1. Adebiyi E, Jennifer Christine MP. Temporal trends and regional variation of heart transplantation in children with intellectual and developmental disabilities. Pediatric transplantation. 2023: e14620.

BACKGROUND: Historically, intellectual and developmental disability (IDD) has been considered an important factor in choosing potential recipients of organ transplants among many transplant centers. This study evaluated the temporal changes at the national and regional levels in the proportion of heart transplantation in children with IDD. METHODS: Children younger than 19 years in the United Network for Organ Sharing (UNOS) database who received heart transplants from 2010 to 2021 were included in this study. The patients were grouped into only definitive intellectual disability, both definitive intellectual and motor disability, only definitive motor disability, and no developmental disability. Multinomial logistic regressions were used to examine the proportion of heart transplants in each category for the whole cohort and each geographic transplant region. RESULTS: There were 4273 pediatric heart transplant recipients included in the study. From 2010 to 2021, the percentages of pediatric heart transplants increased from 3.8% (95% CI, 0.01-0.05) to 5.8% (95% CI, 0.03-0.08) in children with only definitive intellectual disability (OR 0.07; 95% CI, 0.02-0.1, p(trend)  < .002), from 3.4% (95% CI, 0.01-0.05) to 6.6% (95% CI, 0.04-0.09) in children with both definitive intellectual disability and motor disability (OR 0.09; 95% CI, 0.05-0.13, p(trend)  < .001), and from 5.2% (95% CI, 0.02-0.07) to 8.3% (95% CI, 0.05-0.1) in children with only definitive motor disability (OR 0.06; 95% CI, 0.02-0.09, p(trend)  < .002). There were several regional differences in the proportion of children with intellectual and developmental disabilities who received heart transplants. CONCLUSION: There is increasing inclusion of children diagnosed with intellectual and developmental disabilities in heart transplantation. A review of the current allocation policies may address the marked geographic variations found in this study.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bemmouna D, Weiner L. Linehan’s biosocial model applied to emotion dysregulation in autism: a narrative review of the literature and an illustrative case conceptualization. Frontiers in psychiatry. 2023; 14: 1238116.

Emotion dysregulation (ED) is a transdiagnostic difficulty prevalent in autism spectrum condition (ASC). Importantly, recent research has suggested that ED is involved in self-harm and suicidality. Pre-existing models on the etiology of ED in ASC focus mainly on biological factors to ASC features, such as sensory sensitivities, poor flexibility, and sensitivity to change. However, although psychosocial factors seem to play a role in the emergence of ED in ASC as well (e.g., childhood maltreatment and camouflaging), there is a lack of a comprehensive model conceptualizing biosocial factors involved in ED in autistic people. Linehan’s biosocial model (1993) is one of the leading etiological models of ED in borderline personality disorder (BPD). It conceptualizes ED as emerging from transactions between a pre-existing emotional vulnerability in the child and an invalidating developmental environment. Beyond its clinical relevance, Linehan’s model has gathered empirical evidence supporting its pertinence in BPD and in other psychiatric disorders. Although ASC and BPD are two distinct diagnoses, because they may share ED, Linehan’s biosocial model might be useful for understanding the development of ED in ASC. Hence, this article aims to provide an application and extension of Linehan’s model to conceptualize ED in ASC. To do so, we conducted a narrative review of the literature on ED and its underlying factors in ASC from a developmental perspective. To investigate the pertinence of the biosocial model applied to ED in autistic people, we were interested on data on (i) ED and its behavioral correlates in ASC, in relation to the biosocial model, (ii) the potential biological and psychosocial correlates of ED in ASC and (iii) the overlapping difficulties in ASC and BPD. Finally, to assess the pertinence of the model, we applied it to the case of an autistic woman presenting with ED and suicidal behaviors. Our review and application to the case of an autistic woman suggest that ED in ASC encompasses factors related to both biological and psychosocial risk factors as conceptualized in the BPD framework, although in both domains ASC-specific factors might be involved.

