1. Arafa A, Mahmoud O, Salah H, Abdelmonem AA, Senosy S. Maternal and neonatal risk factors for autism spectrum disorder: A case-control study from Egypt. PLoS One;2022;17(6):e0269803.

BACKGROUND: The prevalence of autism spectrum disorder (ASD) has been increasing steadily in Egypt and worldwide. Detecting risk factors for ASD could help initiate screening and risk prevention approaches. Herein, this study aimed to detect several maternal and neonatal risk factors for ASD in Egypt. METHODS: In this case-control study, mothers of children with ASD who were visiting Beni-Suef University Hospital in Egypt (n = 268) were compared to mothers of children without ASD attending one primary school with a kindergarten (n = 504) regarding their preconception, conception, and postconception characteristics. Data were collected using a self-administered questionnaire. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to investigate the possible associations between the collected data and the odds of ASD. RESULTS: In the multivariable-adjusted models, urban residence: OR (95% CI) = 2.33 (1.60-3.38), relative father: 2.63 (1.74-3.96), history of diabetes: 5.98 (1.99-17.97), previous abortion: 2.47 (1.20-13.38), assisted fertility: 4.01 (1.20-13.38), family history of ASD: 7.24 (2.00-26.24), multiple pregnancy: 11.60 (2.54-53.07), exposure to passive smoking during pregnancy: 2.95 (1.86-4.68), vaginal bleeding during pregnancy: 3.10 (1.44-6.67), hypertension with pregnancy: 3.64 (1.06-12.51), preterm labor: 2.64 (1.26-5.57), neonatal convulsions: 14.88 (5.01-44.20), and admission to neonatal intensive care unit 2.13: (1.21-3.74) were associated with the increased odds of ASD. On the other hand, the intake of vitamins during pregnancy: 0.09 (0.06-0.16) and C-section: 0.44 (0.27-0.70) were associated with the decreased odds of ASD. CONCLUSION: This study detected several maternal and neonatal risk factors for ASD in Egyptian children.

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2. Arazi A, Koller J, Zachor DA, Golan O, Sadaka Y, Eytan D, Stolar O, Atzaba-Poria N, Golan H, Menashe I, Meiri G, Gabis LV, Dinstein I. Home-quarantine during the initial Covid-19 outbreak in Israel: parent perceived impact on children with ASD. Heliyon;2022 (Jun);8(6):e09681.

BACKGROUND: Studies have reported that Covid-19 home-quarantine periods have had mostly negative psychological impact on children with ASD and their families. Here we examined parent perceived impact of a 6-week quarantine period imposed in Israel at the beginning of the Covid-19 outbreak, in mid-March 2020. METHODS: An anonymous online questionnaire was completed by parents of 268 children with ASD. Parents rated deterioration/improvement in their child’s behaviors, abilities, mood, sleep, and anxiety along with changes in their own mood, sleep, parenting skills, and family relationships. We performed t-tests and ANOVA analyses to assess the significance of perceived impact on each domain and potential differences in the impact across families with children of different ages, genders, and levels of required support as well as families that experienced different magnitudes of economic hardships. RESULTS: Parents reported significant deterioration in their mood and sleep along with significant improvements in relationships with their spouse and child with ASD, and in their parenting skills. Parents also reported significant increases in the severity of tantrums, anxiety, and restricted and repetitive behavior symptoms along with significant improvements in social and communication abilities of their child with ASD. Ratings were significantly lower in families of ASD children who regularly require more support and in families that experienced economic hardships. CONCLUSIONS: While periods of home-quarantine create numerous hardships for families of children with ASD, they may also offer an opportunity for improving parenting skills, family relationships, and children’s social communication abilities with potential relevance for improving remote services.

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3. Bertrams A. From autistic pragmatic language problems to a negative attitude toward human nature-a serial multiple mediation model. J Psychiatr Res;2022 (Jun 15);152:139-143.

