1. May DM, Neul J, Piña-Garza JE, Kponee-Shovein K, Satija A, Mahendran M, Downes N, Sheng K, Lema N, Boca A, Lefebvre P, Abler V, Youakim JM, Cheng WY. Gastrointestinal manifestations in pediatric and adult patients with Rett syndrome: an analysis of US claims and physician survey data. Journal of comparative effectiveness research. 2023: e230054.

Aim: Patients with Rett syndrome (RTT) experience gastrointestinal (GI) manifestations. This study aimed to describe the prevalence of GI manifestations and the associated medical costs in patients with RTT in the USA. Patients & Methods: The study combined an insurance claims database analysis with a survey of 100 physicians experienced in RTT management. Results: GI manifestations affected 43.0% of 5940 patients, with increased prevalence in pediatric patients (45.6%) relative to adult patients (40.2%). Annualized mean medical cost of managing GI manifestations was $4473. Only 5.9-8.2% of neurologists and pediatricians ranked GI symptom management among the five most important treatment goals. Conclusion: Patients with RTT experience a high burden of GI manifestations, which translate to considerable medical costs. Importantly, the prevalence of GI manifestations was likely underestimated in this study, as only those symptoms which resulted in a healthcare encounter were captured.

Lien vers le texte intégral (Open Access ou abonnement)

2. Aktypi-Bampouranou A, Kalogirou EM, Skamnakis I, Vlachodimitropoulos D, Tosios KI. Spongiotic Gingival Hyperplasia in a Child with Asperger Syndrome: a Case Report. Journal of oral & maxillofacial research. 2023; 14(3): e5.

BACKGROUND: Asperger syndrome is a type of autism spectrum disorder that may affect oral health and dental management. Spongiotic gingival hyperplasia is a rare lesion with unique clinicopathological features and unknown pathogenesis that has not been previously reported in a patient with autism spectrum disorder. The purpose of this case report is to present the first case of spongiotic gingival hyperplasia in a child with Asperger syndrome. METHODS: A 14-year-old boy with Asperger syndrome was referred for diagnosis and management of bright red granular overgrowths of the marginal gingiva and interdental papilla of the mandibular right incisors and marginal gingiva of the mandibular left incisor. A biopsy was performed on the interdental papilla between the mandibular right incisors. RESULTS: Microscopic examination and cytokeratin 19 immunopositivity confirmed the diagnosis of spongiotic gingival hyperplasia. The parents of the patient declined any further intervention, and four months later the gingival lesions, including the biopsied area, did not show any significant difference from the initial examination. CONCLUSIONS: Patients with autism spectrum diseases, such as Asperger syndrome, cannot achieve a good level of oral hygiene. Thus, it is expected that the incidence of spongiotic gingival hyperplasia should be higher in this group of patients, in case oral microbiome participates in its pathogenesis. Management of such lesions is challenging, as such patients do not comply with a proper oral hygiene program and do not cooperate with surgical excision.

Lien vers le texte intégral (Open Access ou abonnement)

3. Vinter LP, Dillon G, Winder B, Harper CA. A Multi-Perspective Qualitative Study About Working With Autistic Individuals in Prison-Based Interventions to Address Sexual Offending. Sexual abuse : a journal of research and treatment. 2023: 10790632231216701.

Research suggests that sexual offending is one of the more common forms of offending behaviour committed by autistic individuals. Despite this, very little research has investigated approaches to rehabilitation for autistic individuals who have sexually offended. The small body of literature that does exist suggests that interventions to address sexual offending may not be sufficiently adapted for this group. In this paper we present an exploratory qualitative study that (i) explores how prison-based interventions to address sexual offending are experienced by autistic individuals with sexual offense convictions and the staff who work with them, and (ii) identifies and explores the features of prison-based sexual offending interventions that may be challenging or beneficial for autistic individuals, from the perspective of those involved in treatment. Semi-structured interviews were conducted with 12 autistic men serving prison sentences for sexual convictions, and 13 members of prison staff. A multi-perspective phenomenologically-informed thematic (MPT) analysis identified three themes of ‘Feeling overwhelmed’, ‘Out of the comfort zone’, and ‘(Dis)connected to others’. These themes highlight some of the key issues relating to the format and delivery of interventions, as well as the impact of the broader prison context on rehabilitation.

