1. Anne A, Saxena S, Mohan KN. Genome-wide methylation analysis of post-mortem cerebellum samples supports the role of peroxisomes in autism spectrum disorder. Epigenomics;2022 (Sep 26)

Aim: We tested the hypothesis that a subset of patients with autism spectrum disorder (ASD) contains candidate genes with high DNA methylation differences (effective values) that potentially affect one of the two alleles. Materials & methods: Genome-wide DNA methylation comparisons were made on cerebellum samples from 30 patients and 45 controls. Results: 12 genes with high effective values, including GSDMD, MMACHC, SLC6A5 and NKX6-2, implicated in ASD and other neuropsychiatric disorders were identified. Monoallelic promoter methylation and downregulation were observed for SERHL (serine hydrolase-like) and CAT (catalase) genes associated with peroxisome function. Conclusion: These data are consistent with the hypothesis implicating impaired peroxisome function/biogenesis for ASD. A similar approach holds promise for identifying rare epimutations in ASD and other complex disorders.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bamgboye MA, Herold KG, Vieira DCO, Traficante MK, Rogers PJ, Ben-Johny M, Dick IE. CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms. J Gen Physiol;2022 (Nov 7);154(11)

The first pathogenic mutation in CaV1.2 was identified in 2004 and was shown to cause a severe multisystem disorder known as Timothy syndrome (TS). The mutation was localized to the distal S6 region of the channel, a region known to play a major role in channel activation. TS patients suffer from life-threatening cardiac symptoms as well as significant neurodevelopmental deficits, including autism spectrum disorder (ASD). Since this discovery, the number and variety of mutations identified in CaV1.2 have grown tremendously, and the distal S6 regions remain a frequent locus for many of these mutations. While the majority of patients harboring these mutations exhibit cardiac symptoms that can be well explained by known pathogenic mechanisms, the same cannot be said for the ASD or neurodevelopmental phenotypes seen in some patients, indicating a gap in our understanding of the pathogenesis of CaV1.2 channelopathies. Here, we use whole-cell patch clamp, quantitative Ca2+ imaging, and single channel recordings to expand the known mechanisms underlying the pathogenesis of CaV1.2 channelopathies. Specifically, we find that mutations within the S6 region can exert independent and separable effects on activation, voltage-dependent inactivation (VDI), and Ca2+-dependent inactivation (CDI). Moreover, the mechanisms underlying the CDI effects of these mutations are varied and include altered channel opening and possible disruption of CDI transduction. Overall, these results provide a structure-function framework to conceptualize the role of S6 mutations in pathophysiology and offer insight into the biophysical defects associated with distinct clinical manifestations.

Lien vers le texte intégral (Open Access ou abonnement)

3. Bolat H, Ünsel-Bolat G, Derin H, Şen A, Ceylaner S. Distinct Autism Spectrum Disorder Phenotype and Hand-Flapping Stereotypes: Two Siblings with Novel Homozygous Mutation in TRAPPC9 Gene and Literature Review. Mol Syndromol;2022 (Jul);13(4):263-269.

OBJECTIVE: Pathogenic mutations of the TRAPPC9 gene are the rare genetic causes of autosomal recessive intellectual disability (ID). There are several features that are not fully penetrant such as microcephaly, dysmorphic facial features, obesity, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and brain abnormalities in TRAPPC9 mutations. METHODS: We performed whole-exome sequencing to evaluate 2 Turkish siblings with ASD and ID born to healthy and consanguineous parents. Parental samples were also analyzed, specifically targeting variants detected in these patients. RESULTS: We present a novel homozygous mutation in the TRAPPC9 gene, c.484G>T (p.Glu162Ter). Additionally, we aim to provide a more comprehensive understanding of the clinical features of a novel homozygous TRAPPC9 mutation. In addition to ID, the siblings in this report suffered from ASD and specific stereotypes as hand-flapping behavior. CONCLUSION: Although there are inconsistencies in the presentation of ASD in TRAPPC9 mutations, repetitive behaviors (hand-flapping) were typical in our cases and several previous reports. The current mutation was described to cause a homozygous premature termination codon that resulted in the absence of the TRAPPC9 protein. We suggest that TRAPPC9 mutations are not only related to ID but also to ASD and hand-flapping behaviors.

Lien vers le texte intégral (Open Access ou abonnement)

4. Burke MM, Cheung WC, Li C, DaWalt L, Segal J, Taylor JL. Parental Perceptions of Service Access for Transition-Aged Youth With Autism During COVID-19. Intellect Dev Disabil;2022 (Oct 1);60(5):369-381.

