortico-striatal and thalamocortical circuits of Nrxn1α^-/- rats. In contrast, auditory-evoked oscillations driven by chirp-modulated tones showed reduced power in cortical areas confined to slower oscillations. Finally, Nrxn1α^-/- rats exhibited altered auditory evoked-potentials and profound deficits in MMN-like responses, explained by reduced prediction error. Despite deficits for auditory stimuli, responses to social stimuli appeared intact. A central hypothesis for psychiatric and neurodevelopmental disorders is that a disbalance of excitation-to-inhibition is underlying oscillatory and sensory deficits. In a first attempt to explore the impact of inhibitory circuit modulation, we assessed the effects of enhancing tonic inhibition via δ-containing GABA_A receptors (using Gaboxadol) on endophenotypes possibly associated with network hyperexcitability. Pharmacological experiments applying Gaboxadol showed genotype-specific differences, but failed to normalize oscillatory or sensory processing abnormalities. In conclusion, our study revealed endophenotypes in Nrxn1α^-/- rats that could be used as translational biomarkers for drug development in psychiatric disorders.

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19. Jasoliya M, Gu J, AlOlaby RR, Durbin-Johnson B, Chedin F, Tassone F. Profiling Genome-Wide DNA Methylation in Children with Autism Spectrum Disorder and in Children with Fragile X Syndrome. Genes. 2022; 13(10).

Autism spectrum disorder (ASD) is an early onset, developmental disorder whose genetic cause is heterogeneous and complex. In total, 70% of ASD cases are due to an unknown etiology. Among the monogenic causes of ASD, fragile X syndrome (FXS) accounts for 2-4% of ASD cases, and 60% of individuals with FXS present with ASD. Epigenetic changes, specifically DNA methylation, which modulates gene expression levels, play a significant role in the pathogenesis of both disorders. Thus, in this study, using the Human Methylation EPIC Bead Chip, we examined the global DNA methylation profiles of biological samples derived from 57 age-matched male participants (2-6 years old), including 23 subjects with ASD, 23 subjects with FXS with ASD (FXSA) and 11 typical developing (TD) children. After controlling for technical variation and white blood cell composition, using the conservatory threshold of the false discovery rate (FDR ≤ 0.05), in the three comparison groups, TD vs. AD, TD vs. FXSA and ASD vs. FXSA, we identified 156, 79 and 3100 differentially methylated sites (DMS), and 14, 13 and 263 differential methylation regions (DMRs). Interestingly, several genes differentially methylated among the three groups were among those listed in the SFARI Gene database, including the PAK2, GTF2I and FOXP1 genes important for brain development. Further, enrichment analyses identified pathways involved in several functions, including synaptic plasticity. Our preliminary study identified a significant role of altered DNA methylation in the pathology of ASD and FXS, suggesting that the characterization of a DNA methylation signature may help to unravel the pathogenicity of FXS and ASD and may help the development of an improved diagnostic classification of children with ASD and FXSA. In addition, it may pave the way for developing therapeutic interventions that could reverse the altered methylome profile in children with neurodevelopmental disorders.

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20. Jeon M, Esposito G, Halstead E, Haghighatfard A, Dimitriou D, Neoh MJY. Cross-country comparison of parental reports and objective measures of sleep patterns of typically developing children and autistic children between the UK and South Korea. Sleep medicine. 2022; 101: 162-77.

Sleep duration and disturbances in typically developing (TD) children have been found to vary across countries. Given the impact of culture on sleep patterns in TD children, it is also necessary to examine the impact of culture on sleep patterns in children with atypical development. However, previous studies have often relied only on parent reports of children’s sleep. Hence, the present study conducted a cross-cultural comparison of sleep duration and disturbances of school-aged TD children and autistic children in the UK and South Korea (hereafter Korea) using both subjective and objective sleep measurements. Cultural differences were observed in both actigraphy measures and parent reports of children’s sleep duration and disturbances. Both TD children and autistic children in Korea had a later bedtime, later getting up time and shorter nocturnal sleep duration than their peers in the UK (p < .05). Furthermore, greater parent-reported sleep disturbances were reported in TD children in Korea compared to TD children in the UK and in autistic children in the UK compared to autistic children in Korea. Correlational analyses indicated that most parent-reported measures of children's sleep did not significantly correlate with objective measures and child reports, suggesting that studies on children's sleep can benefit by collecting data from multiple sources. Taken together, these findings suggest a cultural influence on sleep duration and disturbances of both TD children and autistic children. This study raises questions for further research to identify factors underlying cultural differences in children's sleep duration and disturbances.

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21. Jiang L, He R, Li Y, Yi C, Peng Y, Yao D, Wang Y, Li F, Xu P, Yang Y. Predicting the long-term after-effects of rTMS in autism spectrum disorder using temporal variability analysis of scalp EEG. Journal of neural engineering. 2022; 19(5).

Objective.Repetitive transcranial magnetic stimulation (rTMS) emerges as a useful therapy for autism spectrum disorder (ASD) clinically. Whereas the mechanisms of action of rTMS on ASD are not fully understood, and no biomarkers until now are available to reliably predict the follow-up rTMS efficacy in clinical practice.Approach.In the current work, the temporal variability was investigated in resting-state electroencephalogram of ASD patients, and the nonlinear complexity of related time-varying networks was accordingly evaluated by fuzzy entropy.Main results.The results showed the hyper-variability in the resting-state networks of ASD patients, while three week rTMS treatment alleviates the hyper fluctuations occurring in the frontal-parietal and frontal-occipital connectivity and further contributes to the ameliorative ASD symptoms. In addition, the changes in variability network properties are closely correlated with clinical scores, which further serve as potential predictors to reliably track the long-term rTMS efficacy for ASD.Significance.The findings consistently demonstrated that the temporal variability of time-varying networks of ASD patients could be modulated by rTMS, and related variability properties also help predict follow-up rTMS efficacy, which provides the potential for formulating individualized treatment strategies for ASD (ChiCTR2000033586).

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22. Johansson AM, Rudolfsson T, Bäckström A, Rönnqvist L, von Hofsten C, Rosander K, Domellöf E. Development of Motor Imagery in School-Aged Children with Autism Spectrum Disorder: A Longitudinal Study. Brain sciences. 2022; 12(10).

