1. Archibald AD, Smith MJ, Burgess T, Scarff KL, Elliott J, Hunt CE, Barns-Jenkins C, Holt C, Sandoval K, Siva Kumar V, Ward L, Allen EC, Collis SV, Cowie S, Francis D, Delatycki MB, Yiu EM, Massie RJ, Pertile MD, du Sart D, Bruno D, Amor DJ. {{Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests}}. {Genet Med};2017 (Oct 26)
PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.ResultsScreening of 12,000 individuals revealed 610 carriers (5.08%; 1 in 20): 342 CF, 35 FXS, 241 SMA (8 carriers of 2 conditions), approximately 88% of whom had no family history. At least 94% of CF and SMA carriers’ partners were tested. Fifty couples (0.42%; 1 in 240) were at increased risk of having a child with one of the conditions (14 CF, 35 FXS, and 1 SMA) with 32 pregnant at the time of testing. Of these, 26 opted for prenatal diagnosis revealing 7 pregnancies affected (4 CF, 2 FXS, 1 SMA).ConclusionThe combined affected pregnancy rate is comparable to the population risk for Down syndrome, emphasizing the need to routinely offer carrier screening. The availability of appropriate genetic counseling support and a collaborative approach between laboratory teams, genetics services, health professionals offering screening, and support organizations is essential.Genet Med advance online publication, 26 October 2017; doi:10.1038/gim.2017.134.
Lien vers le texte intégral (Open Access ou abonnement)
2. Ciaramidaro A, Bolte S, Schlitt S, Hainz D, Poustka F, Weber B, Freitag C, Walter H. {{Transdiagnostic deviant facial recognition for implicit negative emotion in autism and schizophrenia}}. {Eur Neuropsychopharmacol};2017 (Dec 21)
Impaired facial affect recognition (FAR) is observed in schizophrenia and autism spectrum disorder (ASD) and has been linked to amygdala and fusiform gyrus dysfunction. ASD patient’s impairments seem to be more pronounced during implicit rather than explicit FAR, whereas for schizophrenia data are inconsistent. However, there are no studies comparing both patient groups in an identical design. The aim of this three-group study was to identify (i) whether FAR alterations are equally present in both groups, (ii) whether they are present rather during implicit or explicit FAR, (iii) and whether they are conveyed by similar or disorder-specific neural mechanisms. Using fMRI, we investigated neural activation during explicit and implicit negative and neutral FAR in 33 young-adult individuals with ASD, 20 subjects with paranoid-schizophrenia and 25 IQ- and gender-matched controls individuals. Differences in activation patterns between each clinical group and controls, respectively were found exclusively for implicit FAR in amygdala and fusiform gyrus. In addition, the ASD group additionally showed reduced activations in medial prefrontal cortex (PFC), bilateral dorso-lateral PFC, ventro-lateral PFC, posterior-superior temporal sulcus and left temporo-parietal junction. Although subjects with ASD showed more widespread altered activation patterns, a direct comparison between both patient groups did not show disorder-specific deficits in neither patient group. In summary, our findings are consistent with a common neural deficit during implicit negative facial affect recognition in schizophrenia and autism spectrum disorders.
Lien vers le texte intégral (Open Access ou abonnement)
3. Grimm RP, Solari EJ, McIntyre NS, Zajic M, Mundy PC. {{Comparing growth in linguistic comprehension and reading comprehension in school-aged children with autism versus typically developing children}}. {Autism Res};2017 (Dec 21)
Many children with autism spectrum disorders (ASD) struggle with reading comprehension. Linguistic comprehension is an important predictor of reading comprehension, especially as children progress through elementary school and later grades. Yet, there is a dearth of research examining longitudinal relations between linguistic comprehensions in school-age children with ASD compared to typically-developing peers (TD). This study compared the developmental trajectories of linguistic and reading comprehension in samples of children with ASD and age-matched TD peers. Both groups were administered measures of linguistic and reading comprehension multiple times over a 30-month period. Latent growth curve modeling demonstrated children with ASD performed at significantly lower levels on both measures at the first timepoint and these deficits persisted across time. Children with ASD exhibited growth in both skills comparable to their TD peers, but this was not sufficient to enable them to eventually achieve at a level similar to the TD group. Due to the wide age range of the sample, age was controlled and displayed significant effects. Findings suggest linguistic comprehension skills are related to reading comprehension in children with ASD, similar to TD peers. Further, intervention in linguistic comprehension skills for children with ASD should begin early and there may be a finite window in which these skills are malleable, in terms of improving reading comprehension skills. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: There is relatively little research concerning reading comprehension development in children with ASD and how they compare to TD peers. This study found children with ASD began at lower achievement levels of linguistic comprehension and reading comprehension than TD peers, but the skills developed at a similar rate. Intervening early and raising initial levels of linguistic and reading comprehension may enable children with ASD to perform similarly to TD peers over time.
