1. Corrigendum to « Self-compassion, mental health, and parenting: Comparing parents of autistic and non-autistic children ». Autism. 2024: 13623613241299946.

Lien vers le texte intégral (Open Access ou abonnement)

2. Negative effects on oral motor function after submandibular and parotid botulinum neurotoxin A injections for drooling in children with developmental disabilities. Dev Med Child Neurol. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

3. Retraction: Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder. PLoS One. 2024; 19(11): e0312885.

Lien vers le texte intégral (Open Access ou abonnement)

4. Aldrees A, Ojo S, Wanliss J, Umer M, Khan MA, Alabdullah B, Alsubai S, Innab N. Data-centric automated approach to predict autism spectrum disorder based on selective features and explainable artificial intelligence. Front Comput Neurosci. 2024; 18: 1489463.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by notable challenges in cognitive function, understanding language, recognizing objects, interacting with others, and communicating effectively. Its origins are mainly genetic, and identifying it early and intervening promptly can reduce the necessity for extensive medical treatments and lengthy diagnostic procedures for those impacted by ASD. This research is designed with two types of experimentation for ASD analysis. In the first set of experiments, authors utilized three feature engineering techniques (Chi-square, backward feature elimination, and PCA) with multiple machine learning models for autism presence prediction in toddlers. The proposed XGBoost 2.0 obtained 99% accuracy, F1 score, and recall with 98% precision with chi-square significant features. In the second scenario, main focus shifts to identifying tailored educational methods for children with ASD through the assessment of their behavioral, verbal, and physical responses. Again, the proposed approach performs well with 99% accuracy, F1 score, recall, and precision. In this research, cross-validation technique is also implemented to check the stability of the proposed model along with the comparison of previously published research works to show the significance of the proposed model. This study aims to develop personalized educational strategies for individuals with ASD using machine learning techniques to meet their specific needs better.

Lien vers le texte intégral (Open Access ou abonnement)

5. Amini-Khoei H, Taei N, Dehkordi HT, Lorigooini Z, Bijad E, Farahzad A, Madiseh MR. Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic-Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress. Phytother Res. 2024.

A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51-53 to PND 58-60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant properties.

Lien vers le texte intégral (Open Access ou abonnement)

6. Ando M, Taki I, Yamazaki T, Hida N. Medication adherence among Japanese patients with developmental disabilities: a survey study. Front Psychiatry. 2024; 15: 1431604.

AIM: Developmental disabilities (DD) often persist into adulthood, necessitating early and continuous treatment. Although pharmacotherapy is a viable treatment option, managing medication can be challenging. Prior research has not explored medication use among patients with DD in Japan. Thus, this study aimed to identify the medication challenges faced by these patients. METHODS: A questionnaire survey was administered to 200 outpatients to collect data on the number of prescribed medications, the timing of administration, the frequency of missed doses, and the use of medication notebooks. This was a prospective observational study without intervention and a random sampling. RESULTS: The survey revealed that 57.0% of the participants were non-adherent to their medication regimen. Specifically, medication non-adherence rates were 44.7% among individuals with autism spectrum disorder (ASD), 86.9% for those with attention deficit hyperactivity disorder (ADHD), and 30.4% for patients with comorbid ASD and ADHD. Despite 48.3% of the participants taking measures to prevent forgetting their medication, 65.3% of them still failed to take their medication as prescribed. The possession rate of medication record books was 96.0%. CONCLUSION: The study indicates that the frequency of medication non-adherence among patients with DD in Japan mirrors that in other countries. Patients who reported taking preventative measures still experienced high rates of non-adherence, suggesting limited effectiveness of these strategies. It is essential to develop more effective measures to improve adherence, enhance disease awareness, and increase understanding of medication instructions. The high possession rate of medication record books suggests they could play a significant role in managing DD, and their use is expected to increase in the future.