Services are critical for youth with autism spectrum disorder (ASD), especially during the transition to adulthood. Under the best of circumstances, though, it can be difficult to access needed adult services. With COVID-19, services were more difficult to obtain and retain. In this study, we explored parent perceptions of accessing new services and maintaining current services during the first year of the COVID-19 pandemic. Structured interviews were conducted with 65 parents of transition-aged youth (aged 16-26) with ASD living in three states (IL, TN, and WI) in the United States. None of the participants reported receiving new services during the pandemic, and many struggled to access services via online applications. In addition, participants reported that service suspensions and changes in modality (e.g., from in-person to telehealth) were spearheaded by professionals and not families. Participants, especially those in TN, were more likely to pay out-of-pocket for services during the COVID-19 pandemic to compensate for service disruptions. Implications for research and practice are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

5. Buro AW, Gray HL, Kirby RS, Marshall J, Rolle L, Holloway J. Parent and Adolescent Attitudes Toward a Virtual Nutrition Intervention for Adolescents with Autism Spectrum Disorder. Adv Neurodev Disord;2022 (Sep 17):1-13.

OBJECTIVES: This qualitative study examined acceptability, perceived benefits, and unintended consequences of a virtual implementation of an 8-week theory-driven nutrition intervention (BALANCE) for adolescents with autism spectrum disorder (ASD). METHODS: Twenty-one parent interviews and six adolescent focus groups or interviews (n = 12; group size ranged 1-5) were conducted. Data were collected virtually via Microsoft Teams and analyzed for a priori and emergent themes. RESULTS: The intervention was generally acceptable. Adolescents and parents reported that they were comfortable with the virtual format and the interactive group setting. Parents of adolescents 15 years and older emphasized the importance of autonomy/independence. Participants reported changes in adolescents’ psychosocial determinants of dietary intake, including knowledge and self-efficacy, as well as diet changes (e.g., self-regulation). CONCLUSIONS: The virtual implementation of BALANCE was acceptable according to adolescents with ASD and their parents based on their reported perceptions and feelings about the intervention. The findings suggest that many adolescents with ASD may benefit from virtual group interventions. Quantitative research is needed to examine behavioral outcomes of the BALANCE intervention.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cleary M, West S, Kornhaber R, McLean L. Dispersed Responsibility of a Collective Problem: Autism, Suicidality and the Failure of Knowledge Translation. Issues Ment Health Nurs;2022 (Sep 26):1-6.

Lien vers le texte intégral (Open Access ou abonnement)

7. Erridge S, Kerr-Gaffney J, Holvey C, Coomber R, Barros DAR, Bhoskar U, Mwimba G, Praveen K, Symeon C, Sachdeva-Mohan S, Sodergren MH, Rucker JJ. Clinical outcome analysis of patients with autism spectrum disorder: analysis from the UK Medical Cannabis Registry. Ther Adv Psychopharmacol;2022;12:20451253221116240.

INTRODUCTION: Cannabis-based medicinal products (CBMPs) have been identified as a promising novel therapeutic for symptoms and comorbidities related to autism spectrum disorder (ASD). However, there is a paucity of clinical evidence of their efficacy and safety. Objective: This case series aims to assess changes to health-related quality of life and the incidence of adverse events in patients treated with CBMPs for associated symptoms of ASD enrolled on the UK Medical Cannabis Registry (UKMCR). METHODS: Patients treated with CBMPs for ASD-related symptoms for a minimum of 1 month were identified from the UKMCR. Primary outcomes were changes in validated patient-reported outcome measures [Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), 5-level version of the EQ-5D (EQ-5D-5L) index values] at 1, 3 and 6 months compared with baseline. Adverse events were recorded and analysed. Statistical significance was determined by p < 0.050. RESULTS: Seventy-four patients with ASD were included in the analysis. The mean age of participants was 32.7 (±11.6) years. There were significant improvements in general health-related quality of life and sleep as assessed by the EQ-5D-5L, SQS and GAD-7 at 1 and 3 months, with sustained changes in EQ-5D-5L and SQS at 6 months (p < 0.010). There were 180 (243.2%) adverse events reported by 14 (18.9%) participants. If present, adverse events were commonly mild (n = 58; 78.4%) or moderate (n = 81; 109.5%), rather than severe (n = 41; 55.4%). CONCLUSION: This study demonstrated an associated improvement in general health-related quality of life, and anxiety- and sleep-specific symptoms following initiation of treatment with CBMPs in patients with ASD. These findings, while promising, are limited by the confines of the study which lacks a control arm and is subject to attrition bias. Therefore, further evaluation is required with randomised controlled trials.

