Pubmed du 21/06/19

vendredi 21 juin 2019

1. Abdelli LS, Samsam A, Naser SA. Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder. Sci Rep ;2019 (Jun 19) ;9(1):8824.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by glia over-proliferation, neuro-inflammation, perturbed neural circuitry, and gastrointestinal symptoms. The role of gut dys-biosis in ASD is intriguing and should be elucidated. We investigated the effect of Propionic acid (PPA), a short-chain fatty acid (SCFA) and a product of dys-biotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation and inflammation. hNSCs proliferated to 66 neuropsheres when exposed to PPA versus 45 in control. The neurosphere diameter also increased at day 10 post PPA treatment to (Mean : 193.47 um +/- SEM : 6.673 um) versus (154.16 um +/- 9.95 um) in control, p < 0.001. Pre-treatment with beta-HB, SCFA receptor inhibitor, hindered neurosphere expansion (p < 0.001). While hNSCs spontaneously differentiated to (48.38% +/- 6.08%) neurons (Tubulin-IIIbeta positive) and (46.63% +/- 2.5%) glia (GFAP positive), PPA treatment drastically shifted differentiation to 80% GFAP cells (p < 0.05). Following 2 mM PPA exposure, TNF-alpha transcription increased 4.98 fold and the cytokine increased 3.29 fold compared to control (P < 0.001). Likewise, GPR41 (PPA receptor) and pro-survival p-Akt protein were elevated (p < 0.001). PTEN (Akt inhibitor) level decreased to (0.42 ug/ul +/- 0.04 ug/ul) at 2 mM PPA compared to (0.83 ug/ul +/- 0.09 ug/ul) in control (p < 0.001). PPA at 2 mM decreased neurite outgrowth to (80.70 um +/- 5.5 um) compared to (194.93 um +/- 19.7 um) in control. Clearly, the data supports a significant role for PPA in modulating hNSC patterning leading to gliosis, disturbed neuro-circuitry, and inflammatory response as seen in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

2. Black MH, Chen NT, Lipp OV, Bolte S, Girdler S. Complex facial emotion recognition and atypical gaze patterns in autistic adults. Autism ;2019 (Jun 19):1362361319856969.

While altered gaze behaviour during facial emotion recognition has been observed in autistic individuals, there remains marked inconsistency in findings, with the majority of previous research focused towards the processing of basic emotional expressions. There is a need to examine whether atypical gaze during facial emotion recognition extends to more complex emotional expressions, which are experienced as part of everyday social functioning. The eye gaze of 20 autistic and 20 IQ-matched neurotypical adults was examined during a facial emotion recognition task of complex, dynamic emotion displays. Autistic adults fixated longer on the mouth region when viewing complex emotions compared to neurotypical adults, indicating that altered prioritization of visual information may contribute to facial emotion recognition impairment. Results confirm the need for more ecologically valid stimuli for the elucidation of the mechanisms underlying facial emotion recognition difficulty in autistic individuals.

Lien vers le texte intégral (Open Access ou abonnement)

3. Boutrus M, Gilani SZ, Alvares GA, Maybery MT, Tan DW, Mian A, Whitehouse AJO. Increased facial asymmetry in autism spectrum conditions is associated with symptom presentation. Autism Res ;2019 (Jun 21)

A key research priority in the study of autism spectrum conditions (ASC) is the discovery of biological markers that may help to identify and elucidate etiologically distinct subgroups. One physical marker that has received increasing research attention is facial structure. Although there remains little consensus in the field, findings relating to greater facial asymmetry (FA) in ASC exhibit some consistency. As there is growing recognition of the importance of replicatory studies in ASC research, the aim of this study was to investigate the replicability of increased FA in autistic children compared to nonautistic peers. Using three-dimensional photogrammetry, this study examined FA in 84 autistic children, 110 typically developing children with no family history of the condition, and 49 full siblings of autistic children. In support of previous literature, significantly greater depth-wise FA was identified in autistic children relative to the two comparison groups. As a further investigation, increased lateral FA in autistic children was found to be associated with greater severity of ASC symptoms on the Autism Diagnostic Observation Schedule, second edition, specifically related to repetitive and restrictive behaviors. These outcomes provide an important and independent replication of increased FA in ASC, as well as a novel contribution to the field. Having confirmed the direction and areas of increased FA in ASC, these findings could motivate a search for potential underlying brain dysmorphogenesis. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : This study looked at the amount of facial asymmetry (FA) in autistic children compared to typically developing children and children who have siblings with autism. The study found that autistic children, compared to the other two groups, had greater FA, and that increased FA was related to greater severity of autistic symptoms. The face and brain grow together during the earliest stages of development, and so findings of facial differences in autism might inform future studies of early brain differences associated with the condition.

