1. Ding Y, Zhang T, Cao W, Zhang L, Xu X. A multi-frequency approach of the altered functional connectome for autism spectrum disorder identification. Cereb Cortex;2024 (Aug 1);34(8)

Autism spectrum disorder stands as a multifaceted and heterogeneous neurodevelopmental condition. The utilization of functional magnetic resonance imaging to construct functional brain networks proves instrumental in comprehending the intricate interplay between brain activity and autism spectrum disorder, thereby elucidating the underlying pathogenesis at the cerebral level. Traditional functional brain networks, however, typically confine their examination to connectivity effects within a specific frequency band, disregarding potential connections among brain areas that span different frequency bands. To harness the full potential of interregional connections across diverse frequency bands within the brain, our study endeavors to develop a novel multi-frequency analysis method for constructing a comprehensive functional brain networks that incorporates multiple frequencies. Specifically, our approach involves the initial decomposition of functional magnetic resonance imaging into distinct frequency bands through wavelet transform. Subsequently, Pearson correlation is employed to generate corresponding functional brain networks and kernel for each frequency band. Finally, the classification was performed by a multi-kernel support vector machine, to preserve the connectivity effects within each band and the connectivity patterns shared among the different bands. Our proposed multi-frequency functional brain networks method yielded notable results, achieving an accuracy of 89.1%, a sensitivity of 86.67%, and an area under the curve of 0.942 in a publicly available autism spectrum disorder dataset.

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2. Jakobsen KD, Callesen K, Larsen EB, Pedersen OBV, Didriksen M, Ostrowski SR, Christensen KB. Validity of the Systemizer Profile Questionnaire: A New Tool to Identify Cognitive, Mentalizing, Sensory, Social, and Systemizing Abilities in Adults with Autism-Spectrum-Disorders With and Without Comorbid ADHD. J Autism Dev Disord;2024 (Aug 17)

PURPOSE: Systemizer Profile Questionnaire (SPQ), which has not been used before, investigates difficulties in mentalisation, sensory- and/or social sensitivity and social cognition (MSSSC) in subjects with Autism-Spectrum-Disorders (ASD) with and without Attention-Deficit-Hyperactivity-Disorder (ADHD). The aim of this study was to evaluate the reliability and validity of the SPQ domains, and to assess the predictive validity of the SPQ against the Ritvo Autism Asperger Diagnostic Scale (RAADS). METHODS: Three-hundred-fifty-four study subjects with ICD-10 verified ASD confirmed by RAADS and 354 controls matched on age group and gender were recruited and evaluated systematically with SPQ, standardized questions about demographic and clinical data. Hypothesized SPQ subscales formed from 85 items were evaluated using confirmatory factor analysis (CFA). Resulting revised sub-scales were confirmed using item response theory (IRT) and the predictive validity of the SPQ scores was evaluated using RAADS scores above 64 as the standard. RESULTS: Twenty-two of the original 85 items were removed, resulting in an instrument with 63 items across nine psychometrically valid domains. These domains had high sensitivity (range: 0.64 to 0.84), and high specificity (range: 0.73 to 0.90). Positive predictive values (range: 0.76 to 0.89) and negative predictive values (range: 0.69 to 0.90) were also high. For the total SPQ score the sensitivity was 0.95, the specificity was 0.87, the positive predictive value was 0.88 and the negative predictive value was 0.95. CONCLUSION: SPQ domains are valid descriptions/profiles of MSSSC given that ASD is confirmed by RAADS, though irrelevant if not, as SPQ is not a diagnostic instrument.

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3. Megagiannis P, Mei Y, Yan RE, Yuan L, Wilde JJ, Eckersberg H, Suresh R, Tan X, Chen H, Farmer WT, Cha K, Le PU, Catoire H, Rochefort D, Kwan T, Yee BA, Dion P, Krishnaswamy A, Cloutier JF, Stifani S, Petrecca K, Yeo GW, Murai KK, Feng G, Rouleau GA, Ideker T, Sanjana NE, Zhou Y. Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes. Cell Rep;2024 (Aug 27);43(8):114637.