Lien vers le texte intégral (Open Access ou abonnement)
4. Ka M, Kim WY. {{ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway}}. {Neurobiol Dis};2017 (Dec 21)
Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing moue cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.
Lien vers le texte intégral (Open Access ou abonnement)
5. Kalsner L, Twachtman-Bassett J, Tokarski K, Stanley C, Dumont-Mathieu T, Cotney J, Chamberlain S. {{Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications}}. {Mol Genet Genomic Med};2017 (Dec 21)
BACKGROUND: Genetic testing of children with autism spectrum disorder (ASD) is now standard in the clinical setting, with American College of Medical Genetics and Genomics (ACMGG) guidelines recommending microarray for all children, fragile X testing for boys and additional gene sequencing, including PTEN and MECP2, in appropriate patients. Increasingly, testing utilizing high throughput sequencing, including gene panels and whole exome sequencing, are offered as well. METHODS: We performed genetic testing including microarray, fragile X testing and targeted gene panel, consistently sequencing 161 genes associated with ASD risk, in a clinical population of 100 well characterized children with ASD. Frequency of rare variants identified in individual genes was compared with that reported in the Exome Aggregation Consortium (ExAC) database. RESULTS: We did not diagnose any conditions with complete penetrance for ASD; however, copy number variants believed to contribute to ASD risk were identified in 12%. Eleven children were found to have likely pathogenic variants on gene panel, yet, after careful analysis, none was considered likely causative of disease. KIRREL3 variants were identified in 6.7% of children compared to 2% in ExAC, suggesting a potential role for KIRREL3 variants in ASD risk. Children with KIRREL3 variants more often had minor facial dysmorphism and intellectual disability. We also observed an increase in rare variants in TSC2. However, analysis of variant data from the Simons Simplex Collection indicated that rare variants in TSC2 occur more commonly in specific racial/ethnic groups, which are more prevalent in our population than in the ExAC database. CONCLUSION: The yield of genetic testing including microarray, fragile X (boys) and targeted gene panel was 12%. Gene panel did not increase diagnostic yield; however, we found an increase in rare variants in KIRREL3. Our findings reinforce the need for racial/ethnic diversity in large-scale genomic databases used to identify variants that contribute to disease risk.
Lien vers le texte intégral (Open Access ou abonnement)
6. Kang DW, Ilhan ZE, Isern NG, Hoyt DW, Howsmon DP, Shaffer M, Lozupone CA, Hahn J, Adams JB, Krajmalnik-Brown R. {{Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders}}. {Anaerobe};2017 (Dec 21)
Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.
Lien vers le texte intégral (Open Access ou abonnement)
7. Knaus TA, Kamps J, Foundas AL, Tager-Flusberg H. {{Atypical PT anatomy in children with autism spectrum disorder with expressive language deficits}}. {Brain Imaging Behav};2017 (Dec 19)
Deficits in communication are a core feature of autism spectrum disorder (ASD), however, structural language abilities are highly variable, ranging from minimally verbal to superior linguistic skills. Differences in the anatomy of cortical language regions, including anterior and posterior areas, have been found in ASD. It remains unclear, however, if anatomical differences distinguish individuals with impaired expressive language from those without such deficits. In addition, anatomical differences have not been explored in children with extremely low expressive language. This study included 34 boys with ASD, 7-11 years old, including an expressive language impaired group (n = 17) and an average-high language group (n = 17). The language impaired group was subdivided into a low (n = 9) and extremely low (n = 8) language subgroup for exploratory analyses to determine whether children with ASD with extremely low expressive language abilities exhibit distinct anatomy. Gray matter volume of the pars triangularis, pars opercularis, and planum temporale (PT) were measured on MRIs. PT volume was smaller in the ASD group with expressive language impairment relative to those without language deficits. The right PT volume was also positively correlated with language scores. The exploratory analyses revealed differences in the left PT, with smaller volume in the extremely low language subgroup, relative to the average and moderately low language groups. Results suggest that smaller PT volumes in both hemispheres are associated with severe language impairments in ASD. The PT may therefore, be a biomarker of language outcome in young children with ASD, with more studies of PT anatomy necessary.