Lien vers le texte intégral (Open Access ou abonnement)

4. Campbell-Scherer D. Evidence from large Danish cohort does not support an association between the MMR vaccine and autism : facts in a post-truth world. BMJ Evid Based Med ;2019 (Jun 19)

Lien vers le texte intégral (Open Access ou abonnement)

5. Durbin A, Jung JKH, Chung H, Lin E, Balogh R, Lunsky Y. Prevalence of intellectual and developmental disabilities among first generation adult newcomers, and the health and health service use of this group : A retrospective cohort study. PLoS One ;2019 ;14(6):e0215804.

BACKGROUND : Attention to research and planning are increasingly being devoted to newcomer health, but the needs of newcomers with disabilities remain largely unknown. This information is difficult to determine since population-level data are rarely available on newcomers or on people with intellectual and developmental disabilities (IDD), although in Ontario, Canada these databases are accessible. This study compared the prevalence of IDD among first generation adult newcomers to adult non-newcomers in Ontario, and assessed how having IDD affected the health profile and health service use of newcomers. METHODS : This population-based retrospective cohort study of adults aged 19-65 in 2010 used linked health and social services administrative data. Prevalence of IDD among newcomers (n = 1,649,633) and non-newcomers (n = 6,880,196) was compared. Among newcomers, those with IDD (n = 2,830) and without IDD (n = 1,646,803) were compared in terms of health conditions, and community and hospital service use. RESULTS : Prevalence of IDD was lower in newcomers than non-newcomers (171.6 versus 898.3 per 100,000 adults, p<0.0001). Among newcomers, those with IDD were more likely than those without IDD to have comorbid physical health disorders, non-psychotic, psychotic and substance use disorders. Newcomers with IDD were also more likely to have psychiatry visits, and frequent emergency department visits and hospitalizations. CONCLUSION : First generation adult newcomers have lower rates of IDD than non-newcomers. How much of this difference is attributable to admission policies that exclude people expected to be high health service users versus how much is attributable to our methodological approach is unknown. Finding more medical and psychiatric comorbidity, and more health service use among newcomers with IDD compared to newcomers without IDD is consistent with patterns observed in adults with IDD more generally. To inform polices that support newcomers with IDD future research should investigate reasons for the prevalence finding, barriers and facilitators to timely health care access, and pathways to care.

Lien vers le texte intégral (Open Access ou abonnement)

6. Ess KC, Franz DN. Everolimus for cognition/autism in children with tuberous sclerosis complex : Definitive outcomes deferred. Neurology ;2019 (Jun 19)

Lien vers le texte intégral (Open Access ou abonnement)

7. Ferguson RH, Falcomata TS, Ramirez-Cristoforo A, Vargas Londono F. An Evaluation of the Effects of Varying Magnitudes of Reinforcement on Variable Responding Exhibited by Individuals With Autism. Behav Modif ;2019 (Jun 19):145445519855615.

Interventions aimed at increasing communicative response variability hold particular importance for individuals with autism spectrum disorders (ASD). Several procedures have been demonstrated in the applied and translational literature to increase response variability. However, little is known about the relationship between reinforcer magnitude and response variability. In the basic literature, Doughty, Giorno, and Miller evaluated the effects of reinforcer magnitude on behavioral variability by manipulating reinforcer magnitude across alternating relative frequency threshold contingencies, with results suggesting that larger reinforcers induced repetitive responding. The purpose of this study was to translate Doughty et al.’s findings to evaluate the relative effects of different magnitudes of reinforcement on communicative response variability in children with ASD. A Lag 1 schedule of reinforcement was in place during each condition within an alternating treatments design. Magnitudes of reinforcement contingent on variable communicative responding were manipulated across the two conditions. Inconsistent with basic findings, the results showed higher levels of variable communicative responding associated with the larger magnitude of reinforcement. These outcomes may have potential implications for interventions aimed at increasing response variability in individuals with ASD, as well as future research in this area.