Lien vers le texte intégral (Open Access ou abonnement)

3. Black B, Hunter S, Cottrell H, Dar R, Takahashi N, Ferguson BJ, Valter Y, Porges E, Datta A, Beversdorf DQ. Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. Frontiers in psychiatry. 2023; 14: 1238328.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has potential clinical application for autism spectrum disorder (ASD). At-home sessions are necessary to allow delivery of repeated sessions, and remove burden on patients for daily visits, and reduce costs of clinic delivery. Our objective was to validate a protocol for remote supervised administration for home delivery of taVNS using specially designed equipment and platform. METHODS: An open-label design was followed involving administration by caretakers to 12 patients with ASD (ages:7-16). Daily 1-h sessions over 2 weeks were administered under remote supervision. The primary outcome was feasibility, which was assessed by completion rate, stimulation tolerability, and confirmation of programmed stimulation delivery. The secondary measures were initial efficacy assessed by Childhood Anxiety Sensitivity Index-Revised (CASI-R), Parent Rated Anxiety Scale for Youth with ASD (PRAS-ASD), and Clinician Global Impression (CGI) scales. Sleep measures were also tracked using Cleveland Adolescent Sleep Questionnaire (CASQ). RESULTS: Across 132 sessions, we obtained an 88.5% completion rate. A total of 22 expected adverse events were reported with headache being the most common followed by transient pain, itchiness, and stinging at the electrode site. One subject dropped out of the study unrelated to the stimulation or the study. Average scores of anxiety (CASI-R, PRAS-ASD, and CGI) and sleepiness (CASQ) were all improved at the 2 week time point. While not powered to determine efficacy, benefits were suggested in this open label pilot. CONCLUSION: Remotely supervised, proxy-administered, at-home delivery of taVNS is feasible in patients with ASD. Initial efficacy supports pursuing larger scale trials.

Lien vers le texte intégral (Open Access ou abonnement)

4. Cardon G, Buckhannon M, Rojas D. Fundamental Behavioral and Neurophysiologic Relationships Between Sensory Processing, Intolerance of Uncertainty, and Autistic Traits in Children: A Hybrid Approach. Biological psychology. 2023: 108712.

Sensory differences are common and often challenging for autistic children. Furthermore, atypical sensory processing is associated with autistic traits and other autism-related behaviors, such as intolerance of uncertainty (IU). Such traits and their relatedness vary continuously across autistic and non-autistic children alike. However, the underlying neural correlates of these continuous variables, and their associations, are not well understood. Therefore, this study examined relationships between sensory processing, IU, autistic traits, and associated resting state brain connectivity, across a sample of both autistic (n=30) and non-autistic (n=26) children. In addition to computing behavioral correlations between these factors, we carried out independent component network functional connectivity analysis to investigate associations between cortical and cerebellar networks and behavioral results between groups and across our entire sample. Across-group correlations between sensory processing, autistic traits, and IU were significant. In addition, data demonstrated overlapping sensory processing and intolerance of uncertainty scores, spanning the groups. Brain (rs-fMRI)-behavioral relationships revealed strong associations between sensory, large-scale resting state, and cerebellar networks and behavioral scores. Overall, our findings suggest that sensory differences are related to IU and autistic traits across the population. Neurophysiologic data pointed to functional connectivity between sensory cortices and supramodal brain networks. These findings provide evidence for the continuous variation of behaviors common to autism throughout the entire population and their neurobiological correlates.

Lien vers le texte intégral (Open Access ou abonnement)

5. Chen L, Xiong XY, Yao TT, Gui LN, Luo F, Du Y, Cheng Y. Blood exosome sensing via neuronal insulin-like growth factor-1 regulates autism-related phenotypes. Pharmacological research. 2023: 106965.