Lien vers le texte intégral (Open Access ou abonnement)
8. Lai X, Wu X, Hou N, Liu S, Li Q, Yang T, Miao J, Dong Z, Chen J, Li T. {{Vitamin A Deficiency Induces Autistic-Like Behaviors in Rats by Regulating the RARbeta-CD38-Oxytocin Axis in the Hypothalamus}}. {Mol Nutr Food Res};2017 (Dec 21)
SCOPE: Vitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic-like behaviors via the transcription factor retinoic acid receptor beta (RARbeta)-regulated cluster of differentiation 38 (CD38)-oxytocin (OXT) axis. METHODS AND RESULTS: Gestational VAD or VA supplementation (VAS) rat models were established, and the autistic-like behaviors in the offspring rats were investigated. The different expression levels of RARbeta and CD38 in hypothalamic tissue and serum retinol and OXT concentration were tested. Primary cultured rat hypothalamic neurons were treated with all trans retinoic acid (atRA) and recombinant adenoviruses carrying the rat RARbeta (AdRARbeta) or RNA interference virus RARbeta-siRNA (siRARbeta) were used to infect neurons to change RARbeta signal. Western blotting, chromatin immunoprecipitation (ChIP) and intracellular Ca(2+) detections were used to investigate the primary regulatory mechanism of RARbeta in the CD38-OXT signaling pathway. We found that gestational VAD increased autistic-like behaviors and decreased the expression levels of hypothalamic RARbeta and CD38 and serum OXT levels in the offspring. VAS ameliorated these autistic-like behaviors and increased the expression levels of RARbeta, CD38 and OXT in the gestational VAD pups. In vitro, atRA increased the Ca(2+) excitability of neurons, which might further promote the release of OXT. Different CD38 levels were induced in the neurons by infection with different RARbeta adenoviruses. Furthermore, atRA enhanced the binding of RARbeta to the proximal promoter of CD38, indicating a potential up-regulation of CD38 transcriptional activity by RARbeta. CONCLUSIONS: Gestational VAD might be a risk factor for autistic-like behaviors due to the RARbeta signal suppression of CD38 expression in the hypothalamus of the offspring, which improved with VAS during the early-life period. The nutritional status during pregnancy and the early-life period is important in rats. This article is protected by copyright. All rights reserved.
Lien vers le texte intégral (Open Access ou abonnement)
9. Lekovich J, Man L, Xu K, Canon C, Lilienthal D, Stewart JD, Pereira N, Rosenwaks Z, Gerhardt J. {{CGG repeat length and AGG interruptions as indicators of fragile X-associated diminished ovarian reserve}}. {Genet Med};2017 (Dec 21)
PurposeFragile X premutation (PM) carriers may experience difficulties conceiving a child probably due to fragile X-associated diminished ovarian reserve (FXDOR). We investigated which subgroups of carriers with a PM are at higher risk of FXDOR, and whether the number of AGG interruptions within the repeat sequence further ameliorates the risk.MethodsWe compared markers of ovarian reserve, including anti-Mullerian hormone, antral follicle count, and number of oocytes retrieved between different subgroups of patients with a PM.ResultsWe found that carriers with midrange repeats size (70-90 CGG) demonstrate significantly lower ovarian reserve. Additionally, the number of AGG interruptions directly correlated with parameters of ovarian reserve. Patients with longer uninterrupted CGG repeats post-AGG interruptions had the lowest ovarian reserve.ConclusionThis study connects AGG interruptions and certain CGG repeat length to reduced ovarian reserve in carriers with a PM. A possible explanation for our findings is the proposed gonadotoxicity of the FMR1 transcripts. Reduction of AGG interruptions could increase the likelihood that secondary RNA structures in the FMR1 messenger RNA are formed, which could cause cell dysfunction within the ovaries. These findings may provide women with guidance regarding their fertility potential and accordingly assist with their family planning.GENETICS in MEDICINE advance online publication, 21 December 2017; doi:10.1038/gim.2017.220.
Lien vers le texte intégral (Open Access ou abonnement)
10. Mash LE, Reiter MA, Linke AC, Townsend J, Muller RA. {{Multimodal approaches to functional connectivity in autism spectrum disorders: An integrative perspective}}. {Dev Neurobiol};2017 (Dec 21)
Atypical functional connectivity has been implicated in autism spectrum disorders (ASDs). However, the literature to date has been largely inconsistent, with mixed and conflicting reports of hypo- and hyper-connectivity. These discrepancies are partly due to differences between various neuroimaging modalities. Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and magnetoencephalography (MEG) measure distinct indices of functional connectivity (e.g., blood-oxygenation level-dependent [BOLD] signal vs. electrical activity). Furthermore, each method has unique benefits and disadvantages with respect to spatial and temporal resolution, vulnerability to specific artifacts, and practical implementation. Thus far, functional connectivity research on ASDs has remained almost exclusively unimodal; therefore, interpreting findings across modalities remains a challenge. Multimodal integration of fMRI, EEG, and MEG data is critical in resolving discrepancies in the literature, and working toward a unifying framework for interpreting past and future findings. This review aims to provide a theoretical foundation for future multimodal research on ASDs. First, we will discuss the merits and shortcomings of several popular theories in ASD functional connectivity research, using examples from the literature to date. Next, the neurophysiological relationships between imaging modalities, including their relationship with invasive neural recordings, will be reviewed. Finally, methodological approaches to multimodal data integration will be presented, and their future application to ASDs will be discussed. Analyses relating transient patterns of neural activity (« states ») are particularly promising. This strategy provides a comparable measure across modalities, captures complex spatiotemporal patterns, and is a natural extension of recent dynamic fMRI research in ASDs. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol, 2017.