Lien vers le texte intégral (Open Access ou abonnement)

8. Fisher WW, Felber JM, Phillips LA, Craig AR, Paden AR, Niemeier JJ. Treatment of resistance to change in children with autism. J Appl Behav Anal ;2019 (Jun 20)

"Resistance to change" represents a core symptom of autism that we conceptualized and assessed as resulting in part due to factors known to govern free-operant choice. During a free-choice baseline, participants chose between problematic, resistive responses and an appropriate alternative response. During the asymmetrical-choice condition, we delivered their most highly preferred item if the participant chose the alternative response (i.e., differential reinforcement of alternative behavior [DRA]). During the guided- (Experiment 1) and singular- (Experiment 2) choice conditions, we prompted participants to choose the alternative response and then delivered their most highly preferred item (i.e., DRA with escape extinction). All participants learned to tolerate (Experiment 1) or choose (Experiment 2) the alternative response when we combined DRA with escape extinction. After exposure to escape extinction, two participants showed strong maintenance effects with DRA alone. We discuss these finding relative to the effects of DRA and escape extinction on resistance to change.

Lien vers le texte intégral (Open Access ou abonnement)

9. Goodwin MS, Mazefsky CA, Ioannidis S, Erdogmus D, Siegel M. Predicting aggression to others in youth with autism using a wearable biosensor. Autism Res ;2019 (Jun 21)

Unpredictable and potentially dangerous aggressive behavior by youth with Autism Spectrum Disorder (ASD) can isolate them from foundational educational, social, and familial activities, thereby markedly exacerbating morbidity and costs associated with ASD. This study investigates whether preceding physiological and motion data measured by a wrist-worn biosensor can predict aggression to others by youth with ASD. We recorded peripheral physiological (cardiovascular and electrodermal activity) and motion (accelerometry) signals from a biosensor worn by 20 youth with ASD (ages 6-17 years, 75% male, 85% minimally verbal) during 69 independent naturalistic observation sessions with concurrent behavioral coding in a specialized inpatient psychiatry unit. We developed prediction models based on ridge-regularized logistic regression. Our results suggest that aggression to others can be predicted 1 min before it occurs using 3 min of prior biosensor data with an average area under the curve of 0.71 for a global model and 0.84 for person-dependent models. The biosensor was well tolerated, we obtained useable data in all cases, and no users withdrew from the study. Relatively high predictive accuracy was achieved using antecedent physiological and motion data. Larger trials are needed to further establish an ideal ratio of measurement density to predictive accuracy and reliability. These findings lay the groundwork for the future development of precursor behavior analysis and just-in-time adaptive intervention systems to prevent or mitigate the emergence, occurrence, and impact of aggression in ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Unpredictable aggression can create a barrier to accessing community, therapeutic, medical, and educational services. The present study evaluated whether data from a wearable biosensor can be used to predict aggression to others by youth with autism spectrum disorder (ASD). Results demonstrate that aggression to others can be predicted 1 min before it occurs with high accuracy, laying the groundwork for the future development of preemptive behavioral interventions and just-in-time adaptive intervention systems to prevent or mitigate the emergence, occurrence, and impact of aggression to others in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

10. Honma M, Itoi C, Midorikawa A, Terao Y, Masaoka Y, Kuroda T, Futamura A, Shiromaru A, Ohta H, Kato N, Kawamura M, Ono K. Contraction of distance and duration production in autism spectrum disorder. Sci Rep ;2019 (Jun 19) ;9(1):8806.

Autism spectrum disorder (ASD) presents certain hallmark features associated with cognitive and social functions, however, the ability to estimate self-generated distance and duration in individuals with ASD are unclear. We compared the performance of 20 ASD individuals with 20 typical developments (TDs) with respect to two tasks : (1) the drawing of a line of a specified distance (10 or 20 cm) and (2) waiting for a specified time (10 or 20 s). We observed that both the line distances and waiting times were substantially shorter in the ASD group than in the TD group. Furthermore, a trait of "attention to detail," as measured by the Autism-Spectrum Quotient, correlated with some distance and duration productions observed in individuals with ASD. We suggest that attentional functions are related to the contraction of distance and duration in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

11. LaGasse AB, Manning RCB, Crasta JE, Gavin WJ, Davies PL. Assessing the Impact of Music Therapy on Sensory Gating and Attention in Children With Autism : A Pilot and Feasibility Study. J Music Ther ;2019 (Jun 21)