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an adeno-associated virus (AAV)-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting chromatin remodelers in reactive gliosis and neuroinflammation in injury and neurological diseases.

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4. Ni HC, Chen YL, Lin HY. Feasibility and Tolerability of Daily Theta Burst Stimulation in Autistic Youth with Intellectual Disabilities and Minimally Speaking Status: A Pilot Double-Blind Randomized Sham-Controlled Trial. J Autism Dev Disord;2024 (Aug 17)

Scarce clinical trials involving autistic people with intellectual disability (ID) and minimally speaking (MS) status have been a substantial unmet research need in the field. Although earlier studies have demonstrated the feasibility and beneficial potentials of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in intellectually able autistic people, the feasibility and tolerability of applying rTMS in autistic people with ID/MS has never been studied. We conducted the world-first 4-week randomized, double-blind, sham-controlled pilot trial to investigate the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS) over the left DLPFC in autistic youth with ID/MS. 25 autistic youth with ID/MS (aged 8-30 years) were randomized to a 20-session 4-week daily iTBS (n = 13) vs. sham stimulation (n = 12) with follow-up 4 and 8 weeks, respectively, after the last stimulation. A retention rate was 100% in our study. Adverse events of local pain (38%) and dizziness (8%) were only noted in the active group. All adverse events were mild and transient. There were no seizures, new behavioral problems, or other severe/serious adverse events noted. No participants dropped out due to adverse events. With a small sample size, we did not find any beneficial signal of DLPFC iTBS. Our pilot data suggest regular daily TBS treatment for four weeks is feasible, well tolerated and safe in autistic youth with ID/MS. Future randomized controlled trials with sufficiently powered samples are needed to investigate the beneficial potential of rTMS/TBS for autistic people with ID/MS.

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5. Okkenhaug I, Jensen MR, Solhaug S. Barriers and Facilitators for Physical Activity Among Children and Youth With Autism-A Scoping Review. J Phys Act Health;2024 (Aug 16):1-15.

BACKGROUND: The purpose of this scoping review was to systematically synthesize barriers and facilitators for physical activity (PA) among children and youth with autism spectrum disorders (ASD) across the socioecological model. METHODS: Five electronic databases were searched in March 2022 for studies examining barriers and facilitators for PA among children and youth with ASD. An updated search was performed in April 2024. The framework synthesis method was utilized, and the socioecological model was the chosen framework. RESULTS: Fifty-four studies published from 2008 to 2024 were included. Among the included studies, 57% included the perspectives of children and youth with ASD alone or together with proxies (eg, parents, teachers, and coaches), while 43% included only the perspectives of proxies. Barriers and facilitators on the intrapersonal and interpersonal levels were most substantial. The analysis led to 2 main categories of barriers and facilitators, those unique to children and youth with ASD, and those similar to what had been identified through research on children and youth, both typically developing and with other disabilities. CONCLUSIONS: This comprehensive scoping review shows the complexity of factors contributing to barriers and facilitators for PA among children and youth with ASD, and highlights both the factors unique to this population and more general factors affecting PA participation. The findings from this synthesis might be used to guide the development of inclusive PA in physical education, organized sports, and other community PA arenas.

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6. Schlink A, Kasari C. Characterizing social communication among minimally verbal children with autism: An application of item response theory. Autism Res;2024 (Aug 16)

Minimally verbal children constitute a portion of the autism spectrum. The paucity of proper measurement tools that sensitively and accurately assess behaviors has been one limiting factor in the improved knowledge of these children. Short of creating and validating a new measurement tool for this subpopulation, this study took an alternative and more immediate approach: conduct a secondary data analysis and examine an existing social communication measure, the Early Social Communication Scales (ESCS), with item response theory. The final sample consisted of 453 minimally verbal children culled from four different completed studies. The IRT models analyzed the frequency of social communication gestures from the ESCS and returned an objective difficulty hierarchy regarding initiations of joint attention and behavior regulation gestures. The best-fitting and final model was a zero-inflated negative binomial model (ZINBM), which determined that joint attention gestures were, on average, more difficult than behavior regulation gestures. Joint attentional shows and gives were essentially absent in the children’s repertoire, and behavior regulation reaches were the easiest gestures for this sample. The ZINBM separately modeled children with some gestures and children who did not present with any gestures and determined that behavior regulation reaches and gives were likely the first gestures a child will eventually exhibit among children with no gestures. Methodological contributions and potential future applications of IRT are discussed.