Lien vers le texte intégral (Open Access ou abonnement)

8. Hadoush H, Hadoush A. Modulation of Resting-State Brain Complexity After Bilateral Cerebellar Anodal Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorders: a Randomized Controlled Trial Study. Cerebellum;2022 (Sep 26)

BACKGROUND: Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders characterized by aberrant neural networks. Cerebellum is best known for its role in controlling motor behaviors; however, recently, there have been significant reports showed that dysfunction in cerebellar-cerebral networks contributes significantly to many of the clinical features of ASD. Hereby, this is a randomized controlled trial (RCT) study examining the potential modulating effects of bilateral anodal tDCS stimulation over cerebellar hemispheres on the resting-state brain complexity in children with ASD. METHODS: Thirty-six children with ASD (aged 4-14) years old were divided equally and randomly into a tDCS treatment group, which underwent 10 sessions (20-min duration, five sessions/per week) of bilateral anodal tDCS stimulation applied over left and right cerebellar hemispheres, and control group underwent the same procedures, but with sham tDCS stimulation. Resting-state brain complexity was evaluated through recording and calculating the approximate entropy (ApxEnt) values of the resting-state electroencephalograph (EEG) data obtained from a 64-channel EEG system before and after the interventions. RESULTS: Repeated measures of ANOVA showed that tDCS had significant effects on the treatment group (Wilks’ Lambda = 0.29, F (15, 16) = 2.67, p = 0.03) compared with the control group. Analyzed data showed a significant increase in the averaged ApxEnt values in the right frontal cortical region (F (1, 16) = 10.46, p = 0.005) after the bilateral cerebellar anodal tDCS stimulation. Besides, the Cohen’s d effect size showed a large effect size (0.70-0.92) of bilateral cerebellar anodal tDCS on the ApxEnt values increases in the left and right frontal cortical regions, the right central cortical region, and left parietal cortical region. However, there were no any significant differences or increases in the brain complexity before and after the sham tDCS stimulation of the control group. CONCLUSION: Bilateral cerebellar anodal tDCS modulated and increased the brain complexity in children with ASD with no any reported adverse effect. Hereby, cerebellum and cerebellar-cerebral circuitry would serve as a promising target for non-invasive brain stimulation and neuro-modulation as a therapeutic intervention.

Lien vers le texte intégral (Open Access ou abonnement)

9. Hirai M, Asada K, Kato T, Ikeda T, Hakuno Y, Ikeda A, Matsushima K, Awaya T, Okazaki S, Funabiki Y, Murai T, Heike T, Hagiwara M, Yamagata T, Tomiwa K, Kimura R. Comparison of the Social Responsiveness Scale-2 among Individuals with Autism Spectrum Disorder and Williams Syndrome in Japan. J Autism Dev Disord;2022 (Sep 27)

This study examined the similarities/differences between the social phenotypes of Williams syndrome (WS) and autism spectrum disorder (ASD). As cultural norms may affect symptom evaluation, this study administered the Social Responsiveness Scale-2 to Japanese individuals with WS (n = 78, 4.4-44.0 years) and ASD (n = 75, 4.7-55.4 years). The scores for Social Motivation and Social Communication were significantly more severe in the ASD than WS group. Overall, the similarities and differences between the social phenotypes of the syndromes were consistent with the findings of a recent study conducted in the UK, except for the social awareness subscale score. This highlights the importance of cross-cultural investigations of WS and ASD.

Lien vers le texte intégral (Open Access ou abonnement)

10. Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord;2022 (Sep 27);14(1):52.

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151.

Lien vers le texte intégral (Open Access ou abonnement)

11. Kim JH, Hughes OE, Demissie SA, Kunzier TJ, Cheung WC, Monarrez EC, Burke MM, Rossetti Z. Lessons Learned From Research Collaboration Among People With and Without Developmental Disabilities. Intellect Dev Disabil;2022 (Oct 1);60(5):405-415.

Research related to the developmental disability (DD) community should include collaboration with individuals with DD. Unfortunately, people with DD are infrequently involved in research projects in meaningful ways, and there is little guidance about how to collaborate equitably with researchers with DD. The purpose of this article is to share lessons learned from a collaborative research study among researchers with and without DD using both qualitative and quantitative methods to develop and examine the effectiveness of a civic engagement intervention for transition-aged youth with disabilities. It includes how our research team compensated researchers with DD, clarified team member roles, leveraged the expertise of researchers with DD in using both qualitative and quantitative methods, and integrated technology throughout the research process.