Lien vers le texte intégral (Open Access ou abonnement)
11. Meiri G, Azoulay H, Menashe I. {{Characteristics Associated with Drug Prescription and Compliance Among Young Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2017 (Dec 21)
OBJECTIVES: Psychotropic drugs are prescribed to people with autism spectrum disorder (ASD) usually as a means to alleviate comorbidities associated with the disorder. However, despite the uncertainty regarding the efficacy of these treatments for ASD, their prevalence is continuously increasing. The goal of this study was to understand the characteristics associated with drug prescription and compliance among young children with ASD. MATERIALS AND METHODS: We studied patterns of drug utilization in a population-based sample of 211 young children with ASD in Southern Israel. Data regarding drug prescription and compliance (percentage of purchased drugs out of total prescriptions) were acquired from the electronic records of these patients. Compliance rates (CRs) were calculated as percentage of purchased drugs of the total number of prescriptions. RESULTS: A total of 122 prescriptions were made for 75 children in our sample. Drug prescription was significantly associated with the severity of ASD and the types of comorbidity (p < 0.05). Atypical antipsychotic drugs were the most prevalent drugs (49 children; 23.2%), followed by stimulants (28 children; 13.2%) and first-generation antipsychotic drugs (16 children; 7.6%). The average CR in our sample was 75% +/- 3% with about half of the children demonstrating full compliance, and less than fifth of them not complying at all with their drug prescription. CR had a positively linear association with ASD severity at a marginal statistical significance of p = 0.06. No other variables were statistically associated with drug compliance in our study. CONCLUSIONS: Our results highlight the significant effect of ASD severity on both the prescription and CRs of drugs among young children with ASD. Further examination of drug utilization for longer periods and larger samples will help confirming our findings and test the effects of other variables on these pharmaceutical parameters. Lien vers le texte intégral (Open Access ou abonnement)
12. Tewolde FG, Bishop DVM, Manning C. {{Visual Motion Prediction and Verbal False Memory Performance in Autistic Children}}. {Autism Res};2017 (Dec 21)
Recent theoretical accounts propose that atypical predictive processing can explain the diverse cognitive and behavioral features associated with autism, and that difficulties in making predictions may be related to reduced contextual processing. In this pre-registered study, 30 autistic children aged 6-14 years and 30 typically developing children matched in age and non-verbal IQ completed visual extrapolation and false memory tasks to assess predictive abilities and contextual processing, respectively. In the visual extrapolation tasks, children were asked to predict when an occluded car would reach the end of a road and when an occluded set of lights would fill up a grid. Autistic children made predictions that were just as precise as those made by typically developing children, across a range of occlusion durations. In the false memory task, autistic and typically developing children did not differ significantly in their discrimination between items presented in a list and semantically related, non-presented items, although the data were insensitive, suggesting the need for larger samples. Our findings help to refine theoretical accounts by challenging the notion that autism is caused by pervasively disordered prediction abilities. Further studies will be required to assess the relationship between predictive processing and context use in autism, and to establish the conditions under which predictive processing may be impaired. Autism Res 2017. (c) 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: It has been suggested that autistic individuals have difficulties making predictions and perceiving the overall gist of things. Yet, here we found that autistic children made similar predictions about hidden objects as non-autistic children. In a memory task, autistic children were slightly less confused about whether they had heard a word before, when words were closely related in meaning. We conclude that autistic children do not show difficulties with this type of prediction.
Lien vers le texte intégral (Open Access ou abonnement)
13. Eapen V, Grove R, Aylward E, Joosten AV, Miller SI, Van Der Watt G, Fordyce K, Dissanayake C, Maya J, Tucker M, DeBlasio A. {{Transition from early intervention program to primary school in children with autism spectrum disorder}}. {World J Clin Pediatr};2017 (Nov 8);6(4):169-175.
AIM: To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism. METHODS: Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child’s school adjustment. The relationship between child characteristics and school outcomes was evaluated. RESULTS: Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement. CONCLUSION: Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential.
