1. Adıgüzel E, Çiçek B, Ünal G, Aydın MF, Barlak-Keti D. Probiotics and prebiotics alleviate behavioral deficits, inflammatory response, and gut dysbiosis in prenatal VPA-induced rodent model of autism. Physiol Behav;2022 (Sep 10):113961.

Autism spectrum disorders are neuropsychiatric conditions characterized by social interaction and communication disorders and repetitive stereotypical behaviors. These disorders are also accompanied by inflammatory findings. Bidirectional communication between microbiome, gut and brain has been discovered as a major mechanism influencing core symptoms and biomarkers of autism. Therefore, the modulation of the gut microbiota in autism has recently attracted interest. In this study, probiotic- and prebiotic-mediated modulation of the gut microbiota was compared in terms of different symptoms and findings in an experimental autism model. Valproic acid (VPA) (500 mg/kg) was administered to Wistar rats (on prenatal day 12.5) to induce autistic-like behaviors. Based on the supply of probiotics and prebiotics, animals were grouped as control (saline), autistic (prenatal VPA), probiotic (prenatal VPA + 22.5 × 10(9) cfu/day probiotic), prebiotic (prenatal VPA + 100 mg/day prebiotic), and combined treatment (prenatal VPA + 22.5 × 10(9) cfu/day probiotic + 100 mg/day prebiotic). After the treatment process, behavioral tests (social behaviors, anxiety, stereotypical behavior, sensorimotor gating, and behavioral despair) and biochemical analyses (serum and brain tissue) were conducted, and the quantities of some phyla and genera were determined in stool samples. Significant positive effects of probiotic and combined treatments were observed on the sociability, social interaction, and anxiety parameters. In addition, all three treatments had positive effects on stereotypical behavior. However, the treatments did not affect sensorimotor gating deficits and behavioral despair. Further, probiotic treatment reversed the VPA-induced increase and decrease in serum IL-6 and IL-10 levels, respectively. Combined treatment also significantly increased the IL-10 levels. Prenatal VPA exposure decreased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex of the brain; however, combined treatment reversed this decrease. Prenatal VPA exposure also caused a decrease in Bacteroidetes/Firmicutes ratio in the gut microbiota, while the probiotic treatment significantly increased this ratio. These findings indicate that probiotic- and prebiotic-mediated microbial modulation may represent a new therapeutic approach to alleviate autistic-like symptoms.

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2. Carey H, Tanner K, Ratliff-Schaub K, Baldino M, Kelly N, Andridge RR. Early Developmental Trends in High-Risk Neonates Later Diagnosed With Autism Spectrum Disorder. Pediatr Phys Ther;2022 (Sep 12)

PURPOSE: We hypothesized that clinical data from a neonatal intensive care unit (NICU) infant developmental follow-up clinic would identify early manifestations of autism spectrum disorder (ASD). METHODS: One hundred forty-four infants were identified; 72 later diagnosed with ASD and 72 controls. Retrospective chart review provided data from the Test of Infant Motor Performance (TIMP) and the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), between 8 and 26 months of age. RESULTS: Between-group comparisons indicated no significant group difference in TIMP scores; however, Bayley-III scaled scores differed between the groups at 2 administration times. The within-group Bayley-III change scores declined significantly more for the ASD group in cognitive and communication subtests. CONCLUSION: High-risk neonates, due to prematurity or morbidity, later diagnosed with ASD demonstrated statistically significant differences, including a more precipitous drop in Bayley-III scores over time. Early, longitudinal developmental surveillance for neonates at risk of ASD is critical. What this adds to the evidence: Early identification of ASD is critical to optimize developmental outcomes in young children, including infants born prematurely or with neonatal morbidity, who are perceived to have an increased risk for ASD. Despite these findings, minimal research has been conducted to evaluate the utility of commonly administered norm-referenced developmental surveillance instruments to identify possible early signs of ASD in this high-risk population due to prematurity or neonatal morbidity and not familial association. The present study analyzed retrospectively collected clinical data from a NICU developmental follow-up clinic for 144 infants, 72 of which were later diagnosed with ASD and 72 sex- and gestational age-matched controls. Results demonstrated statistically significant poorer Bayley-III outcomes for the ASD group compared with controls at 2 different study time points, including a more precipitous drop in Bayley-III scaled scores over time. This study highlights the importance of early and longitudinal developmental surveillance for high-risk neonates at risk of ASD.

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3. Conrow-Graham M, Williams JB, Martin J, Zhong P, Cao Q, Rein B, Yan Z. A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders. Brain;2022 (Sep 14);145(9):3250-3263.

ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain. Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression of ADNP and POGZ in the prefrontal cortex, a region highly implicated in neurodevelopmental disorders. To understand the functional role of these neurodevelopmental disorder risk factors, we used viral-based gene transfer to investigate how Adnp or Pogz deficiency in mouse prefrontal cortex affects behavioural, transcriptomic and synaptic function. Mice with prefrontal cortex deficiency of Adnp or Pogz exhibited specific impairment of cognitive task performance. RNA-sequencing revealed that Adnp or Pogz deficiency induced prominent upregulation of overlapping genes enriched in neuroinflammation, similar to the elevation of pro-inflammatory genes in humans with neurodevelopmental disorders. Concomitantly, Adnp or Pogz deficiency led to the significant increase of pro-phagocytic microglial activation in prefrontal cortex, as well as the significant decrease of glutamatergic transmission and postsynaptic protein expression. These findings have uncovered the convergent functions of two top risk factors for autism spectrum disorder and intellectual disability in prefrontal cortex, providing a mechanism linking chromatin, transcriptional and synaptic dysregulation to cognitive deficits associated with neurodevelopmental disorders.

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4. Di Donato N, Guerrini R, Billington CJ, Barkovich AJ, Dinkel P, Freri E, Heide M, Gershon ES, Gertler TS, Hopkin RJ, Jacob S, Keedy SK, Kooshavar D, Lockhart PJ, Lohmann DR, Mahmoud IG, Parrini E, Schrock E, Severi G, Timms AE, Webster RI, Willis MJH, Zaki MS, Gleeson JG, Leventer RJ, Dobyns WB. Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders. Brain;2022 (Sep 14);145(9):3274-3287.

Reelin, a large extracellular protein, plays several critical roles in brain development and function. It is encoded by RELN, first identified as the gene disrupted in the reeler mouse, a classic neurological mutant exhibiting ataxia, tremors and a ‘reeling’ gait. In humans, biallelic variants in RELN have been associated with a recessive lissencephaly variant with cerebellar hypoplasia, which matches well with the homozygous mouse mutant that has abnormal cortical structure, small hippocampi and severe cerebellar hypoplasia. Despite the large size of the gene, only 11 individuals with RELN-related lissencephaly with cerebellar hypoplasia from six families have previously been reported. Heterozygous carriers in these families were briefly reported as unaffected, although putative loss-of-function variants are practically absent in the population (probability of loss of function intolerance = 1). Here we present data on seven individuals from four families with biallelic and 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants have moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile. Thorough literature analysis supports a causal role for monoallelic RELN variants in four seemingly distinct phenotypes including frontotemporal lissencephaly, epilepsy, autism and probably schizophrenia. Notably, we observed a significantly higher proportion of loss-of-function variants in the biallelic compared to the monoallelic cohort, where the variant spectrum included missense and splice-site variants. We assessed the impact of two canonical splice-site variants observed as biallelic or monoallelic variants in individuals with moderately affected or normal cerebellum and demonstrated exon skipping causing in-frame loss of 46 or 52 amino acids in the central RELN domain. Previously reported functional studies demonstrated severe reduction in overall RELN secretion caused by heterozygous missense variants p.Cys539Arg and p.Arg3207Cys associated with lissencephaly suggesting a dominant-negative effect. We conclude that biallelic variants resulting in complete absence of RELN expression are associated with a consistent and severe phenotype that includes cerebellar hypoplasia. However, reduced expression of RELN remains sufficient to maintain nearly normal cerebellar structure. Monoallelic variants are associated with incomplete penetrance and variable expressivity even within the same family and may have dominant-negative effects. Reduced RELN secretion in heterozygous individuals affects only cortical structure whereas the cerebellum remains intact. Our data expand the spectrum of RELN-related neurodevelopmental disorders ranging from lethal brain malformations to adult phenotypes with normal brain imaging.

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5. Fabio RA, Chiarini L, Canegallo V. Pain in Rett syndrome: a pilot study and a single case study on the assessment of pain and the construction of a suitable measuring scale. Orphanet J Rare Dis;2022 (Sep 14);17(1):356.