Lien vers le texte intégral (Open Access ou abonnement)

12. Li D, Mei L, Li H, Hu C, Zhou B, Zhang K, Qiao Z, Xu X, Xu Q. Brain structural alterations in young girls with Rett syndrome: A voxel-based morphometry and tract-based spatial statistics study. Front Neuroinform;2022;16:962197.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function variants in the MECP2 gene, currently with no cure. Neuroimaging is an important tool for obtaining non-invasive structural and functional information about the in vivo brain. Multiple approaches to magnetic resonance imaging (MRI) scans have been utilized effectively in RTT patients to understand the possible pathological basis. This study combined developmental evaluations with clinical severity, T1-weighted imaging, and diffusion tensor imaging, aiming to explore the structural alterations in cohorts of young girls with RTT, idiopathic autism spectrum disorder (ASD), or typical development. Voxel-based morphometry (VBM) was used to determine the voxel-wised volumetric characteristics of gray matter, while tract-based spatial statistics (SPSS) was used to obtain voxel-wised properties of white matter. Finally, a correlation analysis between the brain structural alterations and the clinical evaluations was performed. In the RTT group, VBM revealed decreased gray matter volume in the insula, frontal cortex, calcarine, and limbic/paralimbic regions; TBSS demonstrated decreased fractional anisotropy (FA) and increased mean diffusivity (MD) mainly in the corpus callosum and other projection and association fibers such as superior longitudinal fasciculus and corona radiata. The social impairment quotient and clinical severity were associated with these morphometric alterations. This monogenic study with an early stage of RTT may provide some valuable guidance for understanding the disease pathogenesis. At the same time, the pediatric-adjusted analytic pipelines for VBM and TBSS were introduced for significant improvement over classical approaches for MRI scans in children.

Lien vers le texte intégral (Open Access ou abonnement)

13. Luo X, Xiong Y, Gu M, Huang L, Lu Z, Zhong X, Zou S. Reliability and validity of the repetitive behavior scale-revised for young Chinese children with autism spectrum disorder in Jiangxi Province. Front Pediatr;2022;10:939841.

Restricted and repetitive behaviors (RRBs) are one of the two main diagnostic features of autism spectrum disorder (ASD). To date, a growing body of research on RRB in children with ASD has recently attracted academic attention. The Repetitive Behavior Scale-Revised (RBS-R) was primarily intended for use in evaluating RRBs observed in ASD. This study recruited 381 Chinese children with ASD aged 2-4 years to measure the reliability and validity of the RBS-R. Confirmatory factor analysis (CFA) was applied to the structuring models of the four proposed structural models, indicating that a 6-factor model demonstrated good internal consistency and the best fit based on common overall fit indices. These findings suggest the utility of the Chinese version of RBS-R.

Lien vers le texte intégral (Open Access ou abonnement)

14. Mattheisen M, Grove J, Als TD, Martin J, Voloudakis G, Meier S, Demontis D, Bendl J, Walters R, Carey CE, Rosengren A, Strom NI, Hauberg ME, Zeng B, Hoffman G, Zhang W, Bybjerg-Grauholm J, Bækvad-Hansen M, Agerbo E, Cormand B, Nordentoft M, Werge T, Mors O, Hougaard DM, Buxbaum JD, Faraone SV, Franke B, Dalsgaard S, Mortensen PB, Robinson EB, Roussos P, Neale BM, Daly MJ, Børglum AD. Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. Nat Genet;2022 (Sep 26)

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

Lien vers le texte intégral (Open Access ou abonnement)

15. McKinney WS, Kelly SE, Unruh KE, Shafer RL, Sweeney JA, Styner M, Mosconi MW. Corrigendum: Cerebellar volumes and sensorimotor behavior in autism spectrum disorder. Front Integr Neurosci;2022;16:1020980.

[This corrects the article DOI: 10.3389/fnint.2022.821109.].

Lien vers le texte intégral (Open Access ou abonnement)

16. Mishra A, Singla R, Kumar R, Sharma A, Joshi R, Sarma P, Kaur G, Prajapat M, Bhatia A, Medhi B. Granulocyte Colony-Stimulating Factor Improved Core Symptoms of Autism Spectrum Disorder via Modulating Glutamatergic Receptors in the Prefrontal Cortex and Hippocampus of Rat Brains. ACS Chem Neurosci;2022 (Sep 27)