It has recently been found that individuals high in autistic traits tend to believe that they are usually not treated fairly. In the present study, it is assumed that such a lowered personal belief in a just world is based on cumulative humiliation experiences that stem from autistic pragmatic language problems (e.g., communicating in a monotonous voice, not being « in tune » with others during conversations). Furthermore, the less individuals believe that they receive fair treatment, the more they may develop a negative attitude toward human nature (i.e., believing that humans are generally untrustworthy, unfair, and unhelpful). The serial multiple mediation model reflecting these assumptions received initial empirical support in a nonclinical sample (N = 344). Implications for professional health care are addressed.

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4. Borra D, Magosso E, Castelo-Branco M, Simoes M. A Bayesian-optimized design for an interpretable convolutional neural network to decode and analyze the P300 response in autism. J Neural Eng;2022 (Jun 15)

OBJECTIVE: P300 can be analyzed in autism spectrum disorder (ASD) to derive biomarkers and can be decoded in BCIs to reinforce ASD impaired skills. Convolutional neural networks (CNNs) have been proposed for P300 decoding, outperforming traditional algorithms but they i) do not investigate optimal designs in different training conditions; ii) lack in interpretability. To overcome these limitations, an interpretable CNN (ICNN), that we recently proposed for motor decoding, has been modified and adopted here, with its optimal design searched via Bayesian optimization. APPROACH: The ICNN provides a straightforward interpretation of spectral and spatial features learned to decode P300. The Bayesian-optimized (BO) ICNN design was investigated separately for different training strategies (within-subject, within-session, and cross-subject) and BO models were used for the subsequent analyses. Specifically, transfer learning (TL) potentialities were investigated by assessing how pretrained cross-subject BO models performed on a new subject vs. random-initialized models. Furthermore, within-subject BO-derived models were combined with an Explanation Technique (ICNN+ET) to analyze P300 spectral and spatial features. MAIN RESULTS: The ICNN resulted comparable or even outperformed existing CNNs, at the same time being lighter. Bayesian-optimized ICNN designs differed depending on the training strategy, needing more capacity as the training set variability increased. Furthermore, TL provided higher performance than networks trained from scratch. The ICNN+ET analysis suggested the frequency range [2, 5.8] Hz as the most relevant, and spatial features showed a right-hemispheric parietal asymmetry. The ICNN+ET-derived features, but not ERP-derived features, resulted significantly and highly correlated to ADOS clinical scores. SIGNIFICANCE: This study substantiates the idea that a CNN can be designed both accurate and interpretable for P300 decoding, with an optimized design depending on the training condition. The novel ICNN-based analysis tool was able to better capture ASD neural signatures than traditional ERP analysis, possibly paving the way for identifying novel biomarkers.

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5. Clarke L, Fung LK. The impact of autism-related training programs on physician knowledge, self-efficacy, and practice behavior: A systematic review. Autism;2022 (Jun 13):13623613221102016.

Autism spectrum disorder is estimated to impact 1.5 million children and almost 5.5 million adults. However, most physicians do not receive training on how to provide care to this increasingly large group of people. After performing a systematic review of the literature and screening over 4,500 unique articles focused on the effectiveness of autism-specific training programs designed for physicians and physician trainees, we determined that 17 studies met the pre-determined criteria for inclusion in this systematic review. The results reported by these studies suggest that by completing specialized training programs related to autism, physicians were more knowledgeable on topics related to the condition, more confident in their ability to provide care to autistic individuals, and more likely to screen their patients for autism spectrum disorder. However, further studies with higher quality data are needed to validate these findings and provide additional insight on the ability of these programs to improve physician behavior and patient outcomes. We are therefore advocating that medical educators develop and evaluate specialized autism training programs with an increased focus on improving physician behavior related to all aspects of providing care to autistic people.

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6. Cleary DB, Bunney A, Henry L, Renton M, Granich J, Green J, Maybery MT, Whitehouse AJO. A Parent-Mediated Intervention for Newborns at Familial Likelihood of Autism: Initial Feasibility Study in the General Population. Adv Neurodev Disord;2022 (Jun 9):1-12.