Autism spectrum disorder (ASD) is a diagnosis based on social communication deficits and prevalence of repetitive stereotyped behaviors, but sensorimotor disturbances are commonly exhibited. This longitudinal study aimed at exploring the development of the ability to form mental motor representations (motor imagery; MI) in 14 children with ASD and 17 typically developing (TD) children at 7, 8 and 9 years of age. MI was investigated using a hand laterality paradigm from which response times (RT) and error rates were extracted and compared with performance on a visually based mental rotation task (VI). A criterion task was used to ensure that the children could perform the task. The results showed wide performance variability in the ASD group with more failures than TD in the MI criterion task, especially at 7 years. For all age levels and both the MI and VI tasks, the error rates were significantly higher and RTs longer for the ASD group compared with TD. Signs of MI strategies were however noted in the ASD group as biomechanically constrained orientations had longer RTs than less constrained orientations, a RT pattern that differed from the VI task. The presence of MI in the ASD group was most evident at 9 years, but the error rates remained high at all ages, both in the MI and VI task. In comparison, the TD group showed stable MI strategies at all ages. These findings indicate that MI ability is delayed and/or impaired in children with ASD which may be related to difficulties performing required mental rotations.

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

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

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24. Li C, Zhang T, Li J. Identifying autism spectrum disorder in resting-state fNIRS signals based on multiscale entropy and a two-branch deep learning network. Journal of neuroscience methods. 2022; 383: 109732.

BACKGROUND: The demand for early and precise identification of autism spectrum disorder (ASD) presented a challenge to the prediction of ASD with a non-invasive neuroimaging method. NEW METHOD: A deep learning model was proposed to identify children with ASD using the resting-state functional near-infrared spectroscopy (fNIRS) signals. In this model, the input was the pattern of brain complexity represented by multiscale entropy of fNIRS time-series signals, with the purpose to solve the problem of deep learning analysis when the raw signals were limited by length and the number of subjects. The model consisted of a two-branch deep learning network, where one branch was a convolution neural network and the other was a long short-term memory neural network based on an attention mechanism. RESULTS: Our model could achieve an identification accuracy of 94%. Further analysis used the SHapley Additive exPlanations (SHAP) method to balance the accuracy and the number of optical channels, thus reducing the complexity of fNIRS experiment. COMPARISON WITH PREVIOUSLY USED METHOD(S): in identification accuracy, our model was about 14% higher than previously used deep learning models with the same input and 4% higher than the same model but directly using fNIRS signals as input. We could obtain a discriminative accuracy of 90% with nearly half of the measurement channels by the SHAP method. CONCLUSIONS: Using the pattern of brain complexity as input was effective in the deep learning model when the fNIRS signals were insufficient. With the SHAP method, it was possible to reduce the number of optical channels, while maintaining high accuracy in ASD identification.

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25. Li H, Shi B, Wang X, Cao M, Chen J, Liu S, Zhan X, Jin C, Gui Z, Jing J, Zhu Y. Associations of emotional/behavioral problems with accelerometer-measured sedentary behavior, physical activity and step counts in children with autism spectrum disorder. Frontiers in public health. 2022; 10: 981128.

BACKGROUND: The evidence for associations of emotional/behavioral status with sedentary behavior (SB), physical activity (PA) and step counts is scarce in children with autism spectrum disorder (ASD). Also, ASD-related deficiencies may affect actual levels of PA. We aimed to describe accelerometer-measured SB, PA and step counts in children with ASD, and to examine the associations of emotional/behavioral problems with SB, PA and step counts after assessing associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies. METHODS: A total of 93 ASD children, aged 6-9 years, were recruited from the Center for Child and Adolescent Psychology and Behavioral Development of Sun Yat-sen University in Guangzhou, China. Participants wore an accelerometer for seven consecutive days. Of the original 93, 78 participants’ accelerometer-measured valid PA were obtained, and the data were shown as time spent in SB, light, moderate, moderate-to-vigorous and vigorous PA, and step counts. Participants’ emotional/behavioral problems were assessed via the Strengths and Difficulties Questionnaire (SDQ), and anxiety symptoms were evaluated by the Screen for Child Anxiety Related Emotional Disorders (SCARED). ASD-associated deficiencies include restricted repetitive behaviors (Repetitive Behavior Scale-Revised), poor social competence (Social Responsiveness Scale Second Edition) and motor development restrictions (Developmental Coordination Disorder Questionnaire). RESULTS: Of the 78 participants, daily vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) averaged 15.62 and 51.95 min, respectively. After adjustment for covariates, SDQ emotional symptoms (β = -0.060, p = 0.028) were inversely associated with the average daily minutes in VPA. Meanwhile, SDQ emotional symptoms (β = -0.033, p = 0.016) were inversely associated with the average daily MVPA minutes in the crude model. After adjustment for covariates, SCARED somatic/panic (β = -0.007, p = 0.040) and generalized anxiety (β = -0.025, p = 0.014) were negatively associated with the average daily VPA minutes; SCARED total anxiety (β = -0.006, p = 0.029) was conversely associated with daily MVPA duration. After adjustment for covariates, no significant associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies were found (p > 0.05). CONCLUSIONS: Accelerometer-measured SB, PA and step counts showed no associations with ASD-related deficiencies. On this basis, we further found that the emotional symptoms were inversely associated with VPA and MVPA. These results emphasize the importance of VPA and MVPA in children with ASD. The longitudinally investigations on the directionality of these associations between emotional symptoms with VPA and MVPA are needed in the future.

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26. Lin TL, Lu CC, Chen TW, Huang CW, Lu JJ, Lai WF, Wu TS, Lai CH, Lai HC, Chen YL. Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii. International journal of molecular sciences. 2022; 23(21).

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.

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27. Mahjani B, Birnbaum R, Buxbaum Grice A, Cappi C, Jung S, Avila MN, Reichenberg A, Sandin S, Hultman CM, Buxbaum JD, Grice DE. Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders. Genes. 2022; 13(10).

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

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28. Majerczyk D, Ayad EG, Brewton KL, Saing P, Hart PC. Systemic maternal inflammation promotes ASD via IL-6 and IFN-γ. Bioscience reports. 2022; 42(11).