The development and progression of autism spectrum disorder (ASD) is characterized by multiple complex molecular events, highlighting the importance of the prefrontal brain regions in this process. Exosomes are nanovesicles that play a critical role in intercellular communication. Peripheral systems influence brain function under both physiological and pathological conditions. We investigated whether this influence was mediated by the direct sensing of peripheral blood exosomes by brain cells. Administration of serum exosomes from rats with valproic acid-induced ASD resulted in ASD-related phenotypes in mice, whereas exosomes from normal rats did not exhibit such effects. RNA sequencing and bioinformatics analysis suggested that negative regulation of medial prefrontal cortex (mPFC) insulin-like growth factor 1 (IGF-1) by exosome-derived miR-29b-3p may contribute to these ASD-associated effects. Further evidence showed that miR-29b-3p-enriched exosomes crossed the blood-brain barrier to reach the mPFC, subsequently inducing the suppression of IGF-1 expression in neurons. Optogenetic activation of excitatory neurons in the mPFC improved behavioral abnormalities in exosome-treated mice. The addition of exogenous IGF-1 or inhibition of miR-29b-3p expression in the mPFC also rescued the ASD-related phenotypes in mice. Importantly, administration of miR-29b-3p-enriched serum exosomes from human donors with ASD into the mouse medial prefrontal cortex was sufficient to induce hallmark ASD behaviors. Together, our findings indicate that blood-brain cross-talk is crucial for ASD pathophysiology and that the brain may sense peripheral system changes through exosomes, which could serve as the basis for future neurological therapies.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cummings KK, Jung J, Zbozinek TD, Wilhelm FH, Dapretto M, Craske MG, Bookheimer SY, Green SA. Shared and distinct biological mechanisms for anxiety and sensory over-responsivity in youth with autism versus anxiety disorders. Journal of neuroscience research. 2023.

Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants’ SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.

Lien vers le texte intégral (Open Access ou abonnement)

7. Douglas S, Sedgewick F. Experiences of interpersonal victimization and abuse among autistic people. Autism : the international journal of research and practice. 2023: 13623613231205630.

What do we already know?Autistic people are more likely to have negative life experiences than non-autistic people, from bullying and ostracization, to being victims of crime, to unemployment and homelessness. This includes being victims of intimate partner violence, sexual assault and domestic abuse. Quantitative work has suggested that as many as 90% of autistic people experience these forms of abuse in some form during their lives, but there is little work asking them to talk about harmful relationships in their own words.What does this article add?This article reports on interviews with 24 autistic adults about their experiences of being victims of intimate partner violence, sexual assault and/or domestic abuse. Some of the themes which came from these interviews are shared with non-autistic victims, but others appeared unique to autistic people. One of these was evidence for unique autism-related vulnerabilities, as well as the impact the abuse had on their relationships long term. Participants also talked about how the sex and relationship education they had received had inadequately prepared them for adult relationships, and how this had contributed to their struggle to recognize and react to abusive behaviour.Implications for practice, research and policyPolicies around intimate partner violence and sexual assault need to be updated to account for the different ways in which neurodivergent people (people whose brains process information differently from the majority) may discuss their experiences, rather than looking for ‘standard narratives’ as an indicator of a need for support. Relationship and sex education should be tailored for autistic young people to help them recognize abusive behaviours, and include how to respond to these safely. We recommend that future research tries to focus specifically on the abuse experiences of autistic men, non-binary and trans people, who have been under-represented in studies to date. In addition, much less is known about the abuse experiences of autistic people of colour or autistic people with intellectual disabilities, who also need to be actively included in these discussions.

Lien vers le texte intégral (Open Access ou abonnement)

8. Klitzman R, Bezborodko E, Chung WK, Appelbaum PS. Receiving de novo genetic diagnoses for autism with intellectual disability: parents’ views of impacts on families’ reproductive decisions. Journal of community genetics. 2023.