OBJECTIVES: Developmental theory and previous studies support the potential value of prodromal interventions for infants at elevated likelihood of developing autism. Past research has supported the efficacy of parent-mediated prodromal therapies with infants from as early as 7 months. We outline the rationale for implementing interventions following this model from even earlier in development and report on the feasibility of a novel intervention developed following this model of parent-mediated infant interventions. METHODS: We report a feasibility study (n = 13) of a parent-mediated, video-aided intervention, beginning during pregnancy, focussed on parent-infant interactions. The study evaluated the feasibility of this intervention initially with a general population sample. Feasibility was assessed across four domains (acceptability, implementation, practicality and integration) using self-report questionnaire, semi-structured interviews with parents and therapists, attendance and assessment completion. RESULTS: Feasibility assessment shows that the intervention was acceptable, with all participants reporting that they had benefited from the program, with perceived positive benefits to their understanding of and communication with their infant, and that they had integrated program teachings into everyday life. The intervention was implemented as planned with 100% attendance for the core sessions. Changes to minimise the number of antenatal sessions was suggested to improve practicality. CONCLUSIONS: This study found initial feasibility for this intervention in a general population sample. This suggests parent-mediated video feedback interventions are a promising format to be implemented within the perinatal developmental time period.

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7. Gauld C, Maquet J, Micoulaud-Franchi JA, Dumas G. Popular and Scientific Discourse on Autism: Representational Cross-Cultural Analysis of Epistemic Communities to Inform Policy and Practice. J Med Internet Res;2022 (Jun 15);24(6):e32912.

BACKGROUND: Social media provide a window onto the circulation of ideas in everyday folk psychiatry, revealing the themes and issues discussed both by the public and by various scientific communities. OBJECTIVE: This study explores the trends in health information about autism spectrum disorder within popular and scientific communities through the systematic semantic exploration of big data gathered from Twitter and PubMed. METHODS: First, we performed a natural language processing by text-mining analysis and with unsupervised (machine learning) topic modeling on a sample of the last 10,000 tweets in English posted with the term #autism (January 2021). We built a network of words to visualize the main dimensions representing these data. Second, we performed precisely the same analysis with all the articles using the term « autism » in PubMed without time restriction. Lastly, we compared the results of the 2 databases. RESULTS: We retrieved 121,556 terms related to autism in 10,000 tweets and 5.7×109 terms in 57,121 biomedical scientific articles. The 4 main dimensions extracted from Twitter were as follows: integration and social support, understanding and mental health, child welfare, and daily challenges and difficulties. The 4 main dimensions extracted from PubMed were as follows: diagnostic and skills, research challenges, clinical and therapeutical challenges, and neuropsychology and behavior. CONCLUSIONS: This study provides the first systematic and rigorous comparison between 2 corpora of interests, in terms of lay representations and scientific research, regarding the significant increase in information available on autism spectrum disorder and of the difficulty to connect fragments of knowledge from the general population. The results suggest a clear distinction between the focus of topics used in the social media and that of scientific communities. This distinction highlights the importance of knowledge mobilization and exchange to better align research priorities with personal concerns and to address dimensions of well-being, adaptation, and resilience. Health care professionals and researchers can use these dimensions as a framework in their consultations to engage in discussions on issues that matter to beneficiaries and develop clinical approaches and research policies in line with these interests. Finally, our study can inform policy makers on the health and social needs and concerns of individuals with autism and their caregivers, especially to define health indicators based on important issues for beneficiaries.

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8. Gross C, Banerjee A, Tiwari D, Longo F, White AR, Allen AG, Schroeder-Carter LM, Krzeski JC, Elsayed NA, Puckett R, Klann E, Rivero RA, Gourley SL, Bassell GJ. Correction to: Isoform-selective phosphoinositide 3-kinase inhibition ameliorates a broad range of fragile X syndrome-associated deficits in a mouse model. Neuropsychopharmacology;2022 (Jun 14)

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9. Hamoudi W, Tripathi MK, Ojha SK, Amal H. A cross-talk between nitric oxide and the glutamatergic system in a Shank3 mouse model of autism. Free Radic Biol Med;2022 (Jun 15)

