Pubmed du 30/05/19

jeudi 30 mai 2019

1. Ali A, Vasileva S, Langguth M, Alexander S, Cui X, Whitehouse A, McGrath JJ, Eyles D. Developmental Vitamin D Deficiency Produces Behavioral Phenotypes of Relevance to Autism in an Animal Model. Nutrients ;2019 (May 27) ;11(5)

Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and hyper-activities. There are several other clinical features that are commonly comorbid with ASD, including olfactory impairments, anxiety and delays in motor development. Here we investigate these features in an animal model related to ASD-the DVD-deficient rat. Compared to controls, both DVD-deficient male and female pups show altered ultrasonic vocalizations and stereotyped repetitive behavior. Further, the DVD-deficient animals had delayed motor development and impaired motor control. Adolescent DVD-deficient animals had impaired reciprocal social interaction, while as adults, these animals were hyperactive. The DVD-deficient model is associated with a range of behavioral features of interest to ASD.

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2. Alsayedhassan B, Lee J, Banda DR, Kim Y, Griffin-Shirley N. Practitioners’ perceptions of the picture exchange communication system for children with autism. Disabil Rehabil ;2019 (May 30):1-6.

Backgound : Autism spectrum disorder impacts social-communication. Picture Exchange Communication System is one of the methods to improve communication skills in individuals with autism. In spite of numerous studies on the effectiveness of Picture Exchange Communication System, no studies were conducted to examine the perceptions of practitioners who used the strategy. Method : An online survey was conducted with 120 practitioners (44 teachers and 76 therapists ; 80.8% 20-49 years old ; 80.8% graduate education) who used the Picture Exchange Communication System with children with autism. Using rating scales, practitioners reported their knowledge of Picture Exchange Communication System and their perceptions about importance, benefits, and barriers of utilizing Picture Exchange Communication System. Results : Practitioners reported they were confident when implementing Picture Exchange Communication System and considered integrating Picture Exchange Communication System at school to be important. Also, the practitioners indicated that Picture Exchange Communication System was easy to use and effective to develop communication skills in children with autism. However, they found that using Picture Exchange Communication System was time consuming. Conclusion : It is important to hear the viewpoints of practitioners concerning the use of Picture Exchange Communication System for individuals with autism spectrum disorder. This study found Picture Exchange Communication System is a useful strategy but has some barriers concerning its use. Future research is needed to confirm the current findings with a larger sample. IMPLICATIONS FOR REHABILITATION Many students with autism spectrum disorder are non-verbal and may benefit from augmentative and alternative communication methods. Picture Exchange Communication System, one of the augmentative and alternative communication methods, has been widely used by professionals and parents to improve communication skills of children with autism spectrum disorder who are non-verbal or have complex communication needs. Practitioners indicated that Picture Exchange Communication System was easy to use and effective to develop communication skills in children with autism spectrum disorder. However, they found that it is time consuming. Practitioners need ongoing support when implementing the Picture Exchange Communication System.

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3. Cai Y, Zhong H, Li X, Xiao R, Wang L, Fan X. The Liver X Receptor Agonist TO901317 Ameliorates Behavioral Deficits in Two Mouse Models of Autism. Front Cell Neurosci ;2019 ;13:213.

Autism spectrum disorder (ASD) is a developmental disability characterized by social deficits and repetitive stereotyped behaviors. There are currently no drugs available for the treatment of the core symptoms of ASD, suggesting an urgent need for new therapeutic strategies. The neurobiology of autism is complex, but emerging research indicates that defects in hippocampal neurogenesis are associated with ASD in both humans and mouse models of ASD, leading to the suggestion that restoring neurogenesis may be a novel therapeutic approach for ASD. Here, we found that postnatal treatment with TO901317 (TO), a potent liver X receptor (LXR) agonist, typically activated LXRbeta and its target genes in the hippocampus, and alleviated the social deficits and stereotypical behaviors in BTBR T+ tf/J (BTBR) and valproic acid (VPA)-induced mouse models. In addition, we further confirmed that TO postnatal treatment also rescued the inhibition of adult hippocampal neurogenesis in these two models. In summary, our study suggests that LXR agonist targeting hippocampal neurogenesis may represent a novel potential therapy for ASD.

