1. Arutiunian V, Gomozova M, Minnigulova A, Davydova E, Pereverzeva D, Sorokin A, Tyushkevich S, Mamokhina U, Danilina K, Dragoy O. Structural brain abnormalities and their association with language impairment in school-aged children with Autism Spectrum Disorder. Scientific reports. 2023; 13(1): 1172.

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD) but its neural basis is poorly understood. Using structural magnetic resonance imaging (MRI), the present study provides the whole-brain comparison of both volume- and surface-based characteristics between groups of children with and without ASD and investigates the relationships between these characteristics in language-related areas and the language abilities of children with ASD measured with standardized tools. A total of 36 school-aged children participated in the study: 18 children with ASD and 18 age- and sex-matched typically developing controls. The results revealed that multiple regions differed between groups of children in gray matter volume, gray matter thickness, gyrification, and cortical complexity (fractal dimension). White matter volume and sulcus depth did not differ between groups of children in any region. Importantly, gray matter thickness and gyrification of language-related areas were related to language functioning in children with ASD. Thus, the results of the present study shed some light on the structural brain abnormalities associated with language impairment in ASD.

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2. Bilgiç A, Ferahkaya H, Karagöz H, Kılınç İ, Energin VM. Serum claudin-5, claudin-11, occludin, vinculin, paxillin, and beta-catenin levels in preschool children with autism spectrum disorder. Nordic journal of psychiatry. 2023: 1-6.

AIM: Increased intestinal and blood-brain barriers (BBB) permeability has been suggested to have a role in autism spectrum disorder (ASD). Claudin-5, claudin-11, occludin, β-catenin, vinculin, and paxillin are crucial components of these barriers. This study assessed concentrations of these molecules in preschool children with ASD. METHODS: A total of 80 children with ASD and 40 controls aged 18-60 months were enrolled in this study. Serum levels of biochemical variables were determined using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum claudin-11, occludin, and β-catenin levels were significantly higher in the ASD group than in the control group. However, no significant difference for serum claudin-5, vinculin, and paxillin levels was detected between the groups. CONCLUSION: These findings suggest that claudin-11, occludin, and β-catenin may be involved in the pathogenesis of ASD. These proteins may affect the brain by causing dysregulation in intestinal or blood-brain barrier permeability or with other unknown mechanisms.

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3. Cong J, Zhuang W, Liu Y, Yin S, Jia H, Yi C, Chen K, Xue K, Li F, Yao D, Xu P, Zhang T. Altered default mode network causal connectivity patterns in autism spectrum disorder revealed by Liang information flow analysis. Human brain mapping. 2023.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with severe cognitive impairment in social communication and interaction. Previous studies have reported that abnormal functional connectivity patterns within the default mode network (DMN) were associated with social dysfunction in ASD. However, how the altered causal connectivity pattern within the DMN affects the social functioning in ASD remains largely unclear. Here, we introduced the Liang information flow method, widely applied to climate science and quantum mechanics, to uncover the brain causal network patterns in ASD. Compared with the healthy controls (HC), we observed that the interactions among the dorsal medial prefrontal cortex (dMPFC), ventral medial prefrontal cortex (vMPFC), hippocampal formation, and temporo-parietal junction showed more inter-regional causal connectivity differences in ASD. For the topological property analysis, we also found the clustering coefficient of DMN and the In-Out degree of anterior medial prefrontal cortex were significantly decreased in ASD. Furthermore, we found that the causal connectivity from dMPFC to vMPFC was correlated with the clinical symptoms of ASD. These altered causal connectivity patterns indicated that the DMN inter-regions information processing was perturbed in ASD. In particular, we found that the dMPFC acts as a causal source in the DMN in HC, whereas it plays a causal target in ASD. Overall, our findings indicated that the Liang information flow method could serve as an important way to explore the DMN causal connectivity patterns, and it also can provide novel insights into the nueromechanisms underlying DMN dysfunction in ASD.

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4. Ishiura H, Tsuji S, Toda T. Recent advances in CGG repeat diseases and a proposal of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculophryngodistal myopathy (FNOP) spectrum disorder. Journal of human genetics. 2023.