Autism spectrum disorder (ASD) is a neurological disorder that manifests during early development, impacting individuals through their ways of communicating, social behaviors, and their ability to perform day-to-day activities. There have been different proposed mechanisms on how ASD precipitates within a patient, one of which being the impact cytokines have on fetal development once a mother’s immune system has been activated (referred to as maternal immune activation, MIA). The occurrence of ASD has long been associated with elevated levels of several cytokines, including interleukin-6 (IL-6) and interferon gamma (IFN-γ). These proinflammatory cytokines can achieve high systemic levels in response to immune activating pathogens from various extrinsic sources. Transfer of cytokines such as IL-6 across the placental barrier allows accumulation in the fetus, potentially inducing neuroinflammation and consequently altering neurodevelopmental processes. Individuals who have been later diagnosed with ASD have been observed to have elevated levels of IL-6 and other proinflammatory cytokines during gestation. Moreover, the outcome of MIA has been associated with neurological effects such as impaired social interaction and an increase in repetitive behavior in animal models, supporting a mechanistic link between gestational inflammation and development of ASD-like characteristics. The present review attempts to provide a concise overview of the available preclinical and clinical data that suggest cross-talk between IL-6 and IFN-γ through both extrinsic and intrinsic factors as a central mechanism of MIA that may promote the development of ASD.

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29. Manfredi F, Riefoli F, Coviello M, Dibello D. The Management of Toe Walking in Children with Autism Spectrum Disorder: « Cast and Go ». Children (Basel, Switzerland). 2022; 9(10).

BACKGROUND: Toe walking is associated with autism spectrum disorders (ASD). Correction of this « behavior » is a health challenge. The toe walker is affected by the contact refusal with the outside world: touching the ground as little as possible, trying to avoid any contact. A structured equines foot is a possible consequence. METHOD: We present the « Cast and Go » protocol, used in 22 idiopathic toe walker children with ASD treated from 2015 to 2020. The treatment was performed by a single senior experienced doctor with botulinum injection, ankle casts and rehabilitative therapies. All patients underwent pre- and post-treatment clinical evaluation using ankle dorsiflexion angle and casting number as treatment. We aimed to identify the intervention with the shortest acquisition time for the management of toe walking. RESULTS: Our findings demonstrated the baseline ankle dorsiflexion angle influenced the casting number (p < 0.01) and male patients had a higher baseline ankle dorsiflexion angle than female patients (p < 0.01). No adverse events were observed. CONCLUSIONS: These findings suggested that the « Cast and Go » protocol could be a promising, dynamic and effective practice for toe walking disease in ASD patients.

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30. Marzi C, Narzisi A, Milone A, Masi G, Pirrelli V. Reading Behaviors through Patterns of Finger-Tracking in Italian Children with Autism Spectrum Disorder. Brain sciences. 2022; 12(10).

The paper proposes an ecological and portable protocol for the large-scale collection of reading data in high-functioning autism spectrum disorder (ASD) children based on recording the finger movements of a subject reading a text displayed on a tablet touchscreen. By capitalizing on recent evidence that movements of a finger that points to a scene or text during visual exploration or reading may approximate eye fixations, we focus on recognition of written content and function words, pace of reading, and accuracy in reading comprehension. The analysis showed significant differences between typically developing and ASD children, with the latter group exhibiting greater variation in levels of reading ability, slower developmental pace in reading speed, less accurate comprehension, greater dependency on word length and word frequency, less significant prediction-based processing, as well as a monotonous, steady reading pace with reduced attention to weak punctuation. Finger-tracking patterns provides evidence that ASD readers may fail to integrate single word processing into major syntactic structures and lends support to the hypothesis of an impaired use of contextual information to predict upcoming stimuli, suggesting that difficulties in perception may arise as difficulties in prediction.

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31. Mihalache D, Sokol-Hessner P, Feng H, Askari F, Reyes N, Moody EJ, Mahoor MH, Sweeny TD. Gaze perception from head and pupil rotations in 2D and 3D: Typical development and the impact of autism spectrum disorder. PloS one. 2022; 17(10): e0275281.

The study of gaze perception has largely focused on a single cue (the eyes) in two-dimensional settings. While this literature suggests that 2D gaze perception is shaped by atypical development, as in Autism Spectrum Disorder (ASD), gaze perception is in reality contextually-sensitive, perceived as an emergent feature conveyed by the rotation of the pupils and head. We examined gaze perception in this integrative context, across development, among children and adolescents developing typically or with ASD with both 2D and 3D stimuli. We found that both groups utilized head and pupil rotations to judge gaze on a 2D face. But when evaluating the gaze of a physically-present, 3D robot, the same ASD observers used eye cues less than their typically-developing peers. This demonstrates that emergent gaze perception is a slowly developing process that is surprisingly intact, albeit weakened in ASD, and illustrates how new technology can bridge visual and clinical science.

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32. Miller HL, Templin TN, Fears NE, Sherrod GM, Patterson RM, Bugnariu NL. Movement smoothness during dynamic postural control to a static target differs between autistic and neurotypical children. Gait & posture. 2022; 99: 76-82.

BACKGROUND: Autistic children and adults have known differences in motor performance, including postural instability and atypical gross motor control. Few studies have specifically tested dynamic postural control. This is the first study to quantify movement smoothness and its relationship to task performance during lateral dynamic postural control tasks in autism. RESEARCH QUESTION: We sought to test the hypothesis that autistic children would have less smooth movements to lateral static targets compared to neurotypical children, and that this difference would relate to specific movement strategies. METHODS: We used camera-based motion-capture to measure spatiotemporal characteristics of lateral movement of a marker placed on the C7 vertebrae, and of markers comprising trunk and pelvis segments during a dynamic postural movements to near and far targets administered in an immersive virtual environment. We tested a sample of 15 autistic children and 11 age-matched neurotypical children. We quantified movement smoothness using log dimensionless jerk. RESULTS: Autistic children exhibited more medial-lateral pelvic position range of motion compared to neurotypical children, and used a stepping strategy more often compared to neurotypical children. Autistic children also had higher log dimensionless jerk than neurotypical children for motion of the C7 marker. All participants had higher log dimensionless jerk for far targets than for near targets. Autistic children had longer trial durations than neurotypical children, and younger children had longer trial durations than older children across diagnostic groups. SIGNIFICANCE: The stepping strategy observed more often in the autistic group likely contributed to log dimensionless jerk and reduced movement smoothness. This strategy is indicative of either an attempt to prevent an impending loss of balance, or an attempt to compensate for and recover from a loss of balance once it is detected.

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33. Monteiro CE, Da Silva E, Sodré R, Costa F, Trindade AS, Bunn P, Costa ESG, Di Masi F, Dantas E. The Effect of Physical Activity on Motor Skills of Children with Autism Spectrum Disorder: A Meta-Analysis. International journal of environmental research and public health. 2022; 19(21).

