1. Davis J. Individuals with autism are at a higher associated risk of developing cardiometabolic diseases. Evid Based Nurs;2023 (Dec 26)

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2. Gibson JM, Vazquez AH, Yamashiro K, Jakkamsetti V, Ren C, Lei K, Dentel B, Pascual JM, Tsai PT. Cerebellar contribution to autism-relevant behaviors in fragile X syndrome models. Cell Rep;2023 (Dec 26);42(12):113533.

Cerebellar dysfunction has been linked to autism spectrum disorders (ASDs). Although cerebellar pathology has been observed in individuals with fragile X syndrome (FXS) and in mouse models of the disorder, a cerebellar functional contribution to ASD-relevant behaviors in FXS has yet to be fully characterized. In this study, we demonstrate a critical cerebellar role for Fmr1 (fragile X messenger ribonucleoprotein 1) in ASD-relevant behaviors. First, we identify reduced social behaviors, sensory hypersensitivity, and cerebellar dysfunction, with loss of cerebellar Fmr1. We then demonstrate that cerebellar-specific expression of Fmr1 is sufficient to impact social, sensory, cerebellar dysfunction, and cerebro-cortical hyperexcitability phenotypes observed in global Fmr1 mutants. Moreover, we demonstrate that targeting the ASD-implicated cerebellar region Crus1 ameliorates behaviors in both cerebellar-specific and global Fmr1 mutants. Together, these results demonstrate a critical role for the cerebellar contribution to FXS-related behaviors, with implications for future therapeutic strategies.

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3. Gomathi M, Dhivya V, Padmavathi V, Pradeepkumar M, Robert Wilson S, Kumar NS, Balachandar V. Genetic Instability and Disease Progression of Indian Rett Syndrome Patients. Mol Neurobiol;2023 (Dec 26)

Rett syndrome (RTT) is the rare neurodevelopmental disorder caused by mutations in methyl CpG binding protein 2 (MECP2) gene with a prevalence of 1:10,000 worldwide. The hallmark clinical features of RTT are developmental delay, microcephaly, repetitive behaviours, gait abnormalities, respiratory abnormalities and seizures. Still, the understanding on the diagnosis of RTT among clinicians are less. The aim of our work was to study various clinical manifestations and a spectrum of MECP2 genetic heterogeneity in RTT patients from South Indian population. We screened 208 autistic patients and diagnosed 20 RTT patients, who were further divided into classical RTT (group I; N = 11) and variant RTT (group II; N = 9). The clinical severity of RTT was measured using RSSS, RSBQ, SSI, SSS and RTT gross motor scale. The biochemical analysis showed that thyroid-stimulating hormone (TSH), plasma dopamine and cholesterol levels were higher in group I when compared to group II, whereas the level of blood pressure, calcium, ferritin and high-density lipoprotein levels were significantly decreased in both RTT groups, when compared to the control group. The genetic mutational spectrum of MECP2 mutations were found in 12/20 of RTT patients, which revealed the occurrence of 60% pathogenic mutation and 20% unknown mutation and it was correlated with the clinical finding of respiratory dysfunction, scoliosis and sleeping problems. The significant results of this study provided clinical and genetic aspects of RTT diagnosis and proposed the clinicians to screen abnormal cholesterol, calcium and TSH levels tailed with MECP2 gene mutations for early prognosis of disease severity.

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4. Jin X, Zhang K, Lu B, Li X, Yan CG, Du Y, Liu Y, Lu J, Luo X, Gao X, Liu J. Shared atypical spontaneous brain activity pattern in early onset schizophrenia and autism spectrum disorders: evidence from cortical surface-based analysis. Eur Child Adolesc Psychiatry;2023 (Dec 26)

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD.

