1. Berding K, Donovan SM. {{Dietary Patterns Impact Temporal Dynamics of Fecal Microbiota Composition in Children With Autism Spectrum Disorder}}. {Frontiers in nutrition}. 2019; 6: 193.
Environmental factors such as diet are known influencers on gastrointestinal (GI) microbiota variability and some diseases are associated with microbial stability. Whether microbial variability is related to symptoms of Autism Spectrum Disorder (ASD) and how diet impacts microbial stability in ASD is unknown. Herein, temporal variability in stool microbiota in relation to dietary habits in 2-7 years-old children with ASD (ASD, n = 26) and unaffected controls (CONT, n = 32) was investigated. Fecal samples were collected at baseline, 6-weeks and 6-months. Bacterial composition was assessed using 16S rRNA sequencing. Short fatty acid (SCFA) concentrations were analyzed by gas chromatography. Nutrient intake was assessed using a 3-day food diary and dietary patterns (DP) were empirically derived from a food frequency questionnaire. Social deficit scores (SOCDEF) were assessed using the Pervasive Developmental Disorder Behavior Inventory-Screening Version (PDDBI-SV). GI symptoms were assessed using the GI severity index. Overall, temporal variability in microbial structure, and membership did not differ between the groups. In children with ASD, abundances of Clostridiaceae, Streptophyta, and Clostridiaceae Clostridium, varied significantly, and concentrations of all SCFAs decreased over time. Variability in community membership was negatively correlated with median SOCDEF scores. Additionally, Clostridiales, Lactococcus, Turicibacter, Dorea, and Phascolarctobacterium were components of a more stable microbiota community in children with ASD. DP1, characterized by vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with changes in species diversity, abundance of Erysipelotricaceae, Clostridiaceae Clostridium, and Oscillospira and concentrations of propionate, butyrate, isobutyrate and isovalerate in children with ASD. DP2 characterized by fried, protein and starchy foods, « Kid’s meals, » condiments, and snacks was associated with variations in microbiota structure, abundance of Clostridiaceae Clostridium, and Oscillospira and changes in all SCFA concentrations. However, no association between microbial stability and SOCDEF or GI severity scores were observed. In conclusion, microbiota composition varies over time in children with ASD, might be related to social deficit scores and can be impacted by diet. Future studies investigating the physiological effect of the changes in specific microbial taxa and metabolites are needed to delineate the impact on ASD symptomology.
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2. Caffarelli C, Gonnelli S, Pitinca MDT, Camarri S, Al Refaie A, Hayek J, Nuti R. {{Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome}}. {BMC Med Genet}. 2020; 21(1): 21.
BACKGROUND: More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects. METHODS: In 232 women with Rett syndrome (mean age 13.8 +/- 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe. RESULTS: As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05). CONCLUSION: This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk. Lien vers le texte intégral (Open Access ou abonnement)
3. Chakraborti B, Verma D, Guhathakurta S, Jaiswal P, Singh AS, Sinha S, Ghosh S, Mukhopadhyay K, Mohanakumar KP, Rajamma U. {{Gender-Specific Effect of 5-HT and 5-HIAA on Threshold Level of Behavioral Symptoms and Sex-Bias in Prevalence of Autism Spectrum Disorder}}. {Front Neurosci}. 2019; 13: 1375.
Platelet hyperserotonemia in a subset of Autism Spectrum Disorder (ASD) probands, efficacy of selective serotonin reuptake inhibitors (SSRIs) in reducing behavioral deficits and gender-bias in normal serotonin (5-hydroxy tryptamine or 5-HT) synthesis suggest disruption in stringent regulation of serotonin metabolism in ASD. Therefore, we investigated the changes in 5-HT and 5-hydroxy indole acetic acid (5-HIAA) in ASD probands to assess its effect on the behavior of male and female probands. ASD cases (n = 215) were examined using childhood autism rating scale (CARS). Platelet 5-HT (104 cases and 26 controls) and platelet/plasma 5-HIAA (73 cases and 17 controls) were estimated using high performance liquid chromatography coupled with electrochemical detector (HPLC-ECD). In male probands, we observed increase in platelet 5-HT content in association with increase in the score for adaptive responses and increase in platelet 5-HIAA levels with concomitant decline in the score for intellectual response. Age did not influence the neurochemical parameters, but imitation, listening responses and nonverbal communication scores decreased with age. Conversely in female probands, plasma 5-HIAA level significantly attenuated with age, when platelet 5-HT content remained unchanged. Interestingly, platelet/plasma 5-HT and plasma 5-HIAA were higher in female controls. Female probands displayed severe autism-associated behaviors. Overall results indicate gender-bias in 5-HT and 5-HIAA regulation, which probably increases the threshold level of ASD phenotypes in the females, thereby affecting ASD prevalence in a sex-specific manner.
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4. Choi B, Nelson CA, Rowe ML, Tager-Flusberg H. {{Reciprocal Influences Between Parent Input and Child Language Skills in Dyads Involving High- and Low-Risk Infants for Autism Spectrum Disorder}}. {Autism Res}. 2020.