OBJECTIVE: The present study was aimed at analyzing the effect of physical activity on motor coordination in children with ASD. METHODS: On 28 June 2021, a systematic review with meta-analysis was performed using the following databases: MEDLINE, SciELO, LILACS, PEDro, SPORTDiscus, CINAHL, SCOPUS, Web of Science, Cochrane, and Science Direct. We analyzed the methodological quality and risk of bias using the Jadad scale and Cochrane tool, respectively. Motor coordination results were meta-analyzed using the RevMan program. Two independent researchers used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool to assess the level of evidence from the meta-analysis. RESULTS: We found four studies in the listed databases and five randomized clinical trials were included in the meta-analysis that included 109 children with ASD. Children with ASD who performed physical activity did not present significantly better motor coordination than control children (p = 0.12). CONCLUSIONS: Considering the clinical importance of physical activity for children with ASD, this systematic review with meta-analysis showed that physical activity had no statistically significant effects on coordination in individuals with ASD.

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34. Nekar DM, Lee DY, Hong JH, Kim JS, Kim SG, Seo YG, Yu JH. Effects of Augmented Reality Game-Based Cognitive-Motor Training on Restricted and Repetitive Behaviors and Executive Function in Patients with Autism Spectrum Disorder. Healthcare (Basel, Switzerland). 2022; 10(10).

Restricted and repetitive behaviors (RRBs) and executive dysfunction are widely acknowledged as core features and hallmarks in patients with autism spectrum disorder (ASD). This study aimed to investigate the effects of augmented reality (AR) using motivational games with cognitive-motor exercises on RRBs, executive function (EF), attention, and reaction time in patients with ASD. Twenty-four patients (range from 6 to 18 years) diagnosed with ASD were recruited from local social welfare centers and randomly allocated to the AR game-based cognitive-motor training group (study group) or the conventional cognitive training group (control group). Both groups completed 30 min training sessions, twice a week for four weeks. Outcome measures were conducted before and after the intervention. As a result, improvements were observed in all the subscales of the RRBs in the study group except for self-injurious and ritualistic behavior. Significant improvements were observed in EF and reaction time in the study group, which was significantly higher compared to the control group. With the present findings, we can suggest that cognitive-motor training using AR game-based content generates positive effects on improving executive function reaction time and accuracy of responses and has a limited effect on RRBs in patients with ASD. This can be proposed as a complementary intervention associated with individualized daily management.

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35. Noda Y. A Paradigm Shift in Understanding the Pathological Basis of Autism Spectrum Disorder: From the Womb to the Tomb. Journal of personalized medicine. 2022; 12(10).

Autism Spectrum Disorder (ASD) is currently diagnosed based on clinical assessment of behavioral characteristics […].

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36. Pradhan A, Chester V, Padhiar K. Classification of Autism and Control Gait in Children Using Multisegment Foot Kinematic Features. Bioengineering (Basel, Switzerland). 2022; 9(10).

Previous research has demonstrated that children with autism walk with atypical ankle kinematics and kinetics. Although these studies have utilized single-segment foot (SSF) data, multisegment foot (MSF) kinematics can provide further information on foot mechanics. Machine learning (ML) tools allow the combination of MSF kinematic features for classifying autism gait patterns. In this study, multiple ML models are investigated, and the most contributing features are determined. This study involved 19 children with autism and 21 age-matched controls performing walking trials. A 34-marker system and a 12-camera motion capture system were used to compute SSF and MSF angles during walking. Features extracted from these foot angles and their combinations were used to develop support vector machine (SVM) models. Additional techniques-S Hapley Additive exPlanations (SHAP) and the Shapley Additive Global importancE (SAGE) are used for local and global importance of the black-box ML models. The results suggest that models based on combinations of MSF kinematic features classify autism patterns with an accuracy of 96.3%, which is higher than using SSF kinematic features (83.8%). The relative angle between the metatarsal and midfoot segments had the highest contribution to the classification of autism gait patterns. The study demonstrated that kinematic features from MSF angles, supported by ML models, can provide an accurate and interpretable classification of autism and control patterns in children.

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37. Quinn LA, Gilley SP, Ta AD, Frank BS, Foley CB, Moore JM. Case report: Pulmonary hypertensive crisis leading to cardiac arrest during endoscopic evaluation in a 6-year-old boy with autism, severe malnutrition, and undiagnosed scurvy. Frontiers in pediatrics. 2022; 10: 1008507.

Pediatric gastroenterologists are often responsible for the evaluation of malnutrition in the setting of selective eating. Endoscopic evaluation for conditions including eosinophilic esophagitis and celiac disease can help to identify and treat mucosal disease contributing to food selectivity. However, undiagnosed micronutrient deficiencies can cause cardiovascular derangements that significantly increase a patient’s anesthetic risk. Vitamin C deficiency in particular, alone or in combination with severe malnutrition, is associated with a severe but reversible form of pulmonary arterial hypertension that, while life threatening in the acute phase, may significantly improve within days of starting ascorbic acid replacement therapy. Here we present a case of a 6-year-old boy with autism spectrum disorder (ASD), severe malnutrition, and undiagnosed chronic vitamin C deficiency who developed a pulmonary hypertensive crisis after induction of general anesthesia leading to cardiac arrest during endoscopic evaluation. While the association between food selectivity among youth with neurodevelopmental differences and vitamin C deficiency is well-described, and pulmonary hypertension is a recognized rare complication of scurvy, extant literature has not addressed next steps to improve patient outcomes. Using this case report as a foundation, we discuss specific patient populations to screen and treat for micronutrient deficiencies prior to anesthesia and propose a novel clinical algorithm for pre-anesthesia risk stratification and mitigation in patients specifically at risk for scurvy and associated pulmonary hypertension.

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38. Raz N, Heller I, Lombardi T, Marino G, Davidson EM, Eyal AM. Terpene-Enriched CBD oil for treating autism-derived symptoms unresponsive to pure CBD: Case report. Frontiers in pharmacology. 2022; 13: 979403.