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5. Kwok WM, Bourke-Taylor H, Carey S, McKenzie M. Occupational Therapy Observation Tool-Adjustment Support Details for autistic children: Investigation of content validity and clinical utility. Aust Occup Ther J;2023 (Dec 26)

INTRODUCTION: Standardised testing is crucial for autistic children to receive appropriate interventions, necessary services, and funding. Behaviours associated with autism can hinder children’s test performance and participation. The 18-item, two-page Occupational Therapy Observation Tool-Adjustment Support Details (OTOT-ASD) is used in conjunction with standardised assessments. The OTOT-ASD enables the recording of autism-related behaviours and the reasonable assessment accommodations made to support participation in testing. The current study aims to investigate the content validity and clinical utility of the OTOT-ASD from occupational therapists’ perspectives. METHOD: A specifically designed online questionnaire was distributed Victoria-wide to occupational therapists with clinical experience with autistic children. The questionnaire was designed in line with the COnsensus-based Standards for selection of health Measurement INstruments (COSMIN), including relevance, comprehensiveness, and comprehensibility of items evaluated for content validity. Applicability and clinical usefulness were also investigated. Quantitative data were analysed using descriptive statistics. RESULTS: Seventy-one occupational therapists responded to the questionnaire and 46 provided a full dataset. Over 96% of the respondents considered documenting behaviours and testing accommodations as important, yet less than 45% reported having resources to record this information. Ninety-five percent of the respondents perceived the OTOT-ASD to be useful in clinical practice. Over 70% agreed that OTOT-ASD items were significantly relevant to practice and comprehensive. To improve comprehensibility, identified items were altered following feedback. CONCLUSION: The findings suggest that the OTOT-ASD is clinically useful and content validity is sound. Further research on other psychometric properties of the OTOT-ASD and users’ qualitative experiences in utilising the tool is recommended.

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6. Laubscher E, Pope L, Light J. « You Just Want to Be Able to Communicate With Your Child »: Parents’ Perspectives on Communication and AAC Use for Beginning Communicators on the Autism Spectrum. Am J Speech Lang Pathol;2023 (Dec 26):1-20.

PURPOSE: For young children on the autism spectrum who are beginning communicators, augmentative and alternative communication (AAC) can support language development and participation in meaningful interactions. AAC is more likely to be effective when services align with the needs and priorities of the child’s family. To better understand family perspectives, this study investigated the communication and AAC experiences of parents of young beginning communicators on the autism spectrum. METHOD: The study used a phenomenological qualitative design. Eight caregivers of seven children on the autism spectrum participated in semistructured interviews, and thematic analysis was used to identify themes within the data. RESULTS: Five main themes and 15 subthemes emerged from the data. Parents situated communication and AAC experiences within the context of complex, busy lives. They discussed the value of communication and benefits of AAC, but described numerous challenges related to obtaining, learning, and implementing AAC that evolved over time as needs and skills changed. Parents discussed their children’s individuality and the need for AAC systems and services to fit the unique needs of their child and their family. They also emphasized ways in which communication outcomes were affected by factors external to the child and the family, including factors related to professional services and the U.S. health care and educational systems. CONCLUSIONS: The results affirm the need to consider the family and the broader social system when providing AAC services to young children on the autism spectrum. Provision of family-centered services is critical to successful AAC. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24881562.

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7. Nettles SA, Ikeuchi Y, Lefton KB, Abbasi L, Erickson A, Agwu C, Papouin T, Bonni A, Gabel HW. MeCP2 represses the activity of topoisomerase IIβ in long neuronal genes. Cell Rep;2023 (Dec 26);42(12):113538.

A unique signature of neurons is the high expression of the longest genes in the genome. These genes have essential neuronal functions, and disruption of their expression has been implicated in neurological disorders. DNA topoisomerases resolve DNA topological constraints and facilitate neuronal long gene expression. Conversely, the Rett syndrome protein, methyl-CpG-binding protein 2 (MeCP2), can transcriptionally repress long genes. How these factors regulate long genes is not well understood, and whether they interact is not known. Here, we identify and map a functional interaction between MeCP2 and topoisomerase IIβ (TOP2β) in mouse neurons. We profile neuronal TOP2β activity genome wide, detecting enrichment at regulatory regions and gene bodies of long genes, including MeCP2-regulated genes. We show that loss and overexpression of MeCP2 alter TOP2β activity at MeCP2-regulated genes. These findings uncover a mechanism of TOP2β inhibition by MeCP2 in neurons and implicate TOP2β dysregulation in disorders caused by MeCP2 disruption.

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8. Riccioni A, Siracusano M, Arturi L, Scoppola C, Ferrara M, Frattale I, Galasso C, Gialloreti LE, Mazzone L. Short report: Autistic symptoms in Sotos syndrome, preliminary results from a case-control study. Res Dev Disabil;2023 (Dec 26);145:104655.

