1. Ahmadi BBM, Afarinesh MR, Jafaripour L, Sheibani V. Alteration in social interaction and tactile discrimination of juvenile autistic-like rats following tactile stimulation and whisker deprivation. Brain and behavior. 2023: e2993.

INTRODUCTION: Autism spectrum disorder is a developmental disorder that can affect sensory-motor behaviors in the valproic acid (Val) rodent model of autism. Although whisker deprivation (WD) induces plastic changes in the cortical neurons, tactile stimulation (TS) during the neonatal period may reverse it. Here, we investigate the interaction effects of TS and WD on behavioral and histologic features of barrel cortex neurons in juvenile Val-treated. METHODS: Control (CTL, CTL-TS, CTL-WD, and CTL-TS-WD groups) and Val-treated (Val, Val-TS, Val-WD, and Val-TS-WD groups) rats of both sexes were subjected to behavioral tests of social interaction, and novel texture recognition, and Nissl staining. The TS groups were exposed to sensory stimulation for 15 min, three times/day; moreover, all whiskers in the WD groups were trimmed every other day from postnatal days 1 to 21. RESULTS: Both prenatal valproic acid administration and postnatal WD decreased the rats’ performance percentage of the Val and CTL-WD groups of both sexes compared with the CTL groups in the social interaction and texture discrimination tests. Following TS, the performance of the Val-TS-WD group increased significantly compared to the Val group (p < .05), whereas the performance of the CTL-TS-WD group rescued to the CTL group. Nissl staining results also revealed the neuron degeneration percentage in the barrel field area of the Val and CTL-WD groups was increased significantly (p < .05) compared with the CTL group. In this regard, TS decreased the neuron degeneration percentage of the Val-TS-WD and the CTL-TS-WD groups, compared with the CTL group, significantly (p < .05). CONCLUSION: TS in juvenile male and female rats can act as a modulator and compensate for the behavioral and histological consequences of WD and prenatal valproic acid exposure.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bohlen JF, Cleary CM, Das D, Sripathy SR, Sadowski N, Shim G, Kenney RF, Buchler IP, Banerji T, Scanlan TS, Mulkey DK, Maher BJ. Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt-Hopkins syndrome. Brain : a journal of neurology. 2023.

Pitt-Hopkins syndrome is an autism spectrum disorder caused by autosomal dominant mutations in the human transcription factor 4 gene (TCF4). One pathobiological process caused by murine Tcf4 mutation is a cell autonomous reduction in oligodendrocytes and myelination. In this study, we show that the promyelinating compounds, clemastine, sobetirome and Sob-AM2 are effective at restoring myelination defects in a Pitt-Hopkins syndrome mouse model. In vitro, clemastine treatment reduced excess oligodendrocyte precursor cells and normalized oligodendrocyte density. In vivo, 2-week intraperitoneal administration of clemastine also normalized oligodendrocyte precursor cell and oligodendrocyte density in the cortex of Tcf4 mutant mice and appeared to increase the number of axons undergoing myelination, as EM imaging of the corpus callosum showed a significant increase in the proportion of uncompacted myelin and an overall reduction in the g-ratio. Importantly, this treatment paradigm resulted in functional rescue by improving electrophysiology and behaviour. To confirm behavioural rescue was achieved via enhancing myelination, we show that treatment with the thyroid hormone receptor agonist sobetirome or its brain penetrating prodrug Sob-AM2, was also effective at normalizing oligodendrocyte precursor cell and oligodendrocyte densities and behaviour in the Pitt-Hopkins syndrome mouse model. Together, these results provide preclinical evidence that promyelinating therapies may be beneficial in Pitt-Hopkins syndrome and potentially other neurodevelopmental disorders characterized by dysmyelination.

Lien vers le texte intégral (Open Access ou abonnement)

3. Borre ED, Myers E, Hamilton Lopez M, Kurtzberg J, Shaz B, Troy J, Sanders Schmidler GD. The potential cost-effectiveness of novel cord blood therapies in children with autism spectrum disorder. PloS one. 2023; 18(4): e0282906.