Nitric oxide (NO) is a multifunctional signaling molecule that plays a crucial role in synaptic transmission and neuronal function. Pioneering studies show that nitric oxide (NO) and S-nitrosylation (SNO, the NO-mediated posttranslational modification) can engender nitrosative stress in the brain, contributing to neurodegenerative diseases. Little is known, however, about the aberrant NO signaling in neurodevelopmental disorders including autism spectrum disorder (ASD). We have recently shown that the Shank3 mutation in mice representing a model of ASD causes excessive NO levels and aberrant protein SNO. The glutamatergic system is involved in ASD, specifically in SHANK3 pathology. We used SNOTRAP technology to identify the SNO-proteome in the brain of the Shank3 mutant mice to understand the role of SNO in the glutamatergic system during the development of these mice. We conducted a systems biology analysis of the SNO-proteome to investigate the biological processes and signaling pathways in the brain of juvenile and adult Shank3 mutant and wild-type mice. The Shank3 mutation caused significant SNO-enrichment of a glutamate signaling pathway in the juvenile and adult mutant mice, although different protein subsets were S-nitrosylated in both ages. Cellular compartments analysis showed that « glutamatergic Synapse » is SNO-enriched significantly in the mutant mice of both ages. We also found eight S-nitrosylated proteins involved in glutamate transmission in both ages. 38 SNO-proteins found in the mutant mice are among the high-risk SFARI gene list. Biochemical examination shows a reduction in the levels of NMDA Receptor (NR1) in the cortex and striatum of the mutant mice of both ages. Neuronal NOS knockdown in SHSY-5Yrescued NR1 levels. In conclusion, this study reveals novel SNO of key glutamatergic proteins in Shank3 mutant mice and revealed a cross-talk between nitric oxide and the glutamatergic system.

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10. Hessl D, Rosselot H, Miller R, Espinal G, Famula J, Sherman SL, Todd PK, Cabal Herrera AM, Lipworth K, Cohen J, Hall DA, Leehey M, Grigsby J, Weber JD, Alusi S, Wheeler A, Raspa M, Hudson T, Sobrian SK. The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness. J Med Genet;2022 (Jun 14)

FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies.

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11. Klorfeld-Auslender S, Paz Y, Shinder I, Rosenblatt J, Dinstein I, Censor N. A distinct route for efficient learning and generalization in autism. Curr Biol;2022 (Jun 7)

Visual skill learning is the process of improving responses to surrounding visual stimuli.(1) For individuals with autism spectrum disorders (ASDs), efficient skill learning may be especially valuable due to potential difficulties with sensory processing(2) and challenges in adjusting flexibly to changing environments.(3)(,)(4) Standard skill learning protocols require extensive practice with multiple stimulus repetitions,(5-7) which may be difficult for individuals with ASD and create abnormally specific learning with poor ability to generalize.(4) Motivated by findings indicating that brief memory reactivations can facilitate skill learning,(8)(,)(9) we hypothesized that reactivation learning with few stimulus repetitions will enable efficient learning in individuals with ASD, similar to their learning with standard extensive practice protocols used in previous studies.(4)(,)(10)(,)(11) We further hypothesized that in contrast to experience-dependent plasticity often resulting in specificity, reactivation-induced learning would enable generalization patterns in ASD. To test our hypotheses, high-functioning adults with ASD underwent brief reactivations of an encoded visual learning task, consisting of only 5 trials each instead of hundreds. Remarkably, individuals with ASD improved their visual discrimination ability in the task substantially, demonstrating successful learning. Furthermore, individuals with ASD generalized learning to an untrained visual location, indicating a unique benefit of reactivation learning mechanisms for ASD individuals. Finally, an additional experiment showed that without memory reactivations ASD subjects did not demonstrate efficient learning and generalization patterns. Taken together, the results provide proof-of-concept evidence supporting a distinct route for efficient visual learning and generalization in ASD, which may be beneficial for skill learning in other sensory and motor domains.

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12. Lo T, Kushima I, Aleksic B, Kato H, Nawa Y, Hayashi Y, Otgonbayar G, Kimura H, Arioka Y, Mori D, Ozaki N. Sequencing of selected chromatin remodelling genes reveals increased burden of rare missense variants in ASD patients from the Japanese population. Int Rev Psychiatry;2022 (Feb 17);34(2):154-167.