Lien vers le texte intégral (Open Access ou abonnement)

4. Mehra S, Salinas-Miranda AA, Buro AW, Marshall J, Kirby RS. The role of adverse childhood experiences in obesity among adolescents with autism spectrum disorder: National survey of Children’s health 2018-2019. Disability and health journal. 2023: 101550.

BACKGROUND: Adolescents with autism spectrum disorder (ASD) are at an increased risk of overweight/obesity and adverse childhood experiences (ACEs). OBJECTIVE: This study examined whether ACEs increased the odds of overweight/obesity in adolescents with ASD. METHODS: This cross-sectional study used National Survey of Children’s Health (NSCH) 2018-2019 data (N = 31,533 children ages 10-17 years, including n = 480 children with mild ASD and n = 423 children with moderate/severe ASD with normal or overweight/obese BMI). Parent-reported body mass index (BMI) was coded as overweight/obesity vs. normal weight. The independent variable was the count of nine ACEs. Binary logistic regression was conducted, controlling for social ecological factors. RESULTS: The odds of overweight/obesity in adolescents with ASD with 1-2 ACEs (OR 1.3, CI 1.1-1.4) and 3+ ACEs (OR 1.6, CI 1.3-2.0) were higher than those with 0 ACEs; odds increased with higher counts of ACEs. Household income level was the most significant sociodemographic influence on odds of obesity in adolescents with ASD (0-99 % Federal Poverty Level: OR 1.9, CI 1.6-2.3). Adolescents with moderate/severe ASD (OR 1.7, CI 1.2-2.5) and mild ASD (OR 1.6, CI 1.0-2.4) had higher odds of overweight/obesity after accounting for ACEs, race/ethnicity, sex, household income, and physical activity. CONCLUSION: Findings indicated ACEs are associated with ASD, which calls for integration of ACEs information within trauma-informed care practices for obesity prevention and intervention for adolescents with ASD. Persistent disparities of overweight/obesity exist by race/ethnicity, sex, and household income within this population, which indicates the need for tailoring trauma-informed approaches to the unique needs of this population.

Lien vers le texte intégral (Open Access ou abonnement)

5. Twala B, Molloy E. On effectively predicting autism spectrum disorder therapy using an ensemble of classifiers. Scientific reports. 2023; 13(1): 19957.

An ensemble of classifiers combines several single classifiers to deliver a final prediction or classification decision. An increasingly provoking question is whether such an ensemble can outperform the single best classifier. If so, what form of ensemble learning system (also known as multiple classifier learning systems) yields the most significant benefits in the size or diversity of the ensemble? In this paper, the ability of ensemble learning to predict and identify factors that influence or contribute to autism spectrum disorder therapy (ASDT) for intervention purposes is investigated. Given that most interventions are typically short-term in nature, henceforth, developing a robotic system that will provide the best outcome and measurement of ASDT therapy has never been so critical. In this paper, the performance of five single classifiers against several multiple classifier learning systems in exploring and predicting ASDT is investigated using a dataset of behavioural data and robot-enhanced therapy against standard human treatment based on 3000 sessions and 300 h, recorded from 61 autistic children. Experimental results show statistically significant differences in performance among the single classifiers for ASDT prediction with decision trees as the more accurate classifier. The results further show multiple classifier learning systems (MCLS) achieving better performance for ASDT prediction (especially those ensembles with three core classifiers). Additionally, the results show bagging and boosting ensemble learning as robust when predicting ASDT with multi-stage design as the most dominant architecture. It also appears that eye contact and social interaction are the most critical contributing factors to the ASDT problem among children.

