1. Abdulhameed O, Al-Helaly L. METHIONINE SULFOXIDE REDUCTASE A AND NEUROTRANSMISSION ENZYMES IN AUTISM SPECTRUM DISORDER AND DYSTOCIA RELATED AUTISTICS. Georgian Med News;2024 (May)(350):36-41.

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme that repairs the oxidation of methionine residues in proteins and free methionine in autism spectrum disorder (ASD). The present study aimed to assess the level of MsrA and neurotransmission enzymes in ASD individuals. Results confirmed that ASD associated with significant (P<0.05) reduction of MsrA and modulated mission enzymes. The role of MsrA as repair enzyme should be taken into account for study the activity of brain enzymes and proteins in ASD including ASMT that has a role in melatonin problems production in ASD due to higher AANAT level. The influence of MsrA also should be studied with MAT in mice to give more evidence.

Lien vers le texte intégral (Open Access ou abonnement)

2. Attallah A, Ardourel M, Gallazzini F, Lesne F, De Oliveira A, Togbé D, Briault S, Perche O. Lack of FMRP in the retina: Evidence of a retinal specific transcriptomic profile. Exp Eye Res;2024 (Sep);246:110015.

Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype. Over the last decade, a visual neurosensorial phenotype had been described in the FXS patients as well as in the murine model (Fmr1(-/y)mice), characterized by retinal deficits associated to retinal perception alterations. However, although the transcriptomic profile in the absence of FMRP has been studied in the cerebral part of the central nervous system (CNS), there are no actual data for the retina which is an extension of the CNS. Herein, we investigate the transcriptomic profile of mRNA from whole retinas of Fmr1(-/y)mice. Interestingly, we found a specific signature of Fmrp absence on retinal mRNA expression with few common genes compared to other brain studies. Gene Ontology on these retinal specific genes demonstrated an enrichment in retinal development genes as well as in synaptic genes. These alterations could be linked to the reported retinal phenotype of the FXS condition. In conclusion, we describe for the first time, retinal-specific transcriptomic changes in the absence of FMRP.

Lien vers le texte intégral (Open Access ou abonnement)

3. Brown L, Bacon A, Pacey V, Ilhan E. The Targeted Motor Control Screening Tool Is Valid for 4-Year-Old Children. Phys Ther;2024 (Aug 2);104(8)

OBJECTIVE: The objective was to determine the validity of the Targeted Motor Control (TMC) screening tool with the Neurosensory Motor Developmental Assessment (NSMDA) in 4-year-old children. METHODS: In this single cohort observational study, children (3 years 9 months to 4 years 5 months) completed the TMC and the NSMDA in a randomized order 5 to 14 days apart. RESULTS: Seventy-six children (mean age = 4 years 2 months; standard deviation = 2.5 months; n = 35 male) completed both assessments. Forty-two children performed within the normal range on the NSMDA. There were significant and positive moderate correlations between the item totals overall and for each area on the NSMDA and the TMC (r = 0.40-0.61), and between the NSMDA functional grade for each area and the corresponding TMC areas (r = 0.47-0.67). However, the correlation between the NSMDA sensorimotor functional grade and the TMC sensory score was significant but low and positive (r = 0.35). The optimal cut-off score for detecting children at risk of atypical development on the TMC was a score of <9 (n = 42) (sensitivity = 82.4%; specificity = 66.7%), with a positive likelihood ratio of 2.47 (95% confidence interval [CI] = 1.57-3.89) and a negative likelihood ratio of 0.26 (95% CI = 0.12-0.56). CONCLUSION: The TMC is a valid screening tool to identify 4-year-old children at risk of motor delay. IMPACT: Early identification of developmental concerns using a validated screening tool is recommended. The TMC is a valid performance-based screening tool that can be used to identify children at risk of atypical motor development who would benefit from further developmental assessment so that, if indicated, timely intervention can be implemented.

Lien vers le texte intégral (Open Access ou abonnement)

4. Bu LK, Jia PP, Huo WB, Pei DS. Assessment of Probiotics’ Impact on Neurodevelopmental and Behavioral Responses in Zebrafish Models: Implications for Autism Spectrum Disorder Therapy. Probiotics Antimicrob Proteins;2024 (Aug 1)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder; the prevalence of which has been on the rise with unknown causes. Alterations in the gut-brain axis have been widely recognized in ASD patients, and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. However, the effectiveness and mechanisms of multiple probiotics on zebrafish models are still not clearly revealed. This study aims to use the germ-free (GF) and conventionally raised (CR) AB wild-type zebrafish and the mutant Tbr1b(-/-) and Katnal2(-/-) lines as human-linked ASD animal models to evaluate the effects of multiple probiotics on mitigating developmental and behavioral defects. Results showed that the addition of probiotics increased the basic important developmental indexes, such as body length, weight, and survival rate of treated zebrafish. Moreover, the Lactobacillus plantarum and Lactobacillus rhamnosus affected the behavior of CR zebrafish by increasing their mobility, lowering the GF zebrafish manic, and mitigating transgenic zebrafish abnormal behavior. Moreover, the expression levels of key genes related to gamma-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT) as important neuropathways to influence the appearance and development of autism-related disorders, including gad1b, tph1a, htr3a, th, and slc6a3, were significantly activated by some of the probiotics’ treatment at some extent. Taken together, this study indicates the beneficial effects of different probiotics, which may provide a novel understanding of probiotic function in related diseases’ therapy.