While whole genome sequencing and long-read sequencing have become widely available, more and more focuses are on noncoding expanded repeats. Indeed, more than half of noncoding repeat expansions related to diseases have been identified in the five years. An exciting aspect of the progress in this field is an identification of a phenomenon called repeat motif-phenotype correlation. Repeat motif-phenotype correlation in noncoding repeat expansion diseases is first found in benign adult familial myoclonus epilepsy. The concept is extended in the research of CGG repeat expansion diseases. In this review, we focus on newly identified CGG repeat expansion diseases, update the concept of repeat motif-phenotype correlation in CGG repeat expansion diseases, and propose a clinical concept of FNOP (fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculopharyngodistal myopathy)-spectrum disorder, which shares clinical features and thus probably share some common disease pathophysiology, to further facilitate discussion and progress in this field.

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5. Laverty C, Agar G, Sinclair-Burton L, Oliver C, Moss J, Nelson L, Richards C. The 10-year trajectory of aggressive behaviours in autistic individuals. Journal of intellectual disability research : JIDR. 2023.

BACKGROUND: Aggressive behaviours are common in people with neurodevelopmental conditions, contributing to poorer quality of life and placement breakdown. However, there is limited empirical research documenting the prevalence and persistence of aggressive behaviours in autism. In this longitudinal study, aggressive behaviours were investigated in a sample of autistic individuals over 10 years. METHODS: Caregivers of autistic individuals, both with and without intellectual disability, completed questionnaires relating to the presence of aggressive behaviours at T1 [N = 229, mean age in years 11.8, standard deviation (SD) 5.9], T2 (T1 + 3 years, N = 81, mean age in years 15.1, SD 5.9) and T3 (T1 + 10 years, N = 54, mean age in years 24.5, SD 8.1). Analyses examined the presence and persistence of aggressive behaviours and the predictive value of established correlates of aggression. RESULTS: Aggressive behaviours were common at baseline (61.6%) but only persistent in 30% of the sample over 10 years. Higher composite scores of overactivity and impulsivity at T1 were significantly associated with the persistence of aggressive behaviours at T2 (P = 0.027) and T3 (P = 0.012) with medium effect size. CONCLUSIONS: Aggressive behaviours are common in autism, but reduce with age. Behavioural correlates of attention deficit hyperactivity disorder (ADHD) predict the presence and persistence of aggressive behaviour and as such may be useful clinical indicators to direct proactive intervention resources to ameliorate aggressive behaviours.

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6. Octavia A, Sitthisettapong T, Dewanto I. Structural-visual approach for dental examination in children with autism spectrum disorder: A systematic review. Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2023.

INTRODUCTION: Conducting Dental examination in children with autism is challenging due to the limitation in cooperativeness that is caused by impairment of communication, social interaction, and sensory sensitivities. AIMS: This study aims to provide evidence base for the structural-visual approach in reducing uncooperativeness behavior to dental care in children with autism spectrum disorder (ASD). METHODS: Searches were conducted in the electronic databases PubMed, PsycINFO, and Cochrane from inception to October 2021 (CRD42022383409). Randomized controlled trials (RCTs), non-RCTs, and pre/post-test and qualitative studies that conducting visual pedagogy and visual learning methods were included. The quality of evidence was assessed with Cochrane Collaboration’s Risk of Bias Tool for RCTs, Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) for non-RCTs, and Critical Appraisal Skill Program (CASP) for qualitative studies. RESULTS: The initial search identified 270 studies, and 256 remained after removing duplicates. After screening titles and abstracts, 62 studies were remained for full-text assessed, and finally 13 eligible studies were selected for reviews. The studies analyzed various structural-visual interventions, participants, study design, countries, and outcomes. CONCLUSION: The structural-visual approach could reduce uncooperative behavior in children with ASD. Future study should investigate the wide range of age and varied behavior approach as the evidence-based of the clinical management.

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7. Sgritta M, Vignoli B, Pimpinella D, Griguoli M, Santi S, Bialowas A, Wiera G, Zacchi P, Malerba F, Marchetti C, Canossa M, Cherubini E. Impaired synaptic plasticity in an animal model of autism exhibiting early hippocampal GABAergic-BDNF/TrkB signaling alterations. iScience. 2023; 26(1): 105728.