Lien vers le texte intégral (Open Access ou abonnement)

6. Lebeña A, Faresjö Å, Faresjö T, Ludvigsson J. Clinical implications of ADHD, ASD, and their co-occurrence in early adulthood-the prospective ABIS-study. BMC psychiatry. 2023; 23(1): 851.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are childhood-onset disorders associated with functional and psychosocial impairments that may persist into adulthood, leading to serious personal and societal costs. OBJECTIVE: This study aimed to examine the socio-economic difficulties, physical and mental comorbidities, and psycho-social vulnerabilities associated with ADHD, ASD, and their co-occurrence among young adults. METHODS: 16 365 families with children born 1997-1999, were involved in the prospective population-based ABIS study (All Babies in Southeast Sweden). A total of 6 233 ABIS young adults answered the questionnaire at the 17-19-year follow-up and were included in this case-control study. Diagnoses of ADHD and ASD from birth up to 17 years of age were obtained from the Swedish National Diagnosis Register. N=182 individuals received a single diagnosis of ADHD, n=78 of ASD, and n=51 received both diagnoses and were considered the co-occurrence group. Multiple multinomial logistic regression analyses were performed. RESULTS: In the univariate analyses all three conditions were significantly associated with concentration difficulties, worse health quality, lower socio-economic status, lower faith in the future, less control over life, and lower social support. In the adjusted analyses, individuals with ADHD were almost three-times more likely to have less money compared with their friends (aOR 2.86; p < .001), experienced worse sleep quality (aOR 1.50; p = .043) and concentration difficulties (aOR 1.96; p < .001). ASD group were two-fold more likely to experience concentration difficulties (aOR 2.35; p = .002) and tended not to have faith in the future (aOR .63; p = .055), however, showed lesser risk-taking bahaviours (aOR .40; p < .001). Finally, the co-occurrence was significantly associated with unemployment (aOR 2.64; p = .007) and tended to have a higher risk of autoimmune disorders (aOR 2.41; p = .051), however, showed a 51% lower risk of stomach pain (aOR .49; p = .030). CONCLUSIONS: All these conditions significantly deteriorated several areas of life. ADHD/ASD co-occurrence is a heavy burden for health associated with several psychosocial vulnerabilities, that shared a similar morbidity pattern with ADHD although showed less risk cognitive and behavioral profile, similar to the ASD group. Long-term follow-up and support for individuals with these conditions over the life course are crucial.

Lien vers le texte intégral (Open Access ou abonnement)

7. Kretz PF, Wagner C, Mikhaleva A, Montillot C, Hugel S, Morella I, Kannan M, Fischer MC, Milhau M, Yalcin I, Brambilla R, Selloum M, Herault Y, Reymond A, Collins SC, Yalcin B. Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein. Genome biology. 2023; 24(1): 261.

BACKGROUND: Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus. RESULTS: We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic cells, yet its function is not understood. Here, we find MVP expression highly specific to the limbic system and show that Mvp regulates neuronal morphology, postnatally and specifically in males. We also recapitulate a previously reported genetic interaction and show that Mvp(+/-);Mapk3(+/-) mice exhibit behavioral deficits, notably decreased anxiety-like traits detected in the elevated plus maze and open field paradigms. CONCLUSIONS: Our study highlights multiple gene drivers in neuroanatomical phenotypes, interacting with each other through complex relationships. It also provides the first evidence for the involvement of the major vault protein in the regulation of brain size and neuroanatomy, specifically in male mice.

Lien vers le texte intégral (Open Access ou abonnement)

8. S AH, A MA, Azouz T, S SK, A MS, A AE-S. Beneficial Effect of Erythropoietin on Ameliorating Propionic Acid-Induced Autistic-Like Features in Young Rats. Acta histochemica et cytochemica. 2023; 56(5): 77-86.

Autism is a neurodevelopmental disorder that impairs communication and social interaction. This study investigated the possible beneficial effects of erythropoietin (EPO) on experimental autistic-like behaviors induced by propionic acid (PPA). Twenty-four rats were distributed into three groups: (i) control; (ii) PPA_Gp: daily injected subcutaneously with PPA for five consecutive days; PPA+EPO-Gp: injected with PPA, then received intraperitoneal injection of EPO once daily for two weeks. Behavioral changes in the rats were assessed. Specimens from the cerebellar hemispheres were subjected to histological and ultrastructure examination, immunohistochemistry for glial fibrillary acidic protein (GFAP) and calbindin-D28K, and biochemical analysis for glutathione peroxidase (GSH-Px), malondialdehyde (MDA), gamma amino-butyric acid (GABA), and serotonin. PPA-Gp showed significant behavioral impairment, with a significant depletion in GSH-px, GABA, and serotonin and a significant increase in MDA. Histological examination revealed reduced Purkinje cell count with ultrastructural degeneration, irregularly arranged nerve fibers in the molecular layer, astrogliosis, and significantly decreased calbindin-immunostaining compared to the control. EPO protected cerebellar structure, increased Purkinje cell count, improved neuronal morphology, reduced PPA-induced autistic-like features, alleviated neuronal oxidative stress, increased intercellular antioxidant levels, and suppressed inflammation. EPO provided significant protection against PPA-induced autistic features in rats, with structural preservation of Purkinje cells.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lopez-Rodriguez AB, Murray CL, Kealy J, Towns C, Roche A, Nazmi A, Doran M, Lowry JP, Cunningham C. Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder. Molecular autism. 2023; 14(1): 43.

BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

Lien vers le texte intégral (Open Access ou abonnement)

10. Luermans J, Fleming J, O’Shea R, Barlow-Stewart K, Palmer EE, Leffler M. « We are not a typical family anymore »: Exploring the experiences and support needs of fathers of children with Fragile X syndrome in Australia. American journal of medical genetics Part A. 2023.

A diagnosis of the X-linked condition Fragile X syndrome (FXS) in a child commonly reveals the mother’s carrier status. Previous research focused on the genetic counseling process for the child and maternal family, despite calls for more research on the support needs of fathers. This study explored experiences and support needs of fathers at least 1 year after their child’s FXS diagnosis to understand barriers and enablers and optimize health outcomes for the family. In-depth interviews were conducted with 11 fathers recruited through the Australian Genetics of Learning Disability Service and the Fragile X Association. Deidentified transcripts were analyzed using thematic analysis guided by an inductive approach. Four themes emerged: (1) making life easier through understanding-yesterday and today, (2) the path to a new normal-today and tomorrow, (3) seeking information and support, and (4) what men want. Fathers reported diagnostic odysseys, postdiagnostic grief, and challenges adjusting. They highlighted difficulties in understanding their child’s unique behaviors and needs, responding to their partner’s psychological support needs, planning for their child’s future, and navigating complex health and disability systems. Participants suggested health professionals facilitate father-to-father support and psychological counseling. These findings highlight the unmet needs of fathers and suggest that a strengths-based approach is critically important given the recognized mental health impact.

Lien vers le texte intégral (Open Access ou abonnement)

11. Karnik A, Malhi G, Ho T, Riffle S, Keller K, Kim SJ. Factors Associated with Pre-Research Recruitment in Autism and Related Developmental Disorders. Journal of autism and developmental disorders. 2023.

PURPOSE: Access to research programs and increased diversity in research enrollment may be key to improving diverse populations’ health and healthcare outcomes. To facilitate research recruitment, a Research Registry (« Registry »), a pre-recruitment database, was developed at an urban tertiary Autism Center (« Autism Center »). In this study, we examined whether disparities in research participation occur in the pre-research recruitment (pre-recruitment) stage. METHODS: We compared demographic factors of patients seen at the Autism Center (but not enrolled in the Registry) vs. patients enrolled in the Registry. We also examined whether demographic factors differ among the Registry participants who were enrolled in the Registry by signing an informed consent form (ICF) vs. by returning a research interest form (RIF). RESULTS: A total of 18,522 patients (including 1092 patients in the Registry with 403 patients via ICF and 689 patients via RIF) were included in this study. English as the primary language, White race, Non-Hispanic ethnicity, and younger age at their first clinic encounter were associated with the Registry. In the Registry sample, the RIF group had a higher proportion of non-English as a primary language, Medicaid insurance, longer distance from the Autism Center, and lower median household income (based on their ZIP code) than the ICF group. CONCLUSIONS: This study suggests that disparities may have existed in the pre-research recruitment stage. To achieve equity in both clinical and research advancements in autism and related developmental disorders, further efforts are needed to equitably disseminate research opportunities to patients of diverse backgrounds.

Lien vers le texte intégral (Open Access ou abonnement)

12. Ikeda A, Hakuno Y, Asada K, Ikeda T, Yamagata T, Hirai M. Development of emotion comprehension in children with autism spectrum disorder and Williams syndrome. Autism research : official journal of the International Society for Autism Research. 2023.