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4. Chansa-Kabali T, Nyoni J, Mwanza H. Awareness and Knowledge Associated with Autism Spectrum Disorders Among University Students in Zambia. J Autism Dev Disord ;2019 (May 28)

Experiences with Autism Spectrum Disorders (ASDs) in sub-Saharan Africa are characterized with lots of uncertainty, including lack of awareness and knowledge. This study examined ASD awareness and knowledge among 488 University of Zambia undergraduate students using an autism awareness and knowledge survey. Study findings on awareness revealed a high proportion of students-seventy-nine percent (79%) had never heard of ASD before the survey. Significant variation in aspects of ASD knowledge was explained by gender, having children, internet use and school of study. Implications of low levels of ASD awareness and knowledge is a call to invest in ASD awareness campaigns through different platforms in order to promote ASD knowledge that translates into increased ASD understanding for better service provision in Zambia.

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5. Hamed NO, Laila Al A, Osman MA, Elkhawad AO, Bjorklund G, Qasem H, Zayed N, El-Ansary A. Determination of neuroinflammatory biomarkers in autistic and neurotypical Saudi children. Metab Brain Dis ;2019 (May 30)

To identify neuroinflammatory biomarkers in patients with various severity of autism spectrum disorder (ASD) increases the insight about the pathogenesis and pathophysiology of this neurodevelopmental disorder. The aim of the present study was to analyze the levels in plasma of TGFbeta2, Heat shock protein 70 (HSP70), and hematopoietic prostaglandin D2 synthase (H-PGDS) in Saudi ASD children and healthy age-matched neurotypical controls. Also, it was in the present study examined the correlation among these neuroinflammatory biomarkers and the sensory deficit exhibited by the ASD children. Blood samples from 38 Saudi children with ASD and 32 age-matched neurotypical controls were withdrawn after an overnight fast. For the blood taking 3 mL EDTA containing blood collection tubes was used. The samples were centrifuged for 20 min (4 degrees C ; 3000xg) directly after the blood sampling. The harvested plasma was used for in vitro quantification of TGF-beta2, HSP70, and H-PGDS by using the sandwich enzyme immunoassay. Receiver operating characteristic (ROC) analysis and predictiveness curves showed that each of TGF-beta2, HSP70 or H-PGDS alone could not be used as a predictive neuroinflammatory biomarker for ASD. However, when TGF-beta2 and HSP70 were combined in one ROC curve, the AUC was increased to an appreciable value that makes them together robust predictors of variation between the ASD and neurotypical control groups. Overall, it was in the present study found significant differences for TGF-beta2 and HSP70 when the ASD and neurotypical control groups were compared, independently of the sensory deficit level. In conclusion, the present study highlights the usefulness of TGF-beta2, HSP70, and H-PGDS as diagnostic tools to differentiate between ASD and neurotypical control children, but not among subgroups of ASD children exhibiting different severity levels of sensory dysfunction. The presented data also suggest the effectiveness of ROC as a powerful statistical tool, which precisely can measure a combined effect of neuroinflammatory biomarkers intended for diagnostic purposes.

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6. Harmsen IE. Empathy in Autism Spectrum Disorder. J Autism Dev Disord ;2019 (May 30)

Empathy is an essential component of human social life. It requires the ability to understand another’s mental state and respond with an appropriate emotion or action. Individuals with autism spectrum disorder (ASD) have been described to exhibit atypical empathic responses which limit communication and social interactions. This review highlights the clinical characteristics and mechanisms underlying empathy in ASD by summarizing 61 peer-reviewed articles. Studies characterized empathic differences due to sex, age, intelligence, and disorder severity and provided valuable insights into the roles that genetics, neural networks, and sensory processing have in eliciting empathy. This knowledge will lead to improved diagnostics and therapies to improve social cognition, emotional recognition, and the empathic response in patients with ASD.