Lien vers le texte intégral (Open Access ou abonnement)

5. Castro K, Frye RE, Silva E, Vasconcelos C, Hoffmann L, Riesgo R, Vaz J. Feeding-Related Early Signs of Autism Spectrum Disorder: A Narrative Review. J Pers Med;2024 (Aug 2);14(8)

Feeding difficulties are prevalent among individuals with autism spectrum disorder (ASD). Nevertheless, the knowledge about the association between feeding-related early signs and child development remains limited. This review aimed to describe the signs and symptoms related to feeding during child development and to explore their relevance to the diagnosis of ASD. Specialists in nutrition and/or ASD conducted a search of MEDLINE, PsycINFO, and Web of Science databases. Although studies in typically developing children demonstrate age-related variations in hunger and satiety cues, the literature about early feeding indicators in ASD is scarce. Challenges such as shortened breastfeeding duration, difficulties in introducing solid foods, and atypical mealtime behaviors are frequently observed in children with ASD. The eating difficulties experienced during childhood raise concerns for caregivers who base their feeding practices on their perceptions of food acceptance or refusal. Considering the observed associations between feeding difficulties and ASD, the importance of recognizing feeding-related signs according to developmental milestones is emphasized to alert medical professionals that deviation in the formation of feeding habits and skills could indicate the need for ASD diagnostic investigation.

Lien vers le texte intégral (Open Access ou abonnement)

6. Chen YJ, Sideris J, Watson LR, Crais ER, Baranek GT. Developmental Impacts of Early Sensory Patterns on School-Age Adaptive, Maladaptive, and Participation Outcomes in Autistic and Non-autistic Children. J Autism Dev Disord;2024 (Aug 2)

Early sensory differences may cascade into later social-communication difficulties in autism, yet their impacts on broader functional outcomes have remained understudied. This study aimed to conduct a comprehensive investigation into the longitudinal impacts of sensory patterns, including sensory hyperresponsiveness, hyporesponsiveness, and sensory repetitions/seeking behavior, on various school-age outcome domains among a community sample of children with autistic and non-autistic conditions. We prospectively followed 1,517 children with caregiver-reported sensory questionnaires across three timepoints from infancy to school age. A subsample (n = 389; 88 with reported autism diagnosis/concerns) was further assessed with adaptive, maladaptive and participation outcome measures at age 6-7. Structural equation modeling approaches were used to evaluate the multivariate associations between latent growth parameters (i.e., intercepts and slopes) of sensory patterns and school-age outcomes. Increasing sensory hyperresponsiveness was directly associated with poorer adaptive/maladaptive outcomes and indirectly with lower participation in activities with higher functional demands across settings at school age. Elevated sensory hyporesponsiveness was associated with lower adaptive functioning, more externalizing problems, and lower classroom participation. Trajectories of sensory patterns accounted for more unique variances in adaptive functioning and participation in daily life settings with higher functional and environmental demands among autistic children compared to their non-autistic peers.

Lien vers le texte intégral (Open Access ou abonnement)

7. Dingwall R, May C, Letschert J, Renoir T, Hannan AJ, Burrows EL. Attenuated responses to attention-modulating drugs in the neuroligin-3(R451C) mouse model of autism. J Neurochem;2024 (Aug 2)

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3(R451C)). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3(R451C) mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3(R451C) mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3(R451C) mouse model of autism, supporting further targeted investigation.

Lien vers le texte intégral (Open Access ou abonnement)

8. Gehdu BK, Press C, Gray KLH, Cook R. Autistic adults have insight into their relative face recognition ability. Sci Rep;2024 (Aug 1);14(1):17802.