OBJECTIVE: To model the long-term clinical and economic outcomes of potential cord blood therapy in autism spectrum disorder (ASD). STUDY DESIGN: Markov microsimulation of ASD over the lifespan was used to compare two strategies: 1) standard of care (SOC), including behavioral and educational interventions, and 2) novel cord blood (CB) intervention in addition to SOC. Input data reflecting behavioral outcomes included baseline Vineland Adaptive Behavior Scale (VABS-3), monthly VABS-3 changes, and CB intervention efficacy on adaptive behavior based on a randomized, placebo-controlled trial (DukeACT). Quality-adjusted life-years (QALYs) were correlated to VABS-3. Costs for children with ASD ($15,791, ages 2-17 years) and adults with ASD ($56,559, ages 18+ years), and the CB intervention (range $15,000-45,000) were incorporated. Alternative CB efficacy and costs were explored. RESULTS: We compared model-projected results to published data on life-expectancy, mean VABS-3 changes, and lifetime costs. Undiscounted lifetime QALYs in the SOC and CB strategies were 40.75 and 40.91. Discounted lifetime costs in the SOC strategy were $1,014,000, and for CB ranged from $1,021,000-$1,058,000 with CB intervention cost ($8,000-$45,000). At $15,000 cost, CB was borderline cost-effective (ICER = $105,000/QALY). In one-way sensitivity analysis, CB cost and efficacy were the most influential parameters on CB ICER. CB intervention was cost-effective at costs<$15,000 and efficacies ≥2.0. Five-year healthcare payer projected budgetary outlays at a $15,000 CB cost were $3.847B. CONCLUSIONS: A modestly effective intervention designed to improve adaptive behavior in autism can be cost-effective under certain circumstances. Intervention cost and efficacy most affected the cost-effectiveness results and should be targeted to increase economic efficiency.

Lien vers le texte intégral (Open Access ou abonnement)

4. Bylemans T, Heleven E, Asselman E, Baetens K, Deroost N, Baeken C, Van Overwalle F. Sex differences in autistic adults: A preliminary study showing differences in mentalizing, but not in narrative coherence. Acta psychologica. 2023; 236: 103918.

Studying autism might be a complex endeavor due to its clinical heterogeneity. Little is currently known about potential sex differences in autistic adults, especially regarding mentalizing and narrative coherence. In this study, male and female participants told a personal story about one of their most positive and most negative life events and performed two mentalizing tasks. One of these mentalizing tasks was a recently developed Picture and Verbal Sequencing task that has shown cerebellar recruitment, and which requires mentalizing in a sequential context (i.e., participants chronologically ordered scenarios that required true and false belief mentalizing). Our preliminary comparison shows that males were faster and more accurate on the Picture Sequencing task compared to female participants when ordering sequences involving false beliefs, but not true beliefs. No sex differences were found for the other mentalizing and narrative tasks. These results highlight the importance of looking at sex differences in autistic adults and provide a possible explanation for sex-related differences in daily life mentalizing functions, which suggest a need for more sensitive diagnosis and tailored support.

Lien vers le texte intégral (Open Access ou abonnement)

5. Cano-Villagrasa A, Moya-Faz FJ, López-Zamora M. Relationship of epilepsy on the linguistic-cognitive profile of children with ASD: A systematic review of the literature. Frontiers in psychology. 2023; 14: 1101535.

INTRODUCTION: The prevalence of comorbidity between epilepsy and Autism Spectrum Disorder (ASD) in the pediatric age increased significantly in recent years. The onset of epilepsy negatively influences the abilities of the user with ASD. Thus, epilepsy will be a disabling factor that will reduce the cognitive-linguistic skills of users with ASD. The main objective of this work is to review the current scientific literature and to compare the relationship of epilepsy on the development of cognitive and linguistic skills of children with ASD. METHODS: In this regard, a systematic search was carried out in the main sources (Medline, PubMed, WOS, ResearchGate and Google Scholar). 481 articles were identified, from which, after meeting the different inclusion and exclusion criteria, a total of 18 studies of relevance to the objectives of this work were selected. RESULTS: The results reflect that, at a global level, epilepsy significantly influences the performance of cognitive- linguistic skills in people with ASD. DISCUSSION: In conclusion, epilepsy in the ASD population leads to a reduction in cognitive and linguistic abilities, which respond to the different types of epilepsy and their location, significantly impacting the quality of life and basic activities of daily living of the user with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cupaioli FA, Mosca E, Magri C, Gennarelli M, Moscatelli M, Raggi ME, Landini M, Galluccio N, Villa L, Bonfanti A, Renieri A, Fallerini C, Minelli A, Marabotti A, Milanesi L, Fasano A, Mezzelani A. Author Correction: Assessment of haptoglobin alleles in autism spectrum disorders. Scientific reports. 2023; 13(1): 6321.