BACKGROUND: An extremely heterogeneous neuropsychological phenotype has been reported in Sotos Syndrome (SoS), including socio-communicative and behavioral difficulties referred to Autism Spectrum Disorder (ASD). Nonetheless, to date, only few data are available on the topic. AIM: To investigate ASD symptoms within a sample of children with SoS in comparison to a matched control group of individuals with idiopathic ASD. METHODS: A convenience sample of SoS (n = 33, age: 9.8 ± 4.1) and ASD (n = 33, age: 9.9 ± 4.1), was included. Autistic symptoms’ assessment was performed through the administration of the Autism Diagnostic Observation Schedule-Second Edition- ADOS-2, the Social Responsiveness Scale -SRS and the Social Communication Questionnaire-SCQ. RESULTS: 72.7% of SoS children presented mild to moderate levels of ASD symptoms as measured by the ADOS-2. Oneway ANOVA analysis showed that SoS individuals presenting lower IQ demonstrated higher ASD symptom’s level (p = 0.01). No statistically significant differences emerged between the SoS and ASD groups within the SRS total score domain (p = 0.95). CONCLUSIONS AND IMPLICATIONS: Our results support the evidence for an increased risk for ASD in SoS, suggesting that the ASD symptoms’ assessment should be regularly performed in SoS children, with subsequent important implications in terms of therapeutic strategies and later outcome.

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9. Shuster CL, Sheinkopf SJ, McGowan EC, Hofheimer JA, O’Shea TM, Carter BS, Helderman JB, Check J, Neal CR, Pastyrnak SL, Smith LM, Loncar C, Dansereau LM, DellaGrotta SA, Marsit CJ, Lester BM. Two-Year Autism Risk Screening and 3-Year Developmental Outcomes in Very Preterm Infants. JAMA Pediatr;2023 (Dec 26)

IMPORTANCE: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings. OBJECTIVE: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Neonatal Neurobehavior and Outcomes for Very Preterm Infants was a longitudinal, multisite cohort study. Enrollment occurred April 2014 to June 2016, and analyses were conducted from November 2022 to May 2023. Data were collected across 9 university-affiliated neonatal intensive care units (NICUs). Inclusion criteria were infants born less than 30 weeks’ gestational age, a parent who could read and speak English and/or Spanish, and residence within 3 hours of the NICU and follow-up clinic. EXPOSURES: Prematurity and use of the 2-stage parent-report autism risk screening tool at age 2 years. MAIN OUTCOMES AND MEASURES: Outcomes include cognitive, language, motor composites on Bayley Scales for Infant and Toddler Development, third edition (Bayley-III) and internalizing, externalizing, total problems, and pervasive developmental disorder (PDD) subscale on the Child Behavior Checklist (CBCL) at age 3 years. Generalized estimating equations tested associations between the 2-stage parent-report autism risk screening tool and outcomes, adjusting for covariates. RESULTS: A total of 467 children (mean [SD] gestational age, 27.1 [1.8] weeks; 243 male [52%]) were screened with the 2-stage parent-report autism risk screening tool at age 2 years, and outcome data at age 3 years were included in analyses. Mean (SD) maternal age at birth was 29 (6) years. A total of 51 children (10.9%) screened positive on the 2-stage parent-report autism risk screening tool at age 2 years. Children with positive screening results were more likely to have Bayley-III composites of 84 or less on cognitive (adjusted odds ratio [aOR], 4.03; 95% CI, 1.65-9.81), language (aOR, 5.38; 95% CI, 2.43-11.93), and motor (aOR, 4.74; 95% CI, 2.19-10.25) composites and more likely to have CBCL scores of 64 or higher on internalizing (aOR, 4.83; 95% CI, 1.88-12.44), externalizing (aOR, 2.69; 95% CI, 1.09-6.61), and PDD (aOR, 3.77; 95% CI, 1.72-8.28) scales. CONCLUSIONS AND RELEVANCE: Results suggest that the 2-stage parent-report autism risk screening tool administered at age 2 years was a meaningful screen for developmental delays in very preterm infants, with serious delays detected at age 3 years.