The PI20 is a self-report questionnaire that assesses the presence of lifelong face recognition difficulties. The items on this scale ask respondents to assess their face recognition ability relative to the rest of the population, either explicitly or implicitly. Recent reports suggest that the PI20 scores of autistic participants exhibit little or no correlation with their performance on the Cambridge Face Memory Test-a key measure of face recognition ability. These reports are suggestive of a meta-cognitive deficit whereby autistic individuals are unable to infer whether their face recognition is impaired relative to the wider population. In the present study, however, we observed significant correlations between the PI20 scores of 77 autistic adults and their performance on two variants of the Cambridge Face Memory Test. These findings indicate that autistic individuals can infer whether their face recognition ability is impaired. Consistent with previous research, we observed a wide spread of face recognition abilities within our autistic sample. While some individuals approached ceiling levels of performance, others met the prevailing diagnostic criteria for developmental prosopagnosia. This variability showed little or no association with non-verbal intelligence, autism severity, or the presence of co-occurring alexithymia or ADHD.

Lien vers le texte intégral (Open Access ou abonnement)

9. Ghanouni P, Raphael R, Seaker L, Casey A. How to build resiliency in autistic individuals: an implication to advance mental health. BMC Psychol;2024 (Aug 1);12(1):420.

INTRODUCTION: Individuals on the autism spectrum (ASD) often experience poor mental health and coping strategies compared to their peers due to social exclusion and co-occurring conditions. Resiliency has been identified as a key factor in preventing adverse outcomes and promoting mental health. Therefore, it is important to determine what strategies can be used to build resiliency among autistic individuals. The current paper is one of the first studies that aims to collect information from autistic individuals and their caregivers on potential strategies to enhance resiliency. METHODS: We interviewed 18 participants from various provinces in Canada, comprising of 13 autistic individuals and 5 parents. We used thematic analysis to identify patterns in the data. RESULTS: Thematic analysis revealed three themes to indicate strategies that could be used to enhance resiliency, including: (a) self-reliant strategies, (b) using community-based facilities, and (c) contextual and individual characteristics. CONCLUSION: Although the body of literature on resiliency is evolving, this paper provides a unique perspective as it is one of the few studies that considers the experiences of individuals on the spectrum. In addition, this study focuses on identifying and describing specific strategies that can be used to enhance resiliency and mental health, which consequently can help address the existing gaps in knowledge and practice.

Lien vers le texte intégral (Open Access ou abonnement)

10. Hwang DJ, Kim TK. The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions. J Physiol Sci;2024 (Aug 2);74(1):39.

Many experts have extensively studied the potential of exercise as a treatment option for psychiatric conditions, including depression and autism spectrum disorder (ASD). Despite their core symptoms, these conditions exhibits comparable component traits, an anxiety. In this study, we explored the effect of exercise on behavioral abnormalities in psychiatric conditions, focusing on its intensity and emotional resilience. Shank3B knockout (KO(SED)) mice displaying self-injurious repetitive behavior and C57BL/6J mice, susceptible to stress as ASD and depression model, respectively, were subjected to moderate-intensity exercise (ME) for 2 weeks. ME mitigated the core symptoms (excessive grooming traits and behavioral despair) but did not exert a significant anxiolytic effect. Notably, exercise intensity has emerged as a critical determinant of its efficacy, as evidenced by a lower ventilation threshold and anxiolytic effect mediated by low-intensity exercise. The findings substantiate the notion that exercise is promising as a disease-modifying treatment, but intensity matters for emotional resilience.

Lien vers le texte intégral (Open Access ou abonnement)

11. Jeglum SR, Cicero A, DeBrine J, Livingston CP. Emergency Department Utilization Due to Challenging Behavior in Children and Adolescents Diagnosed with Autism Spectrum Disorder. Behav Sci (Basel);2024 (Aug 2);14(8)

Children and adolescents with autism spectrum disorder (ASD) are at a greater risk of seeking emergency department (ED) services during behavioral crises, such as acute aggression, suicidal or homicidal ideation, self-injury, or other types of challenging behavior (e.g., pica, dangerous behaviors). Research demonstrates children and adolescents with ASD often return to the ED due to challenging behavior, suggesting that gaps in care exist (e.g., follow-up appointments, referrals). However, the current knowledge basis is largely based on data from other countries. Given the unique landscape of healthcare in the United States, it is prudent to elucidate characteristics of children and adolescents with ASD who are seeking emergency care due to challenging behavior, as well as systems-level factors that both contribute to our understanding of challenging behavior and ASD in ED settings. In this study, we focus on frequency and characteristics of children and adolescents with ASD presenting to the ED with challenging behavior over the course of a 6-year period in the Midwest region of the United States. Clinical implications for ED staff are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

12. Kaye AD, Allen KE, Smith Iii VS, Tong VT, Mire VE, Nguyen H, Lee Z, Kouri M, Jean Baptiste C, Mosieri CN, Kaye AM, Varrassi G, Shekoohi S. Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review. Cureus;2024 (Jul);16(7):e63671.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such as chronic constipation and diarrhea. Both the extensive list of ASD-associated disorders and adverse effects from commonly prescribed medications for patients with ASD can impact presenting symptomatology. It is important to keep these potential interactions in mind when considering additional drug treatments or complementary therapies. This review addresses current literature involving novel pharmacological treatments such as oxytocin, bumetanide, acetylcholinesterase inhibitors, and memantine. It also discusses additional therapies such as diet intervention, acupuncture, music therapy, melatonin, and the use of technology to aid education. Notably, several of these therapies require more long-term research to determine efficacy in specific ASD groups within this patient population.

