1. Benazzato C, Lojudice F, Pöehlchen F, Leite PEC, Manucci AC, Van der Linden V, Jungmann P, Sogayar MC, Bruni-Cardoso A, Russo FB, Beltrão-Braga P. Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome. Sci Rep;2024 (Aug 3);14(1):18002.

Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

Lien vers le texte intégral (Open Access ou abonnement)

2. Jiang Y, Li R, Li X. [Report of a child with Bainbridge-Ropers syndrome due to a novel variant of ASXL3 gene and a literature review]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2024 (Aug 10);41(8):966-972.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a child with Bainbridge-Ropers syndrome (BRPS). METHODS: A child with BRPS who had visited Nanjing Children’s Hospital on June 26, 2019 was selected as the study subject. Clinical data of the child was reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was a 6-month-old girl with peculiar facial features, feeding difficulties, malnutrition, global developmental delay, hypotonia, mildly elevated aminotransferase and ulnar deviation. Results of WES showed that she has harbored a c.1533_1534del variant of the ASXL3 gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. No similar case had been retrieved from the HGMD and ClinVar databases. No frequency for this variant among Asian populations was available in the ExAC, 1000 Genomes, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1533_1534del variant of the ASXL3 gene was determined to be likely pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The ASXL3 gene c.1533_1534del variant probably underlay the BRPS in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling for children with similar disorders.

Lien vers le texte intégral (Open Access ou abonnement)

3. Levine AA, Cole MB, Michals AL, Wang N, Rubenstein E. Inequities in medicaid home- and community-based services waiver enrollment among people with intellectual and/or developmental disabilities: A nationwide claims-based analysis. Disabil Health J;2024 (Aug 2):101676.

BACKGROUND: States use Medicaid 1915(c) waiver programs to enable access to home- and community-based services for people with intellectual and/or developmental disabilities (I/DD). However, enrollment rates and potential inequities are not well documented, impeding efforts to improve care access and quality for waiver program enrollees, especially for racially minoritized beneficiaries experiencing compounded barriers to services and supports. OBJECTIVE: To characterize year-by-year 1915(c) waiver program enrollment among Medicaid-enrolled adults with I/DD from 2016 to 2019 and to analyze population-level inequities by type of I/DD and racial/ethnic group. METHODS: Our data source was 2016-2019 Medicaid Transformed Medicaid Statistical Information System Analytic Files Demographic and Eligibility files for beneficiaries with Down syndrome, autism, and intellectual disability. We used generalized estimating equation linear models to estimate the associations of type of I/DD and racial/ethnic group with the probability of 1915(c) waiver program enrollment and reported (1) unadjusted estimates and (2) estimates adjusted for demographics with state and year fixed effects. RESULTS: From 2016 to 2019, across all types of I/DD and racial/ethnic groups, unadjusted 1915(c) waiver program enrollment rates ranged from 40 to 60 % nationwide. We found modest growth in 1915(c) I/DD waiver program enrollment but persistent inequities over time. Compared to beneficiaries with intellectual disabilities, beneficiaries with autism were less likely to enroll while beneficiaries with Down syndrome were more likely. While some racial/ethnic groups had higher unadjusted mean enrollment, after adjustment, racially minoritized beneficiaries were 3.66-12.0 percentage points less likely to enroll compared to white non-Hispanic beneficiaries. CONCLUSIONS: Given extensive waiting lists for 1915(c) waiver programs, Medicaid programs should evaluate existing enrollment and authorization processes and consider alternative HCBS program authorities.

Lien vers le texte intégral (Open Access ou abonnement)

4. McMahon CM, McClain MB, Haverkamp CR, Harris B. Re-Evaluating the Appropriateness of the « Don’t Know » Response Option: Guessing Rate as a Source of Systematic Error on Autism Knowledge Assessments. J Autism Dev Disord;2024 (Aug 3)