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7. Skvortsova L, Perfilyeva A, Bespalova K, Kuzovleva Y, Kabysheva N, Khamdiyeva O. 7p22.3 microdeletion: a case study of a patient with congenital heart defect, neurodevelopmental delay and epilepsy. Orphanet J Rare Dis;2024 (Aug 16);19(1):301.

BACKGROUND: Chromosome 7 has regions enriched with low copy repeats (LCRs), which increase the likelihood of chromosomal microdeletion disorders. Documented microdeletion disorders on chromosome 7 include both well-known Williams syndrome and more rare cases. It is noteworthy that most cases of various microdeletions are characterized by phenotypic signs of neuropsychological developmental disorders, which, however, have a different genetic origin. The localization of the microdeletions, the genes included in the region, as well as the structural features of the sequences of these genes have a cumulative influence on the phenotypic characteristics of the individuals for each specific case and the severity of the manifestations of disorders. The consideration of these features and their detailed analysis is important for a correct and comprehensive assessment of the disease. RESULTS: The article describes a clinical case of 7p22.3 microdeletion in a patient with congenital heart defect and neurological abnormalities – epilepsy, combined with moderate mental and motor developmental delay. CONCLUSIONS: Through detailed genetic analyses, we are improving the clinical description of the rare 7p22.3 microdeletion and thus creating a basis for future genetic counseling and research into targeted therapies.

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8. Tang K, Hill E, Pellicano E, Thompson C, Myers B. Barriers to and enablers of the transition from child and adolescent to adult mental health services for autistic young people and/or those with attention deficit hyperactivity disorder: protocol for a scoping review. BMJ Open;2024 (Aug 17);14(8):e083373.

INTRODUCTION: Autistic young people and/or those with attention deficit hyperactivity disorder (ADHD) who have co-occurring mental health conditions experience significant challenges when transitioning from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS). However, barriers and facilitators to this service transition are poorly understood for this population. This scoping review aims to synthesise the available evidence on barriers and enablers to the transition from CAMHS to AMHS for autistic young people and/or those with ADHD. METHODS AND ANALYSIS: Arksey and O’Malley’s six-step framework for scoping reviews will be used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will guide the reporting of this review. Electronic databases of Medline, PsycINFO, CINAHL, Scopus, ProQuest Central and Google Scholar will be searched for relevant articles published in English with no date limitations. Title, abstract and full-text screening will be completed by two independent reviewers. Studies will be eligible for inclusion if the article focuses on (1) adolescents and/or young people (aged 18-24) with a primary diagnosis of autism spectrum disorder and/or ADHD (population) and (2) describes factors associated with service or care transitions (concept) (3) from CAMHS to AMHS (context). Study quality will be evaluated using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields. Data describing the factors that enable or inhibit the transition from CAMHS to AMHS will be extracted and synthesised using the Bronfenbrenner’s social ecological model as a framework for organising and reporting results. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be disseminated via peer-reviewed publications and presented at conferences. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/BZPQF.