Parents of children with autism who receive genetic diagnoses of de novo variants face challenges in understanding the implications for reproductive decision-making. We interviewed 28 parents who received de novo genetic diagnoses for their child’s autism and intellectual disability (ID). These genetic variants proved to have reproductive implications for not only the child’s parents, but the child and his/her neurotypical siblings, aunts, uncles, and cousins. Parents had often already finished building their families but varied, overall, in whether the results had affected, or might have influenced, their reproductive decisions. Parents’ views were shaped by factors related to not only genetics, but also parental age, financial considerations, competing hopes and visions for their family’s future, perceived abilities to care for an additional child with similar symptoms, and the extent of the child’s symptoms. Members of a couple sometimes disagreed about whether to have more children. Parents pondered, too, the possibility of preimplantation genetic testing, though misunderstandings about it arose. Children with autism vary widely in their abilities to understand the reproductive implications of genetic diagnoses for themselves. Neurotypical offspring were much relieved to understand that their own children would not be affected. While some autism self-advocates have been concerned that genetic testing related to autism could lead to eugenics, the present data, concerning de novo genetic findings, raise other perspectives. These data, the first to explore several key aspects of the reproductive implications of genetic diagnoses for this group, have important implications for future practice, education, and research-e.g., concerning various family members.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lachiewicz AM, Stackhouse TM, Burgess K, Burgess D, Andrews HF, Choo TH, Kaufmann WE, Kidd SA. Sensory Symptoms and Signs of Hyperarousal in Individuals with Fragile X Syndrome: Findings from the FORWARD Registry and Database Multisite Study. Journal of autism and developmental disorders. 2023.

This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns.

Lien vers le texte intégral (Open Access ou abonnement)

10. Laue HE, Moroishi Y, Jackson BP, Palys TJ, Baker ER, Korrick SA, Madan JC, Karagas MR. Bacterial Modification of the Association Between Arsenic and Autism-Related Social Behavior Scores. Exposure and health. 2023; 15(2): 347-54.

Arsenic is related to neurodevelopmental outcomes and is associated with the composition of the gut microbiome. Data on the modifying role of the microbiome are limited. We probed suggestive relationships between arsenic and social behaviors to quantify the modifying role of the infant gut microbiome. We followed children for whom arsenic concentrations were quantified in 6-week-old toenail clippings. Scores on the Social Responsiveness Scale (SRS-2), which measures autism-related social behaviors, were provided by caregivers when the child was approximately 3 years of age. Metagenomic sequencing was performed on infant stools collected at 6 weeks and 1 year of age. To evaluate modification by the top ten most abundant species and functional pathways, we modeled SRS-2 total T-scores as a function of arsenic concentrations, microbiome features dichotomized at their median, and an interaction between exposure and the microbiome, adjusting for other trace elements and sociodemographic characteristics. As compared to the standardized population (SRS-2 T-scores = 50), participants in our study had lower SRS-2 scores (n = 78, mean = 44, SD = 5).The relative abundances of several functional pathways identified in 6-week stool samples modified the arsenic-SRS-2 association, including the pathways of valine and isoleucine biosynthesis; we observed no association among those with high relative abundance of each pathway [β = – 0.67 (95% CI – 1.46, 0.12)], and an adverse association [β = 1.67 (95% CI 0.3, 3.04), p(interaction)= 0.05] among infants with low relative abundance. Our findings indicate the infant gut microbiome may alter neurodevelopmental susceptibility to environmental exposures.

Lien vers le texte intégral (Open Access ou abonnement)

11. Maltman N, Willer R, Sterling A. An Exploratory Study of Pragmatic Language Use Across Contexts With the Pragmatic Rating Scale-School Age Among Autistic Boys and Boys With Fragile X Syndrome Plus Autism. Journal of speech, language, and hearing research : JSLHR. 2023: 1-11.