Cannabidiol (CBD) rich products are successfully used in some countries for treating symptoms associated with autism spectrum disorder (ASD). Yet, CBD provides insufficient intervention in some individuals, or for some characterizing symptoms of ASD, raising the need for improved compositions. The current study presents a case wherein pure CBD was sufficient for treating ASD during childhood and early adolescence. However, it became insufficient during puberty accompanied by increased hyperactivity, agitation, and frequent severe aggressive behavior. Increasing the CBD dose did not result in significant improvement. Enriching the pure CBD with a carefully selected blend of anxiolytic and calming terpenes, resulted in gradual elimination of those aggressive events. Importantly, this was achieved with a significantly reduced CBD dose, being less than one-half the amount used when treating with pure CBD. This case demonstrates a strong improvement in efficacy due to terpene enrichment, where pure CBD was not sufficient. Combined with terpenes’ high safety index and the ease with which they can be incorporated into cannabinoid-containing products, terpene-enriched CBD products may provide a preferred approach for treating ASD and related conditions. The careful selection of terpenes to be added enables maximizing the efficacy and tailoring the composition to particular and changing needs of ASD subjects, e.g., at different times of the day (daytime vs nighttime products).

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39. Reeves P, McConnell D, Phelan SK. The (radical) role of belonging in shifting and expanding understandings of social inclusion for people labelled with intellectual and developmental disabilities. Sociology of health & illness. 2022.

There is a gap between the desired outcomes of social inclusion policy and the everyday experiences of people labelled with intellectual and developmental disabilities. Despite belonging rhetorically named in social inclusion policy and practice, belonging is often absent in the lives of people labelled with intellectual and developmental disabilities and remains undertheorised in its relationship to social inclusion. In this paper, we explore the role belonging might play in narrowing the gap between how social inclusion is theorised and how it is experienced. Drawing on critical disability and feminist relational theories, we outline a relational conceptualisation of belonging and use it to ‘crip’ the construct of social inclusion. Exploring the synergies and tensions that surface when social inclusion and belonging are held together as discrete but interconnected constructs, we name four conceptual shifts and expansions that allow us to see social inclusion differently. Through the centring of the experiences of people labelled with intellectual and developmental disabilities, we explore the ways belonging can help to reimagine inclusion from assimilationist, static, objective and formal towards inclusion as fluid, negotiated, (inter)subjective, (in)formal and intimate.

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40. Roman-Urrestarazu A, Yang JC, van Kessel R, Warrier V, Dumas G, Jongsma H, Gatica-Bahamonde G, Allison C, Matthews FE, Baron-Cohen S, Brayne C. Autism incidence and spatial analysis in more than 7 million pupils in English schools: a retrospective, longitudinal, school registry study. The Lancet Child & adolescent health. 2022; 6(12): 857-68.

BACKGROUND: Understanding how certain factors affect autism incidence can help to identify inequities in diagnostic access. We aimed to investigate the incidence of autism in England as a function of geography and sociodemographics, examining spatial distribution across health service boundaries. METHODS: In this retrospective, longitudinal, school registry study, we sourced data for the years 2014-17 from the summer school census, which is a component of the National Pupil Database, a government registry of pupils under state education in England. Our main outcome was the incidence of autism in the English state-funded education system, defined by the amount of new autism-specific Education, Health and Care Plans or autism-specific special education needs and disability support recorded during each summer school census year since the 2014 baseline. After excluding prevalent cases in 2014, we calculated unadjusted incidence and age-adjusted, sex-adjusted incidence per 100 000 person-years per subsequent school year and by various sociodemographic categories and local authority districts. We report spatial effects using local indicators of spatial association. We used a three-level mixed-effects logistic regression model with two random intercepts (lower-layer super output area [a geographical area in England containing 1000-3000 residents] and pupil identifier) to calculate odds ratios (ORs) for autism incidence, adjusting for age, sex, ethnicity, claimed eligibility for free school meals, ethnic density quintile, Index of Multiple Deprivation quintile, first language spoken at home, and year, with our reference category being White girls without claimed eligibility for free school meals who speak English as their first language. FINDINGS: Between 2014 and 2017, our total sample included 31 580 512 person-years and 102 338 newly diagnosed autistic pupils, corresponding to an unadjusted annual autism incidence of 429•1 cases per 100 000 person-years (95% CI 426•4-431•7) and an age-adjusted, sex-adjusted annual incidence of 426•9 cases per 100 000 person-years (423•5-430•4). The adjusted incidence of autism was slightly higher in 2014-15 than in 2015-16 or 2016-17, and, of the age groups, pupils aged 1-3 years, 4-6 years, and 10-12 years had the highest incidence of autism. Adjusted autism incidence in boys was 3•9-times the incidence in girls (668•6 cases per 100 000 person-years [95% CI 662•5-674•6] vs 173•2 cases per 100 000 person-years [170•1-176•3]). Across ethnic groups, adjusted incidence was highest in pupils who had an unclassified ethnicity (599•4 cases per 100 000 person-years [574•5-624•3]) or were Black (466•9 cases per 100 000 person-years [450•8-483•0]). However, in our fully adjusted mixed-effects logistic regression model, we observed lower odds of autism among Asian (OR 0•65 [0•59-0•71]), Black (0•84 [0•77-0•92]), and Chinese (0•62 [0•42-0•92]) girls compared with White girls when these groups had not claimed free school meals and spoke English as a first language. Boys from all ethnicities irrespective of first language spoken and free school meals status had increased odds of autism compared with White girls with no claimed eligibility for free school meals who spoke English as their first language. We also found that claimed free school meal eligibility, first language spoken, sex, and ethnicity differentially impacted the odds of autism. Our spatial analysis showed significant spatial autocorrelation across lower-layer super output areas in England, with 2338 hotspots (high-incidence areas surrounded by other high-incidence areas). INTERPRETATION: The incidence of autism varies across sex, age, ethnicity, and geographical location. Environmental and social factors might interact with autism aetiology. Speaking a language other than English and economic hardship might increase access barriers to autism diagnostic services, autism-specific Education, Health and Care Plans, and school-level support. FUNDING: The Commonwealth Fund, the Institute for Data Valorization, the Fonds de recherche du Québec-Santé, Calcul Quebec, the Digital Research Alliance of Canada, the Wellcome Trust, the Innovative Medicines Initiative, the Autism Centre of Excellence, the Simons Foundation Autism Research Initiative, the Templeton World Charitable Fund, the Medical Research Council, the National Institute for Health and Care Research Cambridge Biomedical Research Centre, and the National Institute for Health and Care Research Applied Research Collaboration East of England-Population Evidence and Data Science.