Lien vers le texte intégral (Open Access ou abonnement)

7. Hasler M, Fideli Ü S, Susi A, Hisle-Gorman E. Examining the relationship between autism spectrum disorder and neural tube defects. Congenital anomalies. 2023.

Folate and vitamin B(12) deficiencies have been strongly associated with neural tube defects, preliminary research suggests folate and B(12) deficiency may also be associated with autism spectrum disorder (ASD). We examined the association between neural tube defects and ASD as a further avenue to examine the hypothesis that ASD is related to maternal folate and B(12) deficiency during pregnancy. A retrospective case-control study was performed using the Military Health System Data Repository. Cases and matched controls were followed from birth until at least 6 months after their first autism diagnosis. International Classification of Diseases, 9th Revision, codes were used to identify neural tube defects in the health records. A total of 8760 cases between the ages of 2 and 18 years were identified. The prevalence of any neural tube defect was 0.11% in children without ASD and 0.64% in children with ASD. Children with autism were over 6 times as likely to have a neural tube defect. The increased odds of neural tube defect in children diagnosed with ASD, found through our methodology, supports prior studies. Although additional studies are needed to elucidate the relationship between ASD and maternal folate and vitamin B(12) deficiency during pregnancy this study supports their use during pregnancy.

Lien vers le texte intégral (Open Access ou abonnement)

8. Hatch B, Kadlaskar G, Miller M. Diagnosis and treatment of children and adolescents with autism and ADHD. Psychology in the schools. 2023; 60(2): 295-311.

Attention-deficit/hyperactivity disorder (ADHD) and autism are neurodevelopmental disorders that emerge in childhood. There is increasing recognition that ADHD and autism frequently co-occur. Yet, questions remain among clinicians regarding the best ways to evaluate and treat co-occurring autism and ADHD. This review outlines issues relevant to providing evidence-based practice to individuals and families who may be experiencing difficulties associated with co-occurring autism and ADHD. After describing the complexities of the co-occurrence of autism and ADHD, we present practical considerations for best practice assessment and treatment of co-occurring autism and ADHD. Regarding assessment, this includes considerations for interviewing parents/caregivers and youth, using validated parent and teacher rating scales, conducting cognitive assessments, and conducting behavior observations. Regarding treatment, consideration is given to behavioral management, school-based interventions, social skills development, and the use of medications. Throughout, we note the quality of evidence that supports a particular component of assessment or treatment, highlighting when evidence is most relevant to those with co-occurring autism and ADHD across stages of development. In light of the current evidence for assessment and treatment of co-occurring autism and ADHD, we conclude by outlining practical implications for clinical and educational practice.

Lien vers le texte intégral (Open Access ou abonnement)

9. Jane A, Kanigsberg L, Patel A, Eldon S, Anagnostou E, Brian J, Penner M. Summative content analysis of the recommendations from Project ECHO Ontario Autism. Frontiers in rehabilitation sciences. 2023; 4: 1096314.