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7. Inoue R, Sakaue Y, Kawada Y, Tamaki R, Yasukawa Z, Ozeki M, Ueba S, Sawai C, Nonomura K, Tsukahara T, Naito Y. Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder. J Clin Biochem Nutr ;2019 (May) ;64(3):217-223.

Prebiotic dietary water-soluble fiber obtained from partially hydrolyzed guar gum was added to diets of children with autism spectrum disorders who presented constipation symptoms. Supplementation with partially hydrolyzed guar gum altered gut microbiota and significantly increased the frequency of defecation per week and altered the gut microbiota. In addition, supplementation with partially hydrolyzed guar gum significantly (p<0.05) decreased and tended to decrease (p = 0.07) the concentrations of serum interleukin-1beta and tumor necrosis factor-alpha, respectively. More importantly, supplementation with partially hydrolyzed guar gum significantly ameliorated behavioral irritability as per the Aberrant Behavior Checklist, Japanese Version. The present study demonstrated that supplementation with partially hydrolyzed guar gum to diets of constipated autism spectrum disorders children helped improve constipation and gut dysbiosis symptoms, which in turn helped attenuate the level of serum inflammation cytokines and behavioral irritability.

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8. Kang EK, Xanthopoulos MS, Kim JY, Arevalo C, Shults J, Beck SE, Marcus CL, Tapia IE. Adherence to Positive Airway Pressure for the Treatment of Obstructive Sleep Apnea in Children With Developmental Disabilities. J Clin Sleep Med ;2019 (May 24)

STUDY OBJECTIVES : To determine whether adherence to positive airway pressure (PAP) differs in children with developmental disabilities (DD) compared to typically developing (TD) children. METHODS : PAP adherence of 240 children initiated on PAP for obstructive sleep apnea (OSA) was retrospectively analyzed. Adherence between groups, expressed as percentage of nights used and hours of usage on nights used at 3 and 6 months, was compared. Predictive factors of adherence were studied using a median regression model. RESULTS : A total of 103 children with DD (median [interquartile range] age = 7.9 [3.2-13.1] years) and 137 TD (11.0 [5.5-16.1], P = .005) children were included. Percentage of nights used was significantly higher in children with DD at 3 (DD = 86.7 [33.9-97.9], TD = 62.9 [30.8-87.8] P = .01) and 6 months (DD = 90.0 [53.3-100], TD = 70.7[29.2-90.8], P = .003). Hours of usage on nights used at 3 and 6 months were similar between groups (DD = 5.0 [1.4-7.9], TD = 4.6 [1.9-7.2], P = .715 ; DD = 6.4 [1.8-8.3], TD = 5.7 [2.5-7.3], P = .345, respectively). This adherence measure improved over time in both groups (DD, P = .007 ; TD, P = .005). At 6 months, higher median neighborhood income and titration at or before 6 months were significantly predictive for percentage of nights used ; higher PAP pressure was significantly predictive for hours of usage in both groups. CONCLUSIONS : Children with DD had better PAP adherence expressed as percentage of nights used than TD children. Hours of usage on nights used at 3 and 6 months were similar between groups and improved over time. Higher income and titration at or before 6 months were predictive of adherence in all children. These findings indicate that children with DD can successfully wear PAP.

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9. Kang H, Zhao J, Jiang X, Li G, Huang W, Cheng H, Duan R. Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model. Mol Brain ;2019 (May 28) ;12(1):52.

Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integration of various guidance cues provided by a series of cell types, which guide axons to reach their final positions within the MB neuropils. Netrins are axonal guidance molecules that are conserved regulators of embryonic nerve cord patterning. However, whether they contribute to MB morphogenesis has not yet been evaluated. Here, we find that Netrin-B (NetB) is highly expressed in the MB lobes, regulating lobe length through genetic interactions with the receptors Frazzled and Uncoordinated-5 from 24 h after pupal formation onwards. We observe that overexpression of NetB causes severe beta lobe fusion in the MB, which is similar to the MB defects seen in the Drosophila model of fragile X syndrome (FXS). Our results further show that fragile-X mental retardation protein FMRP inhibits the translational activity of human ortholog Netrin-1 (NTN1). Knock-down of NetB significantly rescues the MB defects and ameliorates deficits in the learning and memory in FXS model Drosophila. These results indicate a critical role for NetB in MB lobe extension and identify NetB as a novel target of FMRP which contributes to learning and memory.