Children with autism spectrum disorder (ASD) frequently demonstrate atypical processing of sensory information and deficits in attentional abilities. These deficits may impact social and academic functioning. Although music therapy has been used to address sensory and attentional needs, there are no studies including physiologic indicators of sensory processing to determine the impact of music therapy. The objective of this study was to determine the feasibility of conducting study protocols, determine the adequacy of electroencephalography (EEG) and behavioral measures in identifying attentional differences in children with ASD compared with typically developing (TD) children, and to gather preliminary evidence of intervention effects on brain responses and attention outcomes. Seven children with high functioning ASD ages 5 -12 and seven age- and gender-matched TD completed procedures measuring brain responses (EEG) and behaviors (the Test of Everyday Attention for Children). Children with ASD then completed a 35-min individual music therapy attention protocol delivered by a board-certified music therapist ten times over 5 weeks. Children with ASD completed measures of brain responses and behavior post-intervention to determine pre- to post-test differences. Consent and completion rates were 100% for children who met the study criteria. Feasibility measures indicated that measures of brain responsivity could be used to determine attentional differences between children with ASD and typical children. Initial outcome data for brain responses and behavior indicated positive trends for the impact of music therapy on selective attention skills.

Lien vers le texte intégral (Open Access ou abonnement)

12. Leonzino M, Ponzoni L, Braida D, Gigliucci V, Busnelli M, Ceresini I, Duque-Wilckens N, Nishimori K, Trainor BC, Sala M, Chini B. Impaired approach to novelty and striatal alterations in the oxytocin receptor deficient mouse model of autism. Horm Behav ;2019 (Jun 17)

Long-standing studies established a role for the oxytocin system in social behavior, social reward, pair bonding and affiliation. Oxytocin receptors, implicated in pathological conditions affecting the social sphere such as autism spectrum disorders, can also modulate cognitive processes, an aspect generally overlooked. Here we examined the effect of acute (pharmacological) or genetic (Oxtr(-/-)) inactivation of oxytocin receptor-mediated signaling, in male mice, in several cognitive tests. In the novel object recognition test, both oxytocin receptor antagonist treated wild type animals and Oxtr(-/-) mice lacked the typical preference for novelty. Oxtr(-/-) mice even preferred the familiar object ; moreover, their performance in the Morris water maze did not differ from wild types, suggesting that oxytocin receptor inactivation did not disrupt learning. Because the preference for novel objects could be rescued in Oxtr(-/-) mice with longer habituation periods, we propose that the loss of novelty preferences following Oxtr inactivation is due to altered processing of novel contextual information. Finally, we observed an increased expression of excitatory synaptic markers in the striatum of Oxtr(-/-) mice and a greater arborization and higher number of spines/neuron in the dorsolateral area of this structure, which drives habit formation. Our data also indicate a specific reshaping of dorsolateral striatal spines in Oxtr(-/-) mice after exposure to a novel environment, which might subtend their altered approach to novelty, and support previous work pointing at this structure as an important substrate for autistic behaviors.

Lien vers le texte intégral (Open Access ou abonnement)

13. Lim YH, Lee HC, Falkmer T, Allison GT, Tan T, Lee WL, Morris SL. Postural control adaptation to optic flow in children and adults with autism spectrum disorder. Gait Posture ;2019 (Jun 10) ;72:175-181.

BACKGROUND : Sensory reweighting is important for humans to flexibly up-weigh and down-weigh sensory information in dynamic environments. There is an element of time involved in the sensory reweighting process. A longer time spent on sensory reweighting may increase the destabilizing effect of postural control. Individuals with autism spectrum disorder (ASD) are reported to have poor postural control. It is uncertain if a different sensory reweighting process underlies the postural control deficit in children and adults with ASD. RESEARCH QUESTION : To explore the sensory reweighting capability in ASD, the present study examined whether the temporal domains of postural control differed in children and adults, with and without ASD under various optic flow conditions. METHODS : Thirty-three children (8-12 years old) and 33 adults (18-50 years old) with and without ASD underwent quiet standing in six radial optic flow conditions. Each condition lasted for 60s and was shown twice to all participants. For each optic flow condition, changes in postural response within-trial and between-trials were measured. RESULTS : Under various optic flow illusions, both children with and without ASD took a longer time to restore their posture compared with adults with and without ASD. Nonetheless, all groups demonstrated comparable abilities to adjust their posture to one that is close to the baseline position after one exposure to the optic flow stimulation. SIGNIFICANCE : The present study showed that the temporal domains of postural control under different optic flow conditions were similar between individuals with and without ASD from the same age group. The ability to down-weigh visual information efficiently comes with the developmental progression of the sensory reweighting system. These findings suggest that the sensory reweighting process does not elucidate the postural control deficits in individuals with ASD and thus alternative explanations to determine the underlying mechanism for postural instability are needed.