BACKGROUND: Practitioners report a lack of knowledge and confidence in treating autistic children, resulting in unmet healthcare needs. The Extension of Community Healthcare Outcomes (ECHO) Autism model addresses this through discussion of participant-generated cases, helping physicians provide best-practice care through co-created recommendations. Recommendations stemming from ECHO cases have yet to be characterized and may help guide the future care of autistic children. Our objective was to characterize and categorize case discussion recommendations from Project ECHO Ontario Autism to better identify gaps in clinician knowledge. METHODS: We conducted a summative content analysis of all ECHO Ontario Autism case recommendations to identify categories of recommendations and their frequencies. Two researchers independently coded recommendations from five ECHO cases to develop the coding guide. They then each independently coded all remaining cases and recommendations from three cycles of ECHO held between October 2018 to July 2021, meeting regularly with the ECHO lead to consolidate the codes. A recommendation could be identified with more than one code if it pertained to multiple aspects of autism care. Categories from the various codes were identified and the frequency of each code was calculated. RESULTS: Of the 422 recommendations stemming from 62 cases, we identified 55 codes across ten broad categories. Categories included accessing community resources (n = 224), referrals to allied health and other providers (n = 202), ongoing autism care (n = 169), co-occurring mental and physical health conditions (n = 168), resources and tools for further learning (n = 153), physician to provide education and coaching to families (n = 150), promoting parent and family wellness (n = 104), supporting community autism diagnosis (n = 97), promoting patient empowerment and autonomy (n = 87), and COVID-19 (n = 26). CONCLUSION: This is the first time that recommendations from ECHO Autism have been characterized and grouped into categories. Our results show that advice for autism identification and management spans many different facets of community-based care. Specific attention should be paid to providing continued access to education about autism, streamlining referrals to allied health providers, and a greater focus on patient- and family-centered care. Physicians should have continued access to autism education to help fill knowledge gaps and to facilitate families’ service navigation.

Lien vers le texte intégral (Open Access ou abonnement)

10. Kasari C, Shire S, Shih W, Landa R, Levato L, Smith T. Spoken language outcomes in limited language preschoolers with autism and global developmental delay: RCT of early intervention approaches. Autism research : official journal of the International Society for Autism Research. 2023.

Preschool autistic children with significant global developmental delays and very limited language skills are at high risk for remaining minimally verbal at entry into primary school. This study compared two early intervention models for improving social communication and spoken language outcomes in 164 children who received intervention in their community preschool program for 6 months, with a six-month follow-up. The primary outcome measure was a standardized language assessment, and secondary measures focused on social communication. Results indicated children on average made 6 months gain in language development in the active 6 months of intervention with no difference between intervention models. Children who initiated joint attention more frequently, or who had higher receptive language at baseline made more progress if assigned to receive JASPER, a naturalistic developmental behavioral intervention. Children who received Discrete Trial Training made greater spoken language progress from exit to follow-up. These findings suggest that progress can be made in autistic children who have very little spoken language and who receive targeted early interventions. Individual trajectories vary and depend in part on initial abilities in social communication and receptive language. Future research might consider methods to systematically personalize approaches to fit child characteristics and family preference. LAY SUMMARY: This study compared two different early intervention approaches for teaching spoken language to minimally verbal, globally delayed autistic preschoolers. Children were given an hour of therapy daily for 6 months and then reassessed 6 months later. The majority of the 164 participants were from historically excluded populations (low income and minority), and therapy was delivered in school community settings by expert clinicians. Results indicated that the participants made significant progress regardless of intervention approach: 6 months gain in standardized language scores over 6 months, but slower progress during the period after therapy ended. Children who initiated joint attention more frequently, or who had higher language understanding at baseline made more progress if assigned to receive JASPER, a naturalistic developmental behavioral intervention. Children who received Discrete Trial Training made greater language progress during 6-month period after therapy ended. These findings suggest that progress can be made in children with ASD who have very little spoken language and who receive targeted early interventions.

Lien vers le texte intégral (Open Access ou abonnement)

11. Lee YF, Wu MC, Ma KS, Huang JY, Wei JC. Association of early childhood constipation with the risk of autism spectrum disorder in Taiwan: Real-world evidence from a nationwide population-based cohort study. Frontiers in psychiatry. 2023; 14: 1116239.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental problem that presents with limited interests, repetitive behaviors, and deficits in reciprocal communication and social interactions. Mounting evidence indicates that an imbalanced gut microbiota contributes to autism via the gut-brain axis. Constipation may result in alteration of the gut microbiota. The clinical influence of constipation on ASD has not been fully researched. Thus, in this study we aimed to evaluate whether early childhood constipation influenced the risk of developing ASD using a nationwide population-based cohort study. METHODS: We identified 12,935 constipated children aged 3 years or younger from the National Health Insurance Research Database (NHIRD) in Taiwan from 1997 to 2013. Non-constipated children were also selected from the database and propensity score matching of age, gender, and underlying comorbidities was conducted with a ratio of 1:1. Kaplan-Meier analysis was applied to determine different levels of constipation severity and cumulative incidence of autism. Subgroup analysis was also applied in this study. RESULTS: The incidence rate of ASD was 12.36 per 100,000 person-months in the constipation group, which was higher than the rate of 7.84 per 100,000 person-months noted in the non-constipation controls. Constipated children had a significantly higher risk of autism when compared to the non-constipation group (crude relative risk = 1.458, 95% CI = 1.116-1.904; adjusted hazard ratio = 1.445, 95% CI = 1.095-1.907).Moreover, among constipated children, a higher number of laxative prescriptions, male gender, constipation during infancy, and atopic dermatitis were significantly associated with higher risks of ASD when compared to the non-constipation group. CONCLUSION: Constipation in early childhood was correlated with a significantly increased risk of ASD. Clinicians should pay attention to the possibility of ASD in constipated children. Further research is necessary to study the possible pathophysiological mechanisms of this association.