Lien vers le texte intégral (Open Access ou abonnement)
14. Rollins NK. {{An Imaging Glimpse into the Autistic Brain}}. {Radiology};2018 (Jan);286(1):227-228.
Lien vers le texte intégral (Open Access ou abonnement)
15. Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, Johnston MV, Rangaramanujam K, Blue ME, Kannan S. {{Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome}}. {J Neuroinflammation};2017 (Dec 19);14(1):252.
BACKGROUND: Rett syndrome (RTT) is a pervasive developmental disorder that is progressive and has no effective cure. Immune dysregulation, oxidative stress, and excess glutamate in the brain mediated by glial dysfunction have been implicated in the pathogenesis and worsening of symptoms of RTT. In this study, we investigated a new nanotherapeutic approach to target glia for attenuation of brain inflammation/injury both in vitro and in vivo using a Mecp2-null mouse model of Rett syndrome. METHODS: To determine whether inflammation and immune dysregulation were potential targets for dendrimer-based therapeutics in RTT, we assessed the immune response of primary glial cells from Mecp2-null and wild-type (WT) mice to LPS. Using dendrimers that intrinsically target activated microglia and astrocytes, we studied N-acetyl cysteine (NAC) and dendrimer-conjugated N-acetyl cysteine (D-NAC) effects on inflammatory cytokines by PCR and multiplex assay in WT vs Mecp2-null glia. Since the cysteine-glutamate antiporter (Xc(-)) is upregulated in Mecp2-null glia when compared to WT, the role of Xc(-) in the uptake of NAC and L-cysteine into the cell was compared to that of D-NAC using BV2 cells in vitro. We then assessed the ability of D-NAC given systemically twice weekly to Mecp2-null mice to improve behavioral phenotype and lifespan. RESULTS: We demonstrated that the mixed glia derived from Mecp2-null mice have an exaggerated inflammatory and oxidative stress response to LPS stimulation when compared to WT glia. Expression of Xc(-) was significantly upregulated in the Mecp2-null glia when compared to WT and was further increased in the presence of LPS stimulation. Unlike NAC, D-NAC bypasses the Xc(-) for cell uptake, increasing intracellular GSH levels while preventing extracellular glutamate release and excitotoxicity. Systemically administered dendrimers were localized in microglia in Mecp2-null mice, but not in age-matched WT littermates. Treatment with D-NAC significantly improved behavioral outcomes in Mecp2-null mice, but not survival. CONCLUSIONS: These results suggest that delivery of drugs using dendrimer nanodevices offers a potential strategy for targeting glia and modulating oxidative stress and immune responses in RTT.
Lien vers le texte intégral (Open Access ou abonnement)
16. Li TY. {{[Improve pediatrician’s ability of identification, evaluation and management of children with autism spectrum disorder]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):881-883.
Lien vers le texte intégral (Open Access ou abonnement)
17. {{[Consensus on early identification screening and early intervention for autism spectrum disorder]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):890-897.
Lien vers le texte intégral (Open Access ou abonnement)
18. Zhu J, Guo M, Yang T, Lai X, Lei YY, He ML, Chen J, Li TY. {{[Association between behavioral problems and gastrointestinal disorders among children with autism spectrum disorder]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):905-910.
Objective: To investigate the relationship between gastrointestinal disorders (GID) and core symptoms or behavioral problems among the children with autism spectrum disorder (ASD) . Method: Totally 328 children with ASD and 202 normal controls were enrolled in this cross-sectional study from August 2013 to October 2016. The information about the gastrointestinal disorders, behavioral and emotional problems was collected by using questionnaires. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC) were used to assess the core symptoms of the children with ASD. Neurodevelopmental status was evaluated with Gesell Developmental Scale (GDS). These variables were analyzed by using student’s t-test and chi-square test. Result: The prevalence of GID was significantly higher in the children with ASD than in the normally developing children (49.4% (162/328) vs.25.7% (52/202), chi(2)=29.039, P=0.000), especially the symptoms of constipation (33.2% (109/328) vs. 13.9% (28/202)), diarrhea (9.5%(31/328) vs. 1.5% (3/202)), nausea and vomiting (9.5% (31/328) vs. 3.5% (7/202)), and foul defecation (16.5% (54/328) vs. 5.0% (10/202)) (all P<0.05). Among the ASD children, the prevalence of GID was similar between male and female (46.7% (133/285) vs. 46.5%(20/43), chi(2)=0.006, P=0.938), as well as among all age groups (chi(2)=1.907, P=0.862). There was no significant difference in scores of GDS in the ASD children with or without GID (all P>0.05). Compared with ASD children without GID (n=166), the ASD children with GID (n=162) got higher scores in the « Body and Object Use » of ABC scale ( (16.4+/-9.3) vs. (12.3+/-6.7) scores, t=2.258, P=0.028), and had more emotional problems (63.6% (103/162) vs. 49.4% (82/166), chi(2)=6.707, P=0.010). Moreover, the score of behavior problems questionnaire was higher in the ASD children with GID ( (35.3+/-16.8) vs. (16.1+/-13.6) scores, t=5.748, P=0.000). Conclusion: Children with ASD have higher risk of GID than the normal developing children. While the stereotyped behaviors, problem behaviors and emotional problems are severer in the ASD children with GID. Hence, it is important to provide comprehensive treatment and management for these groups of children.