Lien vers le texte intégral (Open Access ou abonnement)

14. Nogay NH, Nahikian-Nelms M. Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation ? A review. Nutr Neurosci ;2019 (Jun 19):1-12.

Introduction : Autism is a neurodevelopmental disorder that negatively affects a child’s interaction and communication with the environment. The signals between intestine, brain, and microbiota change in autism. Altering the composition of microbiota may contribute to the development of clinical symptoms. Diet is one of the most important factors influencing intestinal microbiota. Aim : This study aimed to investigate the role of intestinal microbiota in gastrointestinal (GI) and behavioral problems seen in children with autism and discuss the potential effect of diet on intestinal microbiota in reducing these problems. Methods : The database Web of Science was searched for relevant studies. The combinations of the following terms were used for the search : ’autism’ or ’autistic’ and ’microbiome’ or ’microbiota’ or ’gut bacteria’ or ’gut microbiota’ or ’gut microbiome.’ The analysis included human studies evaluating the relationship between GI problems and/or behavioral problems and intestinal microbiota in autism in the English language with no time limitation. Results : The initial search resulted in 691 studies, with 14 studies fully meeting the inclusion criteria. In these studies, high growth rates of Clostridium histolyticum, C. perfringens, and Sutterella ; high ratio of Escherichia/Shigella ; and low ratio of Bacteroidetes/Firmicutes were generally related to GI problems, while relative abundance of Desulfovibrio, Clostridium spp., and Bacteroides vulgatus were associated with behavior disorders. Conclusions : Published studies on the relationship of gastrointestinal and behavioral problems with gut microbiota in autism are very limited and contradictory. The fact that the results of the studies are not consistent with each other may be explained by the differences in the age of participants, geographical region, sample size, presence of GI problems in the selected control group, and feces or biopsy samples taken from different regions of GI system. With the available information, it is not yet possible to develop a gut microbiota-based nutritional intervention to treat GI symptoms for people with autism.

Lien vers le texte intégral (Open Access ou abonnement)

15. Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY. A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex. Neurology ;2019 (Jun 19)

OBJECTIVE : To investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC). METHODS : In this 12-month, randomized, double-blind, placebo-controlled trial, we attempted to enroll 60 children with TSC and IQ <80, learning disability, special schooling, or autism, aged 4-17 years, without intractable seizures to be assigned to receive everolimus or placebo. Everolimus was titrated to blood trough levels of 5-10 ng/mL. Primary outcome was full-scale IQ ; secondary outcomes included autism, neuropsychological functioning, and behavioral problems. RESULTS : Thirty-two children with TSC were randomized. Intention-to-treat analysis showed no benefit of everolimus on full-scale IQ (treatment effect -5.6 IQ points, 95% confidence interval -12.3 to 1.0). No effect was found on secondary outcomes, including autism and neuropsychological functioning, and questionnaires examining behavioral problems, social functioning, communication skills, executive functioning, sleep, quality of life, and sensory processing. All patients had adverse events. Two patients on everolimus and 2 patients on placebo discontinued treatment due to adverse events. CONCLUSIONS : Everolimus did not improve cognitive functioning, autism, or neuropsychological deficits in children with TSC. The use of everolimus in children with TSC with the aim of improving cognitive function and behavior should not be encouraged in this age group. CLINICALTRIALSGOV IDENTIFIER : NCT01730209. CLASSIFICATION OF EVIDENCE : This study provides Class I evidence that for children with TSC, everolimus does not improve intellectual disability, autism, behavioral problems, or other neuropsychological deficits.

Lien vers le texte intégral (Open Access ou abonnement)

16. Sheikh R, Patino V, Cengher M, Fiani T, Jones EA. Augmenting Sibling Support with Parent-Sibling Training in Families of Children with Autism. Dev Neurorehabil ;2019 (Jun 19):1-11.

Background : Typically developing (TD) siblings are an important part of the family system, but may show strained relationships in families of children with ASD. Objective : We augmented a sibling support group with parent-sibling training in which parents learned (through instructions, modeling, rehearsal, and feedback) how to prompt and reinforce prosocial behaviors in their TD children. Method : We examined the effects of parent-sibling training on parent and TD sibling behaviors in a multiple baseline across families design. Results : Parent prompting and reinforcement of TD sibling prosocial behaviors increase. TD sibling prosocial behaviors such as sharing with and talking to their sibling with ASD also increased. Broader measures of the sibling relationship showed some improvements. Conclusion : Findings suggest ways to support families of children with ASD with future investigations of parent-sibling training examining longer intervention, all family members’ adjustment and relationships, and sibling characteristics that influence response to parent-sibling training.