Lien vers le texte intégral (Open Access ou abonnement)

7. Borrmann D, Friedrich P, Smuda J, Sadowski G. Counteracting the Loss of Release for Indomethacin-Copovidone ASDs. J Pharm Sci. 2024.

This work revisits the changing release behavior of indomethacin(IND)-copovidone amorphous solid dispersions (ASDs) when increasing their drug load (DL). While showing congruent release behavior at DL 0.1, ASDs with DLs of 0.3 and higher show incongruent release finally resulting in a complete loss of release. To study and explain this phenomenon, we modeled the release kinetics of these ASDs and looked into their phase behavior both experimentally and theoretically. We applied a diffusion model to accurately describe experimental release profiles for congruent release, incongruent release as well as for loss of release. Predicted concentration profiles for IND, copovidone, and water within the ASD revealed the formation of an ASD layer that almost exclusively contains amorphous IND. Our phase-diagram predictions and experimental data explain this phenomenon by water-induced phase separation in those parts of the ASD which did absorb water from the dissolution medium. Whereas the evolving copovidone-rich phase dissolved, the IND-rich phase remained undissolved and formed a super-hydrophobic cover of the remaining inner core of the ASD, thus finally completely preventing its dissolution. Higher DLs promote phase separation. This leads to the counterintuitive effect that the higher the DL, the lower the absolute amount of IND released. While the ASD containing 6 mg IND (DL 0.1) released 6 mg IND, the one containing 42 mg IND (DL 0.7) released only 1 mg IND. The theoretical approach applied in this work is for the first time able to quantitatively predict that reducing DL or tablet size could be used to overcome this problem.

Lien vers le texte intégral (Open Access ou abonnement)

8. Cencelli G, Pedini G, Ricci C, Rosina E, Cecchetti G, Gentile A, Aiello G, Pacini L, Garrone B, Ombrato R, Coletta I, Prati F, Milanese C, Bagni C. Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome. Neurobiol Dis. 2024: 106726.

The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause of inherited intellectual disability, is a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates the role of Glycogen Synthase Kinase 3β (GSK3β) in FXS. Several studies have reported GSK3β deregulation in FXS, and its role in mitochondrial function is known. However, the link between disrupted GSK3β activity and mitochondrial dysfunction in FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice and human cell lines from FXS individuals, we uncovered a developmental window where dysregulated GSK3β activity disrupts mitochondrial function. Notably, a partial inhibition of GSK3β activity in FXS fibroblasts from young individuals rescues the observed mitochondrial defects, suggesting that targeting GSK3β in the early stages may offer therapeutic benefits for this condition.

Lien vers le texte intégral (Open Access ou abonnement)

9. Chu MC, Wu HF, Lee CW, Wu CC, Chi H, Ko CY, Lee YC, Tang CW, Chen PS, Lin HC. Soluble epoxide hydrolase deletion rescues behavioral and synaptic deficits. By AMPK-mTOR pathway in autism animals. Prog Neuropsychopharmacol Biol Psychiatry. 2024: 111190.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social defects often accompanied with emotional comorbidities. Aberrations in synaptic function and plasticity are the core feature in the pathophysiology of ASD. Targeting soluble epoxide hydrolase (sEH) has been found to exert protection in a wide-range of pathological conditions. However, the regulation of sEH deficiency on the synaptic deficits of ASD and the underlying mechanisms remain unclear. The valproate (VPA)-treated ASD animal model with genetic sEH knockout was applied in the present study. The results showed that the sEH expression was significantly increased in the prefrontal cortex of VPA-treated animals. Although no effect was found on tail malformation and body weight loss, genetic sEH deletion alleviated social deficits, and fear learning and memory extinction in the VPA-treated mice. After a series of electrophysiological assessments, we found that the beneficial effects of sEH deletion focused on the long-term synaptic plasticity, rather than presynaptic efficiency, in the VPA-treated mice. Furthermore, we observed that the dysregulated AMPK-mTOR pathway was restored under genetic sEH deletion in VPA-treated mice. Taken together, these findings uncovered an important role of sEH deficiency in the synaptic dysfunctions of ASD mediated by AMPK-mTOR pathway, providing a novel therapeutic target for ASD.