Lien vers le texte intégral (Open Access ou abonnement)
19. Han PP, Zou MY, Yang XL, Liu XC, Liang S, Sun CH, Xia W, Wu LJ. {{[Sleep problems and the association with the levels of 6-sulfatoxymelatonin in children with autism spectrum disorder]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):911-915.
Objective: To identify the prevalence of sleep problems in children with autism spectrum disorder (ASD) and to explore the association with the main melatonin metabolite, 6-sulfatoxymelatonin (6-SM). Method: This was a prospective case-control study. Children with ASD were recruited from Child Development and Behavioral Research Center (CDBRC) of the Harbin Medical University and Harbin Special Education School from October 2015 to April 2017 (ASD group) . Healthy controls were selected from five kindergartens and one primary school in Harbin by the stratified cluster random sampling (control group) . The Children’s Sleep Habits Questionnaire (CSHQ) was used to investigate the sleep problems of the two groups. The patients were matched in a 1ratio1 ratio for the age and sex, and the urine samples of case-control pairs were collected in the morning. The level of 6-SM was measured by the enzyme linked immunosorbent assay (ELISA). The student’s t test was used for comparison between the ASD group and control group, and the Pearson correlation analysis was used to determine the correlation difference. Result: A total of 212 ASD children (mean (+/-SD) age was (6.0+/-2.7) years, and 181 patients (85.4%) were male), and a total of 334 healthy children(mean (+/-SD) age was (5.9+/-2.6) years, and 272 patients (81.4%) were male) were recruited. Among them, 101 matched case-control pairs completed the collection of urine samples. According to the statistical analysis, the scores of total CSHQ, bedtime resistance, sleep onset delay, sleep duration, night waking, parasomnia, sleep disordered breathing and daytime sleepiness in children with ASD were significantly higher than those in the control group (48.2+/-6.2 vs. 46.6+/-5.4, 11.4+/-2.5 vs. 10.7+/-2.8, 1.7+/-0.8 vs. 1.5+/-0.7, 4.1+/-1.4 vs. 3.7+/-1.1, 4.2+/-1.5 vs. 3.8+/-1.1, 8.5+/-1.5 vs. 8.3+/-1.4, 3.7+/-1.0 vs. 3.4+/-0.8, 11.7+/-2.5 vs. 12.4+/-2.7, t=3.16, 3.00, 3.23, 2.76, 3.19, 1.99, 3.45,-2.72, P=0.002, 0.003, 0.001, 0.006, 0.002, 0.048, 0.001, 0.007), the level of 6-SM was significantly lower in children with ASD than that of healthy controls ((1.24+/-0.50) vs. (1.68+/-0.63)mug/h, t=-5.50, P<0.01), and the total CSHQ score was negatively correlated with the level of 6-SM (r=-0.50, P<0.01). Conclusion: The children with ASD were at high risk for sleep problems, and the melatonin metabolite of ASD group was abnormal compared with that of the control group. Moreover, there was a negative correlation between the severity of sleep problems and the level of 6-SM in ASD children. The results of our study indicate that the abnormal melatonin metabolism may be one of the causes of sleep problems in children with ASD. Lien vers le texte intégral (Open Access ou abonnement)
20. Dong HY, Wang B, Li HH, Shan L, Jia FY. {{[Correlation between serum 25-hydroxyvitamin D level and core symptoms of autism spectrum disorder in children]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):916-919.