In Neurodevelopmental Disorders, alterations of synaptic plasticity may trigger structural changes in neuronal circuits involved in cognitive functions. This hypothesis was tested in mice carrying the human R451C mutation of Nlgn3 gene (NLG3(R451C) KI), found in some families with autistic children. To this aim, the spike time dependent plasticity (STDP) protocol was applied to immature GABAergic Mossy Fibers (MF)-CA3 connections in hippocampal slices from NLG3(R451C) KI mice. These animals failed to exhibit STD-LTP, an effect that persisted in adulthood when these synapses became glutamatergic. Similar results were obtained in mice lacking the Nlgn3 gene (NLG3 KO mice), suggesting a loss of function. The loss of STD-LTP was associated with a premature shift of GABA from the depolarizing to the hyperpolarizing direction, a reduced BDNF availability and TrkB phosphorylation at potentiated synapses. These effects may constitute a general mechanism underlying cognitive deficits in those forms of Autism caused by synaptic dysfunctions.

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8. Shiani A, Sharafi K, Omer AK, Kiani A, Karamimatin B, Massahi T, Ebrahimzadeh G. A systematic literature review on the association between exposures to toxic elements and an autism spectrum disorder. The Science of the total environment. 2023; 857(Pt 2): 159246.

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by difficulties in social communication and repetitive behaviors. There have been many previous studies of toxic metals in ASD. Therefore, the priority of this study is to review the relationships between exposure to toxic metals and ASD. MATERIALS & METHODS: This study was based on a comprehensive search of international databases, such as Web of Science, Science Direct, Scopus, PubMed, and Google Scholar, for all works related to the subject under discussion from 1982 to 2022. We further summarize published data linked to this topic and discuss with clarifying evidence that agrees and conflicts with the association between exposure to toxic metals, including mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) and ASD. RESULTS: 40 out of 63 papers met the requirements for meta-analysis. Blood Pb levels (standardized mean difference (SMD) = 0.81; 95 % confidence interval (CI): 0.36-1.25), blood Hg (SMD = 0.90; CI: 0.30-1.49), hair Pb (SMD = 1.47; CI: 0.03-2.92), urine As (SMD = 0.65; CI: 0.22-1.09), and urine Al levels (SMD = 0.85; CI: 0.40-1.29) in autistic individuals were significantly higher than those of healthy control (HC). Whereas, blood As levels (SMD = 1.33; CI: -1.32-3.97), hair As (SMD = 0.55; CI: -0.14-1.24), hair Cd (SMD = 0.60; CI: -0.31-1.51), hair Hg (SMD = 0.41; CI: -0.30-1.12), hair Al (SMD = 0.87; CI: -0.02-1.77), urine Pb (SMD = -0.68; CI: -2.55-1.20), urine Cd (SMD = -0.26; CI: -0.94-0.41), and urine Hg levels (SMD = 0.47; CI: -0.09-1.04) in autistic individuals were significantly lower than those of HC. CONCLUSION: Toxic metal content significantly differed between individuals with ASD and HC in the current meta-analysis. The results assist in clarifying the significance of toxic metals as environmental factors in the development of ASD.

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9. Thabault M, Turpin V, Balado É, Fernandes-Gomes C, Huot AL, Cantereau A, Fernagut PO, Jaber M, Galvan L. Age-related behavioral and striatal dysfunctions in Shank3(ΔC/ΔC) mouse model of autism spectrum disorder. The European journal of neuroscience. 2023.

Autism spectrum disorders (ASD) are defined as a set of neurodevelopmental disorders and a lifelong condition. In mice, most of the studies focused on the developmental aspects of these diseases. In this paper, we examined the evolution of motor stereotypies through adulthood in the Shank3ΔC/ΔC mouse model of ASD, and their underlying striatal alterations, at 10 weeks, 20 weeks, and 40 weeks. We highlighted that motor stereotypies worsened at 40 weeks possibly carried by earlier striatal medium spiny neurons (MSN) alterations in GABAergic transmission and morphology. Moreover, we report that 20 weeks could be a critical time-point in the striatal-related ASD physiopathology, and we suggest that MSN alterations may not be the direct consequence of developmental issues, but rather be a consequence of other impairments occurring earlier.

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10. Turowetz J, Wiscons LZ, Maynard DW. Disorder or difference? How clinician-patient interaction and patient age shape the process and meaning of autism diagnosis. Sociology of health & illness. 2023.