Although research has shed light on the development of emotion comprehension in typically developing children, little is known about emotion comprehension in children who are developing atypically. Thus, this study examined the developmental trajectory of emotion understanding in non-clinical (NC) children and children with autism spectrum disorder (ASD) and Williams syndrome (WS) using a Test of Emotion Comprehension. In the test, we measured children’s understanding of (I) recognition of emotions based on facial expressions, (II) external causes of emotions, (III) desire-based emotions, (IV) belief-based emotions, (V) the influence of a reminder on a present emotional state, (VI) regulating an experienced emotion, (VII) hiding an emotional state, (VIII) mixed emotions, and (IX) moral emotions. A Bayesian modeling approach was applied to compare the developmental trajectories of emotion understanding across the syndrome groups. The results revealed that NC children and children with WS followed significantly different developmental trajectories in specific aspects of emotion understanding, while children with ASD followed a very similar path to NC children. Children with ASD and NC children gradually developed an understanding of each component of emotion comprehension as they matured. However, the understanding of some components, such as desire-based emotions, hiding an emotional state, and moral emotions, in children with WS was affected by their Autism Spectrum Quotient scores. This is one of the first cross-syndrome studies to assess the development of emotion comprehension in children with ASD and WS, providing important insights for understanding the nature of disability and advancing the development of intervention programs.

Lien vers le texte intégral (Open Access ou abonnement)

13. da Silva CP, Camuzi D, Reis AHD, Gonçalves AP, Dos Santos JM, Machado FB, Medina-Acosta E, Soares-Lima SC, Santos-Rebouças CB. Identification of a novel epigenetic marker for typical and mosaic presentations of fragile X syndrome. Expert review of molecular diagnostics. 2023.

BACKGROUND: Fragile X syndrome (FXS) is primarily due to CGG repeat expansions in the FMR1 gene. FMR1 alleles are classified as normal (N), intermediate (I), premutation (PM), and full mutation (FM). FXS patients often carry an FM, but size mosaicism can occur. Additionally, loss of methylation boundary upstream of repeats results in de novo methylation spreading to FMR1 promoter in FXS patients. RESEARCH DESIGN AND METHODS: This pilot study investigated the methylation boundary and adjacent regions in 66 males with typical and atypical FXS aged 1 to 30 years (10.86 ± 6.48 years). AmplideX FMR1 mPCR kit was used to discriminate allele profiles and methylation levels. CpG sites were assessed by pyrosequencing. RESULTS: 0 out of 66 FXS patients (60.6%) showed an exclusive FM (n = 40), whereas the remaining (n = 26) exhibited size mosaicism [10 PM_FM (15.15%); 10 N_FM (15.15%); 2 N_PM_FM (3%)]. Four patients (6.1%) had deletions near repeats. Noteworthy, a CpG within FMR1 intron 2 displayed hypomethylation in FXS patients and hypermethylation in controls, demonstrating remarkable specificity, sensitivity, and accuracy when a methylation threshold of 69.5% was applied. CONCLUSIONS: Since intragenic methylation is pivotal in gene regulation, the intronic CpG might be a novel epigenetic biomarker for FXS diagnosis.

Lien vers le texte intégral (Open Access ou abonnement)

14. Bazelmans T, Scerif G, Holmboe K, Gonzalez-Gomez N, Hendry A. Rates of family history of autism and ADHD varies with recruitment approach and socio-economic status. The British journal of developmental psychology. 2023.

Family history (FH) of autism and ADHD is not often considered during the recruitment process of developmental studies, despite high recurrence rates. We looked at the rate of autism or ADHD amongst family members of young children (9 to 46 months) in three UK-based samples (N = 1055) recruited using different methods. The rate of FH-autism or FH-ADHD was 3%-9% for diagnosed cases. The rate was highest in the sample recruited through an online participant pool, which also consisted of the most socio-economically diverse families. Lower parental education and family income were associated with higher rates of FH-ADHD and lower parental education with increased FH-autism. Thus, recruitment strategies have a meaningful impact on neurodiversity and the conclusions and generalizations that can be drawn. Specifically, recruitment using crowdsourcing websites could create a sample that is more representative of the wider population, compared to those recruited through university-related volunteer databases and social media.

Lien vers le texte intégral (Open Access ou abonnement)