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10. Lazaro MT, Taxidis J, Shuman T, Bachmutsky I, Ikrar T, Santos R, Marcello GM, Mylavarapu A, Chandra S, Foreman A, Goli R, Tran D, Sharma N, Azhdam M, Dong H, Choe KY, Penagarikano O, Masmanidis SC, Racz B, Xu X, Geschwind DH, Golshani P. Reduced Prefrontal Synaptic Connectivity and Disturbed Oscillatory Population Dynamics in the CNTNAP2 Model of Autism. Cell Rep ;2019 (May 28) ;27(9):2567-2578.e2566.

Loss-of-function mutations in CNTNAP2 cause a syndromic form of autism spectrum disorder in humans and produce social deficits, repetitive behaviors, and seizures in mice. However, the functional effects of these mutations at cellular and circuit levels remain elusive. Using laser-scanning photostimulation, whole-cell recordings, and electron microscopy, we found a dramatic decrease in excitatory and inhibitory synaptic inputs onto L2/3 pyramidal neurons of the medial prefrontal cortex (mPFC) of Cntnap2 knockout (KO) mice, concurrent with reduced spines and synapses, despite normal dendritic complexity and intrinsic excitability. Moreover, recording of mPFC local field potentials (LFPs) and unit spiking in vivo revealed increased activity in inhibitory neurons, reduced phase-locking to delta and theta oscillations, and delayed phase preference during locomotion. Excitatory neurons showed similar phase modulation changes at delta frequencies. Finally, pairwise correlations increased during immobility in KO mice. Thus, reduced synaptic inputs can yield perturbed temporal coordination of neuronal firing in cortical ensembles.

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11. Leedham A, Thompson A, Smith R, Freeth M. ’I was exhausted trying to figure it out’ : The experiences of females receiving an autism diagnosis in middle to late adulthood. Autism ;2019 (May 30):1362361319853442.

Females often receive autism spectrum condition diagnoses later than males, leaving needs misunderstood. This study aimed to explore the lived experiences of female adults diagnosed with an autism spectrum condition in middle to late adulthood. Eleven autistic females diagnosed over the age of 40 years completed semi-structured interviews, analysed using Interpretative Phenomenological Analysis. Four superordinate themes emerged : A hidden condition (pretending to be normal and fitting in ; mental health and mislabelling), The process of acceptance (initial reactions and search for understanding ; re-living life through a new lens), The impact of others post-diagnosis (initial reactions ; stereotyped assumptions), and A new identity on the autism spectrum (negotiating relationships, connections and community ; changing well-being and views of the self ; the meaning of diagnosis). Findings highlight several factors not previously identified that affect late diagnosis in females, including widespread limited understandings of others. Diagnosis was experienced by several participants as facilitating transition from being self-critical to self-compassionate, coupled with an increased sense of agency. Participants experienced a change in identity that enabled greater acceptance and understanding of the self. However, this was painful to adjust to at such a late stage.

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12. Long S, Zhou H, Li S, Wang T, Ma Y, Li C, Zhou Y, Zhou S, Wu B, Wang Y. The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children. Front Neurol ;2019 ;10:505.

