1. Bakheet SA, Alzahrani MZ, Nadeem A, Ansari MA, Zoheir KM, Attia SM, Al-Ayadhi LY, Ahmad SF. {{Resveratrol treatment attenuates chemokine receptor expression in the BTBR T+tf/J mouse model of autism}}. {Mol Cell Neurosci};2016 (Sep 29);77:1-10.
Autism is a neurodevelopmental disorder categorized by qualitative impairments in social interaction, communication, and repetitive stereotypic behavior. Emerging evidence increasingly suggests that chemokine receptors have a pivotal role in the central nervous system and are involved in the pathogenesis of numerous neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative diseases, but its effect on autism has not been investigated. We investigated the effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3+, CCR5+, CCR7+ and CCR9+, CXCR3+ and CXCR5+) in cluster of differentiation 4-positive (CD4+) T cells in the spleen. We also assessed the mRNA expression of CCR and CXCR receptors in the spleen and brain tissues. Our study revealed that the BTBR and B6 control mice showed different immune profiles. The BTBR mice showed characteristic higher levels of both CCR and CXCR production and expression in CD4+ T cells than the B6 control mice did. Treatment of B6 and BTBR mice with resveratrol (20 and 40mg/kg) induced a substantial decrease in the CCR and CXCR production and expression in CD4+ T cells compared with the respective untreated control groups. Moreover, resveratrol treatment decreased the mRNA expression levels of CCR and CXCR in the spleen and brain tissues. Resveratrol downregulated the chemokine receptor levels, which might provide unique targets for future therapies for autism.
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2. Boschi A, Planche P, Hemimou C, Demily C, Vaivre-Douret L. {{From High Intellectual Potential to Asperger Syndrome: Evidence for Differences and a Fundamental Overlap-A Systematic Review}}. {Front Psychol};2016;7:1605.
Background: An increasing number of clinicians point to similar clinical features between some children with High Intellectual Potential (HIP or « Giftedness » = Total IQ > 2 SD), and children with Autism Spectrum Disorder (ASD) without intellectual or language delay, formerly diagnosed with Asperger Syndrome. Some of these common features are social interaction impairments, special interests, and in some cases high-verbal abilities. The aim of this article is to determine whether these similarities exist at more fundamental levels, other than clinical, and to explore the literature in order to provide empirical support for an overlap between ASD and HIP. Method: First, comparative studies between ASD and HIP children were sought. Because of a lack of data, the respective characteristics of ASD and HIP subjects were explored by a cross-sectional review of different areas of research. Emphasis was placed on psychometric and cognitive evaluations, experimental and developmental assessments, and neurobiological research, following a « bottom-up » procedure. Results: This review highlights the existence of similarities in the neurocognitive, developmental and neurobiological domains between these profiles, which require further study. In addition, the conclusions of several studies show that there are differences between HIP children with a homogeneous Intellectual Quotient profile and children with a heterogeneous Intellectual Quotient profile. Conclusion: HIP seems to cover different developmental profiles, one of which might share features with ASD. A new line of investigation providing a possible starting-point for future research is proposed. Its implications, interesting from both clinical and research perspectives, are discussed.
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3. Donnelly JE, Ptomey LT, Goetz JR, Sullivan DK, Gibson CA, Greene JL, Lee RH, Mayo MS, Honas JJ, Washburn RA. {{Weight management for adolescents with intellectual and developmental disabilities: Rationale and design for an 18month randomized trial}}. {Contemp Clin Trials};2016 (Oct 31)
Adolescents with intellectual and developmental disabilities (IDD) are an underserved group in need of weight management. However, information regarding effective weight management for this group is limited, and is based primarily on results from small, non-powered, non-randomized trials that were not conducted in accordance with current weight management guidelines. Additionally, the comparative effectiveness of emerging dietary approaches, such as portion-controlled meals (PCMs) or program delivery strategies such as video chat using tablet computers have not been evaluated. Therefore, we will conduct an 18month trial to compare weight loss (6months) and maintenance (7-18months) in 123 overweight/obese adolescents with mild to moderate IDD, and a parent, randomized to a weight management intervention delivered remotely using FaceTime on an iPad using either a conventional meal plan diet (RD/CD) or a Stop Light diet enhanced with PCMs (RD/eSLD), or conventional diet delivered during face-to-face home visits (FTF/CD). This design will provide an adequately powered comparison of both diet (CD vs. eSLD) and delivery strategy (FTF vs. RD). Exploratory analyses will examine the influence of behavioral session attendance, compliance with recommendations for diet (energy intake), physical activity (min/day), self-monitoring of diet and physical activity, medications, and parental variables including diet quality, physical activity, baseline weight, weight change, and beliefs and attitudes regarding diet and physical activity on both weight loss and maintenance. We will also complete a cost and contingent valuation analysis to compare costs between RD and FTF delivery.