Objective: To explore the relationship between serum 25-hydroxyvitamin D levels and core symptoms of autism spectrum disorder (ASD) in children. Method: In this cross-sectional study, ASD children 4 to 6 years of age who were diagnosed in Department of Developmental and Behavioral Pediatrics, First Hospital of Jilin university from January to May 2017 were assigned to ASD group, and children for routine growth and development assessment in Jilin province were assigned to control group. The two groups were well matched for age and sex, and none of them had received vitamin D supplementation. Serum 25-hydroxyvitamin D levels were measured by HPLC-MS/MS method. The patients of the ASD group were assessed with autism behavior checklist (ABC), childhood autism rating scale (CARS), social response scale (SRS), and autism treatment evaluation checklist (ATEC). The levels of vitamin D were divided into normal(>0.03 ng/L), insufficient (0.01-0.03 ng/L) and deficient (<0.01 ng/L). Levels of serum vitamin D between the two groups were compared by two independent sample t-test, and the difference in the percentages of normal, insufficient and deficient levels of vitamin D was tested by chi-square test, and correlations between vitamin D levels and the total scores or subscales of ABC, CARS, SRS and ATEC were analyzed by Pearson correlation analysis. Result: The 87 subjects in the ASD group included 75 males and 12 females, with a mean (+/-SD) age of (4.7+/-0.7) years. The 301 subjects in the control group included 249 males and 52 females, with a mean (+/-SD) age of (4.8+/-0.8) years. Serum vitamin D level in ASD children was significantly lower than that of the control group ( (0.021+/-0.008) vs. (0.036+/-0.016) ng/L, t=-8.17, P<0.01), and the between-group percentage difference of normal, insufficient and deficient levels of vitamin D was statistically significant (12 (14%) vs. 186 (62%) , 67 (77%) vs. 113 (37%) , 8 (9%) vs. 2 (1%) , chi(2)=72.1, P<0.01). There were negative correlations between serum vitamin D level in ASD children and total ABC score or ABC subscale scores (body behavior, self-care, language and social interaction)(r=-0.531,-0.397,-0.283,-0.248,-0.262, P=0.000, 0.000, 0.007, 0.020, 0.014). There were negative correlations between serum vitamin D level in ASD children and total CARS score and CARS subscale scores (imitation, nonverbal communication and general impression) (r=-0.352, -0.216, -0.248, -0.216, P=0.001, 0.046, 0.021, 0.046). There were negative correlations between serum vitamin D level in ASD children and SRS behavior subscale or ATEC social interaction subscale (r=-0.536, P=0.005, r=-0.400, P=0.014). Conclusion: Serum 25-hydroxyvitamin D level in children with ASD is obviously lower than that in the healthy control group, and there are negative correlations between vitamin D levels and core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-CCC-13004498. Lien vers le texte intégral (Open Access ou abonnement)
21. Chang C, Qiu NN, Xiao T, Xiao X, Chu KK, Li Y, Wu QR, Fang H, Ke XY. {{[Structural change of the corpus callosum fibers in toddlers with autism spectrum disorder: two-year follow-up]}}. {Zhonghua Er Ke Za Zhi};2017 (Dec 2);55(12):920-925.
Objective: To conduct a follow-up investigation of structural changes of the corpus callosum fibers of toddlers (2 to 5 years of age) with autism spectrum disorder(ASD) and to explore the associations with clinical symptoms. Method: In this prospective randomized controlled study, ASD children who were diagnosed in the Child Mental Health Research Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University from May 2011 to November 2012 were included in the ASD group, and developmentally delayed children were included in the control group (DD group). Diffusion tensor imaging (DTI) data from the two groups were obtained at two age levels: 2-3 years of age, and 4-5 years of age. Region of interest analysis was applied to assess characteristic values of total area and sub-regions of corpus callosum: the fraction anisotropy (FA), the mean diffusivity (MD), the radial diffusivity (RD) and the axial diffusivity (AD). All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Treatment Evaluation Checklist (ATEC). The characteristic values of total area and sub-regions of corpus callosum of ASD group at two age levels were analyzed by paired sample t test; the characteristic values of total area and sub-regions of corpus callosum of ASD group and DD group were analyzed by independent-sample t test; the correlations between FA values of the total area and sub-regions of corpus callosum and ADI-R or ATEC scores were analyzed by Pearson correlation analysis. Result: Forty cases meeting inclusion criteria were enrolled in ASD group, and 31 eligible cases were enrolled in the control group. Four children in the ASD group were lost to follow-up, and 5 children in the control group were lost to follow-up. Longitudinal comparison between the two age subgroups of ASD patients showed that the FA values of the total corpus callosum increased (0.499 55+/-0.027 59 vs. 0.505 83+/-0.086 64, t=4.88, P<0.05), but MD values, RD values and AD values of the total corpus callosum area decreased (0.000 89+/-0.000 03 vs. 0.000 81+/-0.000 14, 0.000 61+/-0.000 04 vs. 0.000 55+/-0.000 09, 0.001 43+/-0.000 03 vs. 0.001 38+/-0.000 