There is still no comprehensive description of the general population regarding clinical features and genetic etiology for co-occurring epilepsy and autism spectrum disorder (ASD) in Chinese children. This study was a retrospective study of children diagnosed with epilepsy and ASD from January 1st, 2015, to May 1st, 2018, at the Children’s Hospital of Fudan University. A total of 117 patients met the inclusion criteria, and 103 subjects were eligible. Among them, 88 underwent genetic testing, and 47 children (53.4%) were identified as having pathogenic or likely pathogenic variants : 39 had single gene mutations (83.0%, 39/47), and eight had copy number variants (17.0%, 8/47), with SCN1A (14.9%, 7/47) and MECP2 (10.6%, 5/47) gene mutations being the most common. Mutations in other genes encoding voltage-gated ion channels including SCN2A, CACNA1A, CACNA1H, CACNA1D, and KCNQ2 were also common, but the number of individual cases for each gene was small. Epilepsy syndrome and epilepsy-associated syndrome were more common (P = 0.014), and higher rates of poly-therapy (P = 0.01) were used in the positive genetic test group than in the negative group. There were no statistically significant differences in drug-refractory epilepsy, ASD severity, or intellectual disability between the positive genetic test group and the negative genetic group. These data strongly indicate the need for ASD screening in children with epilepsy with voltage-gated ion channel gene variants for better diagnosis and early intervention.

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13. Muscas M, Louros SR, Osterweil EK. Lovastatin, not simvastatin, corrects core phenotypes in the fragile X mouse model. eNeuro ;2019 (May 30)

The cholesterol-lowering drug lovastatin corrects neurological phenotypes in animal models of fragile X syndrome (FX), a commonly identified genetic cause of autism and intellectual disability. The therapeutic efficacy of lovastatin is being tested in clinical trials for FX, however the structurally similar drug simvastatin has been proposed as an alternative due to an increased potency and brain penetrance. Here, we perform a side-by-side comparison of the effects of lovastatin and simvastatin treatment on two core phenotypes in Fmr1(-/y) mice versus WT littermates : excessive hippocampal protein synthesis and susceptibility to audiogenic seizures (AGS). We find that simvastatin does not correct excessive hippocampal protein synthesis in the Fmr1(-/y) hippocampus at any dose tested. In fact, simvastatin significantly increases protein synthesis in both Fmr1(-/y) and WT. Moreover, injection of simvastatin does not reduce AGS in the Fmr1(-/y) mouse, while lovastatin significantly reduces AGS incidence and severity versus vehicle treated animals. These results show that unlike lovastatin, simvastatin does not correct core phenotypes in the Fmr1(-/y) mouse model.Significance Statement The statin drug lovastatin is in clinical trials for the treatment of Fragile X Syndrome (FX), and the structurally similar drug simvastatin has been proposed as a viable alternative. This study compares the efficacy of these drugs for ameliorating two major phenotypes in the FX mouse model and shows that although lovastatin is effective in correcting excessive protein synthesis and audiogenic seizures, simvastatin fails to correct either phenotype. These results suggest caution should be used when assuming simvastatin is a suitable substitute for lovastatin with respect to the treatment of FX or other neurodevelopmental disorders.

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14. Oakes LR, Milroy JJ, Hickerson BD. Health disparities and health promotion needs of college students with intellectual and/or developmental disabilities : A systematic literature review. J Am Coll Health ;2019 (May 29):1-12.

Objective : A new population of college students is emerging on campuses across the United States : students with intellectual and/or developmental disabilities (IDD). With this new and growing population of college students, an important question persists : are their health and wellness needs being identified and met ? Participants/Methods : ProQuest Central, WorldCat, General OneFile, and ArticleFirst were searched in June 2017 using the following criteria : health of college students with IDD, health of adults with IDD, health of adolescents with IDD, and peer-reviewed. Twenty-four articles were selected for final review. Results : Specific health and wellness topics were revealed : transition experiences and worries ; college experiences, coping strategies, and support needs ; sexuality, dating, and romantic relationships ; mental health ; and drugs and alcohol. Conclusions : Research on this unique population should continue, and the etiology of health and wellness issues of college students with IDD should be established to develop and implement evidence-based programing.