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41. Rooney T, Stern YS, Hampton LH, Grauzer J, Hobson A, Levin A, Jones MK, Kaat AJ, Roberts MY. Screening for Autism in 2-Year-Old Children: The Application of the Systematic Observation of Red Flags to the Screening Tool for Autism in Toddlers and Young Children. American journal of speech-language pathology. 2022; 31(6): 2759-69.

PURPOSE: A multimeasure approach was developed to capitalize on the strengths of two screening measures: the Screening Tool for Autism in Toddlers and Young Children (STAT), an observational measure of social communication, and the Systematic Observation of Red Flags (SORF), a checklist including restricted and repetitive behavior (RRB) items. This approach offers a novel method of identifying autism in toddlers. METHOD: This was a retrospective study of data collected from a multidisciplinary diagnostic program for 24- to 36-month-olds with developmental delays. Raters with autism expertise but naïve to diagnoses applied the SORF to STAT videos. Psychometrics were derived for the SORF on STAT observations and a multiple-measure approach that used a Least Absolute Shrinkage and Selection Operator modeling framework to construct a STAT-SORF RRB Hybrid, retaining SORF RRB items based on individual predictive abilities. RESULTS: The SORF alone correctly classified 84% of the sample (84% sensitivity and 86% specificity). The STAT-SORF RRB Hybrid model, which retained four SORF RRB items, correctly classified 90% of a validation sample (95% sensitivity and 75% specificity). CONCLUSION: These findings highlight the potential utility of using multiple autism identification tools and regression-based scoring to establish presumptive eligibility and facilitate early access to autism interventions.

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42. Santorelli D, Troilo F, Fata F, Angelucci F, Demitri N, Giardina G, Federici L, Catalano F, Di Matteo A, Travaglini-Allocatelli C. Folding Mechanism and Aggregation Propensity of the KH0 Domain of FMRP and Its R138Q Pathological Variant. International journal of molecular sciences. 2022; 23(20).

The K-homology (KH) domains are small, structurally conserved domains found in proteins of different origins characterized by a central conserved βααβ « core » and a GxxG motif in the loop between the two helices of the KH core. In the eukaryotic KHI type, additional αβ elements decorate the « core » at the C-terminus. Proteins containing KH domains perform different functions and several diseases have been associated with mutations in these domains, including those in the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein crucial for the control of RNA metabolism whose lack or mutations lead to fragile X syndrome (FXS). Among missense mutations, the R138Q substitution is in the KH0 degenerated domain lacking the classical GxxG motif. By combining equilibrium and kinetic experiments, we present a characterization of the folding mechanism of the KH0 domain from the FMRP wild-type and of the R138Q variant showing that in both cases the folding mechanism implies the accumulation of an on-pathway transient intermediate. Moreover, by exploiting a battery of biophysical techniques, we show that the KH0 domain has the propensity to form amyloid-like aggregates in mild conditions in vitro and that the R138Q mutation leads to a general destabilization of the protein and to an increased fibrillogenesis propensity.

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43. Santos A, Caramelo F, Melo JB, Castelo-Branco M. Dopaminergic Gene Dosage Reveals Distinct Biological Partitions between Autism and Developmental Delay as Revealed by Complex Network Analysis and Machine Learning Approaches. Journal of personalized medicine. 2022; 12(10).

The neurobiological mechanisms underlying Autism Spectrum Disorders (ASD) remains controversial. One factor contributing to this debate is the phenotypic heterogeneity observed in ASD, which suggests that multiple system disruptions may contribute to diverse patterns of impairment which have been reported between and within study samples. Here, we used SFARI data to address genetic imbalances affecting the dopaminergic system. Using complex network analysis, we investigated the relations between phenotypic profiles, gene dosage and gene ontology (GO) terms related to dopaminergic neurotransmission from a polygenic point-of-view. We observed that the degree of distribution of the networks matched a power-law distribution characterized by the presence of hubs, gene or GO nodes with a large number of interactions. Furthermore, we identified interesting patterns related to subnetworks of genes and GO terms, which suggested applicability to separation of clinical clusters (Developmental Delay (DD) versus ASD). This has the potential to improve our understanding of genetic variability issues and has implications for diagnostic categorization. In ASD, we identified the separability of four key dopaminergic mechanisms disrupted with regard to receptor binding, synaptic physiology and neural differentiation, each belonging to particular subgroups of ASD participants, whereas in DD a more unitary biological pattern was found. Finally, network analysis was fed into a machine learning binary classification framework to differentiate between the diagnosis of ASD and DD. Subsets of 1846 participants were used to train a Random Forest algorithm. Our best classifier achieved, on average, a diagnosis-predicting accuracy of 85.18% (sd 1.11%) on the test samples of 790 participants using 117 genes. The achieved accuracy surpassed results using genetic data and closely matched imaging approaches addressing binary diagnostic classification. Importantly, we observed a similar prediction accuracy when the classifier uses only 62 GO features. This result further corroborates the complex network analysis approach, suggesting that different genetic causes might converge to the dysregulation of the same set of biological mechanisms, leading to a similar disease phenotype. This new biology-driven ontological framework yields a less variable and more compact domain-related set of features with potential mechanistic generalization. The proposed network analysis, allowing for the determination of a clearcut biological distinction between ASD and DD (the latter presenting much lower modularity and heterogeneity), is amenable to machine learning approaches and provides an interesting avenue of research for the future.

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44. Scheerer NE, Pourtousi A, Yang C, Ding Z, Stojanoski B, Anagnostou E, Nicolson R, Kelley E, Georgiades S, Crosbie J, Schachar R, Ayub M, Stevenson RA. Transdiagnostic Patterns of Sensory Processing in Autism and ADHD. Journal of autism and developmental disorders. 2022.

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD). This study examined the transdiagnostic nature of sensory processing abilities, and their association with features of autism and ADHD, in a large sample of autistic people (n = 495) and people with ADHD (n = 461). Five similar data-driven sensory phenotypes characterized sensory processing abilities, and showed similar patterns of association with features of autism and ADHD, across both diagnostic groups. These results demonstrate the transdiagnostic nature of sensory processing abilities, while contributing to a growing body of literature that suggests the autism and ADHD diagnostic labels have poor explanatory power.

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45. Stark C, Groves NB, Kofler MJ. Is reduced social competence a mechanism linking elevated autism spectrum symptoms with increased risk for social anxiety?. The British journal of clinical psychology. 2022.