Several autism knowledge assessments include « don’t know » as a response option. The inclusion of this response option may lead to systematic error, such that participants’ guessing rate affects the measurement of their autism knowledge. This study examines both predictors of guessing rate for autism knowledge and predictors of autism knowledge, including guessing rate. School-based professionals (n = 396) completed the Autism Spectrum Knowledge Scale Professional Version-Revised (ASKSP-R; McClain et al, Journal of Autism and Developmental Disorders 50(3):998-1006, 2020). and the Autism Stigma and Knowledge Questionnaire (ASK-Q; Harrison et al, Journal of Autism and Developmental Disorders 47(10):3281-3295, 2017). Both assessments include « don’t know » as a response option. Guessing rate was the strongest predictor of autism knowledge across both the ASKSP-R and the ASK-Q assessments. For the ASKSP-R, participants who were school psychologists, practicing for more years, had more autism-related clinical experiences, and who personally knew an autistic person had a higher guessing rate. School psychologists and participants who worked with more autistic students scored higher in autism knowledge. For the ASK-Q, participants with greater self-perceived autism knowledge had a higher guessing rate. Participants with a doctorate degree, who personally knew an autistic person, and who worked with more autistic students scored higher in autism knowledge. Guessing rate can be a source of systematic error on autism knowledge assessments. Potential solutions to correct for guessing rate are examined and recommended for future use.

Lien vers le texte intégral (Open Access ou abonnement)

5. Spencer SD, Pinciotti CM, Murphy C, Hertz A, Wiese AD, Wood JJ, Kendall PC, Storch EA. Concurrent Validity of the Anxiety Disorders Section of the Anxiety Disorder Interview Schedule- Autism Spectrum Addendum (ADIS-ASA) in Autistic Youth. J Autism Dev Disord;2024 (Aug 3)

PURPOSE: Examine the concurrent validity of specific Anxiety Disorders Section of the Anxiety Disorder Interview Schedule for DSM-IV-Autism Spectrum Addendum (ADIS-ASA)-Parent Interview in a sample of 167 autistic youth who met diagnostic criteria for an anxiety-related disorder (M(age) = 9.91; 78.4% male; 82% non-Hispanic; 77.67% White). METHODS: Concurrent validity of Diagnostic and Statistical Manual (DSM)-defined ADIS-ASA anxiety disorder diagnostic caseness was examined via relations with (a) parent-reported dimensions of youth anxiety symptomology and (b) dimensional measures of youth anxiety-related functional impairment, respectively, using logistic regression models and point-biserial correlations. RESULTS: Significant relations were found between separation anxiety disorder and social anxiety disorder (but not generalized anxiety disorder nor obsessive-compulsive disorder) caseness, respectively, and theoretically consistent facets of dimensional youth anxiety symptomology. Relations between ADIS-ASA diagnostic caseness and youth functional impairment-related variables revealed that only separation anxiety disorder demonstrated robust evidence of convergent validity. CONCLUSION: Despite mixed findings concerning relations between ADIS-ASA anxiety disorder diagnostic caseness and dimensional measures of anxiety severity and anxiety-related impairment, the present findings provide further support for the status of the ADIS-ASA as a gold standard for assessment of anxiety in autistic youth. This work also highlights the importance of continuing to improve precision in measurement of anxiety symptomology in autistic youth, with implications for clinical assessment.

Lien vers le texte intégral (Open Access ou abonnement)

6. Zhao Z, Okada N, Yagishita S, Yahata N, Nitta N, Shibata S, Abe Y, Morita S, Kumagai E, Tanaka KF, Suhara T, Takumi T, Kasai K, Jinde S. Correlations of brain structure with the social behavior of 15q11-13 duplication mice, an animal model of autism. Neurosci Res;2024 (Aug 2)

Duplication of chromosome 15q11-13 has been reported to be one of the most frequent cytogenetic copy number variations in autism spectrum disorder (ASD), and a mouse model of paternal 15q11-13 duplication was generated, termed 15q dup mice. While previous studies have replicated some of the behavioral and brain structural phenotypes of ASD separately, the relationship between brain structure and behavior has rarely been examined. In this study, we performed behavioral experiments related to anxiety and social behaviors and magnetic resonance imaging (MRI) using the same set of 15q dup and wild-type mice. 15q dup mice showed increased anxiety and a tendency toward alterations in social behaviors, as reported previously, as well as variability in terms of sociability. MRI analysis revealed that a lower sociability index was correlated with a smaller gray matter volume in the right medial entorhinal cortex. These results may help to understand how variability in behavioral phenotypes of ASD arises even in individuals with the same genetic background and to determine the individual differences in neurodevelopmental trajectory correlated with specific brain structures that underlie these phenotypes.

Lien vers le texte intégral (Open Access ou abonnement)