We examined the language input of parents of infants at high and low familial risk for autism spectrum disorder (ASD) and investigated reciprocal associations between parent input and child language skills in the first 2 years of life. Parent-infant dyads (high-risk: n = 53; low-risk: n = 33), 19 of whom included an infant later diagnosed with ASD, were videotaped during free play interactions at 12, 18, and 24 months. Measures of parent input were derived from parent-child interactions. Children’s language skills were assessed using the Mullen Scales of Early Learning at 12, 18, and 24 months. Results suggested that (a) parents of high- and low-risk infants produced similar word tokens, word types, and proportions of contingent verbal responses, but parents of high-risk infants used shorter mean length of utterances (MLU) than parents of low-risk infants at 18 and 24 months; (b) parents’ MLU at 18 months was positively associated with their infants’ language at the subsequent visit after 6 months, regardless of group; and (c) infants’ language at 18 months was positively associated with parents’ MLU at the subsequent visit after 6 months in the high-risk group only. These findings contribute to our understanding of the mechanisms underlying early language learning of high-risk infants who have an increased risk for language delays and deficits. Autism Res 2020. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Parents provide an important source of language input to their children. In this study, we looked at parent input to infants at high- and low-risk for autism spectrum disorder and relations between parent input and child language in the first 2 years of life. We found that parents of high- and low-risk infants provided similar quantity and quality of input, except shorter average length of utterances at 18 and 24 months in the high-risk group. Also, there were bidirectional relations between parent input and child language at 18 and 24 months in high-risk pairs, suggesting that parents and children collectively shape the early language environment.
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5. Emam B, Shahsavani A, Khodagholi F, Zarandi SM, Hopke PK, Hadei M, Behbahani H, Yarahmadi M. {{Effects of PM2.5 and gases exposure during prenatal and early-life on autism-like phenotypes in male rat offspring}}. {Particle and fibre toxicology}. 2020; 17(1): 8.
BACKGROUND: Epidemiological studies have reported associations between elevated air pollution and autism spectrum disorders (ASD). However, we hypothesized that exposure to air pollution that mimics real world scenarios, is a potential contributor to ASD. The exact etiology and molecular mechanisms underlying ASD are not well understood. Thus, we assessed whether changes in OXTR levels may be part of the mechanism linking PM2.5/gaseous pollutant exposure and ASD. The current in-vivo study investigated the effect of exposure to fine particulate matter (PM2.5) and gaseous pollutants on ASD using behavioral and molecular experiments. Four exposure groups of Wistar rats were included in this study: 1) particulate matter and gaseous pollutants exposed (PGE), 2) gaseous pollutants only exposed (GE), 3) autism-like model (ALM) with VPA induction, and 4) clean air exposed (CAE) as the control. Pregnant dams and male pups were exposed to air pollutants from embryonic day (E0) to postnatal day (PND21). RESULTS: The average +/- SD concentrations of air pollutants were: PM2.5: 43.8 +/- 21.1 mug/m(3), CO: 13.5 +/- 2.5 ppm, NO2: 0.341 +/- 0.100 ppm, SO2: 0.275 +/- 0.07 ppm, and O3: 0.135 +/- 0.01 ppm. The OXTR protein level, catalase activity (CAT), and GSH concentrations in the ALM, PGE, and GE rats were lower than those in control group (CAE). However, the decrements in the GE rats were smaller than other groups. Also in behavioral assessments, the ALM, PGE, and GE rats demonstrated a repetitive /restricted behavior and poor social interaction, but the GE rats had weaker responses compared to other groups of rats. The PGE and GE rats showed similar trends in these tests compared to the VPA rats. CONCLUSIONS: This study suggested that exposure to ambient air pollution contributed to ASD and that OXTR protein may serve as part of the mechanism linking them.
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6. Gladfelter A, VanZuiden C. {{The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder}}. {American journal of speech-language pathology}. 2020: 1-8.
Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.
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7. Gonatopoulos-Pournatzis T, Niibori R, Salter EW, Weatheritt RJ, Tsang B, Farhangmehr S, Liang X, Braunschweig U, Roth J, Zhang S, Henderson T, Sharma E, Quesnel-Vallieres M, Permanyer J, Maier S, Georgiou J, Irimia M, Sonenberg N, Forman-Kay JD, Gingras AC, Collingridge GL, Woodin MA, Cordes SP, Blencowe BJ. {{Autism-Misregulated eIF4G Microexons Control Synaptic Translation and Higher Order Cognitive Functions}}. {Molecular cell}. 2020.