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4. Gaigg SB, Cornell AS, Bird G. {{The psychophysiological mechanisms of alexithymia in autism spectrum disorder}}. {Autism};2016 (Nov 2)
Accumulating evidence indicates that co-occurring alexithymia underlies several facets of the social-emotional difficulties common in individuals with autism spectrum disorder. The mechanisms involved, however, remain poorly understood because measuring alexithymia relies heavily on self-report. To address this issue, carefully matched groups of individuals with autism spectrum disorder and comparison participants rated 70 emotion-inducing pictures on subjectively experienced arousal while skin conductance responses were monitored objectively. The results demonstrated reliable correlations between these subjective and objective measures, and in both groups, around 25% of individual differences in this correlation (i.e. in emotion-relevant interoception) were accounted for by self-reported alexithymia. In the context of the wider literature, this suggests that alexithymia involves a disruption in how physiological arousal modulates the subjective experience of feelings in those with and without a diagnosis of autism spectrum disorder. Since mindfulness-based therapies foster greater awareness of thoughts, feelings and bodily sensations, the findings also have implications for how the symptoms and consequences of alexithymia (e.g. anxiety) might be ameliorated.
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5. Grove R, Hoekstra RA, Wierda M, Begeer S. {{Exploring sex differences in autistic traits: A factor analytic study of adults with autism}}. {Autism};2016 (Nov 2)
Research has highlighted potential differences in the phenotypic and clinical presentation of autism spectrum conditions across sex. Furthermore, the measures utilised to evaluate autism spectrum conditions may be biased towards the male autism phenotype. It is important to determine whether these instruments measure the autism phenotype consistently in autistic men and women. This study evaluated the factor structure of the Autism Spectrum Quotient Short Form in a large sample of autistic adults. It also systematically explored specific sex differences at the item level, to determine whether the scale assesses the autism phenotype equivalently across males and females. Factor analyses were conducted among 265 males and 285 females. A two-factor structure consisting of a social behaviour and numbers and patterns factor was consistent across groups, indicating that the latent autism phenotype is similar among both autistic men and women. Subtle differences were observed on two social behaviour item thresholds of the Autism Spectrum Quotient Short Form, with women reporting scores more in line with the scores expected in autism on these items than men. However, these differences were not substantial. This study showed that the Autism Spectrum Quotient Short Form detects autistic traits equivalently in males and females and is not biased towards the male autism phenotype.
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6. Kim JW, Seung H, Kim KC, Gonzales EL, Oh HA, Yang SM, Ko MJ, Han SH, Banerjee S, Shin CY. {{Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism}}. {Neuropharmacology};2016 (Sep 14);113(Pt A):71-81.
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.
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7. Kushak RI, Winter HS, Buie TM, Cox SB, Phillips CD, Ward NL. {{Analysis of the Duodenal Microbiome in Autistic Individuals: Association with Carbohydrate Digestion}}. {J Pediatr Gastroenterol Nutr};2016 (Nov 2)
OBJECTIVES: There is evidence that symptoms of maldigestion or malabsorption in autistic individuals are related to changes in the indigenous microbiota. Analysis of colonic bacteria has revealed microbial dysbiosis in children with autism; however, characteristics of the duodenal microbiome are not well described. In this study the microbiome of the duodenal mucosa of subjects with autism was evaluated for dysbiosis, bacteria overgrowth and microbiota associated with carbohydrate digestion. The relationship between the duodenal microbiome and disaccharidase activity was analyzed in biopsies from 21 autistic subjects and 19 children without autism. METHODS: Microbiota composition was determined by 16S ribosomal RNA gene sequencing, and disaccharidase activity via biochemical assays. RESULTS: Although subjects with autism had a higher frequency of constipation (p < 0.005), there was no difference in disaccharidase activity between groups. Additionally, no differences in microbiome diversity (species richness and evenness) were observed. Bacteria belonging to the genus Burkholderia were more abundant in subjects with autism, while members of the genus Neisseria were less abundant. At the species level, a relative decrease in abundance of two Bacteroides species and Escherichia coli was found in autistic individuals. There was a positive correlation between the abundance of Clostridium species, and disaccharidase activity, in autistic individuals. CONCLUSION: There are a variety of changes at the genus and species level in duodenal microbiota in children with autism that could be influenced by carbohydrate malabsorption. These observations could be impacted by variations in individual diets, but also may represent a more pervasive dysbiosis that results in metabolites that impact the behavior of autistic children. Lien vers le texte intégral (Open Access ou abonnement)
8. Root JR, Stevenson BS, Davis LL, Geddes-Hall J, Test DW. {{Establishing Computer-Assisted Instruction to Teach Academics to Students with Autism as an Evidence-Based Practice}}. {J Autism Dev Disord};2016 (Nov 3)
Computer-assisted instruction (CAI) is growing in popularity and has demonstrated positive effects for students with disabilities, including those with autism spectrum disorder (ASD). In this review, criteria for group experimental and single case studies were used to determine quality (Horner et al., Exceptional Children 71:165-179, 2005; Gersten et al., Exceptional Children 71:149-164, 2005; National Technical Assistance Center on Transition Center 2015). Included studies of high and adequate quality were further analyzed in terms of content, context, and specific instructional practices. Based on the NTACT criteria, this systematic review has established CAI as an evidence-based practice for teaching academics to students with ASD with support from 10 single-case and two group design studies of high or adequate quality. Suggestions for future research and implications for practice are discussed.