Chronic neuroinflammation-induced anomalous glutamate receptor activation has been identified as one of the important factors in the pathogenesis of autism spectrum disorder (ASD). Thus, the current study was designed to elucidate the neuroprotective effect of the granulocyte colony-stimulating factor (G-CSF), a haemopoietic growth factor, an anti-inflammatory, and a neuroprotectant to decipher the underlying mechanism(s) in the valproic acid (VPA)-induced experimental model of ASD. Experimentally, the ASD rat model was induced by a single dose of VPA (600 mg/kg; i.p.) on gestation day 12.5 to the pregnant female rats. After birth, pups were treated with vehicle, that is, normal saline 0.9% i.p., risperidone (2.5 mg/kg; i.p.), and G-CSF (10, 35, and 70 μg/kg; i.p.) from postnatal day (PND) 23 to 43. All the groups were subjected to various developmental and behavior (???) tests from birth. The rats were sacrificed on PND 55, and their brain was excised and processed for biochemical parameters (oxidative stress, inflammatory markers, BDNF), histological examination (H&E, Nissl staining), NMDA, and AMPA receptor expression by immunohistochemistry, western blot, and real-time polymerase chain reaction evaluation. Also, the possible interaction of the G-CSF with NMDA and AMPA receptors was evaluated using the in silico method. The results of the study showed that in VPA-exposed rats, postnatal treatment of the G-CSF rescued all the behavioral abnormalities, oxidative stress, and inflammatory parameters in a dose-dependent manner while risperidone did not show any significant results. The in silico analysis showed the direct interaction of the G-CSF with NMDA and AMPA receptors. The upregulated expression of NMDA and AMPA both in the prefrontal cortex as well as hippocampus was alleviated by the G-CSF thereby validating its anti-inflammatory and excitoprotective properties. Thus, the G-CSF demonstrated neuroprotection against the core symptoms of autism in the VPA-induced rodent model, making it a potential candidate for the treatment of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Mohan G, Sarma RJ, Iyer M, Kumar NS, Vellingiri B. Highlighting novel genes associated with the classical Rett syndrome patient from India. Genes Dis;2022 (Nov);9(6):1394-1396.

Lien vers le texte intégral (Open Access ou abonnement)

18. Monk R, Whitehouse AJO, Waddington H. The use of language in autism research. Trends Neurosci;2022 (Sep 27)

The past three decades have seen a major shift in our understanding of the strong links between autism and identity. These developments have called for careful consideration of the language used to describe autism. Here, we briefly discuss some of these deliberations and provide guidance to researchers around language use in autism research.

Lien vers le texte intégral (Open Access ou abonnement)

19. Park BY, Kebets V, Larivière S, Hettwer MD, Paquola C, van Rooij D, Buitelaar J, Franke B, Hoogman M, Schmaal L, Veltman DJ, van den Heuvel OA, Stein DJ, Andreassen OA, Ching CRK, Turner JA, van Erp TGM, Evans AC, Dagher A, Thomopoulos SI, Thompson PM, Valk SL, Kirschner M, Bernhardt BC. Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology. Commun Biol;2022 (Sep 27);5(1):1024.

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we carried out a multiscale neural contextualization of shared alterations of cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia). Our framework cross-referenced shared morphological anomalies with respect to cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we identified a cortex-wide dimension of morphological changes that described a sensory-fugal pattern, with paralimbic regions showing the most consistent alterations across conditions. The shared disease dimension was closely related to cortical gradients of microstructure as well as neurotransmitter axes, specifically cortex-wide variations in serotonin and dopamine. Multiple sensitivity analyses confirmed robustness with respect to slight variations in analytical choices. Our findings embed shared effects of common psychiatric conditions on brain structure in multiple scales of brain organization, and may provide insights into neural mechanisms of transdiagnostic vulnerability.

Lien vers le texte intégral (Open Access ou abonnement)

20. Phunsawat P, Chiangjong W, Chutipongtanate S, Dumrongwongsiri O, Thommachot P, Butdawong W, Chuthapisith J. Folate receptor alpha autoantibodies in children with autism spectrum disorder. Biomarkers;2022 (Sep 27):1-5.

BACKGROUND: Recent research indicates that a number of children with autism generate folate receptor alpha autoantibodies (FRAA), which block transportation of folate across the blood-brain barrier, resulting in cerebral folate deficiency syndrome. Plasma FRAA detection permits precision diagnosis and potentially beneficial folinic acid treatment in FRAA-positive children with autism. OBJECTIVES: To investigate FRAA prevalence in Thai children with autism and evaluate the associations between FRAA-positive status, clinical symptom severity, and adaptive functioning. METHODS: FRAA level was determined in serum samples from 89 children with autism between 2 and 15 years (69 males, 20 females, mean age 7.9 years, SD 3.8). The Childhood Autism Rating Scale-Second Edition (CARS-2) and the Vineland Adaptive Behavior Scales (VABS) were used to evaluate clinical symptom severity and adaptive functioning, respectively. RESULTS: Of 89 children, 30 (33.7%) were FRAA-positive. FRAA-positive children with autism had significantly poorer mean VABS Adaptive Behavior Composite scores (p = 0.02) and Communication scores (p = 0.02) than FRAA-negative children with autism. There was no association between FRAA level and clinical symptom severity (CARS-2 score) (p = 0.09). CONCLUSIONS: The findings demonstrate the presence of FRAA in children with autism and that FRAA status is associated with poorer adaptive functioning.