Lien vers le texte intégral (Open Access ou abonnement)

10. Coppola S, Nocerino R, Oglio F, Golia P, Falco MC, Riccio MP, Carucci L, Rea T, Simeone S, Garotti R, Marani N, Bravaccio C, Canani RB. Adverse food reactions and alterations in nutritional status in children with autism spectrum disorders: results of the NAFRA project. Ital J Pediatr. 2024; 50(1): 228.

BACKGROUND: To assess the adverse food reactions (AFR) prevalence in children with autism spectrum disorder (ASD) and in non-ASD healthy controls (NASD). Nutritional status alterations, food selectivity and adherence to Mediterranean Diet (MD) were also evaluated. METHODS: The NAFRA (Nutritional status and Adverse Food Reactions in children with Autism Spectrum Disorder) project was an observational, case-control, comparative study conducted at a tertriary center for pediatrics involving Caucasian patients of both sexes, aged 18 months-7 years, with a diagnosis of ASD, and matched NASD controls. RESULTS: From October 2017 to December 2023, 100 ASD patients [79 male, mean (± SD) age 49.9 months (± 15.4)] and 100 NASD controls [75 male, mean (± SD) age 49.8 months (± 17.7)] were enrolled at the Pediatric Section of the Department of Translational Medical Science of the University of Naples Federico II. A significantly higher prevalence of AFR was observed in ASD patients if compared with NASD (16% vs. 2%, p = 0.001), mainly due to a higher prevalence of food allergy (7% vs. 1%, p = 0.03). A significantly higher prevalence of food intolerance and celiac disease was also observed in ASD children. The rate of obesity was significantly higher in ASD patients compared to NASD. Food selectivity and low MD-adherence were more frequent in ASD children (26% vs. 2%, p < 0.0001 and 28% vs. 16%, p = 0.041, respectively). CONCLUSIONS: The high rate of AFR, obesity and unhealthy dietary habits observed in ASD children strongly suggest the importance of a multidisciplinary approach, providing early diagnosis of AFR and appropriate nutritional management to improve core and associated ASD-related conditions. TRIAL REGISTRATION: The NAFRA Project was registered on https://clinicaltrials.gov/ with the identifier NCT04719923. Registered 18 January 2021. https://clinicaltrials.gov/study/NCT04719923 .

Lien vers le texte intégral (Open Access ou abonnement)

11. Fan L, Li Q, Shi Y, Li X, Liu Y, Chen J, Sun Y, Chen A, Yang Y, Zhang X, Wang J, Wu L. Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder. BMC Med. 2024; 22(1): 504.

BACKGROUND: Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. METHODS: The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. RESULTS: Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. CONCLUSIONS: S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

12. Gargot T, Vachaud A, Gilard C, Audrain A, Gomot M, Guidotti M, Briend F, Malvy J, Bonnet Brilhault F. A Compressive Armchair (OTO) to Perform Deep Pressure Therapy in Children With Autism Spectrum Disorder: User-Centered Design and Feasibility Study. JMIR Hum Factors. 2024; 11: e55754.