Lien vers le texte intégral (Open Access ou abonnement)

12. Ma Y, Lee LY, Zhang X. Affiliate stigma and related factors among parents of autism spectrum condition: A pilot study from mainland China. Autism & developmental language impairments. 2023; 8: 23969415231168567.

BACKGROUND: Autistic individuals show differences in social and behavioral performances. Autism-related stigma affects autistic children as well as their caregivers (e.g., parents). Research has shown that stigmatizing reactions from others toward caregivers of autistic children are common and that these caregivers suffer from affiliate stigma. AIMS: To examine the level of affiliate stigma among parents of autistic children and its predictive factors in mainland China. METHODS: This was a cross-sectional study involving parents of autistic children from mainland China. The sample consisted of 183 parents (mean age  =  36.5 years). The measures assessed included demographic characteristics, and parents completed two questionnaires. The Social Responsiveness Scale (SRS) was used to evaluate the characteristics of children by their parent’s subjective assessments, and the Affiliate Stigma Scale (ASS) was used to investigate the affiliate stigma level of parents. RESULTS: The affiliate stigma levels of parents of autistic children were high, and the mean score of the affect subscale was higher than those of the other subscales. The mean ASS score differed significantly between employed and unemployed parents, those aged under 40 and over 40, and high- and low-income parents. The hierarchical regression analysis showed that parents’ age, monthly household income, and mean SRS score were significant predictors of the mean ASS score. The results indicated that parents of autistic children and their children need more social support and inclusion in mainland China. CONCLUSION: The present study confirms the importance of studying primary caregivers (i.e., parents) in the context of traditional mainland Chinese culture. Although preliminarily, findings showed that the affiliate stigma levels of parents are high in mainland China, probably due to the influence of traditional cultural values. Moreover, considering the importance of autistic child characteristics, our results suggest that we should increase public knowledge of autism, enrich the general understanding of autism, and reduce the autism-related stigma of parents in mainland Chinese societies.

Lien vers le texte intégral (Open Access ou abonnement)

13. Manono MN, Clasquin-Johnson MG. ‘Yebo, it was a great relief’: How mothers experience their children’s autism diagnoses. African journal of disability. 2023; 12: 1101.

BACKGROUND: There is an emerging body of knowledge on the lived experiences of parenting a child with autism from a maternal perspective. Mothers’ reactions to their children’s autism diagnoses have been identified as a key factor influencing their children’s long-term outcomes. OBJECTIVES: This qualitative study aimed to explore how South African mothers experience their children’s autism diagnoses. METHOD: Telephonic interviews were conducted with 12 mothers from KwaZulu-Natal to understand their experiences prior, during and following their children’s autism diagnoses. The data were analysed thematically according to the values of ubuntu, social support, culture, tradition, interpersonal relationships, interconnectedness and continuity and compared to the existing scholarship, employing an Afrocentric theoretical lens. RESULTS: The participants held strong cultural and religious beliefs which influenced the entire diagnosis process. Some, who waited a long time, turned to traditional healers or religious leaders. While some reported feeling relieved after the diagnosis, in the sense of at least having a name for their child’s condition, they also reported feeling overwhelmed by the realisation that there is no cure for autism. Over time, mothers’ feelings of guilt and anxiety declined, and they became increasingly resilient and empowered as their understanding of the meaning of their children’s autism diagnosis deepened, but many continued to pray for a miracle. CONCLUSION: Future research should focus on how to enhance support for mothers and their children during each of the three phases of autism diagnosis: prior, during and following their children’s autism diagnoses. CONTRIBUTION: The study highlighted the crucial role of community-based religious and cultural organisations in providing appropriate support to mothers and their children diagnosed with autism, aligned to the values of ubuntu, social support, culture, tradition, interpersonal relationships, interconnectedness and continuity.