Lien vers le texte intégral (Open Access ou abonnement)

13. Khandjian EW, Moss T, Rose TM, Robert C, Davidovic L. The fragile X proteins’ enigma: to be or not to be nucleolar. Front Cell Dev Biol;2024;12:1448209.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kikuchi K, Michikawa T, Morokuma S, Hamada N, Ikeda S, Shimada Y, Kato K, Ochiai M, Tsuji M, Shimono M, Yoshino K, Suga R, Kawamoto T, Ohga S. Infants’ early recovery from sleep disturbance is associated with a lower risk of developmental delay in the Japan Environment and Children’s Study. Sci Rep;2024 (Aug 1);14(1):17773.

To examine whether patterns, such as the timings of onset or recovery from sleep disturbance, are associated with later developmental problems, including autism spectrum disorder (ASD). Mothers participating in the Japan Environment and Children’s Study with a child aged 3 years were included in the analyses. Children were assessed for short sleep and frequent awakenings at 1 month, 6 months, and 1 year of age. Developmental problems were evaluated at 3 years of age based on ASD diagnosis and developmental delay, using the Japanese translation of the Ages and Stages Questionnaire (ASQ) 3rd edition. Sleep disturbance patterns were classified by onset age, and developmental problem risks were examined based on onset/recovery ages. Among 63,418 mother-infant dyads, 0.4% of infants were later diagnosed with ASD, and 14.4% had abnormal scores on any ASQ domains. The later the onset of short sleep, the lower the risk of abnormal ASQ scores (RR of short sleep onset at 1 year: 1.41; 6 months: 1.52; 1 month: 1.57). The earlier the infants recovered from short sleep persistence, the lower the risk of developmental delay (RR of remittance of sleep problems identified at 1 month by 6 months: 1.07; 1 year: 1.31; not before 1 year: 1.57). Although not all patterns were significant, later short sleep onset and earlier recovery were associated with lower ASD risk. These findings may have significant implications for future interventions in infant development.

Lien vers le texte intégral (Open Access ou abonnement)

15. Kristofik A, Demps KL. Reimagining Support for Autistic Indigenous Children in the United States: Addressing Under-Identification and Service Gaps. Neuropsychiatr Dis Treat;2024;20:1503-1511.

Although the original purpose of this article was to provide a comprehensive review of services provided for autistic children among Indigenous communities in Texas, USA, the authors’ encounter with a significant paucity in availability of data and relevant reports on Indigenous services for ASD spurred the choice of a perspective article instead as it allows a more critical view into the pitfalls surrounding the state of autism services. The meager documentation availability presents a dilemma for both researchers and Indigenous communities since it often leads to misrepresentations of data, and limits understanding of existing support systems. This perspective article addresses these issues and serves to highlight the complexity of collecting data among Indigenous populations across the United States. Specifically, it emphasizes the challenges faced in Texas, shedding light on the various barriers such as variations in cultural identity, government trust, cultural awareness, and disability identity that impede data-collection efforts in providing effective services to Indigenous populations. We advocate for a radical transformation in understanding how to approach and report the prevalence of possible ASD autism among Indigenous children to provide effective and tailored services. Ultimately, this transformation aims to secure the necessary data to provide services that effectively complement the existing support systems within individual Indigenous communities to enable their fullest and most equitable participation in society. The discussion calls for a comprehensive roadmap to achieve the goal of increasing Indigenous data collection and availability while the conclusion outlines a suggested roadmap to achieve the goals of increasing data generation and available services to Indigenous communities, and ultimately, improving services for Indigenous children with ASD in Texas and their families.