BACKGROUND: Deep pressure therapy (DPT) is widely used to reduce anxiety in children with autism spectrum disorder (ASD), but evidence of its efficacy is limited. OBJECTIVE: This study aims to design a usable, nonstigmatizing compressive armchair that can be easily controlled, electronically, by the user. METHODS: A user-centered approach was used to assess the usability of the device. Testing was carried out in a day hospital for children with ASD in France, with a convenience sample of children with severe forms of ASD and intellectual deficiency (N=39). The Witteman design guideline was used. The System Usability Scale and time of use were reported. RESULTS: The final product is a compressive armchair designed to be user centered, with 4 different cells that can be inflated to induce tailored pressure on the body. The pressure level is recorded electronically. Usability was between good and excellent. The device was used by 39 children, once or twice weekly, over a period of 31 months. Each session lasted between 3 and 20 minutes. The armchair takes up less space than a hug machine. Performing sessions with the chair is feasible. CONCLUSIONS: First clinical impressions show a decrease in anxiety, improved emotional regulation, and improved attention. DPT is widely used in occupational therapy and frequently requested by parents, but efficacy studies are too scarce to make evidence-based recommendations for its use. The results presented here support further controlled efficacy studies of DPT in the treatment of anxiety in children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

13. Han TH, Chae KY, Han B, Kim JH, Ha EK, Rhie S, Han MY. Early onset and increasing disparities in neurodevelopmental delays from birth to age 6 in children from low socioeconomic backgrounds. J Neurodev Disord. 2024; 16(1): 60.

OBJECTIVE: To analyze the complex relationship between socioeconomic status (SES) and neurodevelopmental achievements by investigating the temporal dynamics of these associations from birth to age 6. METHODS: This retrospective cohort study was conducted over 6 years using population-based data from the National Health Insurance Service and integrated data from the National Health Screening Program for Infants and Children. Participants were children born between 2009 and 2011 in Korea without neurodevelopmental delays with potential developmental implications. We analyzed results from the Korean Developmental Screening Test, administered at age 6, which covered overall assessment and six domains of gross and fine motor function, cognition, language, sociality, and self-care. The secondary outcome was to determine when neurodevelopmental outcomes began after birth and how these differences changed over time. RESULTS: Of 276,167 individuals (49.2% males), 66,325, 138,980, and 60,862 had low, intermediate, and high SES, respectively. Neurodevelopmental delays observed across all developmental domains were more prevalent in the low-SES group than in the high-SES group. Disparities in neurodevelopment according to these statuses were apparent as early as age 2 and tended to increase over time (interaction, P < 0.001). The cognition and language domains exhibited the most substantial disparities between SES levels. These disparities persisted in subgroup analyses of sex, birthweight, head circumference, birth data, and breastfeeding variables. CONCLUSIONS: Low SES was significantly associated with an increased risk of adverse neurodevelopmental outcomes in preschool children, particularly those affecting cognitive and language domains. These differences manifested in early childhood and widened over time.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kalani L, Kim BH, de Chavez AR, Roemer A, Mikhailov A, Merritt JK, Good KV, Chow RL, Delaney KR, Hendzel MJ, Zhou Z, Neul JL, Vincent JB, Ausió J. Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms. Hum Mol Genet. 2024; 33(21): 1833-45.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.5 to 3 fold increase. We also explored the potential involvement of the MeCP2 PEST domains in the proteasome-mediated regulation of MeCP2. Finally, we used the R294X mutant to gain further insight into the controversial competition between MeCP2 and histone H1 in the chromatin context. Interestingly, in R294X, MeCP2 E1 and E2 isoforms were differently affected, where the E1 isoform contributes to much of the overall protein increase observed, while E2 decreases by half. The modes of MeCP2 regulation, thus, appear to be differently regulated in the two isoforms.

Lien vers le texte intégral (Open Access ou abonnement)

15. Kamlowsky ME, Dozier CL, Leslie SC, Kanaman KC, Diaz de Villegas SC. Effects of social interaction on leisure item preference and reinforcer efficacy for children with autism. J Appl Behav Anal. 2024.