Lien vers le texte intégral (Open Access ou abonnement)

17. Sullivan JM, De Rubeis S, Schaefer A. Convergence of spectrums : neuronal gene network states in autism spectrum disorder. Curr Opin Neurobiol ;2019 (Jun 17) ;59:102-111.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by social deficits and restrictive and/or repetitive behaviors. The breadth of ASD symptoms is paralleled by the multiplicity of genes that have been implicated in its etiology. Initial findings revealed numerous ASD risk genes that contribute to synaptic function. More recently, genomic and gene expression studies point to altered chromatin function and impaired transcriptional control as additional risk factors for ASD. The consequences of impaired transcriptional alterations in ASD involve consistent changes in synaptic gene expression and cortical neuron specification during brain development. The multiplicity of genetic and environmental factors associated with ASD risk and their convergence onto common molecular pathways in neurons point to ASD as a disorder of gene regulatory networks.

Lien vers le texte intégral (Open Access ou abonnement)

18. Wong CCY, Smith RG, Hannon E, Ramaswami G, Parikshak NN, Assary E, Troakes C, Poschmann J, Schalkwyk LC, Sun W, Prabhakar S, Geschwind DH, Mill J. Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue. Hum Mol Genet ;2019 (Jul 1) ;28(13):2201-2211.

Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular aetiology of ASD, we quantified genome-wide patterns of DNA methylation in 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex and cerebellum (CB)] dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the CB. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically defined subtype of ASD, were characterized by striking differences in DNA methylationacross a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.

Lien vers le texte intégral (Open Access ou abonnement)

19. Wong WR, Brugman KI, Maher S, Oh JY, Howe K, Kato M, Sternberg PW. Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans. Hum Mol Genet ;2019 (Jul 1) ;28(13):2271-2281.

Autism spectrum disorder (ASD) involves thousands of alleles in over 850 genes, but the current functional inference tools are not sufficient to predict phenotypic changes. As a result, the causal relationship of most of these genetic variants in the pathogenesis of ASD has not yet been demonstrated and an experimental method prioritizing missense alleles for further intensive analysis is crucial. For this purpose, we have designed a pipeline that uses Caenorhabditis elegans as a genetic model to screen for phenotype-changing missense alleles inferred from human ASD studies. We identified highly conserved human ASD-associated missense variants in their C. elegans orthologs, used a CRISPR/Cas9-mediated homology-directed knock-in strategy to generate missense mutants and analyzed their impact on behaviors and development via several broad-spectrum assays. All tested missense alleles were predicted to perturb protein function, but we found only 70% of them showed detectable phenotypic changes in morphology, locomotion or fecundity. Our findings indicate that certain missense variants in the C. elegans orthologs of human CACNA1D, CHD7, CHD8, CUL3, DLG4, GLRA2, NAA15, PTEN, SYNGAP1 and TPH2 impact neurodevelopment and movement functions, elevating these genes as candidates for future study into ASD. Our approach will help prioritize functionally important missense variants for detailed studies in vertebrate models and human cells.

Lien vers le texte intégral (Open Access ou abonnement)


Accès direct au catalogue en ligne !

Vous pouvez accéder directement au catalogue en ligne du centre de documentation du CRA Rhône-Alpes en cliquant sur l’image ci-dessous :

Cliquez pour consulter le catalogue

Formations pour les Familles et les Proches

le détail des programmes de formation à l’attention des familles et des proches de personnes avec TSA est disponible en cliquant sur l’image ci-dessous.

Formation pour les Aidants Familiaux {JPEG}

Sensibilisation à l’usage des tablettes au CRA !

Toutes les informations concernant les sensibilisations du CRA aux tablettes numériques en cliquant sur l’image ci-dessous :

1-Formation à l’état des connaissances de l’autisme

Plus d’information sur la formation gratuite que dispense le CRA en cliquant sur l’image ci-dessous :

Formation à l'état des connaissances de l'autisme {JPEG}

4-Accéder au Livret Autisme Auvergne Rhône-Alpes (LAARA)

Prenez connaissance du Livret Autisme Auvergne Rhône-Alpes, projet de répertoire régional des structures médico-sociales. En cliquant sur l’image ci-dessous :

Cliquer pour accéder au LAARA