Lien vers le texte intégral (Open Access ou abonnement)

14. Moser M, Müllner C, Ferro P, Albermann K, Jenni OG, von Rhein M. The role of well-child visits in detecting developmental delay in preschool children. BMC pediatrics. 2023; 23(1): 180.

BACKGROUND: Early detection of developmental delay (DD) in preschool children is crucial for counselling parents, initiating diagnostic work-up, and starting early intervention (EI). METHODS: We conducted a register study of all preschool children referred for EI in the Canton of Zurich, Switzerland, in 2017 (N = 1,785) and used an online survey among primary care physicians (PCPs, N = 271) to evaluate the care service of DD children. RESULTS: PCPs accounted for 79.5% of all referrals by physicians and had correctly referred over 90% of the children in need of EI at an average age of 39.3 months (SD 8.9). In the survey, which represents 59.2% of all pediatricians and 11.3% of all general practitioners in the Canton, PCPs reported performing a mean of 13.5 (range 0-50, SD 10.7) well-child visits per week to preschool children and estimated well-child visits to be the most frequent type of consultation (66.7%) for the identification of DD. Parents’ hesitancy in accepting further evaluation or support were reported by 88.7%. CONCLUSIONS: Most preschool children with DD are identified in well-child visits. These visits represent an ideal opportunity for early detection of developmental impairment and initiation of EI. Carefully addressing parents’ reservations could reduce the rate of refusal, thus improving early support for children with DD.

Lien vers le texte intégral (Open Access ou abonnement)

15. Nisar S, Haris M. Neuroimaging genetics approaches to identify new biomarkers for the early diagnosis of autism spectrum disorder. Molecular psychiatry. 2023.

Autism-spectrum disorders (ASDs) are developmental disabilities that manifest in early childhood and are characterized by qualitative abnormalities in social behaviors, communication skills, and restrictive or repetitive behaviors. To explore the neurobiological mechanisms in ASD, extensive research has been done to identify potential diagnostic biomarkers through a neuroimaging genetics approach. Neuroimaging genetics helps to identify ASD-risk genes that contribute to structural and functional variations in brain circuitry and validate biological changes by elucidating the mechanisms and pathways that confer genetic risk. Integrating artificial intelligence models with neuroimaging data lays the groundwork for accurate diagnosis and facilitates the identification of early diagnostic biomarkers for ASD. This review discusses the significance of neuroimaging genetics approaches to gaining a better understanding of the perturbed neurochemical system and molecular pathways in ASD and how these approaches can detect structural, functional, and metabolic changes and lead to the discovery of novel biomarkers for the early diagnosis of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

16. Pickard K, Burrell TL, Brasher S, Buckley D, Gillespie S, Sharp W, Scahill L. Examining adaptations necessary to support the implementation of a parent-mediated intervention for children with autism spectrum disorder and moderate feeding problems. Autism : the international journal of research and practice. 2023: 13623613231166181.

Moderate feeding problems and disruptive mealtime behaviors are common in children with autism spectrum disorder. Although parent-mediated interventions are able to support feeding problems in autistic children, most research has occurred within specialty clinics when delivered by highly trained clinicians. Thus, the fit of these interventions within community settings is not clear. To address this limitation, this study explored adaptations to a parent-mediated intervention, Managing Eating Aversions and Limited Variety (i.e. MEAL Plan), to improve its fit and use within community settings. Participants were 14 multidisciplinary providers who attended one of the three intensive workgroups that included focus groups about the fit of MEAL Plan in their practice setting. Qualitative analysis was used to determine the main themes that came up within the focus groups. Specific themes included the appropriateness MEAL Plan for autistic and non-autistic children, how providers might adapt their delivery of MEAL Plan, billing and insurance considerations, administrator support for MEAL Plan, and the content and format of ongoing training and consultation. By proactively considering and responding to these factors, it may be possible to enhance MEAL Plan so that it is better able to be delivered and sustained within community practices that support autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

17. Sharghi S, Flunkert S, Daurer M, Rabl R, Chagnaud BP, Leopoldo M, Lacivita E, Hutter-Paier B, Prokesch M. Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models. Frontiers in neuroscience. 2023; 17: 1087788.