We replicated and extended Kanaman et al. (2022) by comparing outcomes of solitary (leisure items only), social (leisure items with social interaction), and combined (leisure items alone and leisure items with social interaction) stimulus preference assessments to determine the extent to which the inclusion of social interaction influenced the outcomes of preference assessments for five children with autism. We then conducted reinforcer assessments to determine the reinforcing efficacy of high- and low-preferred leisure items when presented with and without social interaction. The results showed that both high- and low-preferred items functioned as reinforcers to varying degrees for all participants and the inclusion of social interaction increased the reinforcing efficacy of some items for all participants. Additionally, the results showed that combined preference assessments predicted reinforcer assessment outcomes for two of five participants but produced false-negative outcomes for three participants. Clinical implications and directions for future research are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

16. McGuinness L, Abbot-Smith K, Gambi C. Seeing it in others versus doing it yourself: Social desirability judgements and conversation production data from autistic and non-autistic children. Autism. 2024: 13623613241292172.

During a conversation, on average, autistic individuals are often more likely than non-autistic people to provide an off-topic comment and/or to pause for longer before providing a response. One possible explanation for this is that autistic individuals prefer, or are more tolerant of, unconventional communication styles. To explore this possibility, we investigated whether autistic and non-autistic 9-13-year-olds find off-topic or delayed responding a deterrent to friendship or interaction. Participants listened to scripted conversations and then rated social desirability statements, such as ‘I would enjoy chatting to the [target speaker]’. We also examined the prevalence of these behaviours in children’s own conversational responses. We found that autistic children were just as likely as non-autistic children to dis-prefer unconventional conversational responding. Both groups indicated that they were less likely to want to be friends with the speaker, or to chat with them, when they provided off-topic or delayed responses. However, despite their judgements of others, the same autistic children were more likely to provide off-topic responses themselves than their non-autistic peers, as well as giving fewer on-topic responses which facilitate back-and-forth conversation. Overall, this is problematic for autistic children, as our findings suggest that the tendency to exhibit unconventional conversational behaviours will have negative social consequences, even when interacting with other autistic peers.

Lien vers le texte intégral (Open Access ou abonnement)

17. McKinnon K, Bougoure M, Zhuang S, Tan DW, Magiati I. Exploring the construct validity of the Camouflaging Autistic Traits Questionnaire: A factor analytic study. Autism. 2024: 13623613241287964.

Autistic people describe having to mask or ‘camouflage’ their autistic selves to fit into certain social settings. Many researchers have used the CAT-Q to measure the extent to which autistic people engage in camouflaging. However, some researchers have questioned whether the CAT-Q measures camouflaging or whether it measures other related experiences and behaviours associated with social anxiety, fear of being negatively judged or social autistic traits. In our study, we analysed the CAT-Q to check whether it is indeed similar to or different from these related experiences. To do this, we asked 308 autistic adults to complete the CAT-Q and questionnaires about social anxiety, fear of being negatively judged and autistic social features. Then, we put all the CAT-Q items together with the items from each of the other measures in three separate analyses (called factor analyses) to see how the items would group together. These analyses showed us whether camouflaging behaviours are distinguishable and different from, or cluster together with, these other experiences. We found that most of CAT-Q items grouped together separately from the other measures’ items, suggesting that camouflaging differs from these other related experiences. Only some items from one of the CAT-Q subscales clustered together with some social anxiety and autistic items, suggesting these may need to be teased out better in the future. Generally, our findings show that we can use the CAT-Q to measure camouflaging behaviours among autistic people.

Lien vers le texte intégral (Open Access ou abonnement)

18. Meehan RR, Pennings S. Rett syndrome: interferon-γ to the rescue?. EMBO Mol Med. 2024.

Lien vers le texte intégral (Open Access ou abonnement)

19. Mestre-Sansó F, Canals V, Montoya P, Riquelme I. Combination of motor, sensory and affective tasks in an EEG paradigm for children with developmental disabilities. MethodsX. 2024; 13: 102997.