OBJECTIVES: Approximately 50% of children with autism spectrum disorder (ASD) develop comorbid social anxiety disorder, and this comorbidity predicts poorer treatment outcomes than either syndrome alone. ASD and social anxiety are both associated with reduced social competence as evidenced by difficulties implementing fundamental social skills for successful social interactions, but it remains unclear whether reduced social competence reflects a mechanism that explains the increased risk for social anxiety associated with elevated autism spectrum symptoms. DESIGN/METHODS: To address this gap in the literature, the current study combined multi-informant measures (child, parent and teacher report) with a sample of 194 children with and without psychiatric disorders (ages 8-13; 68 girls; 69% White/Non-Hispanic). Autism spectrum traits, social competence and social anxiety symptoms were measured continuously. RESULTS: Bias-corrected, bootstrapped conditional effects modelling indicated that elevated parent-reported autism spectrum symptoms predicted reduced teacher-perceived social competence (β = -.21) and elevated child self-reported social anxiety (β = .17); reduced social competence accounted for 20% of the autism/social anxiety link (indirect pathway β = .04, ER = .20), and reduced social competence also predicted higher social anxiety independent of autism symptoms (β = -.16; all 95% CIs exclude 0.0, indicating significant effects). Exploratory analyses suggested that these findings were driven primarily by autism spectrum social communication difficulties rather than restricted/repetitive behaviours/interests. CONCLUSIONS: The current findings are consistent with prior work implicating reduced social competence as a risk factor for the development of social anxiety among children with ASD, and extend prior work by demonstrating that this link is robust to control for mono-informant/mono-measure bias, age, sex, SES, majority/minoritized race/ethnicity status, clinical comorbidities, and item overlap across measures.

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46. Tangviriyapaiboon D, Kawilapat S, Sirithongthaworn S, Apikomonkon H, Suyakong C, Srikummoon P, Thumronglaohapun S, Traisathit P. The Optimal Cut-Off Point for Thai Diagnostic Autism Scale and Probability Prediction of Autism Spectrum Disorder Diagnosis in Suspected Children. Healthcare (Basel, Switzerland). 2022; 10(10).

The Thai Diagnostic Autism Scale (TDAS) was developed to diagnose autism spectrum disorder (ASD) under the context and characteristics of the Thai population. Although the tool has an excellent agreement, the interpretation of diagnostic results needs to rely on the optimal cut-off point to maximize efficiency and clarity. This study aims to find an optimal cut-off point for TDAS in the diagnosis of ASD and to compare its agreement with the DSM-5 ASD criteria. This study was conducted on 156 children aged 12-48 months old who were suspected of having ASD and had enrolled from hospitals in the four regions of Thailand in 2017-2018. The optimal cut-off point for TDAS was considered by using receiver operating characteristic (ROC) curves according to the DSM-5 ASD criteria. The areas under the curve (AUCs) for TDAS and ADOS-2 were also compared. Multivariable logistic regression was performed to create a predictive model for the probability of ASD. The AUC of TDAS was significantly higher than that of ADOS-2 (0.8748 vs. 0.7993; p = 0.033). The optimal cut-off point for TDAS was ≥20 points (accuracy = 82.05%, sensitivity = 82.86%, and specificity = 80.93%). Our findings show that TDAS with a cut-off point can yield higher diagnostic accuracy than ADOS-2 and TDAS domain. Diagnosis by using this cut-off point could be useful in practical assessments.

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47. Tangviriyapaiboon D, Traisathit P, Siripornpanich V, Suyakong C, Apikomonkon H, Homkham N, Thumronglaohapun S, Srikummoon P. Detection of Electroencephalographic Abnormalities and Its Associated Factors among Children with Autism Spectrum Disorder in Thailand. Healthcare (Basel, Switzerland). 2022; 10(10).

Epilepsy often causes more severe behavioral problems in children with autism spectrum disorder (ASD) and is strongly associated with poor cognitive functioning. Interestingly, individuals with ASD without a history of epilepsy can have abnormal electroencephalographic (EEG) activity. The aim of this study was to examine associations between EEG abnormalities and the ASD severity in children. The children with ASD who enrolled at the Rajanagarindra Institute of Child Development, Thailand were included in this study. The severity of ASD was measured by interviewing their parents with the Thai autism treatment evaluation checklist. The short sensory profile checklist was used for screening the abnormality of children in each domain. Ordinal logistic regression analysis was used to examine associations between factors potentially linked to EEG abnormalities. Most of the study participants were boys (87.5%) and the median age was 5 years. Among the 128 children, 69.5% showed EEG abnormalities (41.4% slow-wave and 28.1% epileptiform-discharge). The results show that a larger number of symptoms and increased severity of ASD were independently associated with a higher risk of EEG abnormalities. Our results emphasize the need for guidelines on the presence of EEG abnormalities in children with ASD for the early detection of epilepsy and improving treatment outcomes.

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48. Trinchese G, Cimmino F, Cavaliere G, Catapano A, Fogliano C, Lama A, Pirozzi C, Cristiano C, Russo R, Petrella L, Meli R, Mattace Raso G, Crispino M, Avallone B, Mollica MP. The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders. Antioxidants (Basel, Switzerland). 2022; 11(10).

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut-brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease.

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

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

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50. Wu H, Chen X, Zhang S, Li J. Gut Microbiota, the Potential Biological Medicine for Prevention, Intervention and Drug Sensitization to Fight Diseases. Nutrients. 2022; 14(20).

As the largest « immune organ » of human beings, the gut microbiota is symbiotic and mutually beneficial with the human host, playing multiple physiological functions. Studies have long shown that dysbiosis of gut microbiota is associated with almost all human diseases, mainly including type II diabetes, cancers, neurodegenerative diseases, autism spectrum disorder, and kidney diseases. As a novel and potential biological medicine for disease prevention, intervention and drug sensitization, the gut microbiota has attracted more and more attention recently. Although the gut microbiota is a comprehensive microbial community, several star bacteria have emerged as possible tools to fight against various diseases. This review aims to elucidate the relevance of gut microbiota dysbiosis with disease occurrence and progression, and mainly summarizes four well-known genera with therapeutic and sensitizing potential, Akkermansia, Bifidobacterium, Lactobacillus and Parabacteroides, thoroughly elucidate their potential value as biological drugs to treat diverse disease.