Chromatin remodelling is an important process in neural development and is related to autism spectrum disorder (ASD) and schizophrenia (SCZ) aetiology. To further elucidate the involvement of chromatin remodelling genes in the genetic aetiology of ASD and SCZ in the Japanese population, we performed a case-control study. Targeted sequencing was conducted on coding regions of four BAF chromatin remodelling complex genes: SMARCA2, SMARCA4, SMARCC2, and ARID1B in 185 ASD, 432 SCZ patients, and 517 controls. 27 rare non-synonymous variants were identified in ASD and SCZ patients, including 25 missense, one in-frame deletion in SMRACA4, and one frame-shift variant in SMARCC2. Association analysis was conducted to investigate the burden of rare variants in BAF genes in ASD and SCZ patients. Significant enrichment of rare missense variants in BAF genes, but not synonymous variants, was found in ASD compared to controls. Rare pathogenic variants indicated by in silico tools were significantly enriched in ASD, but not statistically significant in SCZ. Pathogenic-predicted variants were located in disordered binding regions and may confer risk for ASD and SCZ by disrupting protein-protein interactions. Our study supports the involvement of rare missense variants of BAF genes in ASD and SCZ susceptibility.

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13. Ma Z, Eaton M, Liu Y, Zhang J, Chen X, Tu X, Shi Y, Que Z, Wettschurack K, Zhang Z, Shi R, Chen Y, Kimbrough A, Lanman NA, Schust L, Huang Z, Yang Y. Deficiency of autism-related Scn2a gene in mice disrupts sleep patterns and circadian rhythms. Neurobiol Dis;2022 (Jun 15);168:105690.

Autism spectrum disorder (ASD) affects ~2% of the population in the US, and monogenic forms of ASD often result in the most severe manifestation of the disorder. Recently, SCN2A has emerged as a leading gene associated with ASD, of which abnormal sleep pattern is a common comorbidity. SCN2A encodes the voltage-gated sodium channel Na(V)1.2. Predominantly expressed in the brain, Na(V)1.2 mediates the action potential firing of neurons. Clinical studies found that a large portion of children with SCN2A deficiency have sleep disorders, which severely impact the quality of life of affected individuals and their caregivers. The underlying mechanism of sleep disturbances related to Na(V)1.2 deficiency, however, is not known. Using a gene-trap Scn2a-deficient mouse model (Scn2a(trap)), we found that Scn2a deficiency results in increased wakefulness and reduced non-rapid-eye-movement (NREM) sleep. Brain region-specific Scn2a deficiency in the suprachiasmatic nucleus (SCN) containing region, which is involved in circadian rhythms, partially recapitulates the sleep disturbance phenotypes. At the cellular level, we found that Scn2a deficiency disrupted the firing pattern of spontaneously firing neurons in the SCN region. At the molecular level, RNA-sequencing analysis revealed differentially expressed genes in the circadian entrainment pathway including core clock genes Per1 and Per2. Performing a transcriptome-based compound discovery, we identified dexanabinol (HU-211), a putative glutamate receptor modulator, that can partially reverse the sleep disturbance in mice. Overall, our study reveals possible molecular and cellular mechanisms underlying Scn2a deficiency-related sleep disturbances, which may inform the development of potential pharmacogenetic interventions for the affected individuals.

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14. Meuffels SA, Kuijpers-Jagtman AM, Tjoa STH, Bonifacio CC, Carvajal Monroy PL. Malocclusion complexity and orthodontic treatment need in children with autism spectrum disorder. Clin Oral Investig;2022 (Jun 15)