PURPOSE: Autistic boys and boys with co-occurring fragile X syndrome and autism spectrum disorder (FXS + ASD) demonstrate similar pragmatic language difficulties. The Pragmatic Rating Scale-School Age (PRS-SA) captures ecologically valid metrics of pragmatic language impairments in these populations. It is traditionally scored based on the Autism Diagnostic Observation Schedule (ADOS), which may limit the use of the PRS-SA more broadly in research and clinical contexts. METHOD: This study evaluated the feasibility of the PRS-SA based on a shorter, semistructured conversational context compared to the ADOS in school-age autistic boys (n = 16) and boys with FXS + ASD (n = 16), matched on ASD traits. Differences across ADOS and conversational contexts and associations with ASD-related social difficulties were evaluated. RESULTS: Findings revealed differences in PRS-SA scores between ADOS and conversational contexts, but only for the FXS + ASD group. Limited associations were observed between PRS-SA scores and ASD traits. CONCLUSIONS: Results from this study indicate the feasibility of using the PRS-SA in a shorter conversational context than the ADOS to assess pragmatic language among autistic boys. For boys with FXS + ASD, contextual differences warrant careful consideration in future work.

Lien vers le texte intégral (Open Access ou abonnement)

12. Muhammad T, Pastore SF, Good K, Ausió J, Vincent JB. Chromatin gatekeeper and modifier CHD proteins in development, and in autism and other neurological disorders. Psychiatric genetics. 2023.

Chromatin, a protein-DNA complex, is a dynamic structure that stores genetic information within the nucleus and adapts to molecular/cellular changes in its structure, providing conditional access to the genetic machinery. ATP-dependent chromatin modifiers regulate access of transcription factors and RNA polymerases to DNA by either « opening » or « closing » the structure of chromatin, and its aberrant regulation leads to a variety of neurodevelopmental disorders. The chromodomain helicase DNA-binding (CHD) proteins are ATP-dependent chromatin modifiers involved in the organization of chromatin structure, act as gatekeepers of genomic access, and deposit histone variants required for gene regulation. In this review, we first discuss the structural and functional domains of the CHD proteins, and their binding sites, and phosphorylation, acetylation, and methylation sites. The conservation of important amino acids in SWItch/sucrose non-fermenting (SWI/SNF) domains, and their protein and mRNA tissue expression profiles are discussed. Next, we convey the important binding partners of CHD proteins, their protein complexes and activities, and their involvements in epigenetic regulation. We also show the ChIP-seq binding dynamics for CHD1, CHD2, CHD4, and CHD7 proteins at promoter regions of histone genes, as well as several genes that are critical for neurodevelopment. The role of CHD proteins in development is also discussed. Finally, this review provides information about CHD protein mutations reported in autism and neurodevelopmental disorders, and their pathogenicity. Overall, this review provides information on the progress of research into CHD proteins, their structural and functional domains, epigenetics, and their role in stem cell, development, and neurological disorders.

Lien vers le texte intégral (Open Access ou abonnement)

13. Ostrolenk A, Courchesne V, Mottron L. A longitudinal study on language acquisition in monozygotic twins concordant for autism and hyperlexia. Brain and cognition. 2023; 173: 106099.

BACKGROUND: Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension abilities, characterizes up to 20% of autistic children. Sometimes perceived as an obstacle to oral language acquisition, hyperlexia may alternatively be the first step in a non-social pathway of language acquisition in autism. METHOD: We describe two monozygotic twin brothers, both autistic and hyperlexic, from the ages of 4 to 8 years old. Following an in-depth diagnostic assessment, we investigated cross-sectionally and longitudinally their verbal and non-verbal cognitive abilities, language, reading and writing skills, interests, and strengths. RESULTS: The twins’ features, including their high non-verbal level of intelligence, their special interests, and their skills in various domains, were highly similar. Their language consisted exclusively of letters and numbers until their fourth year. After that, their vocabulary broadened until they developed full sentences, and their perception-related interests expanded and merged over time to serve the development of other skills. CONCLUSION: Our results show that hyperlexic skills can be harnessed to favor oral language development. Given the strong concordance between the twins’ cognitive and behavioral phenotypes, we discuss the environmental and genetic influence that could explain their abilities.