Lien vers le texte intégral (Open Access ou abonnement)

16. Lacroix A, Harquel S, Barbosa LS, Kovarski K, Garrido MI, Vercueil L, Kauffmann L, Dutheil F, Gomot M, Mermillod M. Reduced spatial frequency differentiation and sex-related specificities in fearful face detection in autism: Insights from EEG and the predictive brain model. Autism Res;2024 (Aug 2)

Face processing relies on predictive processes driven by low spatial frequencies (LSF) that convey coarse information prior to fine information conveyed by high spatial frequencies. However, autistic individuals might have atypical predictive processes, contributing to facial processing difficulties. This may be more normalized in autistic females, who often exhibit better socio-communicational abilities than males. We hypothesized that autistic females would display a more typical coarse-to-fine processing for socio-emotional stimuli compared to autistic males. To test this hypothesis, we asked adult participants (44 autistic, 51 non-autistic) to detect fearful faces among neutral faces, filtered in two orders: from coarse-to-fine (CtF) and from fine-to-coarse (FtC). Results show lower d’ values and longer reaction times for fearful detection in autism compared to non-autistic (NA) individuals, regardless of the filtering order. Both groups presented shorter P100 latency after CtF compared to FtC, and larger amplitude for N170 after FtC compared to CtF. However, autistic participants presented a reduced difference in source activity between CtF and FtC in the fusiform. There was also a more spatially spread activation pattern in autistic females compared to NA females. Finally, females had faster P100 and N170 latencies, as well as larger occipital activation for FtC sequences than males, irrespective of the group. Overall, the results do not suggest impaired predictive processes from LSF in autism despite behavioral differences in fear detection. However, they do indicate reduced brain modulation by spatial frequency in autism. In addition, the findings highlight sex differences that warrant consideration in understanding autistic females.

Lien vers le texte intégral (Open Access ou abonnement)

17. Lee JP, Chang YH, Tseng YL, Chou TL, Chien YL. Pupillary response during social emotion tasks in autism spectrum disorder. Autism Res;2024 (Aug 2)

Autistic individuals encounter challenges in recognizing emotional expressions of others. Pupillary response has been proposed as an indicator of arousal dysregulation or cognitive load. The pupillary response of autistic individuals during socio-affective tasks remains unclear. This study investigated pupillary response in autistic adults when viewing emotional faces/eyes and recognizing emotions during the Reading the Mind in the Eyes Test (RMET) and watching interpersonal touch scenes in the social touch task. The study included 98 participants diagnosed with autism spectrum disorder and 37 typically developing controls (TD). Pupil size was measured using the Tobii X2-30 Eye Tracker. The results showed that autistic adults had larger maximal pupil sizes, smaller minimal pupil sizes, and greater change rates of pupil size, particularly during the RMET Eyes task. Clinical correlations revealed that attention switching difficulty positively correlated with mean pupil size in TD participants, while social communication deficits positively correlated with mean pupil size in autistic participants. In conclusion, our findings suggest atypical pupillary responses in autistic adults during socio-affective tasks, indicating heightened cognitive demand. Further investigation is necessary to understand the underlying mechanisms and their association with autistic traits.

Lien vers le texte intégral (Open Access ou abonnement)

18. 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)

19. Long EE, Johnson MF, Carpenter LA. Autistic Characteristics, Cognitive Impairment, and Sex as Predictors of Anxiety and Depression among Autistic Youth. J Autism Dev Disord;2024 (Aug 2)

Although it is well established that autistic youth are at high risk for anxiety and depression, factors associated with heightened risk within this population are poorly understood. The purpose of this study was to evaluate whether autistic characteristics and cognitive impairment interact to predict anxiety and depression symptoms, and whether the impacts of autistic characteristics and cognitive impairment on anxiety and depression differ for male and female children. Participants comprised 7989 youth (M = 11.23 years) enrolled in SPARK, a national cohort of autistic individuals. Autistic characteristics were assessed via the Social Communication Questionnaire. Anxiety and depression were assessed via the Child Behavior Checklist. Linear regressions were conducted to examine associations between autistic characteristics, cognitive impairment, and symptoms and to test for interactions. The effect of parent-reported autistic characteristics on anxiety was stronger for males than for females, while the effect of cognitive impairment on anxiety was stronger for females than for males. A different pattern was observed for depression. The effect of autistic characteristics on depression was the same for males and females, while cognitive impairment was not associated with depression per parent report. Findings indicate that both male and female children with high levels of autistic characteristics are susceptible to experiencing anxiety and depression, and that autistic female children with intact cognitive abilities are uniquely vulnerable to experiencing anxiety based on parent report. Results have implications for the prevention of internalizing problems in autistic youth, and highlight future directions for longitudinal work examining mechanisms of comorbidity.

Lien vers le texte intégral (Open Access ou abonnement)

20. Pham HH, Benevides TW, Andresen ML, Bahr M, Nicholson J, Corey T, Jaremski JE, Faughnan K, Edelman M, Hernandez-Hons A, Langer C, Shore S, Ausderau K, Burstin H, Hingle ST, Kirk AS, Johnson K, Siasoco V, Budway E, Chin Kit-Wells MD, Cifra-Bean L, Damiani M, Eisenchenk S, Finn C, Friedman M, Onaiwu MG, Haythorn M, Jirikowic T, Lo MC, Mackin C, Mangrum T, Matisse ZA, Merahn S, Myers AL, Nobbie PD, Siebert JH, Skoch MG, Smith I, Stasio BJ, Sullivan MK, Vuong H, Wheeler M, Wigington TG, Woodward C. Advancing Health Policy and Outcomes for People With Intellectual or Developmental Disabilities: A Community-Led Agenda. JAMA Health Forum;2024 (Aug 2);5(8):e242201.