Individuals with neurodevelopmental disorders exhibit overlapping emotional, somatosensory and motor deficits. Although brain processes underlying these impairments have been extensively studied in a separate way, the brain interaction of these inputs is an innovative line of research. Here we present a new EEG methodology for exploring the interactive brain activity of sensorimotor and affective stimuli. The task consists in presenting affective stimuli of different modalities (e.g. affective pictures, affective touch) while simultaneously an arthromotor performs passive joint movements, unseen by the participant. Participants were then required to press one of two buttons to indicate if their joint position agreed with a picture shown in a screen. Pilot data of electroencephalography recordings revealed distinct somatosensory event-related potentials (SEP) when movement was subsequent to affective stimuli, compared to neutral stimuli, as well as a differentiation of SEPs for different neurodevelopmental conditions. Behavioral responses further showed that children with cerebral palsy had more errors to identify their hand position when they were exposed to affective stimuli. This paradigm is a valuable tool to explore the modulative influence of emotion in the sensorimotor brain processing of different populations with joint emotional and sensorimotor impairments, such as children with neurodevelopmental disorders or patients with stroke.•This method allows exploring the interaction between affective and sensoriomotor inputs in an EEG paradigm.

Lien vers le texte intégral (Open Access ou abonnement)

20. Mohamed AF, El-Gammal MA, El-Yamany MF, Khodeir AE. Sigma-1 receptor modulation by fluvoxamine ameliorates valproic acid-induced autistic behavior in rats: Involvement of chronic ER stress modulation, enhanced autophagy and M1/M2 microglia polarization. Prog Neuropsychopharmacol Biol Psychiatry. 2024; 136: 111192.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. While, fluvoxamine (FVX) is an antidepressant and widely prescribed to ASD patients, clinical results are inconclusive and the mechanism of FVX in the management of ASD is unclear. This study determined the potential therapeutic impact of FVX, a sigma-1 receptor (S1R) agonist, against the valproic acid (VPA)-induced model of autism. On gestational day 12.5, Wistar pregnant rats were given a single intraperitoneal (i.p.) injection of either VPA (600 mg/kg) or normal saline (10 mL/kg, vehicle-control). Starting on postnatal day (PND) 21 to PND 50, FVX (30 mg/kg, P·O. daily) and NE-100, (S1R) antagonist, (1 mg/kg, i.p. daily) were given to male pups. Behavior tests and histopathological changes were identified at the end of the experiment. In addition, the cerebellum biomarkers of endoplasmic reticulum (ER) stress and autophagy were assessed. Microglial cell polarization to M1 and M2 phenotypes was also assessed. FVX effectively mitigated the histopathological alterations in the cerebellum caused by VPA. FVX enhanced sociability and stereotypic behaviors in addition to its noteworthy impact on autophagy enhancement, ER stress deterioration, and controlling microglial cell polarization. The current investigation confirmed that the S1R agonist, FVX, can lessen behavioral and neurochemical alterations in the VPA-induced rat model of autism.

Lien vers le texte intégral (Open Access ou abonnement)

21. Moskowitz LJ, Will EA, Black CJ, Roberts JE. The effect of anxiety and autism symptom severity on restricted and repetitive behaviors over time in children with fragile X syndrome. J Neurodev Disord. 2024; 16(1): 61.