OBJECTIVES: This study aimed to investigate the malocclusion complexity and orthodontic treatment need among children with and without autism spectrum disorder (ASD) referred for orthodontic treatment by quantifying the Discrepancy Index (DI) and Index of Orthodontic Treatment Need (IOTN). MATERIALS AND METHODS: Dental records of 48 ASD and 49 non-ASD consecutive patients aged between 9 and 18 years (median age 13.0 years) referred for orthodontic treatment were reviewed and compared. The Discrepancy Index (DI) was quantified to determine the malocclusion complexity, and the Index of Orthodontic Treatment Need (IOTN), including the Dental Health Component (IOTN-DHC) and Aesthetic Component (IOTN-AC), was quantified to determine the orthodontic treatment need. Statistical analysis included descriptive analysis, Pearson chi-square tests, Fisher’s exact test, Mann-Whitney U tests, and several univariate and multivariate regression analyses. The statistical analysis used descriptive analysis, Pearson chi-square test, Fisher’s exact test, and multivariate logistic regression. RESULTS: The results show that both malocclusion complexity (DI, p = 0.0010) and orthodontic treatment need (IOTN-DHC, p = 0.0025; IOTN-AC p = 0.0009) were significantly higher in children with ASD. Furthermore, children with ASD had a higher prevalence of increased overjet (p = .0016) and overbite (p = .031). CONCLUSIONS: Malocclusion complexity and orthodontic treatment need are statistically significantly higher among children with ASD than children without ASD, independent of age and sex. CLINICAL RELEVANCE: Children with autism may benefit from visits to a dental specialist (orthodontist) to prevent, to some extent, developing malocclusions from an early age.

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15. Mishra A, Prabha PK, Singla R, Kaur G, Sharma AR, Joshi R, Suroy B, Medhi B. Epigenetic Interface of Autism Spectrum Disorders (ASDs): Implications of Chromosome 15q11-q13 Segment. ACS Chem Neurosci;2022 (Jun 15);13(12):1684-1696.

Autism spectrum disorders (ASDs) are multifactorial in nature and include both genetic and environmental factors. The increasing evidence advocates an important role of epigenetics in ASD etiology. One of the most common forms of epigenetic changes observed in the case of neurodevelopmental disorders is imprinting which is tightly regulated by developmental and tissue-specific mechanisms. Interestingly, many of these disorders that demonstrate autism-like phenotypes at varying degrees have found involvement of chromosome 15q11-q13 segment. Numerous studies demonstrate occurrence of ASD in the presence of chromosomal abnormalities located mainly in Chr15q11-q13 region. Several plausible candidate genes associated with ASD are in this chromosomal segment, including gamma aminobutyric acid A (GABA(A)) receptor genes GABRB3, GABRA5 and GABRG3, UBE3A, ATP 10A, MKRN3, ZNF, MAGEL2, Necdin (NDN), and SNRPN. The main objective of this review is to highlight the contribution of epigenetic modulations in chromosome 15q11-q13 segment toward the genetic etiology and pathophysiology of ASD. The present review reports the abnormalities in epigenetic regulation on genes and genomic regions located on chromosome 15 in relation to either syndromic (15q11-q13 maternal duplication) or nonsyndromic forms of ASD. Furthermore, studies reviewed in this article demonstrate conditions in which epigenetic dysregulation has been found to be a pathological factor for ASD development, thereby supporting a role for epigenetics in the multifactorial etiologies of ASD. Also, on the basis of the evidence found so far, we strongly emphasize the need to develop future therapeutic strategies as well as screening procedures for ASD that target mechanisms involving genes located on the chromosomal 15q11-q13 segment.

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16. Pangrazzi L, Genovesi S, Balasco L, Cerilli E, Robol C, Zunino G, Piazza S, Provenzano G, Bozzi Y. Immune dysfunction in the cerebellum of mice lacking the autism candidate gene Engrailed 2. J Neuroimmunol;2022 (Jun 15);367:577870.

Immune system dysfunction has been described in autism spectrum disorder. Here we tested the hypothesis that cerebellar defects are accompanied by immune dysfunction in adult mice lacking the autism-candidate gene Engrailed 2 (En2). Gene ontology analyses revealed that biological processes related to immune function were over-represented in the cerebellar transcriptome of En2(-/-) mice. Pro-inflammatory molecules and chemokines were reduced in the En2(-/-) cerebellum compared to controls. Conversely, pro-inflammatory molecules were increased in the peripheral blood of mutant mice. Our results suggest a link between immune dysfunction and cerebellar defects detected in En2(-/-) mice.