Microexons represent the most highly conserved class of alternative splicing, yet their functions are poorly understood. Here, we focus on closely related neuronal microexons overlapping prion-like domains in the translation initiation factors, eIF4G1 and eIF4G3, the splicing of which is activity dependent and frequently disrupted in autism. CRISPR-Cas9 deletion of these microexons selectively upregulates synaptic proteins that control neuronal activity and plasticity and further triggers a gene expression program mirroring that of activated neurons. Mice lacking the Eif4g1 microexon display social behavior, learning, and memory deficits, accompanied by altered hippocampal synaptic plasticity. We provide evidence that the eIF4G microexons function as a translational brake by causing ribosome stalling, through their propensity to promote the coalescence of cytoplasmic granule components associated with translation repression, including the fragile X mental retardation protein FMRP. The results thus reveal an autism-disrupted mechanism by which alternative splicing specializes neuronal translation to control higher order cognitive functioning.
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8. Gupta S, Rajapakse JC, Welsch RE. {{Ambivert degree identifies crucial brain functional hubs and improves detection of Alzheimer’s Disease and Autism Spectrum Disorder}}. {Neuroimage Clin}. 2020; 25: 102186.
Functional modules in the human brain support its drive for specialization whereas brain hubs act as focal points for information integration. Brain hubs are brain regions that have a large number of both within and between module connections. We argue that weak connections in brain functional networks lead to misclassification of brain regions as hubs. In order to resolve this, we propose a new measure called ambivert degree that considers the node’s degree as well as connection weights in order to identify nodes with both high degree and high connection weights as hubs. Using resting-state functional MRI scans from the Human Connectome Project, we show that ambivert degree identifies brain hubs that are not only crucial but also invariable across subjects. We hypothesize that nodal measures based on ambivert degree can be effectively used to classify patients from healthy controls for diseases that are known to have widespread hub disruption. Using patient data for Alzheimer’s Disease and Autism Spectrum Disorder, we show that the hubs in the patient and healthy groups are very different for both the diseases and deep feedforward neural networks trained on nodal hub features lead to a significantly higher classification accuracy with significantly fewer trainable weights compared to using functional connectivity features. Thus, the ambivert degree improves identification of crucial brain hubs in healthy subjects and can be used as a diagnostic feature to detect neurological diseases characterized by hub disruption.
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9. Hirokawa K, Kimura T, Ikehara S, Honjo K, Ueda K, Sato T, Iso H. {{Associations Between Broader Autism Phenotype and Dietary Intake: A Cross-Sectional Study (Japan Environment & Children’s Study)}}. {J Autism Dev Disord}. 2020.
The purpose of the present study was to investigate associations of dietary intake including vitamin D, folate, and n-3 and n-6 polyunsaturated fatty acids (PUFA) in pregnant women with broad autism phenotype (BAP). The Japan Environment and Children’s Study is a government-funded birth cohort study. All complete data of 92,011 were analyzed. The Japanese version of the Autism Spectrum Quotient was used to assess mothers’ BAP level, and a food frequency questionnaire was used to estimate their dietary intake. Mothers with BAP consumed less vegetables, fruits, and fish and shellfish, and they consumed lower folate, vitamin C, vitamin D, and n-3 PUFA than their counterparts. Dietary intervention should be considered for pregnant women with high BAP scores.
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10. Hugo M, Hedegaard J. {{Inclusion through folk high school in Sweden – the experience of young adult students with high-functioning autism}}. {Disabil Rehabil}. 2020: 1-10.
Purpose: The purpose of this study is to provide a description of the learning environment at Folk High School for participants with high-functioning autism and to examine their learning experience at Folk High School.Methods: A qualitative interview study was conducted with 21 participants who were enrolled at Folk High School which had been adapted to suit young adults with high-functioning autism. The interviews were analysed by means of a thematic content analysis which resulted in the identification of 6 themes related to learning experiences at Folk High School.Results: The participants enjoyed themselves and felt secure at Folk High School. They felt that they and their academic endeavours were suitably recognised, acknowledged, and understood. They reported that the teaching was suitably adapted for them and they felt that they could succeed in their studies. A frequent report that they made concerned their experience of clear structures in the teaching process and its predictability. The participants stated that Folk High School has the ability to satisfy each participant’s needs, which entailed lower levels of perceived stress than what they had experienced in their previous schooling. The participants experienced personal development during their time at Folk High School.Conclusions: Folk High School, and its special character, is able to successfully satisfy the needs of participants with high-functioning autism. Many of the participants, for the first time in their lives, experienced a sense of inclusion in an educational system and felt that they could succeed in their studies. However, there exists a risk that they become institutionalised, which entails that the participants function well primarily in Folk High School’s safe and caring environment.Implications for rehabilitationA supportive environment including both formal and social learning is paramount for people with high-functioning autism.Individually adapted teaching that is structured and predictable improve the conditions under which they can focus on their studies and enjoy academic success.The teachers’ relational competence and ability to show interest in each individual are crucial.Social- and special-pedagogic competencies need to co-exist so as to improve learning conditions.Internship/workplace training can provide an important social learning experience for participants, as they learn about themselves and others and as they develop their social competence.To practice living on one’s own is a significant challenge, but it can create opportunities to learn about one’s self and to develop a sense of responsibility and other social skills.