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15. Ohtani-Kaneko R. Crmp4-KO Mice as an Animal Model for Investigating Certain Phenotypes of Autism Spectrum Disorders. Int J Mol Sci ;2019 (May 20) ;20(10)

Previous research has demonstrated that the collapsin response mediator protein (CRMP) family is involved in the formation of neural networks. A recent whole-exome sequencing study identified a de novo variant (S541Y) of collapsin response mediator protein 4 (CRMP4) in a male patient with autism spectrum disorder (ASD). In addition, Crmp4-knockout (KO) mice show some phenotypes similar to those observed in human patients with ASD. For example, compared with wild-type mice, Crmp4-KO mice exhibit impaired social interaction, abnormal sensory sensitivities, broader distribution of activated (c-Fos expressing) neurons, altered dendritic formation, and aberrant patterns of neural gene expressions, most of which have sex differences. This review summarizes current knowledge regarding the role of CRMP4 during brain development and discusses the possible contribution of CRMP4 deficiencies or abnormalities to the pathogenesis of ASD. Crmp4-KO mice represent an appropriate animal model for investigating the mechanisms underlying some ASD phenotypes, such as impaired social behavior, abnormal sensory sensitivities, and sex-based differences, and other neurodevelopmental disorders associated with sensory processing disorders.

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16. Sedgewick F, Leppanen J, Goh F, Hayward H, Happe F, Tchanturia K. Similarities and Differences in Theory of Mind Responses of Patients With Anorexia Nervosa With and Without Autistic Features. Front Psychiatry ;2019 ;10:318.

Theory of Mind (ToM) is the ability to understand and represent mental states of others, a skill that plays a key role in how we interact with people around us. Difficulties with ToM have been posited as an underlying mechanism for autism and implicated in difficulties faced by those with anorexia nervosa (AN). This study examined, both quantitatively and qualitatively, the responses of women between the ages of 14 and 25 years on the Frith-Happe Triangle Animations, a well-validated test of ToM. Participants were split into healthy controls (HCs), AN patients (AN), and AN patients with high levels of autistic features (AN+ASF). We found no significant quantitative differences between groups in performance on the task. Qualitatively, there were differences between groups such that AN patients, especially those in the AN+ASF group, were more focused on describing the videos than creating narratives, were more negative in their interpretations, and were much more anxious about their performance. These qualitative differences have clinical implications, including that not all AN patients with autistic features should be assumed to have difficulties with ToM.

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17. Slagstad K. Asperger, the Nazis and the children - the history of the birth of a diagnosis. Tidsskr Nor Laegeforen ;2019 (May 28) ;139(9)

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18. Sun H, Yang Y, Zhang L, Wu H, Zhang H, Li H. Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder : a meta-analysis. Ann Gen Psychiatry ;2019 ;18:6.

Background : The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs ; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods : A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results : Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions : In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD.

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19. Thom RP, Keary CJ, Palumbo ML, Ravichandran CT, Mullett JE, Hazen EP, Neumeyer AM, McDougle CJ. Beyond the brain : A multi-system inflammatory subtype of autism spectrum disorder. Psychopharmacology (Berl) ;2019 (May 28)

An immune-mediated subtype of autism spectrum disorder (ASD) has long been hypothesized. This article reviews evidence from family history studies of autoimmunity, immunogenetics, maternal immune activation, neuroinflammation, and systemic inflammation, which suggests immune dysfunction in ASD. Individuals with ASD have higher rates of co-morbid medical illness than the general population. Major medical co-morbidities associated with ASD are discussed by body system. Mechanisms by which FDA-approved and emerging treatments for ASD act upon the immune system are then reviewed. We conclude by proposing the hypothesis of an immune-mediated subtype of ASD which is characterized by systemic, multi-organ inflammation or immune dysregulation with shared mechanisms that drive both the behavioral and physical illnesses associated with ASD. Although gaps in evidence supporting this hypothesis remain, benefits of this conceptualization include framing future research questions that will help define a clinically meaningful subset of patients and focusing clinical interactions on early detection and treatment of high-risk medical illnesses as well as interfering behavioral signs and symptoms across the lifespan.

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20. Wood H. Novel insights into autism from single-cell genomics. Nat Rev Neurol ;2019 (May 28)

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