Lien vers le texte intégral (Open Access ou abonnement)

14. Panesi S, Dotti M, Ferlino L. Case Report: A playful digital-analogical rehabilitative intervention to enhance working memory capacity and executive functions in a pre-school child with autism. Frontiers in psychiatry. 2023; 14: 1205340.

BACKGROUND: Autism Spectrum Disorder (ASD) is often associated with deficits in Working Memory Capacity (WMC) and Executive Functions (EFs), as early as the first years of life. Research has shown that, even young children with ASD, WMC and EF deficits can be effectively addressed through interventions employing digital and/or analogical tools. Early intervention is important because executive dysfunction can negatively impact on the quality of life, both of children and their families. However, very few studies have been carried out involving intervention with pre-schoolers with ASD. To fill this gap, we developed an intervention that promotes pre-schoolers’ WMC and EFs by employing both digital apps and analogical playful activities. This study reports on the feasibility of this intervention, which was carried out in a rehabilitative context. METHODS: A male pre-schooler diagnosed with ASD was engaged in a total of 17 intervention sessions, all held in a clinical context, over a nine-week period. Outcomes were measured using a battery of pre- and post-treatment tasks focusing on WMC, EFs and receptive language. The clinician who administered the intervention made written observations and noted any improvements in the child’s performance emerging from the digital and analogical activities. RESULTS: The pre- and post-test scores for the cognitive tasks revealed qualitative improvements in the following cognitive domains: (a) WMC in the language receptive domain; (b) updating in WMC; (c) inhibition, specifically concerning control of motor response; (d) receptive vocabulary. Furthermore, when monitoring the child’s performance, the clinician noted improvement in almost all the playful activities. Particularly notable improvements were observed in interaction with the apps, which the child appeared to find very motivating. CONCLUSION: This study supports feasibility of a playful digital-analogical intervention conducted by a clinician in a rehabilitation context to promote cognitive abilities in pre-schoolers with ASD. Further studies are needed to establish whether the intervention’s effectiveness can be generalized to a broad sample of children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

15. Ryu S, Lee T, Lim Y, Kim H, Yu GE, Kim S, Kim HW. Psychoeducational Profile-Revised, Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Vineland Adaptive Behavior Scale, Second Edition: Comparison of Utility for Developmental Disabilities in Preschool Children. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(4): 258-67.

OBJECTIVES: This study aimed to compare the utility of the Psychoeducational Profile-Revised (PEP-R), Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), and Vineland Adaptive Behavior Scale, Second Edition (VABS-II) for evaluating developmental disabilities (DD) in preschool children. Additionally, we examined the correlations between the PEP-R, KWPPSI- IV, and VABS-II. METHODS: A total of 164 children aged 37-84 months were assessed. Children’s development was evaluated using the PEP-R, K-WPPSIIV, VABS-II, Preschool Receptive-Expressive Language Scale, and Korean Childhood Autism Rating Scale, Second Edition. RESULTS: Of the 164 children, 103 had typical development (TD) and 61 had DD. The mean of the PEP-R Developmental Quotient (DQ), K-WPPSI-IV Full-Scale Intelligence Quotient (FSIQ), and VABS-II Adaptive Behavior Composite (ABC) scores were significantly higher in the TD group than in the DD group (p<0.001). The estimated area under the curve of the PEP-R DQ, K-WPPSI-IV FSIQ, and VABS-II ABC scores was 0.953 (95% confidence interval [CI]=0.915-0.992), 0.955 (95% CI=0.914-0.996), and 0.961 (95% CI=0.932- 0.991), respectively, which did not indicate a statistically significant difference. The PEP-R DQ scores were positively correlated with the K-WPPSI-IV FSIQ (r=0.90, p<0.001) and VABS-II ABC scores (r=0.84, p<0.001). A strong correlation was observed between the KWPPSI- IV FSIQ and VABS-II ABC scores (r=0.89, p<0.001). CONCLUSION: This study found that the PEP-R, K-WPPSI-IV, and VABS-II effectively distinguished DD from TD in preschool children, and no significant differences in utility were observed between them.