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11. Jenabi E, Bashirian S, Khazaei S. {{Association between neonatal jaundice and autism spectrum disorders among children: a meta-analysis}}. {Clinical and experimental pediatrics}. 2020; 63(1): 8-13.
Autism spectrum disorder is a common neurodevelopmental disorder with an unknown etiology. The correlation between neonatal jaundice and the risk of developing autism spectrum disorder was investigated previously. Some studies showed significant associations, whereas others demonstrated no association. In this meta-analysis, we pooled the results of observational studies to examine the association between neonatal jaundice and the risk of autism spectrum disorder among children. We identified all studies published through April 2018 by conducting a literature search using Web of Science, PubMed, and Scopus databases as well as the reference lists of the retrieved studies. The pooled odds ratios (ORs), rate ratio (RR), and their 95% confidence intervals (CIs) were calculated as random effect estimates of association among studies. We conducted a subgroup analysis to explore any potential sources of intergroup heterogeneity. The pooled estimates of OR and RR showed a considerable correlation between neonatal jaundice and ASD among children (OR, 1.35; 95% CI, 1.02-1.68) and (RR, 1.39; 95% CI, 1.05-1.74). A larger effect size was shown in the pooled estimated crude OR than in the adjusted OR (1.75 [0.96-2.54] vs. 1.19 [1.07-1.30]). This study showed that neonatal jaundice may be associated with ASD and may increase the risk of ASD among children.
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12. Kolodny T, Schallmo MP, Gerdts J, Bernier RA, Murray SO. {{Response dissociation in hierarchical cortical circuits: a unique feature of autism spectrum disorder}}. {J Neurosci}. 2020.
A prominent hypothesis regarding the pathophysiology of autism is that an increase in the balance between neural excitation and inhibition results in an increase in neural responses. However, previous reports of population-level response magnitude in individuals with autism have been inconsistent. Critically, network interactions have not been considered in previous neuroimaging studies of E/I in autism. In particular, a defining characteristic of cortical organization is its hierarchical and interactive structure; sensory and cognitive systems are comprised of networks where later stages inherit and build upon the processing of earlier input stages, and also influence and shape earlier stages by top-down modulation. Here we utilized the well-established connections of the human visual system to examine response magnitudes in a higher-order motion processing region (MT+) and its primary input region (V1). Simple visual stimuli were presented to adult individuals with autism spectrum disorders (ASD; n = 24, mean age 23 years, 8 females) and neurotypical controls (n = 24, mean age 22, 8 females) during fMRI scanning. We discovered a strong dissociation of fMRI response magnitude between region MT+ and V1 in individuals with ASD: individuals with high MT+ responses had attenuated V1 responses. The magnitude of MT+ amplification and of V1 attenuation was associated with autism severity, appeared to result from amplified suppressive feedback from MT+ to V1, and was not present in neurotypical controls. Our results reveal the potential role of altered hierarchical network interactions in the pathophysiology of ASD.SIGNIFICANCE STATEMENTAn imbalance between neural excitation and inhibition, resulting in increased neural responses, has been suggested as a pathophysiological pathway to autism, but direct evidence from humans is lacking. In the current study we consider the role of interactions between stages of sensory processing when testing increased neural responses in individuals with autism. We utilized the well-known hierarchical structure of the visual motion pathway to demonstrate a dissociation in the fMRI response magnitude between adjacent stages of processing in autism: responses are attenuated in a primary visual area but amplified in a subsequent higher-order area. This response dissociation appears to rely on enhanced suppressive feedback between regions and reveals a previously unknown cortical network alteration in autism.
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13. Lee KS, Jung SJ, Yoo HJ, Shin YW, Cho YI. {{Validity and Reliability of the Behavior Development Screening for Toddlers-Questionnaire/Parents(BeDevel-Q/P): A Korean Autism Screening Instrument for Infants aged 24-35 Months}}. {Psychiatry investigation}. 2020; 17(1): 47-54.
OBJECTIVE: This study tested the validity and reliability of the Behavior Development Screening for Toddlers-Questionnaire-Parents (BeDevel-Q/P), a new autism spectrum disorder (ASD) screening instrument being developed in South Korea. The parents of 24-35-month-old infants were recruited to complete the questionnaire. METHODS: The participants were 791 infants aged 24-35 months. There were 623 typically developing infants, 88 infants with ASD, and 80 developmentally delayed infants. For test-retest, the participants were surveyed every 1-4 weeks. Participants were recruited nationwide. Subjects’ parents completed the BeDevel-Q/P and concurrent validity questionnaires. The data were used for statistical analysis. RESULTS: A total of 24 items consisting of 16 items from factor 1 (F1), 6 items from factor 2 (F2), and 2 items from factor 3 (F3), were selected for the final BeDevel-Q/P items. CONCLUSION: The factors of the screening instrument developed in this study were analyzed, and three factors were extracted, confirming the theoretical foundation of the BeDevel-Q for the parents of 24-35-month-old infants.