03, t=9.31, 7.90, 8.66, P<0.05 for all comparisons). In the area of corpus callosum genu, FA and AD values increased (t=5.59, 8.48, P<0.05 for both comparisons), but MD and RD values decreased (t=12.67, 11.28, P<0.05 for both comparisns). In the area of corpus callosum body, FA and RD values increased(t=5.46, 8.48, P<0.05 for both comparisons), but MD and AD values decreased (t=8.08, 6.22, P<0.05 for both comparisons). In the area of corpus callosum splenium, MD, RD and AD values decreased (t=6.81, 4.44, 5.51, P < 0.05 for all comparisons). Among the participants 2 to 3 years of age, there were no significantly differences in FA values of total area and sub-regions of corpus callosum between ASD group and the DD group (P > 0.05 for all comparisons); as compared with the DD group, ASD group had higher AD values of total area and splenium of corpus callosum (0.001 43+/-0.000 03 vs. 0.001 40+/-0.000 04, 0.001 34+/-0.000 03 vs. 0.001 32+/-0.000 04, t=1.56, 1.14, P < 0.05 for both comparisons); ASD group had lower AD values but higher RD and MD values of corpus callosum genu (t=0.07, 0.55, 0.07, P < 0.05 for all comparisons); ASD group had lower RD values of corpus callosum body (t=0.07, P < 0.05). Among the participants 4 to 5 years of age, as compared with the DD group, ASD group had higher FA value of total corpus callosum area(0.505 83+/-0.086 64 vs. 0.483 77+/-0.099 30, t=8.56, P < 0.05), lower RD value of total corpus callosum(0.000 55+/-0.000 09 vs. 0.000 56+/-0.000 12, t=14.44, P < 0.05), lower RD values of corpus callosum body (t=2.20, P < 0.05), higher FA values (t=3.35, P < 0.05) but lower AD values of corpus callosum splenium (t=2.20, P < 0.05). A correlation analysis between FA values of total area and sub-regions of corpus callosum and clinical variables showed that the FA values of total area and splenium of corpus callosum in ASD group at 2 to 3 years of age were negatively correlated with the scores of language skills in ATEC (r=-0.35,-0.36, P < 0.05 for both comparisons). And after two years, FA values of total corpus callosum were positively correlated with the scores of social communication in ATEC (r=0.34, P < 0.05). There was no significant correlation between FA values of sub-regions of corpus callosum and the scores of ATEC (P > 0.05 for all comparisons). There was no significant correlation between FA values of total area and sub-regions of corpus callosum and the scores of ADI-R (P > 0.05 for all comparisons). Conclusion: The fiber structure of corpus callosum was still in the process of maturing during the age of 2 to 5 years; however, compared with DD group, ASD group had more extensive structural abnormalities of the corpus callosum fibers as age increased, and the structural abnormalities had correlation with the core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.
Lien vers le texte intégral (Open Access ou abonnement)
22. Huang DN, Jin YT. {{[Advances on the research of the environmental risk factors of children autism]}}. {Zhonghua Yu Fang Yi Xue Za Zhi};2017 (Dec 6);51(12):1128-1131.
Autism spectrum disorder is a lifelong neurodevelopmental disorder, characterized by social interaction and communication impairments, accompanied by repetitive behaviors. Little is known about the causes and contributing factors for autism. It is difficult to prevent and cure, and has become a globe public health problem. With the development in the prevalence of autism, the idea how the environmental factors cause the autism, gains all attentions. Summarizing latest epidemiological studies and experimental evidence, this review is focused on the effect of environmental factors, including air pollutant, heavy metal and pesticides, and discussed the relation between environmental risk factors and autism. The results showed that risks of autism in children may increase following in prenatal exposure to air pollutants, heavy metal and pesticides. It is needed to do the research on the mechanism of environmental risk factor and autism for more prevention, treatment and control suggestions.
Lien vers le texte intégral (Open Access ou abonnement)
23. Rajaratnam A, Shergill J, Salcedo-Arellano M, Saldarriaga W, Duan X, Hagerman R. {{Fragile X syndrome and fragile X-associated disorders}}. {F1000Res};2017;6:2112.
Fragile X syndrome (FXS) is caused by a full mutation on the FMR1 gene and a subsequent lack of FMRP, the protein product of FMR1. FMRP plays a key role in regulating the translation of many proteins involved in maintaining neuronal synaptic connections; its deficiency may result in a range of intellectual disabilities, social deficits, psychiatric problems, and dysmorphic physical features. A range of clinical involvement is also associated with the FMR1 premutation, including fragile X-associated tremor ataxia syndrome, fragile X-associated primary ovarian insufficiency, psychiatric problems, hypertension, migraines, and autoimmune problems. Over the past few years, there have been a number of advances in our knowledge of FXS and fragile X-associated disorders, and each of these advances offers significant clinical implications. Among these developments are a better understanding of the clinical impact of the phenomenon known as mosaicism, the revelation that various types of mutations can cause FXS, and improvements in treatment for FXS.