INTRODUCTION: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology. METHODS: The GABA (B) receptor agonist R-Baclofen and the selective agonist for the 5HT(7) serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD. To evaluate the efficacy of these compounds in more details, we treated BTBR T(+) Itpr3 (tf) /J and B6.129P2-Fmr1 (tm1Cgr) /J mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests. RESULTS: BTBR mice showed motor deficits, elevated anxiety, and highly repetitive behavior of self-grooming. Fmr1-KO mice exhibited decreased anxiety and hyperactivity. Additionally, Fmr1-KO mice’s ultrasonic vocalizations were impaired suggesting a reduced social interest and communication of this strain. Acute LP-211 administration did not affect the behavioral abnormalities observed in BTBR mice but improved repetitive behavior in Fmr1-KO mice and showed a trend to change anxiety of this strain. Acute R-Baclofen treatment improved repetitive behavior only in Fmr1-KO mice. CONCLUSION: Our results add value to the current available data on these mouse models and the respective compounds. Yet, additional studies are needed to further test R-Baclofen and LP-211 as potential treatments for ASD therapy.

Lien vers le texte intégral (Open Access ou abonnement)

18. Steigerwald AJ, Ferguson BJ, Nuraini N, Barnett JC, Takahashi N, Zamzow R, Heilman KM, Beversdorf DQ. Altered Allocation of Vertical Attention in Individuals With Autism Spectrum Disorder. Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology. 2023.

BACKGROUND: Typical adults most frequently orient their attention to other people’s eyes, whereas individuals with autism spectrum disorder (ASD) orient their attention to other people’s mouths. Typical adults also reveal visuospatial biases on tasks such as vertical and horizontal line bisections. Therefore, the difference in face viewing might be related to a more general group difference in the allocation of vertical attention. OBJECTIVE: To use vertical line bisection and quadrisection tasks to evaluate whether individuals with ASD have a more downward-oriented vertical attentional bias than do typical individuals. METHOD: We recruited 20 individuals with ASD and 20 control participants matched for age (6-23 years), IQ, and sex. We asked the individuals to bisect and quadrisect lines on the top and bottom when the vertical lines were placed at the intersection of their right, left, and center egocentric sagittal planes and their coronal plane. The distances from the true midpoint and quadripoint were measured, and between-group performances were compared. RESULTS: No significant difference was found between the ASD and control groups for vertical line bisections or lower line quadrisections. However, when the ASD group was compared with the control group for higher line quadrisections, the ASD group exhibited a greater upward deviation. CONCLUSION: There is no downward vertical attentional spatial bias associated with ASD that could help to explain these individuals’ attentional bias toward the mouth. However, additional studies are required to learn if this atypical upward vertical attentional bias might account for some of the symptoms and signs associated with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

19. Zhao YN, Fan HY, Wang XY, Luo YN, Zhang R, Zheng XY. [Early death and causes of death of patients with autism spectrum disorders: A systematic review]. Beijing da xue xue bao Yi xue ban = Journal of Peking University Health sciences. 2023; 55(2): 375-83.