Lien vers le texte intégral (Open Access ou abonnement)

21. Presnell J, Keesler JM, Thomas-Giyer J. Assessing Alignment Between Intellectual and Developmental Disability Service Providers and Trauma-Informed Care: An Exploratory Study. Intellect Dev Disabil;2022 (Oct 1);60(5):351-368.

People with intellectual and developmental disabilities (IDD) are disproportionately impacted by potentially traumatic experiences; however, organizations serving this population have lagged in their integration of trauma-informed care (TIC). Trauma-informed care is a systemwide response to the pervasiveness of trauma that frequently requires an organizational shift rooted in staff training. Using an online statewide survey, the present study examined beliefs and training among IDD service providers. Responses from 288 service providers suggested some alignment among beliefs and staff training content with TIC principles. Although the findings indicate a foundation for TIC, intentional efforts are needed for IDD agencies to fully embrace TIC.

Lien vers le texte intégral (Open Access ou abonnement)

22. Profeta G, Micangeli G, Tarani F, Paparella R, Ferraguti G, Spaziani M, Isidori AM, Menghi M, Ceccanti M, Fiore M, Tarani L. Sexual Developmental Disorders in Pediatrics. Clin Ter;2022 (Sep-Oct);173(5):475-488.

Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.

Lien vers le texte intégral (Open Access ou abonnement)

23. Schaaf RC, Mailloux Z, Ridgway E, Berruti AS, Dumont RL, Jones EA, Leiby BE, Sancimino C, Yi M, Molholm S. Sensory Phenotypes in Autism: Making a Case for the Inclusion of Sensory Integration Functions. J Autism Dev Disord;2022 (Sep 27)

Sensory features are part of the diagnostic criteria for autism and include sensory hypo/hyper reactivity and unusual sensory interest; however, additional sensory differences, namely differences in sensory integration, have not been routinely explored. This study characterized sensory integration differences in a cohort of children (n = 93) with a confirmed diagnosis of autism (5-9 years) using a standardized, norm-referenced battery. Mean z scores, autism diagnostic scores, and IQ are reported. Participants showed substantial deficits in tactile perception, praxis, balance, visual perception, and visual-motor skills. Relationship with autism diagnostic test scores were weak or absent. Findings suggest additional sensory difficulties that are not typically assessed or considered when characterizing sensory features in autism. These data have implications for a greater understanding of the sensory features in the autism phenotype and the development of personalized treatments.

Lien vers le texte intégral (Open Access ou abonnement)

24. Schalock RL, Luckasson R, Tassé MJ, Shogren KA. The IDD Paradigm of Shared Citizenship: Its Operationalization, Application, Evaluation, and Shaping for the Future. Intellect Dev Disabil;2022 (Oct 1);60(5):426-443.

Changes in the field of intellectual and developmental disabilities (IDD) over the last 5 decades has resulted in the emergence of the shared citizenship paradigm. This paradigm is currently guiding the development of IDD-related policies and practices, and providing a framework for application, research-based inquiry, and evaluation. A shared citizenship paradigm is one that envisions, supports, and requires the engagement and full participation of people with IDD as equal, respected, valued, participatory, and contributing members of every aspect of society. The overall goals of the paradigm are to (a) further advance and focus on people with IDD as active agents in the change process, and (b) improve outcomes for people with IDD, including their access to and opportunity for shared citizenship. This article describes the paradigm’s operationalization, application, evaluation, shaping for the future, and specific strategies to overcome implementation challenges.

Lien vers le texte intégral (Open Access ou abonnement)

25. Siyam N, Abdallah S. Toward automatic motivator selection for autism behavior intervention therapy. Univers Access Inf Soc;2022 (Sep 16):1-23.