IMPORTANCE: At least 10 million people in the United States have an intellectual and/or developmental disability (IDD). People with IDD experience considerably higher rates of poor overall health, chronic conditions including diabetes, mental health challenges, maternal mortality, and preventable deaths. This Special Communication proposes national goals based on a community-led consensus model that advances priority health outcomes for people with IDD and their caregivers/partners and identifies critical policy opportunities and challenges in achieving these goals. A community-led consensus agenda offers a foundation for focusing research, improving data collection and quality measurement, enhancing coverage and payment for services, and investing in a prepared clinical workforce and infrastructure in ways that align with lived experiences and perspectives of community members. OBSERVATIONS: People with IDD prioritize holistic health outcomes and tailored supports and services, driven by personalized health goals, which shift over their life course. Caregivers/partners need support for their own well-being, and easy access to resources to optimize how they support loved ones with IDD. Development of an adequately prepared clinical workforce to serve people with IDD requires national and regional policy changes that incentivize and structure training and continuing education. Ensuring effective and high-value coverage, payment, and clinical decisions requires investments in new data repositories and data-sharing infrastructure, shared learning across public and private payers, and development of new technologies and tools to empower people with IDD to actively participate in their own health care. CONCLUSIONS AND RELEVANCE: Consensus health priorities identified in this project and centered on IDD community members’ perspectives are generalizable to many other patient populations. Public and private payers and regulators setting standards for health information technology have an opportunity to promote clinical data collection that focuses on individuals’ needs, quality measurement that emphasizes person-centered goals rather than primarily clinical guidelines, and direct involvement of community members in the design of payment policies. Clinical education leaders, accrediting bodies, and investors/entrepreneurs have an opportunity to innovate a better prepared health care workforce and shared data infrastructure to support value-based care programs.

Lien vers le texte intégral (Open Access ou abonnement)

21. Saleem S, Habib SH. Effect of Infra Low Frequency (ILF) neurofeedback training on EEG in children with autism spectrum disorders. Pak J Med Sci;2024 (Aug);40(7):1397-1402.

OBJECTIVE: To investigate whether Infra-low frequency Neurofeedback (ILF-NFB) training can improve brain electrical activity in children with autism spectrum disorders ASD. METHOD: This single arm pre and post intervention study was carried out at IBMS (Institute of Basic Medical Sciences), Khyber Medical University, Peshawar and Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad from January 2021 to December 2022. A purposive sampling technique was used. Thirty-five ASD children (male=24; female=11; 7-17 years) were provided with 30 sessions of infra low frequency (ILF) neurofeedback training for 15-20 minutes, during 10 weeks. Childhood Autism Rating Scale (CARS) scoring was done and electroencephalogram (EEG) activity was compared before and after ILF-NF training sessions. RESULTS: Around 62.9% participants had mild-moderate autism and 37.1% had severe autism. Wilcoxon Signed rank test revealed a significant decline in delta (Pre-test=47.31±19.22, Post-test=22.07±6.83; p=<0.001), theta (Pre-test=24.75±16.62, Post-test=12.37±3.59; p=<0.001) and alpha (Pre-test=12.01±9.81, Post-test=4.03±1.61; p=< 0.001) waves. Mann Whitney U test exhibited no significant gender differences in EEG pattern before and after neurofeedback except in theta waves (p=0.03) before the intervention. CONCLUSION: Decline in delta, theta, beta and alpha waves propose that ILF-NF training can be effective in improving the EEG activity. ILF-NFB can be perceived as a valuable non-invasive, non-pharmacological intervention for improving EEG pattern via reintegration of brain activity resulting in increased the attention and focus, enhanced mental stability and cognitive engagement.

Lien vers le texte intégral (Open Access ou abonnement)

22. Schielen SJC, Pilmeyer J, Aldenkamp AP, Zinger S. The diagnosis of ASD with MRI: a systematic review and meta-analysis. Transl Psychiatry;2024 (Aug 2);14(1):318.