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14. Lind T, Lau AS, Gomez C, Rodriguez A, Guan K, Chlebowski C, Zhang A, Chorpita B, Brookman-Frazee L. {{Emergent life events in the delivery of a caregiver-mediated evidence-based intervention for children with autism spectrum disorder in publicly funded mental health services}}. {Autism}. 2020: 1362361319881084.
LAY ABSTRACT: Mental health clinicians often report significant challenges when delivering evidence-based interventions (EBI) in community settings, particularly when unexpected client stressors (or emergent life events; ELEs) interfere with the therapy process. The current study sought to extend the study of ELEs to children with Autism Spectrum Disorder (ASD) by examining the occurrence and impact of ELEs in the context of a collaborative, caregiver-mediated intervention for reducing challenging behaviors in children with ASD. This intervention was An Individualized Mental Health Intervention for children with ASD (referred to as AIM HI). Participants included 38 clinicians and child clients who were enrolled in a community effectiveness trial of AIM HI. Video recordings of 100 therapy sessions were coded for caregiver-reported ELEs and also how well clinicians adhered to the AIM HI protocol. Results indicated that mild to severe ELEs were reported in 36% of therapy sessions, and were reported for 58% of children at some point during the intervention. Children who had a greater number of diagnoses (in addition to the autism diagnosis) tended to have more ELEs. In addition, clinicians with less years of experience tended to have sessions with more ELEs. There was no significant link between ELEs and how well clinicians adhered to the AIM HI protocol. Findings offer implications for the implementation of EBI, particularly the importance of incorporating clinician training in addressing complex presentations and crises in the context of EBIs.
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15. Lobzhanidze G, Japaridze N, Lordkipandize T, Rzayev F, MacFabe D, Zhvania M. {{Behavioral and Brain Ultrastructural Changes Following Systemic Administration of Propionic Acid in Adolescent Male Rats. Further Development of a Rodent Model of Autism}}. {Int J Dev Neurosci}. 2020.
Short chain fatty acids, produced as gut microbiome metabolites but also present in diet, exert broad effects in host physiology. Propionic acid (PPA), along with butyrate and acetate, plays a growing role in health, but also in neurological conditions. Increased PPA exposure in humans, animal models and cell lines elicit diverse behavioral and biochemical changes consistent with organic acidurias, mitochondrial disorders and autism spectrum disorders (ASD). ASD is considered a disorder of synaptic dysfunction and cell signaling, but also neuroinflammatory and neurometabolic components. We examined behavior (Morris water and radial arm mazes) and the ultrastructure of the hippocampus and medial prefrontal cortex (electron microscopy) following a single intraperitoneal (i.p.) injection of PPA (175 mg/kg) in male adolescent rats. PPA treatment showed altered social and locomotor behavior without changes in learning and memory. Both transient and enduring ultrastructural alterations in synapses, astro- and microglia were detected in the CA1 hippocampal area. Electron microscopic analysis showed, PPA treatment significantly decreased total number of synaptic vesicles, presynaptic mitochondria and synapses with a symmetric active zone. Thus, brief systemic administration of this dietary and enteric short chain fatty acid produced behavioral and dynamic brain ultrastructural changes, providing further validation of the PPA model of ASD.
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16. Marchetti A, Miraglia L, Di Dio C. {{Toward a Socio-Material Approach to Cognitive Empathy in Autistic Spectrum Disorder}}. {Front Psychol}. 2019; 10: 2965.
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17. Matsuzaki J, Ku M, Dipiero M, Chiang T, Saby J, Blaskey L, Kuschner ES, Kim M, Berman JI, Bloy L, Chen YH, Dell J, Liu S, Brodkin ES, Embick D, Roberts TPL. {{Delayed Auditory Evoked Responses in Autism Spectrum Disorder across the Life Span}}. {Dev Neurosci}. 2020: 1-11.
The M50 and M100 auditory evoked responses reflect early auditory processes in the primary/secondary auditory cortex. Although previous M50 and M100 studies have been conducted on individuals with autism spectrum disorder (ASD) and indicate disruption of encoding simple sensory information, analogous investigations of the neural correlates of auditory processing through development from children into adults are very limited. Magnetoencephalography was used to record signals arising from the left and right superior temporal gyrus during auditory presentation of tones to children/adolescents and adults with ASD as well as typically developing (TD) controls. One hundred and thirty-two participants (aged 6-42 years) were included into the final analyses (children/adolescents: TD, n = 36, 9.21 +/- 1.6 years; ASD, n = 58, 10.07 +/- 2.38 years; adults: TD, n = 19, 26.97 +/- 1.29 years; ASD, n = 19, 23.80 +/- 6.26 years). There were main effects of group on M50 and M100 latency (p < 0.001) over hemisphere and frequency. Delayed M50 and M100 latencies were found in participants with ASD compared to the TD group, and earlier M50 and M100 latencies were associated with increased age. Furthermore, there was a statistically significant association between language ability and both M50 and M100 latencies. Importantly, differences in M50 and M100 latencies between TD and ASD cohorts, often reported in children, persisted into adulthood, with no evidence supporting latency convergence. Lien vers le texte intégral (Open Access ou abonnement)
18. McCullagh EA, Poleg S, Greene NT, Huntsman MM, Tollin DJ, Klug A. {{Characterization of Auditory and Binaural Spatial Hearing in a Fragile X Syndrome Mouse Model}}. {eNeuro}. 2020; 7(1).