Children with autism spectrum disorder (ASD) usually show little interest in academic activities and may display disruptive behavior when presented with assignments. Research indicates that incorporating motivational variables during interventions results in improvements in behavior and academic performance. However, the impact of such motivational variables varies between children. In this paper, we aim to address the problem of selecting the right motivator for children with ASD using reinforcement learning by adapting to the most influential factors impacting the effectiveness of the contingent motivator used. We model the task of selecting a motivator as a Markov decision process problem. The states, actions and rewards design consider the factors that impact the effectiveness of a motivator based on applied behavior analysis as well as learners’ individual preferences. We use a Q-learning algorithm to solve the modeled problem. Our proposed solution is then implemented as a mobile application developed for special education plans coordination. To evaluate the motivator selection feature, we conduct a study involving a group of teachers and therapists and assess how the added feature aids the participants in their decision-making process of selecting a motivator. Preliminary results indicated that the motivator selection feature improved the usability of the mobile app. Analysis of the algorithm performance showed promising results and indicated improvement of the recommendations over time.

Lien vers le texte intégral (Open Access ou abonnement)

26. Smith JR, DiSalvo M, Green A, Ceranoglu TA, Anteraper SA, Croarkin P, Joshi G. Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Neuropsychol Rev;2022 (Sep 26)

To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges’ g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges’ g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.

Lien vers le texte intégral (Open Access ou abonnement)

27. Vadukapuram R, Elshokiry AB, Trivedi C, Abouelnasr A, Bataineh A, Usmani S, Rodrigues SP, Mansuri Z, Jain SB. Sex Differences in Psychiatric Comorbidities in Adolescents With Autism Spectrum Disorder: A National Inpatient Sample Analysis. Prim Care Companion CNS Disord;2022 (Sep 27);24(5)

Objective: To investigate sex differences in psychiatric comorbidities in adolescents with autism spectrum disorder (ASD). Methods: The US National Inpatient Sample dataset (January 2016 to December 2018) was used for this retrospective study. The patient population was selected by performing a query on all adolescent patients (aged 12-17 years) having ASD with the ICD-10-CM code starting with F84. All missing sex data were excluded. Additional data on mood disorders, anxiety disorders, personality disorders, adjustment disorders, psychotic disorders, attention-deficit/hyperactivity disorder (ADHD)/conduct disorders, sleep-wake disorders, and substance use disorders were collected. Data on psychiatric comorbidities were collected using the ICD-10-CM code provided in the Clinical Classifications Software of the dataset. Results: Mood disorders (37.4% vs 44.1%, P < .001) and anxiety disorders (29.4% vs 37.0%, P < .001) were more prevalent in females compared to males. The prevalence of ADHD and other conduct disorders was significantly higher in males than females (47.7% vs 36.7%, P < .001). Substance use disorders were slightly higher among males compared to females (3.7% vs 3.0%, P = .04). Conclusion: The study findings revealed statistically significant disparities in psychiatric comorbidities among adolescent male and female patients with ASD. These findings could serve as a pilot for larger-scale research with this patient population in the future.

Lien vers le texte intégral (Open Access ou abonnement)

28. Valenti M, Pino MC, Le Donne I, Vagnetti R, Tiberti S, Attanasio M, Mazza M. Adaptive response of Italian young adults with autism to the COVID-19 pandemic: A longitudinal study. Res Dev Disabil;2022 (Sep 12);131:104333.

The COVID-19 pandemic has represented a hazardous situation for individuals with Autism Spectrum Disorder (ASD) and their families. The difficulties, following the COVID-19-derived lockdown, have involved working from home or loss of employment, and the demands of looking after their children without the daily support of specialists. The aim of this study was to evaluate the adaptive behaviour of young adult participants with ASD after the enforcement of lockdown measures in March 2020 in a specialised centre in central Italy, by administering the Italian form of the Vineland Adaptive Behaviour Scales Second Edition (VABS-II), at baseline as well as 6 months and 1 year after the lockdown. Participants with ASD who were not able to access their normal, in-person care – they were only followed at a distance (i.e. telehealth) – declined dramatically in their adaptive behaviour during the first months after the lockdown for some VABS-II dimensions such as the socialisation and daily living domains. The effects of the lockdown on adaptive behaviour remained after 1 year. Our results emphasise the need for immediate, continuous and personal support for people with ASD during and after the restrictions caused by the COVID-19 pandemic, in order to ensure at least partial recovery of adaptive functioning.

Lien vers le texte intégral (Open Access ou abonnement)

29. Wang Y, Huo X, Li W, Xiao L, Li M, Wang C, Sun Y, Sun T. Knowledge Atlas of the Co-Occurrence of Epilepsy and Autism: A Bibliometric Analysis and Visualization Using VOSviewer and CiteSpace. Neuropsychiatr Dis Treat;2022;18:2107-2119.