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10. Tailor G, Telles-Langdon DM, Glazebrook CM. Müller-Lyer Illusion susceptibility is conditionally predicted by autistic trait expression. Exp Brain Res;2023 (Dec 26)

Müller-Lyer (ML) figures bias size estimation consistently, yet different methods can lead to different degrees of illusory bias. Autistic individuals may also be less likely to perceive illusory biases with varying levels of autistic trait expression proposed to modulate reported illusory biases. The Autism-Spectrum Quotient (AQ) and Systemizing Quotient (SQ) are self-report measures that quantify autistic trait expression and systemizing ability in neurotypical individuals. The current study sought to determine if perceptions of illusory size bias negatively correlate with autistic trait expression and the extent to which varying methods of illusion presentation change the magnitude of illusory bias. Thirty neurotypical adults completed both questionnaires as well as four size estimation tasks. Two tasks involved perceptual discrimination of ML figures by concurrent and successive presentation, where participants selected the longer figure by keypress. For Tasks 3 and 4, participants adjusted the size of a non-illusory line (Task 3) or complementary illusory figure (Task 4) to match the perceived length. Overall, task performance was not correlated with autistic trait expression. One exception was a negative correlation with AQ when adjusting a complementary illusory ML figure in Task 4. Illusory biases were also stronger when two illusory figures were presented concurrently. Given these results, illusion susceptibility to the ML is suggested to be reduced with increases in AQ, but only when the method of illusion measurement is adjustment of concurrent illusory figures. Taken together the results provide evidence that traits associated with autism in a neurotypical population may systematically modulate perception.

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11. Venker CE, Lorang E. A commentary on children’s books about autism: What messages do they send about neurodiversity?. Autism Res;2023 (Dec 26)

The past three decades have seen an exponential increase in the publication of children’s books about autism. This increased availability of children’s books is exciting because they have the power to promote understanding, acceptance, and appreciation of neurodiversity. However, growing concerns have been raised by both autistic and non-autistic people that some children’s books about autism may work against neurodiversity, rather than promoting it. This Commentary discusses the strikingly different ways in which children’s books about autism portray key concepts related to neurodiversity, including autistic differences, agency, abilities, and communication. We present concrete examples (including books by autistic authors); highlight the views of autistic and non-autistic parents of autistic children; and discuss how different books may leave readers with different impressions of autism and neurodiversity. Given the vastly different themes that emerge across different books, we conclude that it is important for educators, families, and other members of the autism community to make informed and individualized choices about what books they use for what purpose. We emphasize the need for systematic, high-quality research on children’s books about autism, including content analyses and studies that determine what messages these books send to their intended audience: children. It is vital that autistic people continue to shape this conversation, contributing unique insights that inform research priorities and the methodological approaches used to investigate them.

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12. Weiting Tan D, Rabuka M, Haar T, Pellicano E. ‘It’s a symbolic violence’: Autistic people’s experiences of discrimination at universities in Australia. Autism;2023 (Dec 26):13623613231219744.

Autistic students experience many challenges at university. One significant barrier identified in past research was autistic students’ experiences of discrimination (i.e. being treat differently) and stigma (being judged differently). Our research team included both autistic and non-autistic researchers who designed a project to help explore autistic students’ experiences of stigma and discrimination at Australian universities. We interviewed 21 autistic students who went to a university – some had completed qualifications, and some had not. From our interviews, we identified four themes: (1) ‘My disability is something that people just don’t have a clue about’, (2) ‘the system is really stacked against you’, (3) the onus is on autistic students, and (4) ‘grit and stubbornness’. As a result, we recommended changes in the way courses are written and taught so that autistic people have opportunities that meet their ways of learning. It is also important for university staff to understand the impact of trauma experienced by autistic people and that universities work together with autistic people to design courses and supports that include autistic ways of learning, accessible university processes and identify support needs.

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13. Xu FX, Wang XT, Cai XY, Liu JY, Guo JW, Yang F, Chen W, Schonewille M, De Zeeuw C, Zhou L, Shen Y. Purkinje-cell-specific MeCP2 deficiency leads to motor deficits and autistic-like behavior due to aberrations in PTP1B-TrkB-SK signaling. Cell Rep;2023 (Dec 26);42(12):113559.

Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs.

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