While diagnosing autism spectrum disorder (ASD) based on an objective test is desired, the current diagnostic practice involves observation-based criteria. This study is a systematic review and meta-analysis of studies that aim to diagnose ASD using magnetic resonance imaging (MRI). The main objective is to describe the state of the art of diagnosing ASD using MRI in terms of performance metrics and interpretation. Furthermore, subgroups, including different MRI modalities and statistical heterogeneity, are analyzed. Studies that dichotomously diagnose individuals with ASD and healthy controls by analyses progressing from magnetic resonance imaging obtained in a resting state were systematically selected by two independent reviewers. Studies were sought on Web of Science and PubMed, which were last accessed on February 24, 2023. The included studies were assessed on quality and risk of bias using the revised Quality Assessment of Diagnostic Accuracy Studies tool. A bivariate random-effects model was used for syntheses. One hundred and thirty-four studies were included comprising 159 eligible experiments. Despite the overlap in the studied samples, an estimated 4982 unique participants consisting of 2439 individuals with ASD and 2543 healthy controls were included. The pooled summary estimates of diagnostic performance are 76.0% sensitivity (95% CI 74.1-77.8), 75.7% specificity (95% CI 74.0-77.4), and an area under curve of 0.823, but uncertainty in the study assessments limits confidence. The main limitations are heterogeneity and uncertainty about the generalization of diagnostic performance. Therefore, comparisons between subgroups were considered inappropriate. Despite the current limitations, methods progressing from MRI approach the diagnostic performance needed for clinical practice. The state of the art has obstacles but shows potential for future clinical application.

Lien vers le texte intégral (Open Access ou abonnement)

23. Singh J, Wilkins G, Goodman-Vincent E, Chishti S, Bonilla Guerrero R, Fiori F, Ameenpur S, McFadden L, Zahavi Z, Santosh P. Using Precision Medicine to Disentangle Genotype-Phenotype Relationships in Twins with Rett Syndrome: A Case Report. Curr Issues Mol Biol;2024 (Aug 2);46(8):8424-8440.

Rett syndrome (RTT) is a paediatric neurodevelopmental disorder spanning four developmental stages. This multi-system disorder offers a unique window to explore genotype-phenotype relationships in a disease model. However, genetic prognosticators of RTT have limited clinical value due to the disorder’s heterogeneity on multiple levels. This case report used a precision medicine approach to better understand the clinical phenotype of RTT twins with an identical pathogenic MECP2 mutation and discordant neurodevelopmental profiles. Targeted genotyping, objective physiological monitoring of heart rate variability (HRV) parameters, and clinical severity were assessed in a RTT twin pair (5 years 7 months old) with an identical pathogenic MECP2 mutation. Longitudinal assessment of autonomic HRV parameters was conducted using the Empatica E4 wristband device, and clinical severity was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI) and the Multi-System Profile of Symptoms Scale (MPSS). Genotype data revealed impaired BDNF function for twin A when compared to twin B. Twin A also had poorer autonomic health than twin B, as indicated by lower autonomic metrics (autonomic inflexibility). Hospitalisation, RTT-CGI-S, and MPSS subscale scores were used as measures of clinical severity, and these were worse in twin A. Treatment using buspirone shifted twin A from an inflexible to a flexible autonomic profile. This was mirrored in the MPSS scores, which showed a reduction in autonomic and cardiac symptoms following buspirone treatment. Our findings showed that a combination of a co-occurring rs6265 BDNF polymorphism, and worse autonomic and clinical profiles led to a poorer prognosis for twin A compared to twin B. Buspirone was able to shift a rigid autonomic profile to a more flexible one for twin A and thereby prevent cardiac and autonomic symptoms from worsening. The clinical profile for twin A represents a departure from the disorder trajectory typically observed in RTT and underscores the importance of wider genotype profiling and longitudinal objective physiological monitoring alongside measures of clinical symptoms and severity when assessing genotype-phenotype relationships in RTT patients with identical pathogenic mutations. A precision medicine approach that assesses genetic and physiological risk factors can be extended to other neurodevelopmental disorders to monitor risk when genotype-phenotype relationships are not so obvious.

Lien vers le texte intégral (Open Access ou abonnement)

24. Tian Y, Luo X, Chen J, Rong H, Wang H, Li B, Li J, You X. Children with elevated wheat IgG4 antibody titer in autism spectrum disorder: Clinical presentation and findings associated with gut microbiota. Allergy;2024 (Aug 2)

Lien vers le texte intégral (Open Access ou abonnement)

25. Wang T, Cheng MM, Liu WW, Tan QZ, Liu CH, Yang Y, Yang XL, Zhang YH. [Genotype and phenotype of WWOX gene related developmental and epileptic encephalopathy]. Zhonghua Er Ke Za Zhi;2024 (Aug 2);62(8):752-757.

Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children’s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children’s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Lien vers le texte intégral (Open Access ou abonnement)

26. Westby C, Chen KM, Cheng L, Jithavech P, Maroonroge S. Autism in Taiwan and Thailand: Influences of Culture. Neuropsychiatr Dis Treat;2024;20:1523-1538.