BACKGROUND: Rett Syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births. Severe physical, language, and social impairments impose a wide range of limitations in the quality of life of the patients with RTT. Comorbidities of patients with RTT are varied and cause a lot of pain, but communicating this suffering is difficult for these patients due to their problems, such as apraxia that does not allow them to express pain in a timely manner, and their difficulties with expressive language that also do not permit them to communicate. Two studies, a pilot study and a single case study, investigate the manifestation of pain of patients with RTT and propose a suitable scale to measure it. AIMS OF THIS STUDY: The first aim was to describe pain situations of RTT by collecting information by parents; the second aim was to test and compare existing questionnaires for non-communicating disorders on pain such as Pain assessment in advanced demenzia (PAINAD), the Critical care pain observation tool (CPOT) and the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R) to assess which of them is best related to the pain behavior of patients with RTT. The third aim was to identify the specific verbal and non-verbal behaviors that characterize pain in girls with Rett syndrome, discriminating them from non-pain behaviors. METHOD: Nineteen participants, eighteen girls with RTT and one girl with RTT with 27 manifestations of pain were video-recorded both in pain and base-line conditions. Two independent observers codified the 90 video-recording (36 and 54) to describe their behavioral characteristics. RESULTS: The two studies showed that the most significant pain behaviors expressed by girls with respect to the baseline condition, at the facial level were a wrinkled forehead, wide eyes, grinding, banging teeth, complaining, making sounds, crying and screaming, and the most common manifestations of the body were tremors, forward and backward movement of the torso, tension in the upper limbs, increased movement of the lower limbs and a sprawling movement affecting the whole body. CONCLUSION: The results of the two studies helped to create an easy-to-apply scale that healthcare professionals can use to assess pain in patients with Rett’s syndrome. This scale used PAINAD as its basic structure, with some changes in the items related to the behavior of patients with RTT.

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6. Garrido D, Beretta S, Grabrucker S, Bauer HF, Bayer D, Sala C, Verpelli C, Roselli F, Bockmann J, Proepper C, Catanese A, Boeckers TM. Shank2/3 double knockout-based screening of cortical subregions links the retrosplenial area to the loss of social memory in autism spectrum disorders. Mol Psychiatry;2022 (Sep 13)

Members of the Shank protein family are master scaffolds of the postsynaptic architecture and mutations within the SHANK genes are causally associated with autism spectrum disorders (ASDs). We generated a Shank2-Shank3 double knockout mouse that is showing severe autism related core symptoms, as well as a broad spectrum of comorbidities. We exploited this animal model to identify cortical brain areas linked to specific autistic traits by locally deleting Shank2 and Shank3 simultaneously. Our screening of 10 cortical subregions revealed that a Shank2/3 deletion within the retrosplenial area severely impairs social memory, a core symptom of ASD. Notably, DREADD-mediated neuronal activation could rescue the social impairment triggered by Shank2/3 depletion. Data indicate that the retrosplenial area has to be added to the list of defined brain regions that contribute to the spectrum of behavioural alterations seen in ASDs.

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7. Jassim N, Owen AM, Smith P, Suckling J, Lawson RP, Baron-Cohen S, Parsons O. Perceptual decision-making in autism as assessed by « spot the difference » visual cognition tasks. Sci Rep;2022 (Sep 14);12(1):15458.

Discriminating between similar figures proves to be a remarkably demanding task due to the limited capacity of our visual cognitive processes. Here we examine how perceptual inference and decision-making are modulated by differences arising from neurodiversity. A large sample of autistic (n = 140) and typical (n = 147) participants completed two forced choice similarity judgement tasks online. Each task consisted of « match » (identical figures) and « mismatch » (subtle differences between figures) conditions. Signal detection theory analyses indicated a response bias by the autism group during conditions of uncertainty. More specifically, autistic participants were more likely to choose the « mismatch » option, thus leading to more hits on the « mismatch » condition, but also more false alarms on the « match » condition. These results suggest differences in response strategies during perceptual decision-making in autism.

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8. Joung JW. Factors influencing quality of life in caregivers of adolescents with developmental disabilities. Osong Public Health Res Perspect;2022 (Aug);13(4):298-307.

OBJECTIVES: Caring for adolescents with developmental disabilities (DD) is stressful and challenging, and mothers usually provide care for these children in Korea. This study aimed to identify factors influencing quality of life (QoL) in mothers of adolescents with DD. METHODS: A predictive design was used. Data were collected from a web-based survey administered to a convenience sample of 154 mothers of adolescents with DD from October to November 2020. Data were analyzed using the t-test, analysis of variance, Pearson correlation coefficients, and multiple regression. RESULTS: Perceived health, depression, and family strength were significantly correlated with QoL. Multiple regression showed that family strength, perceived health, depression, and monthly household income influenced the participants’ QoL, and these factors accounted for 69.2% of variance in QoL. Family strength was the factor most strongly affecting QoL (β=0.39). CONCLUSION: The study results indicate that health professionals and policy-makers need to pay attention to the overall QoL and physical and psychological health of mothers of adolescents with DD. Since our findings raise the importance of family strength in the QoL of this population, programs to improve family strength need to be implemented and strengthened. Interventions to improve perceived health and decrease depression should be applied, and knowledge on adolescent characteristics and changes should be delivered to caregivers when providing education and consultations. The findings will be helpful for developing educational and counseling programs for this population.