OBJECTIVE: This study aimed to analyze research on epilepsy in autism and autism in epilepsy using VOSviewer and CiteSpace to identify research hotspots and future directions. METHODS: We searched the Web of Science Core Collection (WoSCC) for relevant studies about epilepsy in autism and autism in epilepsy published from inception to 31 May 2022. VOSviewer and CiteSpace were used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, keywords with citation bursts, and other aspects to construct a knowledge atlas. RESULTS: A total of 473 publications related to epilepsy/autism were retrieved. The number of publications about epilepsy/ASD has generally increased over time, with some fluctuations. The USA (202 papers) and University of California-Los Angeles (15 papers) were the leading country and institution, respectively, in this field. Frye, Richard E. was the most published author (9 papers). Notably, collaboration between institutions, countries, and authors does not appear to be active. Hot topics and research frontiers include intellectual disability and exploring the mechanism of epilepsy/ASD from a genetics perspective. CONCLUSION: This analysis identified the most influential publications, authors, journals, institutions, and countries in the field of epilepsy/ASD research. Using co-occurrence and evolution analyses, the status of the field was identified and future trends were predicted.

Lien vers le texte intégral (Open Access ou abonnement)

30. Weber CF, Lake EMR, Haider SP, Mozayan A, Mukherjee P, Scheinost D, Bamford NS, Ment L, Constable T, Payabvash S. Age-dependent white matter microstructural disintegrity in autism spectrum disorder. Front Neurosci;2022;16:957018.

There has been increasing evidence of White Matter (WM) microstructural disintegrity and connectome disruption in Autism Spectrum Disorder (ASD). We evaluated the effects of age on WM microstructure by examining Diffusion Tensor Imaging (DTI) metrics and connectome Edge Density (ED) in a large dataset of ASD and control patients from different age cohorts. N = 583 subjects from four studies from the National Database of Autism Research were included, representing four different age groups: (1) A Longitudinal MRI Study of Infants at Risk of Autism [infants, median age: 7 (interquartile range 1) months, n = 155], (2) Biomarkers of Autism at 12 months [toddlers, 32 (11)m, n = 102], (3) Multimodal Developmental Neurogenetics of Females with ASD [adolescents, 13.1 (5.3) years, n = 230], (4) Atypical Late Neurodevelopment in Autism [young adults, 19.1 (10.7)y, n = 96]. For each subject, we created Fractional Anisotropy (FA), Mean- (MD), Radial- (RD), and Axial Diffusivity (AD) maps as well as ED maps. We performed voxel-wise and tract-based analyses to assess the effects of age, ASD diagnosis and sex on DTI metrics and connectome ED. We also optimized, trained, tested, and validated different combinations of machine learning classifiers and dimensionality reduction algorithms for prediction of ASD diagnoses based on tract-based DTI and ED metrics. There is an age-dependent increase in FA and a decline in MD and RD across WM tracts in all four age cohorts, as well as an ED increase in toddlers and adolescents. After correction for age and sex, we found an ASD-related decrease in FA and ED only in adolescents and young adults, but not in infants or toddlers. While DTI abnormalities were mostly limited to the corpus callosum, connectomes showed a more widespread ASD-related decrease in ED. Finally, the best performing machine-leaning classification model achieved an area under the receiver operating curve of 0.70 in an independent validation cohort. Our results suggest that ASD-related WM microstructural disintegrity becomes evident in adolescents and young adults-but not in infants and toddlers. The ASD-related decrease in ED demonstrates a more widespread involvement of the connectome than DTI metrics, with the most striking differences being localized in the corpus callosum.

Lien vers le texte intégral (Open Access ou abonnement)

31. Xu Y, Zeng W, Wang Y, Magaña S. Barriers to Service Access for Immigrant Families of Children With Developmental Disabilities: A Scoping Review. Intellect Dev Disabil;2022 (Oct 1);60(5):382-404.

This scoping review explores (a) barriers faced by immigrant families of children with intellectual and developmental disabilities (IDD) when accessing healthcare-related services in the United States, (b) where research stands based on the health disparity research framework, and (c) implications for future health disparities research with this population. Our scoping review found 26 empirical studies published between 2000 and 2020 that met our inclusion criteria. Data were extracted and synthesized based on the stages of research outlined in the health disparity research framework. Overall, immigrant families experienced barriers on multiple levels including patient, provider, and healthcare system levels. Studies focusing on detecting and reducing disparities are emerging. We conclude with recommendations for future research and practice with immigrant families of children with IDD.

Lien vers le texte intégral (Open Access ou abonnement)