This article follows Blaxter’s foundational call for a sociology of diagnosis that addresses the dual aspects of diagnosis-as-category and diagnosis-as-process. Drawing on video recordings from an autism clinic, we show how the process of attaching the diagnosis to a child involves interactions between clinicians, parents and children, and that in the course of such interactions, a diagnostic category officially defined in terms of deficits can instead be formulated in terms of valuable social and cognitive differences. More specifically, we show that the child’s age is crucial for how clinicians formulate the diagnosis: with younger children, clinicians treat autism exclusively as a deficit to be remedied, whereas with older children, clinicians may treat autism either as a deficit or as a social-cognitive difference. Further, because older children are often co-recipients of diagnostic news, we find that clinicians carefully manage the implications such news may have for their self/identity. Finally, we suggest that (1) the equation of a diagnostic category with dysfunction is achieved in interaction; (2) the meaning of a diagnosis may vary with characteristics of its recipients; and (3) that meaning can be worked up by clinicians and recipients in ways that centre difference rather than deficit.

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11. Yang Y, Booker SA, Clegg JM, Quintana-Urzainqui I, Sumera A, Kozic Z, Dando O, Martin Lorenzo S, Herault Y, Kind PC, Price DJ, Pratt T. Identifying foetal forebrain interneurons as a target for monogenic autism risk factors and the polygenic 16p11.2 microdeletion. BMC neuroscience. 2023; 24(1): 5.

BACKGROUND: Autism spectrum condition or ‘autism’ is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. The balance between excitatory and inhibitory neurons in the cerebral cortex is hypothesised to be critical for the aetiology of autism making improved understanding of how risk factors impact on the development of these cells an important area of research. In the current study we aim to combine bioinformatics analysis of human foetal cerebral cortex gene expression data with anatomical and electrophysiological analysis of a 16p11.2(+/-) rat model to investigate how genetic risk factors impact on inhibitory neuron development. METHODS: We performed bioinformatics analysis of single cell transcriptomes from gestational week (GW) 8-26 human foetal prefrontal cortex and anatomical and electrophysiological analysis of 16p11.2(+/-) rat cerebral cortex and hippocampus at post-natal day (P) 21. RESULTS: We identified a subset of human interneurons (INs) first appearing at GW23 with enriched expression of a large fraction of risk factor transcripts including those expressed from the 16p11.2 locus. This suggests the hypothesis that these foetal INs are vulnerable to mutations causing autism. We investigated this in a rat model of the 16p11.2 microdeletion. We found no change in the numbers or position of either excitatory or inhibitory neurons in the somatosensory cortex or CA1 of 16p11.2(+/-) rats but found that CA1 Sst INs were hyperexcitable with an enlarged axon initial segment, which was not the case for CA1 pyramidal cells. LIMITATIONS: The human foetal gene expression data was acquired from cerebral cortex between gestational week (GW) 8 to 26. We cannot draw inferences about potential vulnerabilities to genetic autism risk factors for cells not present in the developing cerebral cortex at these stages. The analysis 16p11.2(+/-) rat phenotypes reported in the current study was restricted to 3-week old (P21) animals around the time of weaning and to a single interneuron cell-type while in human 16p11.2 microdeletion carriers symptoms likely involve multiple cell types and manifest in the first few years of life and on into adulthood. CONCLUSIONS: We have identified developing interneurons in human foetal cerebral cortex as potentially vulnerable to monogenic autism risk factors and the 16p11.2 microdeletion and report interneuron phenotypes in post-natal 16p11.2(+/-) rats.

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12. Zhu HM, Yuan CH, Liu ZS. [Recent research on neurodevelopmental disorders in children]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2023; 25(1): 91-7.

Neurodevelopmental disorders (NDDs) in children are a group of chronic developmental brain disorders caused by multiple genetic or acquired causes, including disorders of intellectual development, developmental speech or language disorders, autism spectrum disorders, developmental learning disorders, attention deficit hyperactivity disorder, tic disorders, and other neurodevelopmental disorders. With the improvement in the research level and the diagnosis and treatment techniques of NDDs, great progress has been made in the research on NDDs in children. This article reviews the research advances in NDDs, in order to further improve the breadth and depth of the understanding of NDDs in children among pediatricians.

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