The prevalence of autism is increasing worldwide. The majority of autism research and development of autism assessments and interventions has been conducted in Western cultures. The prevalence of autism is reportedly lower in Asian versus Western cultures, but this is likely due to lack of personnel and uniform criteria for diagnosing autism. This article describes how two Asian cultures, Taiwan and Thailand, are dealing with the increasing identification of autistic children. National universal healthcare in both Taiwan and Thailand provides a mechanism for assessment and diagnosis of young children, but a lack of a sufficient number of trained professionals limits the availability of intervention services. A focus of research in these cultures has been on parents’ experiences and coping with the stigma and stress of having an autistic child. Cultural values associated with Confucianism and Buddhism influence attitudes toward persons with disability and how parents of autistic children experience and cope with stigma and stress. Both areas have national laws that provide a range of educational opportunities for autistic children, including inclusion into general education classrooms. Special education and general education teachers, however, have little specific training in autism. Speech and language services are rarely offered in public school programs. Available speech and language services are limited to consultation with teachers a few times a year. In general, parents of autistic children are supportive of inclusion programs, but teachers and parents of both autistic and typically developing children express concerns about the ability to implement such programs in ways that are beneficial to all children.

Lien vers le texte intégral (Open Access ou abonnement)

27. Westerveld MF, Malone SA, Clendon S, Bowen R, Hayley G, Paynter J. The home literacy environment of school-age autistic children with high support needs. J Appl Res Intellect Disabil;2024 (Sep);37(5):e13284.

BACKGROUND: As a group, autistic children with high support needs (with adaptive functioning in the range of an intellectual disability) are at risk of significant literacy difficulties. We investigated the parent-reported home literacy environment of this group of children. METHOD: Sixty-two parents of autistic children (4.5 to 18.25 years) attending an autism-specific school completed a home literacy survey reporting on their child’s: (1) alphabet knowledge, (2) interest in reading, (3) activities/interactions around books, (4) reading ability, and (5) writing ability. RESULTS: We found significant positive correlations between parent-reported child interest in reading and literacy-related interactions and skills, but not with child age. Children using spoken words to communicate obtained significantly greater scores on four home-literacy subscales, but not on reading interest. CONCLUSIONS: A better understanding of the home literacy activities of autistic children with high-support needs is needed to inform educational practices aimed at promoting literacy development in this vulnerable population.

Lien vers le texte intégral (Open Access ou abonnement)

28. Yu R, Hafeez R, Ibrahim M, Alonazi WB, Li B. The complex interplay between autism spectrum disorder and gut microbiota in children: A comprehensive review. Behav Brain Res;2024 (Sep 13);473:115177.

Autism spectrum disorder (ASD) is characterized by defects in social communication and interaction along with restricted interests and/or repetitive behavior. Children with ASD often also experience gastrointestinal (GI) problems in fact incidence of GI problems in ASD is estimated up to 80 percent. Intestinal microbiota, which is a collection of trillions of microorganisms both beneficial and potentially harmful bacteria living inside the gut, has been considered one of the key elements of gut disorders. The goal of this review is to explore potential link between gut microbiota and ASD in children, based on the recently available data. This review discusses recent advances in this rapidly expanding area of neurodevelopmental disorders, which focuses on what is known about the changes in composition of gut bacteria in children with ASD, exploration of possible mechanisms via which gut microbiota might influence the brain and thus lead to appearance of ASD symptoms, as well as potential treatments that involve modulation of gut flora to improve symptoms in children with ASD, i.e., probiotics, postbiotics or changes in the diet. Of course, it’s important to keep in mind inherent difficulties in proving of existence of causal relationships between gut bacteria and ASD. There are significant gaps in understanding of the mechanism of gut-brain axis and the mechanisms that underlie ASD. Standardized approaches for research in this area are needed. This review would provide an overview of this exciting emerging field of research.

Lien vers le texte intégral (Open Access ou abonnement)

29. Zarimeidani F, Rahmati R, Mostafavi M, Darvishi M, Khodadadi S, Mohammadi M, Shamlou F, Bakhtiyari S, Alipourfard I. Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?. Inflammation;2024 (Aug 2)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

30. Zhang X, Grove J, Gu Y, Buus CK, Nielsen LK, Neufeld SAS, Koko M, Malawsky DS, Wade E, Verhoef E, Gui A, Hegemann L, Geschwind DH, Wray NR, Havdahl A, Ronald A, St Pourcain B, Robinson EB, Bourgeron T, Baron-Cohen S, Børglum AD, Martin HC, Warrier V. An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles. medRxiv;2024 (Aug 2)

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h(2) (SNP) = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (r(g) = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

Lien vers le texte intégral (Open Access ou abonnement)

31. 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)