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9. Kim SA, Baczewski L, Pizzano M, Kasari C, Sturm A. Discrimination and Harassment Experiences of Autistic College Students and Their Neurotypical Peers: Risk and Protective Factors. J Autism Dev Disord;2022 (Sep 14)

This study examines autistic and non-autistic college students’ experiences of discrimination and harassment and identifies protective and risk factors. A nationwide survey was used to match autistic students (N = 290) and non-autistic students (N = 290) on co-occurring diagnoses and demographic characteristics. Multiple regression and interaction analysis revealed that faculty support was protective against discrimination and harassment regardless of autism status. Habits of mind was particularly protective for autistic students against harassment. Any student who engaged in school-facilitated events was more likely to experience discrimination and harassment, but the risk was heightened for autistic students. Findings highlight the importance of faculty support in fostering positive interpersonal experiences on campus, and demonstrate the need to address deeper college campus issues with respect to neurodiversity.

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10. Kingsdorf S, Pancocha K, Vadurova H, Dosedel T. Piloting an E-Learning Applied Behavior Analysis Course for Caregivers of Children with Autism in the Czech Republic. J Behav Educ;2022 (Sep 8):1-32.

The telehealth model can allow for cost-effective supports in areas where limited applied behavior analysis (ABA) services are available. As a result, e-learning programs for parents of children with autism have become part of the telehealth paradigm. In the Czech Republic, one of the many places where there are limited ABA supports and no available ABA e-learning courses for families, the development of an e-learning course that is freely available, and linguistically and culturally appropriate, is needed. It was anticipated that this course could mirror some of the free e-learning materials available to English-speaking caregivers and provide foundational knowledge to later support more intensive ABA services. Therefore, a pilot study was developed to assess an ABA e-learning course for caregivers in the Czech Republic with the aim of validating its efficacy and assessing whether a synchronous component was needed for the best outcomes. The materials were not meant to replace best practices in more intensive caregiver training but provide foundational skills for later more successful local services. Results demonstrated that a total of 33 caregivers completed the course, making statistically significant gains in their ABA knowledge and rating the course highly. Interestingly, the addition of the synchronous component only impacted the knowledge gain outcome. Suggestions for supporting caregivers in e-learning course completion and directions for future research are additionally explored.

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11. Lahiri R, Nasir M, Kumar M, Kim SH, Bishop S, Lord C, Narayanan S. Interpersonal synchrony across vocal and lexical modalities in interactions involving children with autism spectrum disorder. JASA Express Lett;2022 (Sep);2(9):095202.

Quantifying behavioral synchrony can inform clinical diagnosis, long-term monitoring, and individualised interventions in neuro-developmental disorders characterized by deficit in communication and social interaction, such as autism spectrum disorder. In this work, three different objective measures of interpersonal synchrony are evaluated across vocal and linguistic communication modalities. For vocal prosodic and spectral features, dynamic time warping distance and squared cosine distance of (feature-wise) complexity are used, and for lexical features, word mover’s distance is applied to capture behavioral synchrony. It is shown that these interpersonal vocal and linguistic synchrony measures capture complementary information that helps in characterizing overall behavioral patterns.

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12. Laroui A, Galarneau L, Abolghasemi A, Benachenhou S, Plantefève R, Bouchouirab FZ, Lepage JF, Corbin F, Çaku A. Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome. Sci Rep;2022 (Sep 13);12(1):15386.