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17. Park S, Zikopoulos B, Yazdanbakhsh A. Visual Illusion Susceptibility in Autism: A Neural Model. Eur J Neurosci;2022 (Jun 14)

While atypical sensory perception is reported among individuals with autism spectrum disorder (ASD), the underlying neural mechanisms of autism that give rise to disruptions in sensory perception remain unclear. We developed a neural model with key physiological, functional, and neuroanatomical parameters to investigate mechanisms underlying the range of representations of visual illusions related to orientation perception in typically developed (TD) subjects compared to individuals with ASD. Our results showed that two theorized autistic traits, excitation/inhibition imbalance and weakening of top-down modulation, could be potential candidates for reduced susceptibility to some visual illusions. Parametric correlation between cortical suppression, balance of excitation/inhibition, feedback from higher visual areas on one hand, and susceptibility to a class of visual illusions related to orientation perception on the other hand, provide the opportunity to investigate the contribution and complex interactions of distinct sensory processing mechanisms in ASD. The novel approach used in this study can be used to link behavioral, functional, and neuropathological studies, estimate and predict perceptual and cognitive heterogeneity in ASD, and form a basis for the development of novel diagnostics and therapeutics.

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18. Qiu S, Qiu Y, Li Y, Cong X. Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses. Transl Psychiatry;2022 (Jun 15);12(1):249.

Autism spectrum disorder (ASD) is a class of neurodevelopmental conditions with a large epidemiological and societal impact worldwide. To date, numerous studies have investigated the associations between genetic variants and ASD risk. To provide a robust synthesis of published evidence of candidate gene studies for ASD, we performed an umbrella review (UR) of meta-analyses of genetic studies for ASD (PROSPERO registration number: CRD42021221868). We systematically searched eight English and Chinese databases from inception to March 31, 2022. Reviewing of eligibility, data extraction, and quality assessment were performed by two authors. In total, 28 of 5062 retrieved articles were analyzed, which investigated a combined 41 single nucleotide polymorphisms (SNPs) of nine candidate genes. Overall, 12 significant SNPs of CNTNAP2, MTHFR, OXTR, SLC25A12, and VDR were identified, of which associations with suggestive evidence included the C677T polymorphism of MTHFR (under allelic, dominant, and heterozygote models) and the rs731236 polymorphism of VDR (under allelic and homozygote models). Associations with weak evidence included the rs2710102 polymorphism of CNTNAP2 (under allelic, homozygote, and recessive models), the rs7794745 polymorphism of CNTNAP2 (under dominant and heterozygote models), the C677T polymorphism of MTHFR (under homozygote model), and the rs731236 polymorphism of VDR (under dominant and recessive models). Our UR summarizes research evidence on the genetics of ASD and provides a broad and detailed overview of risk genes for ASD. The rs2710102 and rs7794745 polymorphisms of CNTNAP2, C677T polymorphism of MTHFR, and rs731236 polymorphism of VDR may confer ASD risks. This study will provide clinicians and healthcare decision-makers with evidence-based information about the most salient candidate genes relevant to ASD and recommendations for future treatment, prevention, and research.

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19. Rabelo LN, Queiroz JPG, Castro CCM, Silva SP, Campos LD, Silva LC, Nascimento EB, Martínez-Cerdeño V, Fiuza FP. Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism. J Autism Dev Disord;2022 (Jun 15)

Autism spectrum disorder (ASD) is manifested by abnormal cell numbers and patches of gene expression disruption in higher-order brain regions. Here, we investigated whether layer-specific changes in glia/neuron ratios (GNR) characterize patches in the dorsolateral prefrontal cortex (DL-PFC) of children with ASD. We analyzed high-resolution digital images of postmortem human brains from 11 ASD and 11 non-ASD children obtained from the Autism Study of the Allen Human Brain Atlas. We found the GNR is overall reduced in the ASD DL-PFC. Moreover, layers II-III belonging to patches presented a lower GNR in comparison with layers V-VI. We here provide a new insight into how brain cells are arranged within patches that contributes to elucidate how neurodevelopmental programs are altered in ASD.