The auditory brainstem compares sound-evoked excitation and inhibition from both ears to compute sound source location and determine spatial acuity. Although alterations to the anatomy and physiology of the auditory brainstem have been demonstrated in fragile X syndrome (FXS), it is not known whether these changes cause spatial acuity deficits in FXS. To test the hypothesis that FXS-related alterations to brainstem circuits impair spatial hearing abilities, a reflexive prepulse inhibition (PPI) task, with variations in sound (gap, location, masking) as the prepulse stimulus, was used on Fmr1 knock-out mice and B6 controls. Specifically, Fmr1 mice show decreased PPI compared with wild-type mice during gap detection, changes in sound source location, and spatial release from masking with no alteration to their overall startle thresholds compared with wild-type mice. Last, Fmr1 mice have increased latency to respond in these tasks, suggesting additional impairments in the pathway responsible for reacting to a startling sound. This study further supports data in humans with FXS that show similar deficits in PPI.
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19. Moseley RL, Druce T, Turner-Cobb JM. {{‘When my autism broke’: A qualitative study spotlighting autistic voices on menopause}}. {Autism}. 2020: 1362361319901184.
LAY ABSTRACT: Autistic girls are known to struggle with the onset of menstruation, reporting that during their period, sensory sensitivities are heightened, it becomes more difficult to think clearly and control their emotions and they struggle more with everyday life and self-care. Yet surprisingly, nothing is known about how autistic women handle the menopausal transition in midlife. In non-autistic women, the menopause brings many physical changes and challenging symptoms from hot flushes to feeling more anxious and depressed. Because autistic women are already vulnerable to suicide, poor physical and mental health, and because they may already struggle with planning, controlling their emotions and coping with change, the menopause may be an especially challenging time. Yet, not one single study exists on the menopause in autism, so we conducted an online discussion (focus group) with seven autistic women. They confirmed that very little is known about menopause in autistic people, very little support is available and that menopause might be especially difficult for autistic people. Autism-related difficulties (including sensory sensitivity, socializing with others and communicating needs) were reported to worsen during the menopause, often so dramatically that some participants suggested they found it impossible to continue to mask their struggles. Participants also reported having extreme meltdowns, experiencing anxiety and depression, and feeling suicidal. This study highlights how important it is that professionals pay attention to menopause in autism, and discusses future research directions.
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20. Nambot S, Faivre L, Mirzaa G, Thevenon J, Bruel AL, Mosca-Boidron AL, Masurel-Paulet A, Goldenberg A, Le Meur N, Charollais A, Mignot C, Petit F, Rossi M, Metreau J, Layet V, Amram D, Boute-Benejean O, Bhoj E, Cousin MA, Kruisselbrink TM, Lanpher BC, Klee EW, Fiala E, Grange DK, Meschino WS, Hiatt SM, Cooper GM, Olivie H, Smith WE, Dumas M, Lehman A, Inglese C, Nizon M, Guerrini R, Vetro A, Kaplan ES, Miramar D, Van Gils J, Fergelot P, Bodamer O, Herkert JC, Pajusalu S, Ounap K, Filiano JJ, Smol T, Piton A, Gerard B, Chantot-Bastaraud S, Bienvenu T, Li D, Juusola J, Devriendt K, Bilan F, Poe C, Chevarin M, Jouan T, Tisserant E, Riviere JB, Tran Mau-Them F, Philippe C, Duffourd Y, Dobyns WB, Hevner R, Thauvin-Robinet C. {{De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature}}. {European journal of human genetics : EJHG}. 2020.
TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.
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21. Noyan Erbas A, Ozcebe E, Cak Esen T. {{Investigation of the effect of Hanen’s « More Than Words » on parental self-efficacy, emotional states, perceived social support, and on communication skills of children with ASD}}. {Logopedics, phoniatrics, vocology}. 2020: 1-11.