High plasma matrix metalloproteases-9 (MMP-9) levels have been reported in Fragile X Syndrome in a limited number of animal and human studies. Since the results obtained are method-dependent and not directly comparable, the clinical utility of MMP-9 measurement in FXS remains unclear. This study aimed to compare quantitative gel zymography and ELISA and to determine which method better discriminates abnormal MMP-9 levels of individuals with FXS from healthy controls and correlates with the clinical profile. The active and total forms of MMP-9 were quantified respectively, by gel zymography and ELISA in a cohort of FXS (n = 23) and healthy controls (n = 20). The clinical profile was assessed for the FXS group using the Aberrant Behavior Checklist FXS adapted version (ABC-C(FX)), Adaptive Behavior Assessment System (ABAS), Social Communication Questionnaire (SCQ), and Anxiety Depression and Mood Scale questionnaires. Method comparison showed a disagreement between gel zymography and ELISA with a constant error of - 0.18 [95% CI: - 0.35 to - 0.02] and a proportional error of 2.31 [95% CI: 1.53 to 3.24]. Plasma level of MMP-9 active form was significantly higher in FXS (n = 12) as compared to their age-sex and BMI matched controls (n = 12) (p = 0.039) and correlated with ABC-C(FX) (r(s) = 0.60; p = 0.039) and ADAMS (r(s) = 0.57; p = 0.043) scores. As compared to the plasma total form, the plasma MMP-9 active form better enables the discrimination of individuals with FXS from controls and correlates with the clinical profile. Our results highlight the importance of choosing the appropriate method to quantify plasma MMP-9 in future FXS clinical studies.

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13. Lim M, Carollo A, Dimitriou D, Esposito G. Recent Developments in Autism Genetic Research: A Scientometric Review from 2018 to 2022. Genes (Basel);2022 (Sep 14);13(9)

Genetic research in Autism Spectrum Disorder (ASD) has progressed tremendously in recent decades. Dozens of genetic loci and hundreds of alterations in the genetic sequence, expression, epigenetic transformation, and interactions with other physiological and environmental systems have been found to increase the likelihood of developing ASD. There is therefore a need to represent this wide-ranging yet voluminous body of literature in a systematic manner so that this information can be synthesised and understood at a macro level. Therefore, this study made use of scientometric methods, particularly document co-citation analysis (DCA), to systematically review literature on ASD genetic research from 2018 to 2022. A total of 14,818 articles were extracted from Scopus and analyzed with CiteSpace. An optimized DCA analysis revealed that recent literature on ASD genetic research can be broadly organised into 12 major clusters representing various sub-topics. These clusters are briefly described in the manuscript and potential applications of this study are discussed.

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14. Tamon H, Itahashi T, Yamaguchi S, Tachibana Y, Fujino J, Igarashi M, Kawashima M, Takahashi R, Shinohara NA, Noda Y, Nakajima S, Hirota T, Aoki YY. Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey. BMC Psychiatry;2022 (Sep 14);22(1):608.

BACKGROUND: The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the « new normal, » including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic. METHODS: We recruited participants with a clinical diagnosis of autism spectrum disorder based on DSM-5 diagnostic criteria from two outpatient clinics in Tokyo, Japan, between November 2020 and April 2021 using a convenience sampling methodology. As a result, the participants consisted of 102 children and adolescents (mean (SD) age = 11.6 (5.3)). We collected data on RRB characteristics frequency before and during the pandemic using the CoRonavIruS Health Impact Survey (CRISIS) – Adapted for Autism and Related Neurodevelopmental conditions (AFAR). We then conducted factor analyses to compute the RRB severity composite scores, which are divided into lower- (e.g., sensory seeking), and higher-order (e.g., restricted interest). We also investigated mask-wearing culture using a bespoke questionnaire, and using Spearman’s rank correlation analyses, we examined the relationships between before pandemic RRB characteristics, and the impact of mask-wearing on social communications during the pandemic. RESULTS: We found that children and adolescents who exhibited lower-order RRB before the pandemic had difficulties in going-out with mask-wearing (rho = -0.25, q = .031), more challenges with mask-wearing (rho =  - 0.34, q = .0018), and difficulty in referring to others’ emotions while wearing masks (rho =  - 0.36, q = .0016). We also found an association between higher-order RRB before the pandemic and an uncomfortable sensation (rho =  - 0.42, q = .0002) and difficulties in referring to other’s emotions while wearing masks (rho =  - 0.25, q = .031). CONCLUSIONS: We revealed that various behaviors, such as sensory seeking, repetitive motor mannerisms and movements, and rituals and routines, undertaken before the pandemic could be important predictors of difficulties with mask-wearing and social communication for autistic children and adolescents during the pandemic. Caregivers and teachers wearing masks may need to provide extra support for social communication to autistic children and adolescents showing RRB characteristics frequently.

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15. Tartaglione AM, Villani A, Ajmone-Cat MA, Minghetti L, Ricceri L, Pazienza V, De Simone R, Calamandrei G. Maternal immune activation induces autism-like changes in behavior, neuroinflammatory profile and gut microbiota in mouse offspring of both sexes. Transl Psychiatry;2022 (Sep 14);12(1):384.