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9. Turkstani H, Alfaifi A, Ramachandran M, Bushra A, Stoopler E, France K. Severe manifestation of plasma cell mucositis in a patient with autism spectrum disorder: A unique overlap illustrating challenges with diagnosis and management. Spec Care Dentist;2024 (Aug 16)

Plasma cell mucositis (PCM) is a rare inflammatory condition affecting the oral tissues, often triggered by allergens or inflammation. Autism spectrum disorder (ASD), a neurodevelopmental condition, poses unique challenges in oral care and hygiene due to behavioral and sensory issues. These conditions have not previously been reported in concert but may share risk factors including through the development of inflammation. We present a case of severe PCM in a 23-year-old male with ASD, illustrating diagnostic complexities and management strategies. The patient presented with widespread and severe lesions, raising the possibility of underlying causes. After multiple interventions, including topical steroids and trigger avoidance, the patient achieved near-complete resolution of the oral lesions. Immunohistochemical and serological investigations suggested an underlying monoclonal gammopathy, warranting hematological evaluation. Our case shows how PCM and ASD can affect each other, highlighting the importance of understanding how these conditions interact, and the need for tailored approaches to oral health in this population. Further research is needed to elucidate any pathophysiological or risk-based link between ASD and inflammatory oral conditions and to refine management strategies for PCM in patients with neurodevelopmental disorders.

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10. Vickers ML, Menhinnitt RS, Choi YK, Malacova E, Eriksson L, Churchill AW, Oddy B, Boon K, Randall C, Braun A, Taggart J, Marsh R, Pun P. Comorbidity rates of autism spectrum disorder and functional neurological disorders: A systematic review, meta-analysis of proportions and qualitative synthesis. Autism;2024 (Aug 16):13623613241272958.

Autism spectrum disorder (ASD) and functional neurological disorders (FND) are relatively common conditions, and there has been recent interest in the overlap between them. Both conditions share core features of alexithymia, impaired interoception and deficits in attentional focus. To date, relatively little is known about the comorbidity rates between ASD and FND. This is the first meta-analysis and qualitative synthesis on the subject. We found that around 10% of children presenting with functional seizures have a comorbid ASD diagnosis. People with ASD are more likely than the neurotypical population to have functional somatic disorders, and there is also evidence that ASD rates are higher for other FNDs such as functional motor disorders. Since FND comes with risks of unnecessary medical procedures and investigations, it is important to recognize the potential for people with ASD to have an FND comorbidity.

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11. Washington AM, Mercer AH, Burrows CA, Dager SR, Elison JT, Estes AM, Grzadzinski R, Lee C, Piven J, Pruett JR, Jr., Shen MD, Wilfond B, Wolff J, Zwaigenbaum L, MacDuffie KE. Parent attitudes towards predictive testing for autism in the first year of life. J Neurodev Disord;2024 (Aug 17);16(1):47.

BACKGROUND: Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy. METHODS: Parents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods. RESULTS: Almost all parents in both groups were interested in predictive testing for autism, with some stating they would seek testing only if concerned about their infant’s development. The primary anticipated advantage of testing was to enable access to earlier intervention. Parents also described the anticipated emotions they would feel in response to test results, actions they might take upon learning their infant was likely to develop autism, attitudes towards predicting a child’s future support needs, and the potential impacts of inaccurate prediction. CONCLUSION: In qualitative interviews, parents of infants with and without prior autism experience shared their anticipated motivations and concerns about predictive testing for autism in the first year of life. The primary reported motivators for testing-to have more time to prepare and intervene early-could be constrained by familial resources and service availability. Implications for ethical communication of results, equitable early intervention, and future research are discussed.

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12. Yilmaz Sukranli Z, Korkmaz Bayram K, Taheri S, Cuzin F, Ozkul Y, Rassoulzadegan M. Experimentally altering microRNA levels in embryos alters adult phenotypes. Sci Rep;2024 (Aug 16);14(1):19014.

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, a low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally in mice with two of them, miR19a-3p and miR499a-5p by microinjecting into zygote pronuclei either the complementary sequence or an excess of the microRNA. Both resulted in low levels in the tissues and sperm of the targeted microRNAs and their pri and pre precursors. This method stably modify predetermined levels of miRNAs and identify miRNA alterations that cause changes in autistic behavior and predispose the individual to an inherited disease. Excess miRNA results in single-stranded miRNA variations in both free and DNA-bound RNA (R-loop) fractions in mouse models thus appearing to affect their own transcription. Analysis of miRNAs fractions in human patients blood samples confirm low level of six microRNAs also in R-loop fractions.

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