Lien vers le texte intégral (Open Access ou abonnement)

16. Schwingel GB, Fontes-Dutra M, Ramos B, Riesgo R, Bambini-Junior V, Gottfried C. Preventive effects of resveratrol against early-life impairments in the animal model of autism induced by valproic acid. IBRO neuroscience reports. 2023; 15: 242-51.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive/stereotyped behaviors. Its prevalence is increasing, affecting one in 36 children in the United States. The valproic acid (VPA) induced animal model of ASD is a reliable method for investigating cellular, molecular, and behavioral aspects related to the disorder. Trans-Resveratrol (RSV), a polyphenol with anti-inflammatory and antioxidant effects studied in various diseases, has recently demonstrated the ability to prevent cellular, molecular, sensory, and social deficits in the VPA model. In this study, we examined the effects of prenatal exposure to VPA and the potential preventive effects of RSV on the offspring. METHOD: We monitored gestational weight from embryonic day 6.5 until 18.5 and assessed the onset of developmental milestones and morphometric parameters in litters. The generalized estimating equations (GEE) were used to analyze longitudinal data. RESULTS: Exposure to VPA during rat pregnancy resulted in abnormal weight gain fold-changes on embryonic days 13.5 and 18.5, followed by fewer animals per litter. Additionally, we discovered a positive correlation between weight variation during E15.5-E18.5 and the number of rat pups in the VPA group. CONCLUSION: VPA exposure led to slight length deficiencies and delays in the onset of developmental milestones. Interestingly, the prenatal RSV treatment not only prevented most of these delays but also led to the early onset of certain milestones and improved morphometric characteristics in the offspring. In summary, our findings suggest that RSV may have potential as a therapeutic intervention to protect against the negative effects of prenatal VPA exposure, highlighting its importance in future studies of prenatal neurodevelopmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

17. Wang Z, Qiao D, Chen H, Zhang S, Zhang B, Zhang J, Hu X, Wang C, Cui H, Wang X, Li S. Effects of Fmr1 gene mutations on sex differences in autism-like behavior and dendritic spine development in mice and transcriptomic studies. Neuroscience. 2023.

Fragile X syndrome (FXS) is the most common single gene disorder contributing to autism spectrum disorder (ASD). Although significant sex differences are observed in FXS, few studies have focused on the phenotypic characteristics as well as the differences in brain pathological changes and gene expression in FXS by sex. Therefore, we analyzed sex differences in autism-like behavior and dendritic spine development in two-month-old male and female Fmr1 KO and C57 mice and evaluated the mechanisms at transcriptome level. Results suggest that Fmr1 KO mice display sex differences in autism-like behavior and dendritic spine density. Compared to females, male had more severe effects on anxiety, repetitive stereotype-like behaviors, and socializing, with higher dendritic spine density. Furthermore, two male-biased and five female-biased expressed genes were screened based on KEGG pathway enrichment and protein-protein interaction (PPI) analyses. In conclusion, our findings show mutations in the Fmr1 gene lead to aberrant expression of related genes and affect the sex-differentiated behavioral phenotypes of Fmr1 KO mice by affecting brain development and functional architecture, and suggest future studies should focus on including female subjects to comprehensively reflect the differentiation of FXS in both sexes and develop more precise and effective therapeutic strategies.

Lien vers le texte intégral (Open Access ou abonnement)

18. Yang Y, Wu J, Zhang J, Chen X, Que Z, Wettschurack K, Deming B, Acosta M, Cui N, Eaton M, Zhao Y, Halurkar M, Purba M, Chen I, Xiao T, Suzuki M, Yuan C, Xu R, Koss W, Du D, Chen F, Wu LJ. Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids. Research square. 2023.

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus to understand ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a -deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a -deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a -deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglial-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

Lien vers le texte intégral (Open Access ou abonnement)