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51. Yosep I, Prayogo SA, Kohar K, Andrew H, Mardhiyah A, Amirah S, Maulana S. Managing Autism Spectrum Disorder in the Face of Pandemic Using Internet-Based Parent-Mediated Interventions: A Systematic Review of Randomized Controlled Trials. Children (Basel, Switzerland). 2022; 9(10).

ASD is a neurodevelopmental disorder that is primarily treated with psychosocial intervention. However, it is costly and requires extensive resources to be effective. This inaccessibility is also further worsened by the ongoing COVID-19 pandemic, making the shift to a digital approach a sensible option. Among the available ASD therapies, parent-mediated interventions (PMIs) have a broad application and lower implementation cost. Hence, this systematic review aims to evaluate the potential that telehealth-based PMI holds and explore its feasibility throughout the COVID-19 pandemic. To build up this study, a systematic search through PubMed, Scopus, ProQuest, Wiley, and Cochrane was performed until 14 January 2021. Using the preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we ultimately included six studies in the review. Each study was evaluated utilizing the Cochrane Risk of Bias (ROB)-2 tool. Generally, parents’ outcomes (knowledge, satisfaction, and compliance) were higher in intervention group (E-learning) compared to control (standard treatment or wait-list). Children also showed some improvements in social skill, communication skill, and intelligence after receiving the treatment. In addition, coaching or therapist sessions were found to be crucial as adjuvant to support parents during the intervention. In conclusion, internet-based parent-mediated interventions are promising and recommended for managing ASD patients, in the face of pandemic. However, more variety in study locations is also needed, particularly in low- and middle-income countries, to tackle the knowledge and clinical application gap. Further research should be conducted with a uniform measurement tool to achieve the same perception and reliable pooled analysis.

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52. Yuan HL, Lai CYY, Wong MNK, Kwong TC, Choy YS, Mung SWY, Chan CCH. Interventions for Sensory Over-Responsivity in Individuals with Autism Spectrum Disorder: A Narrative Review. Children (Basel, Switzerland). 2022; 9(10).

Individuals with autism spectrum disorder (ASD) often exhibit sensory over-responsivity (SOR), which is characterized by an overwhelmingly negative reaction to or avoidance of sensory stimulation. Despite the detrimental effects of SOR on people’s personal and social lives, the knowledge of and interventions for the issue remain limited. This paper collates and reviews studies on SOR and information on the potential for effective interventions for people with ASD. This review reveals evidence that SOR has a close relationship with anxiety, depression, insomnia, and family life impairment and an underlying mechanism related to SOR. Four interventions and their theoretical bases in sensory-motor processing are discussed in this paper, namely, physical activity (PA), sensory integration therapy (SIT), mindfulness-based cognitive therapy (MBCT), and cognitive behavioral therapy (CBT). These interventions focus on establishing coping strategies for regulating the emotional response to sensory information, and they have been found to be effective and to have the potential to help children with ASD reduce their SOR behaviors. This paper provides guidance for selecting appropriate interventions and for further investigation of more effective interventions in the future.

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53. Zhang X, Smits M, Curfs L, Spruyt K. Sleep Respiratory Disturbances in Girls with Rett Syndrome. International journal of environmental research and public health. 2022; 19(20).

Individuals with Rett Syndrome (RTT), a rare neurodevelopmental disorder, present disordered breathing during wakefulness. Whilst findings on breathing during sleep are contradictory, the relation between sleep breathing and their clinical features, genetic characteristics, age, and sleep phase is rarely investigated, which is the objective of this study. Overnight polysomnography (PSG) was performed. Sleep macrostructure parameters were compared between the RTT subjects with and without sleep-disordered breathing (SDB). The association between the apnea-hypopnea index (AHI) with age at PSG was tested. Particularly for RTT subjects with SDB, the respiratory indexes in REM and NREM sleep were compared. Stratified analyses per clinical characteristics, genetic characteristics, and clinical features’ severity were performed. Non-parametric statistics were applied. A sample of 11 female RTT subjects, aged 8.69 ± 5.29 years with ten confirmed with MECP2 mutations, were studied. The average AHI was 3.94 ± 1.19/h TST, of which eight (72.73%) had obstructive sleep apnea, i.e., six in 1/h TST ≤ AHI ≤ 5/h TST, and two in AHI > 5/h TST. The mean SpO(2)% was 81.00 ± 35.15%. The AHI was not significantly correlated with their age at PSG (r(s) = -0.15, p = 0.67). Sleep macrostructure in SDB-absent and SDB-present groups was not different. Respiratory indexes in those with obstructive sleep apnea showed no difference between REM and NREM sleep nor any of the strata. In our clinical sample, more than half of the RTT subjects with MECP2 mutations had obstructive sleep apnea in both NREM and REM sleep which was unrelated to their clinical features. Our results also indicated hypoxemia throughout nocturnal sleep in RTT. To conclude, our results suggest that disordered breathing during sleep is prevalently present in RTT as an independent clinical feature.

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54. Zhou L, Zhang L, Xu Y, Yang F, Benson V. Attentional Engagement and Disengagement Differences for Circumscribed Interest Objects in Young Chinese Children with Autism. Brain sciences. 2022; 12(11).

The current study aimed to investigate attentional processing differences for circumscribed interest (CI) and non-CI objects in young Chinese children with autism spectrum condition (ASC) and typically developing (TD) controls. In Experiment 1, a visual preference task explored attentional allocation to cartoon CI and non-CI materials between the two groups. We found that ASC children (n = 22, 4.95 ± 0.59 years) exhibited a preference for CI-related objects compared to non-CI objects, and this effect was absent in the TD children (n = 22, 5.14 ± 0.44 years). Experiment 2 utilized the traditional gap-overlap paradigm (GOP) to investigate attentional disengagement from CI or non-CI items in both groups (ASC: n = 20, 5.92 ± 1.13 years; TD: n = 25, 5.77 ± 0.77 years). There were no group or stimulus interactions in this study. Experiment 3 adopted a modified GOP (MGOP) to further explore disengagement in the two groups (ASC: n = 20, 5.54 ± 0.95 years; TD: n = 24, 5.75 ± 0.52 years), and the results suggested that exogenous disengagement performance was preserved in the ASC group, but the children with ASC exhibited increased endogenous attentional disengagement compared to TD peers. Moreover, endogenous disengagement was influenced further in the presence of CI-related objects in the ASC children. The current results have implications for understanding how the nature of engagement and disengagement processes can contribute to differences in the development of core cognitive skills in young children with ASC.

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