Background: Parents’ emotional states, self-efficacy, and perceived social support levels are crucial elements to consider when planning treatments for children with autism spectrum disorders (ASD). High levels of parental stress, depression, anxiety and low levels of parental efficacy and social support may disrupt the role of parent involvement in early intervention programs. In this study, Hanen’s « More Than Words » (HMTW) intervention was provided to a group of parents with children who had been diagnosed early with ASD.Method: Fourteen parents and their children with ASD (four girls and ten boys) were enrolled in the study. The primary impact of the HMTW intervention on parents’ emotional states, self-efficacy, interactional behaviors, and perceived social support levels and its secondary effect on children’s communication development was investigated in five different time intervals and in three different conditions (pre-intervention, post-intervention, and follow-up).Results: The results indicated that the rate of change in the levels of parents’ self-efficacy, state of anxiety, parental stress, parental interactional behaviors, and childrens’ verbal language performances and interactional behaviors was statistically different in the post-intervention period when compared with the pre-intervention period (p < .05).Conclusions: The HMTW intervention did not only have a positive effect on parents, but also on children with ASD in this study.What this paper adds: This research was an extension of the previous "Hanen's More Than Words" efficacy studies to examine the program's primary effect on parents' emotional states, self-efficacy, interactional behaviors, and perceived social support levels and its secondary effect on children's interactional behavior and language development. The findings of the study confirm that the program has the potential to increase parents' sense of efficacy and the quality of parent-child interactions. The main conclusion is that parents, as the main caregivers, should be involved in the treatment of their young children with ASD. Lien vers le texte intégral (Open Access ou abonnement)
22. Salaeva D, Tarasoff LA, Brown HK. {{Health care utilisation in infants and young children born to women with intellectual and developmental disabilities: A systematic review and meta-analysis}}. {J Intellect Disabil Res}. 2020.
BACKGROUND: Mothers with intellectual and developmental disabilities (IDD) experience socio-economic and health disparities which could impact their offspring’s health care utilisation. We systematically reviewed evidence on health care utilisation in infants and young children of women with and without IDD. METHODS: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from inception to October 2019 for studies examining preventive care, immunisations, emergency department visits, and hospitalisations. Data extraction and quality assessment were performed using standardised tools. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models for outcomes with data available from >/=3 studies. RESULTS: Four articles describing three cohort studies and one cross-sectional study met our criteria. Maternal IDD status was associated with increased neonatal intensive care unit admission rates (pooled OR 2.03; 95% CI 1.31, 3.13). There were no differences in immunisation rates or hospitalisations. CONCLUSIONS: Few studies have examined the impact of maternal IDD status on health care utilisation in their infants and young children. More high-quality studies are needed.
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23. Scott TM, Guo H, Eichler EE, Rosenfeld JA, Pang K, Liu Z, Lalani S, Weimin B, Yang Y, Bacino CA, Streff H, Lewis AM, Koenig MK, Thiffault I, Bellomo A, Everman DB, Jones JR, Stevenson RE, Bernier R, Gilissen C, Pfundt R, Hiatt SM, Cooper GM, Holder JL, Jr., Scott DA. {{BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability and autism spectrum disorder}}. {Human mutation}. 2020.
The bromodomain adjacent to zinc finger 2B gene (BAZ2B) encodes a protein involved in chromatin remodeling. Loss of BAZ2B function has been postulated to cause neurodevelopmental disorders. To determine whether BAZ2B deficiency is likely to contribute to the pathogenesis of these disorders, we performed bioinformatics analyses that demonstrated a high level of functional convergence, during fetal cortical development, between BAZ2B and genes known to cause autism spectrum disorder and neurodevelopmental disorder. We also found an excess of de novo BAZ2B loss-of-function variants in exome sequencing data from previously published cohorts of individuals with neurodevelopmental disorders. We subsequently identified seven additional individuals with heterozygous deletions, stop-gain, or de novo missense variants affecting BAZ2B. All of these individuals have developmental delay, intellectual disability and/or autism spectrum disorder. Taken together, our findings suggest that haploinsufficiency of BAZ2B causes a neurodevelopmental disorder whose cardinal features include developmental delay, intellectual disability and autism spectrum disorder. This article is protected by copyright. All rights reserved.
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24. Smolich L, Charen K, Sherman SL. {{Health knowledge of women with a fragile X premutation: Improving understanding with targeted educational material}}. {Journal of genetic counseling}. 2020.
Women who carry a fragile X premutation are at risk for at least two major health conditions and for transmitting fragile X syndrome (FXS) to their children. The two health concerns include fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to evaluate whether written educational information about these conditions would increase knowledge and facilitate communication. Women with a premutation (N = 142) completed an online pre-test to assess their knowledge of premutation-associated conditions, and 135 women who provided an address received a booklet titled Women’s Health and the Fragile X Premutation. After 3 months, 51.1% completed the post-test. Major gaps in knowledge were related to FXPOI and factors associated with repeat expansion. To determine whether the booklet helped to fill gaps in knowledge, we compared pre- and post-test scores. Scores were significantly increased after receipt of the booklet (p < .05, Wilcoxon signed rank test). Participants answered that the booklet was 'very helpful' (44.6%) or 'somewhat helpful' (38.5%). Twenty-four participants (34.8%) reported using the booklet to explain concepts to family members. Although we found that the booklet provided women with needed information, we found that gaps in knowledge still exist. Lien vers le texte intégral (Open Access ou abonnement)
25. Su Z, Frost EL, Lammert CR, Przanowska RK, Lukens JR, Dutta A. {{tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model}}. {RNA biology}. 2020: 1-13.
tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the foetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5′ tRNA halves from tRNA(Gly), tRNA(Glu), tRNA(Val) and tRNA(Lys) are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 h after MIA and are suppressed thereafter. A group of 5′ tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.