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9. Sabbagh-Haddad A, Haddad DS, Michel-Crosato E, Arita ES. {{Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle}}. {J Appl Oral Sci};2016 (Sep-Oct);24(5):518-523.
Objective:: The purpose of this study was to evaluate the dental radiographic characteristics as described in 40 records of patients with panoramic radiography. Material and Methods:: The patients were in the range of 6-17 years old, and were divided into two groups (20 subjects who were compatible with the normality standard and 20 individuals diagnosed with the FXS), which were matched for gender and age. Analysis of the panoramic radiographic examination involved the evaluation of dental mineralization stage, mandibular angle size, and presence of dental anomalies in both deciduous and permanent dentitions. Results:: The results of radiographic evaluation demonstrated that the chronology of tooth eruption of all third and second lower molars is anticipated in individuals with FXS (p<0.05). In this group, supernumerary deciduous teeth (2.83%), giroversion of permanent teeth (2.31%), and partial anodontia (1.82%) were the most frequent dental anomalies. In addition, an increase was observed in the mandibular angle size in the FXS group (p<0.05). Conclusion:: We conclude that knowledge of dental radiographic changes is of great importance for dental surgeons to plan the treatment of these individuals. Lien vers le texte intégral (Open Access ou abonnement)
10. Toomey M, Schwartz J, Laverdiere M, Tucker CA, Bevans K, Forrest CB, Blum NJ. {{Preliminary Validation of the PROMIS Parent-Proxy Peer Relationships Measure in Children with Autism Spectrum Disorder: A DBPNet Study}}. {J Dev Behav Pediatr};2016 (Oct 31)
OBJECTIVE: To evaluate the content and construct validity of the existing PROMIS Pediatric Parent-Proxy Peer Relationships Measure in 5- to 12-year-old children with autism spectrum disorder (ASD). METHOD: Parents of 121 children aged 5 to 12 years who met DSM-IV criteria for ASD completed the Peer Relationships Measure using computerized adaptive testing (CAT). Parents also completed the Social Responsiveness Scale, Second Edition (SRS-2) and a demographic form. Intelligence quotient test results were extracted from clinical or research records. Five parents participated in semi-structured interviews about their child’s peer relationships and the item content on the Peer Relationships Measure. RESULTS: The children in the sample were primarily male (87%). The sample was racially and ethnically diverse, and parents were predominantly highly educated. The mean T-score (SD) on the Peer Relationships Measure was 36 (8), with a range from 15 to 62. For 98% of subjects, the CAT required administration of 5 items to reach a standard error of measurement of less than 4 T-score units. The Peer Relationships Measure demonstrated a large correlation with the SRS-2 (r = -0.60, p < .0001). In semi-structured interviews, parents reported that the items on the Peer Relationships Measure were relevant to the peer relationships of their child with ASD, but they reported a few challenges related to variability in their children's peer relationships over time and to somewhat limited knowledge of relationships in school. CONCLUSION: The PROMIS Pediatric Parent-Proxy Peer Relationships Measure may be an efficient, precise, and valid measure of peer relationships for 5- to 12-year-old children with ASD. Lien vers le texte intégral (Open Access ou abonnement)
11. Torres AR, Sweeten TL, Johnson RC, Odell D, Westover JB, Bray-Ward P, Ward DC, Davies CJ, Thomas AJ, Croen LA, Benson M. {{Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder}}. {Front Neurosci};2016;10:463.
The « common variant-common disease » hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased vs. matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the « common variant-common disease » hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics. Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14 bp-indel) frequencies are significantly increased by more than 5% over control populations (Table 2). The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2). Three activating KIR genes: 3DS1, 2DS1, and 2DS2 have increased frequencies of 15, 22, and 14% in autism populations, respectively. There is a 6% increase in total activating KIR genes in autism over control subjects. And, more importantly there is a 12% increase in activating KIR genes and their cognate HLA alleles over control populations (Torres et al., 2012a). These data suggest the interaction of HLA ligand/KIR receptor pairs encoded on two different chromosomes is more significant as a ligand/receptor complex than separately in autism.