Autism Spectrum Disorder (ASD) is a sex-biased neurodevelopmental disorder with a male to female prevalence of 4:1, characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests or activities. Microbiota alterations as well as signs of neuroinflammation have been also reported in ASD. The involvement of immune dysregulation in ASD is further supported by evidence suggesting that maternal immune activation (MIA), especially during early pregnancy, may be a risk factor for ASD. The present study was aimed at characterizing the effects of MIA on behavior, gut microbiota and neuroinflammation in the mouse offspring also considering the impact of MIA in the two sexes. MIA offspring exhibited significant ASD-like behavioral alterations (i.e., deficits in sociability and sensorimotor gating, perseverative behaviors). The analysis of microbiota revealed changes in specific microbial taxa that recapitulated those seen in ASD children. In addition, molecular analyses indicated sex-related differences in the neuroinflammatory responses triggered by MIA, with a more prominent effect in the cerebellum. Our data suggest that both sexes should be included in the experimental designs of preclinical studies in order to identify those mechanisms that confer different vulnerability to ASD to males and females.

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16. Teixeira-Machado L, Arida RM, Ziebold C, Barboza AB, Ribeiro L, Teles MC, Rodrigues da Cunha Azevedo G, Silvestre de Paula C, Lowenthal R, Mari de Jesus J. A pilot randomized controlled clinical trial of dance practice for functionality in autistic children and adolescent with all levels of need support. Complement Ther Clin Pract;2022 (Aug 28);49:101650.

OBJECTIVE: This study addressed dance practice intertwining communication, functional independence and social behavior in autistic children and adolescents with all levels of need support. DESIGN: A pilot randomized clinical trial with seventy-two participants between 8 and 15 years old were assessed for eligibility. SETTING: Theater rehearsal room and mental health clinic. INTERVENTIONS: Dance group (n = 17) or control group (n = 19), 24 sessions, once a week, lasting 40 min. MAIN OUTCOME MEASURES: The Autism Behavior Checklist (ABC), Autistic Screening Questionnaire (ASQ), Childhood Autism Rate Scale (CARS), Functional Independence Measure (FIM), and World Health Organization Disability Assessment Schedule (WHODAS, version 2.0, to assess mothers’ functioning) were applied at two time points: baseline and end-point. RESULTS: Differences between dance and control groups were significant at post-intervention for communication (mean difference: 1.31; 99.8%CI: 0.29, 2.32, p < 0.001, d = 0.93); social cognition (mean difference: 1.01; 99.8%CI: 0.13, 1.89, p < 0.001, d = 0.82); autistic behavior (mean difference: 11.82; 99.8%CI: 17.33, -6.31, p < 0.001, d = 1.45). CONCLUSIONS: In this preliminary study, the findings provide ways of communication and social interaction through dance practice by autistic children and adolescents with all levels of support needs. Research on neurodiversity is needed to understand its feasibility and the lifestyle appropriation.

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17. Thudium S, Palozola K, L’Her É, Korb E. Identification of a transcriptional signature found in multiple models of ASD and related disorders. Genome Res;2022 (Sep 14)

Epigenetic regulation plays a critical role in many neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). In particular, many such disorders are the result of mutations in genes that encode chromatin-modifying proteins. However, although these disorders share many features, it is unclear whether they also share gene expression disruptions resulting from the aberrant regulation of chromatin. We examined five chromatin modifiers that are all linked to ASD despite their different roles in regulating chromatin. Specifically, we depleted ASH1L, CHD8, CREBBP, EHMT1, and NSD1 in parallel in a highly controlled neuronal culture system. We then identified sets of shared genes, or transcriptional signatures, that are differentially expressed following loss of multiple ASD-linked chromatin modifiers. We examined the functions of genes within the transcriptional signatures and found an enrichment in many neurotransmitter transport genes and activity-dependent genes. In addition, these genes are enriched for specific chromatin features such as bivalent domains that allow for highly dynamic regulation of gene expression. The down-regulated transcriptional signature is also observed within multiple mouse models of NDDs that result in ASD, but not those only associated with intellectual disability. Finally, the down-regulated transcriptional signature can distinguish between control and idiopathic ASD patient iPSC-derived neurons as well as postmortem tissue, demonstrating that this gene set is relevant to the human disorder. This work identifies a transcriptional signature that is found within many neurodevelopmental syndromes, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in ASD.

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