To study of premature/early death of autistic patients from the perspective of life course can help families, medical institutions and policy makers better deal with the adverse effects of autism. Several studies have shown that autistic patients have a high risk of death, however, the results are still inconsistent. To assess the risk of mortality among the autistic patients, we undertook a comprehensive search of MEDLINE, Web of Science and EMBASE databases. This paper reviewed the studies on the negative disease outcomes of autism spectrum disorders, including the risk of death, causes of death and several research hotspots in this field. Strict inclusion/exclusion criteria were used. Information was extracted from selected papers, tabulated and synthesized. In the study, 15 studies were included, with a total of 216 045 individuals. The main outcome was all-cause mortality in association with autism and the secondary outcome was cause-specific mortality. The results showed that all-cause mortality was higher for the autistic patients (RR=2.32, 95%CI: 1.98-2.72, I(2)=87.1%, P < 0.001). Risk ratio showed a greater inequality for female than male (male: RR=2.00, 95%CI: 1.57-2.55, I(2)=93.2%, P < 0.001; female: RR=4.66, 95%CI: 3.30-6.58, I(2)=92.0%, P < 0.001). Compared with the unnatural death, the risk of natural death was higher (RR=3.44, 95%CI: 1.27-9.26, I(2)=80.2%, P=0.025). As autism had many comorbidities, which would bring more health risks and natural deaths possibilities. There were some structural differences in unnatural death. Accidental injury death and suicide were two kinds of causes. Lacking social skills would weaken the ability to ask for help when encountering injuries. This paper put forward some suggestions for futures. First, to well study the comorbidity can reduce the risk of death from a medical point of view. Second, the scientists and policymakers should pay attention to the social environment and provide a safer environment for the autistic patients. Third, for women and for adolescents without cognitive impairment, due to their high risk of suicide, the society should provide them with more supportive social networks and improve their life satisfaction. Fourth, it is necessary to balance the rehabilitation resources in various regions in China and provide more high-quality lifelong rehabilitation monitoring and care services.

Lien vers le texte intégral (Open Access ou abonnement)

20. Zlatic SA, Werner E, Surapaneni V, Lee CE, Gokhale A, Singleton K, Duong D, Crocker A, Gentile K, Middleton F, Patgiri A, Tarquinio D, Carpenter R, Faundez V. Systemic Metabolic and Mitochondrial Defects in Rett Syndrome Models. bioRxiv : the preprint server for biology. 2023.

Neurodevelopmental disorder genes are broadly expressed supporting the concept that these disorders are systemic diseases that impact neurodevelopment. We tested the systemic disease model focusing on Rett syndrome, which is caused by mutations in MECP2 . Transcriptomes and proteomes of organs and brain regions from Mecp2 -null mice and MECP2 -null human cells were assessed. Widespread changes in the transcriptome and proteome were identified in brain regions and organs of presymptomatic Mecp2 -null male mice and mutant cell lines. The extent of these transcriptome and proteome modifications was similar in cortex, liver, kidney, and skeletal muscle and more pronounced than in the hippocampus and striatum. In particular, Mecp2 – and MECP2 -sensitive proteomes were enriched in synaptic and metabolic annotated gene products, the latter encompassing lipid and mitochondrial pathways. MECP2 mutations altered pyruvate-dependent mitochondrial respiration while maintaining the capacity to use glutamine as a mitochondrial carbon source. We conclude that mutations in Mecp2 / MECP2 perturb lipid and mitochondrial metabolism systemically limiting cellular flexibility to utilize mitochondrial fuels.

Lien vers le texte intégral (Open Access ou abonnement)

21. Zong W, Lu X, Dong G, Zhang L, Li K. Molecular mechanisms of exercise intervention in alleviating the symptoms of autism spectrum disorder: Targeting the structural alterations of synapse. Frontiers in psychiatry. 2023; 14: 1096503.

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder characterized by stereotyped behaviors, specific interests, and impaired social and communication skills. Synapses are fundamental structures for transmitting information between neurons. It has been reported that synaptic deficits, such as the increased or decreased density of synapses, may contribute to the onset of ASD, which affects the synaptic function and neuronal circuits. Therefore, targeting the recovery of the synaptic normal structure and function may be a promising therapeutic strategy to alleviate ASD symptoms. Exercise intervention has been shown to regulate the structural plasticity of synapses and improve ASD symptoms, but the underlying molecular mechanisms require further exploration. In this review, we highlight the characteristics of synaptic structural alterations in the context of ASD and the beneficial effects of an exercise intervention on improving ASD symptoms. Finally, we explore the possible molecular mechanisms of improving ASD symptoms through exercise intervention from the perspective of regulating synaptic structural plasticity, which contributes to further optimizing the related strategies of exercise intervention promoting ASD rehabilitation in future.

Lien vers le texte intégral (Open Access ou abonnement)