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20. Rhinn M, Zapata-Bodalo I, Klein A, Plassat JL, Knauer-Meyer T, Keyes WM. Aberrant induction of p19Arf-mediated cellular senescence contributes to neurodevelopmental defects. PLoS Biol;2022 (Jun);20(6):e3001664.

Valproic acid (VPA) is a widely prescribed drug to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, however, exposure to the developing embryo can cause birth defects, cognitive impairment, and autism spectrum disorder. How VPA causes these developmental defects remains unknown. We used embryonic mice and human organoids to model key features of VPA drug exposure, including exencephaly, microcephaly, and spinal defects. In the malformed tissues, in which neurogenesis is defective, we find pronounced induction of cellular senescence in the neuroepithelial (NE) cells. Critically, through genetic and functional studies, we identified p19Arf as the instrumental mediator of senescence and microcephaly, but, surprisingly, not exencephaly and spinal defects. Together, these findings demonstrate that misregulated senescence in NE cells can contribute to developmental defects.

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21. Sari NP, Jansen PW, Blanken LME, Ruigrok ANV, Prinzie P, Tiemeier H, Baron-Cohen S, van IMH, White T. Maternal age, autistic-like traits and mentalizing as predictors of child autistic-like traits in a population-based cohort. Mol Autism;2022 (Jun 15);13(1):26.

BACKGROUND: Many empirical studies suggest that higher maternal age increases the likelihood of having an autistic child. However, little is known about factors that may explain this relationship or if higher maternal age is related to the number of autistic-like traits in offspring. One possibility is that mothers who have a higher number of autistic-like traits, including greater challenges performing mentalizing skills, are delayed in finding a partner. The goal of our study is to assess the relationship between maternal age, mentalizing skills and autistic-like traits as independent predictors of the number of autistic-like traits in offspring. METHODS: In a population-based study in the Netherlands, information on maternal age was collected during pre- and perinatal enrolment. Maternal mentalizing skills and autistic-like traits were assessed using the Reading the Mind in the Eyes Test and the Autism Spectrum Quotient, respectively. Autistic-like traits in children were assessed with the Social Responsiveness Scale. A total of 5718 mother/child dyads had complete data (M(agechild) = 13.5 years; 50.2% girls). RESULTS: The relationship between maternal age and autistic-like traits in offspring best fits a U-shaped curve. Furthermore, higher levels of autistic features in mothers are linked to higher levels of autistic-like traits in their children. Lower mentalizing performance in mothers is linked to higher levels of autistic-like traits in their children. LIMITATIONS: We were able to collect data on both autistic-like traits and the mentalizing skills test in a large population of mothers, but we did not collect these data in a large number of the fathers. CONCLUSIONS: The relationships between older and younger mothers may have comparable underlying mechanisms, but it is also possible that the tails of the U-shaped curve are influenced by disparate mechanisms.

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22. Schröder SS, Danner UN, Spek AA, van Elburg AA. Problematic eating behaviours of autistic women-A scoping review. Eur Eat Disord Rev;2022 (Jun 14)

AIM: Eating and feeding behaviours of autistic individuals and related consequences have been mainly investigated in autistic children or in autistic adults with intellectual disabilities. Behaviours such as food selectivity or food neophobia have been shown to persist into adolescence and adulthood and are associated with aversive consequences. However, much less is known about the eating behaviours of autistic adults without intellectual disabilities, especially those of women. By means of a scoping review, we aim to assess the extent of the scientific literature on what is known about the eating behaviours of these women and the possible consequences of such eating behaviour. METHOD: Medline, Cochrane, PubMed and PsycInfo databases were searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Five studies met the eligibility criteria and were included in this review. Autistic women not only reported high levels of eating behaviour frequently seen in autism spectrum disorders (ASD), but also high levels of disordered eating behaviour, similar to that of women with eating disorders. CONCLUSIONS: Autistic women seem to exhibit high levels of eating behaviour frequently seen in ASD as well as disordered eating behaviour. Future research needs to shed light on what underlies these problematic eating behaviours, in order to help to adapt current treatment modalities to meet the unique needs of these women.

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