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26. Svoboda E. {{Could the gut microbiome be linked to autism?}}. {Nature}. 2020; 577(7792): S14-s5.
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27. Umesawa Y, Matsushima K, Atsumi T, Kato T, Fukatsu R, Wada M, Ide M. {{Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
Several motor disabilities accompanied with autism spectrum disorder (ASD) are widely known despite limited reports of underlying neural mechanisms. Gamma-aminobutyric acid (GABA) levels in the motor-related cortical areas modulate several motor performances in healthy participants. We hypothesized that abnormal GABA concentrations in the primary motor area (M1) and supplementary motor area (SMA) associate with different motor difficulties for ASD adolescents/adults. We found that increased GABA concentrations in M1 measured using (1)H-magnetic resonance spectroscopy exhibited lower motor performance in tasks requiring increased muscle strength while lower GABA concentrations in SMA were associated with lower scores in tests measuring body coordination. The degrees of neural inhibition in the M1 and SMA regions would contribute to different dimensions of motor disabilities in autism.
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28. Van der Donck S, Dzhelyova M, Vettori S, Mahdi SS, Claes P, Steyaert J, Boets B. {{Rapid neural categorization of angry and fearful faces is specifically impaired in boys with autism spectrum disorder}}. {J Child Psychol Psychiatry}. 2020.
BACKGROUND: Difficulties with facial expression processing may be associated with the characteristic social impairments in individuals with autism spectrum disorder (ASD). Emotional face processing in ASD has been investigated in an abundance of behavioral and EEG studies, yielding, however, mixed and inconsistent results. METHODS: We combined fast periodic visual stimulation (FPVS) with EEG to assess the neural sensitivity to implicitly detect briefly presented facial expressions among a stream of neutral faces, in 23 boys with ASD and 23 matched typically developing (TD) boys. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, happy, sad in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinguishable frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the expression-categorization responses, needing only four sequences of 60 s of recording per condition. RESULTS: Both groups show equal neural synchronization to the general face stimulation and similar neural responses to happy and sad faces. However, the ASD group displays significantly reduced responses to angry and fearful faces, compared to TD boys. At the individual subject level, these neural responses allow to predict membership of the ASD group with an accuracy of 87%. Whereas TD participants show a significantly lower sensitivity to sad faces than to the other expressions, ASD participants show an equally low sensitivity to all the expressions. CONCLUSIONS: Our results indicate an emotion-specific processing deficit, instead of a general emotion-processing problem: Boys with ASD are less sensitive than TD boys to rapidly and implicitly detect angry and fearful faces. The implicit, fast, and straightforward nature of FPVS-EEG opens new perspectives for clinical diagnosis.
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29. Wylie KP, Tregellas JR, Bear JJ, Legget KT. {{Autism Spectrum Disorder Symptoms are Associated with Connectivity Between Large-Scale Neural Networks and Brain Regions Involved in Social Processing}}. {J Autism Dev Disord}. 2020.
The neurobiology of autism spectrum disorder remains poorly understood. The present study addresses this knowledge gap by examining the relationship between functional brain connectivity and Autism Diagnostic Observation Schedule (ADOS) scores using publicly available data from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 107). This relationship was tested across all brain voxels, without a priori assumptions, using a novel statistical approach. ADOS scores were primarily associated with decreased connectivity to right temporoparietal junction, right anterior insula, and left fusiform gyrus (p < 0.05, corrected). Seven large-scale brain networks influenced these associations. Findings largely encompassed brain regions involved in processing socially relevant information, highlighting the importance of these processes in autism spectrum disorder. Lien vers le texte intégral (Open Access ou abonnement)
30. Yasumatsu K, Nagao JI, Arita-Morioka KI, Narita Y, Tasaki S, Toyoda K, Ito S, Kido H, Tanaka Y. {{Bacterial-induced maternal interleukin 17A pathway promotes autistic-like behaviors in mouse offspring}}. {Experimental animals}. 2020.
Maternal immune activation (MIA) by an infection is considered to be an important environmental factor of fetal brain development. Recent animal model on MIA induced by polyinosinic:polycytidylic acid, a mimic of viral infection, demonstrates that maternal interleukin 17A (IL-17A) signaling is required for the development of autism spectrum disorder (ASD)-like behaviors of offspring. However, there is little information on bacterial infection. In this study, we aim to elucidate the influence of MIA induced by lipopolysaccharide (LPS) to mimic a bacterial infection on fetal brain development. We demonstrated that LPS-induced MIA promoted ASD-like behaviors in mouse offspring. We further found that LPS exposure induced acute phase immune response: elevation of serum IL-17A levels in MIA mothers, upregulation of Il17a mRNA expression and increase of IL-17A-producing gammadelta T cells in the uterus, and upregulation of Il17ra mRNA expression in the fetal brain. Blocking of IL-17A in LPS-induced MIA ameliorated ASD-like behaviors in offspring. Our data suggest that bacterial-induced maternal IL-17A pathway promotes ASD-like behaviors in offspring.