BACKGROUND: Restricted and repetitive behaviors (RRBs) are highly prevalent and reduce function in individuals with fragile X syndrome (FXS). As transdiagnostic features of intellectual disability, elevated rates of RRBs in FXS could represent various underlying known co-occurring conditions in FXS such as anxiety or autism spectrum disorder (ASD), yet this distinction has not been investigated. Further, delineating whether RRBs are more indicative of anxiety or ASD in FXS may clarify phenotypic profiles within FXS and improve differential assessment. METHODS: We longitudinally examined the potentially independent or multiplicative effect of ASD and anxiety symptom severity on RRBs in 60 children with FXS. Anxiety was measured using the Child Behavior Checklist (CBCL), ASD severity was measured using the Childhood Autism Rating Scale (CARS), and RRBs were measured using the Repetitive Behavior Scale – Revised (RBS-R). We estimated a series of moderated regression models with anxiety and ASD symptoms at the initial assessment (Time 1) as predictors of RRBs at the outcome assessment two years later (Time 2), along with an anxiety-by-ASD interaction term to determine the potential multiplicative effect of these co-occurring conditions on RRBs. RESULTS: Results identified a significant interaction between ASD and anxiety symptom severity at the initial assessment that predicted elevated sensory-motor RRBs two years later. Increased sensory-motor RRBs were predicted by elevated ASD symptoms only when anxiety symptom severity was low. Likewise, increased sensory-motor RRBs were predicted by elevated anxiety symptoms only when ASD symptom severity was low. Interestingly, this relationship was isolated to Sensory-Motor RRBs, with evidence that it could also apply to total RRBs. CONCLUSIONS: Findings suggest that ASD and anxiety exert independent and differential effects on Sensory-Motor RRBs when at high severity levels and a multiplicative effect when at moderate levels, which has important implications for early and targeted interventions.

Lien vers le texte intégral (Open Access ou abonnement)

22. Putnam OC, Markfeld JE, Wright ST, Feldman JI, Goldblum J, Karpinsky M, Neal AJ, Swanson MR, Harrop C. The use of Language ENvironment Analysis in autism research: A systematic review. Autism. 2024: 13623613241290072.

In research, language ability has historically been measured using structured tasks in laboratory settings. In recent years, there has been a growing emphasis on the need to instead capture language ability in an individual’s natural setting (i.e. through social interaction or in their home). Considering natural language may be particularly important for the autistic population, as an autistic child’s language ability can be very different depending on the setting. One common tool for capturing natural language is the LENA recording system, which takes audio recordings over long periods of time and provides estimates of children’s and caregivers’ speech. The purpose of this systematic review is to summarize the use of LENA in autism research, to highlight the strengths and limitations of the system as identified by researchers, and to provide recommendations for future research and clinical use. We identified 42 autism studies that used LENA in a variety of ways and settings. Most studies used LENA within the guidelines put forth by its creators, and it was most commonly used to understand speech or speech development for autistic children. LENA is a useful tool for clinicians and caregivers to gain some insights into child speech, but those considering using it should be aware of concerns about its accuracy and limitations about the information it provides. In this review, we supplement the official LENA guidelines with specific suggestions for use with the autistic population.

Lien vers le texte intégral (Open Access ou abonnement)

23. Singh Y, Sodhi RK, Kumar H, Bishnoi M, Bhandari R, Kuhad A. Repurposing of niclosamide, an anthelmintic, by targeting ERK/MAPK signaling pathway in the experimental paradigm of autism spectrum disorders. Eur J Pharmacol. 2024; 982: 176902.

AIM: The current study explores niclosamide’s neuroprotective potential in an animal model of autism spectrum disorder (ASD) and goes further to understand how the ERK/MAPK signaling pathway is thought to contribute to this activity. METHODS: In order to create an autism-like phenotype in rats, 4 μl of 1 M PPA was infused intracerebroventricularly. The oral treatment with niclosamide (50 and 100 mg/kg) and risperidone (1 mg/kg) (used as standard) was given from 3rd to 30th day. Between the 14th and 28th day, behavioral assessments were made for sociability, stereotypy, anxiety, depression, novelty preference, repetitive behavior, and perseverative behavior. The animals were euthanized on the 29th day, and oxidative stress markers were assessed in the brain homogenate. The levels of neuroinflammatory cytokines such as TNF-α, IL-6, NF-κB, IFN-γ and glutamate were estimated using ELISA kits. To assess the involvement of the ERK/MAPK signaling pathway, levels of Nrf2 and ERK2 were also measured. KEY FINDINGS: Niclosamide therapy significantly restored behavioral, biochemical, neurological, and molecular impairments. Hence, niclosamide could be a potential neurotherapeutic candidate for further studies for use in ASD.

Lien vers le texte intégral (Open Access ou abonnement)