Pubmed du 31/05/18

jeudi 31 mai 2018

1. Abu-Akel A, Apperly I, Spaniol MM, Geng JJ, Mevorach C. Diametric effects of autism tendencies and psychosis proneness on attention control irrespective of task demands. Sci Rep. 2018 ; 8(1) : 8478.

Our capacity to attend a target while ignoring irrelevant distraction impacts our ability to successfully interact with our environment. Previous reports have sometimes identified excessive distractor interference in both autism and schizophrenia spectrum disorders and in neurotypical individuals with high subclinical expressions of these conditions. Independent of task, we show that the direction of the effect of autism or psychosis traits on the suppression or rejection of a non-target item is diametrical. In Study 1, in which the presence of a salient non-target item hindered performance, higher autism traits were associated with better performance, while higher psychosis traits were associated with worse performance. In Study 2, in which the presence of a salient non-target item facilitated performance, a complete reversal of effects was observed. Future clinical interventions may be informed by the context-specific advantages we observed for the autism and psychosis spectra, and by the need to consider the diametric effects they yield.

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2. Bae SM, Hong JY. The Wnt Signaling Pathway and Related Therapeutic Drugs in Autism Spectrum Disorder. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2018 ; 16(2) : 129-35.

Autism spectrum disorder (ASD) is a series of neurodevelopmental disorder with a large genetic component. However, the pathogenic genes and molecular mechanisms of ASD have not been clearly defined. Recent technological advancements, such as next-generation sequencing, have led to the identification of certain loci that is responsible for the pathophysiology of ASD. Three functional pathways, such as chromatin remodeling, Wnt signaling and mitochondrial dysfunction are potentially involved in ASD. In this review, we will focus on recent studies of the involvement of Wnt signaling pathway components in ASD pathophysiology and related drugs used in ASD treatment.

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3. Elmorsy SA, Soliman GF, Rashed LA, Elgendy H. Dexmedetomidine and propofol sedation requirements in an autistic rat model. Korean journal of anesthesiology. 2018.

Background : Autism is a challenging neurodevelopmental disorder. Previous clinical observations suggest altered sedation requirements for autistic children. Our study aimed to test this observation experimentally with an animal model and, to explore its possible mechanisms. Methods : Eight adult pregnant female Sprague Dawley rats were randomly selected into two groups. Four were injected with intraperitoneal sodium valproate on the gestational day 12 and four were injected with normal saline. On post-natal day 28 the newborn male rats were subjected to an open field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). Times to Loss of Righting Reflex (LORR) and to Return of Righting Reflex (RORR) were recorded. On the next day, all rats were re-sedated and their EEGs were recorded. The rats were sacrificed and hippocampal GABAA and glutamate NMDA receptor gene expression were assessed. Results : Autistic rats showed significantly longer time to LORR and a shorter time to RORR compared to controls (Median time to LORR : 12.0 versus 5.0 for dexmedetomidine and 22.0 and 8.0 for propofol ; p < 0.05). EEG showed a low frequency, high amplitude wave pattern two minutes after LORR in control rats. Autistic rats showed a high frequency, low amplitude awake pattern. Hippocampal GABAA receptor gene expression was significantly less in autistic rats and NMDA gene expression was greater. Conclusions : This study in rat supports the clinical observations of increased anesthetic sedative requirements in autistic children and proposes a mechanism for it.

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4. Gardner LM, Campbell JM, Keisling B, Murphy L. Correlates of DSM-5 Autism Spectrum Disorder Levels of Support Ratings in a Clinical Sample. J Autism Dev Disord. 2018.

The DSM-5 features level of support ratings for social communication (SC) and restrictive and repetitive behaviors (RRB) for individuals with autism spectrum disorder (ASD). We contrasted cognitive, adaptive, and autism severity scores across SC and RRB groups for 158 individuals with ASD diagnosed in a developmental disabilities clinic. Roughly 46% of individuals were identified by licensed psychologists’ clinical judgement as needing Level 2 SC support and 49% were identified as needing Level 2 RRB support. No individuals were rated as needing a combination of Level 1/Level 3 supports across domains. MANOVA and direct discriminant analysis revealed that both SC and RRB groups showed a graded pattern of higher adaptation/lower autism severity to lower adaptation/higher autism severity from Level 1 to Level 3.

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5. Gogou M, Kolios G. Are therapeutic diets an emerging additional choice in autism spectrum disorder management ?. World journal of pediatrics : WJP. 2018.

BACKGROUND : A nutritional background has been recognized in the pathophysiology of autism and a series of nutritional interventions have been considered as complementary therapeutic options. As available treatments and interventions are not effective in all individuals, new therapies could broaden management options for these patients. Our aim is to provide current literature data about the effect of therapeutic diets on autism spectrum disorder. DATA SOURCE : A systematic review was conducted by two reviewers independently. Prospective clinical and preclinical studies were considered. RESULT : Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implementation of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported. CONCLUSION : Despite encouraging laboratory data, there is controversy about the real clinical effect of therapeutic diets in patients with autism. More research is needed to provide sounder scientific evidence.

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6. Gosling CJ, Moutier S. Brief Report : Risk-Aversion and Rationality in Autism Spectrum Disorders. J Autism Dev Disord. 2018.

Risk-aversion and rationality have both been highlighted as core features of decision making in individuals with Autism Spectrum Disorders (ASD). This study tested whether risk-aversion is related to rational decision-making in ASD individuals. ASD and matched control adults completed a decision-making task that discriminated between the use of risk-averse and rational strategies. Results showed that overall, ASD participants were more risk-averse than control participants. Specifically, both groups made similar choices when risk-aversion was the less rational strategy but ASD participants chose more rational options than control participants when risk-aversion was the most rational strategy. This study confirmed that risk-aversion is a core feature of ASD and revealed that ASD individuals can switch their decision-making strategy adaptively to avoid negative consequences.

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7. Heys M, Gibbons F, Haworth E, Medeiros E, Tumbahangphe KM, Wickenden M, Shrestha M, Costello A, Manandhar D, Pellicano E. The Estimated Prevalence of Autism in School-Aged Children Living in Rural Nepal Using a Population-Based Screening Tool. J Autism Dev Disord. 2018.

Few data exist on the prevalence of autism in low-income countries. We translated, adapted and tested the acceptability of a Nepali-language version of a screening tool for autism (Autism Quotient-10). Using this tool, we estimated autism prevalence in 4098 rural Nepali children aged 9-13 years. Fourteen children scored > 6 out of 10, indicative of elevated autistic symptomatology, of which 13 also screened positive for disability. If the AQ-10 screening tool is as sensitive and specific in the Nepali population as it is in the UK, this would yield an estimated true prevalence of 3 in 1000 (95% confidence interval 2-5 in 1000). Future research is required to validate this tool through in-depth assessments of high-scoring children.

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8. Hu Z, Yang Y, Zhao Y, Yu H, Ying X, Zhou D, Zhong J, Zheng Z, Liu J, Pan R, Zhang W, Cheng F, Duan S. APOE hypermethylation is associated with autism spectrum disorder in a Chinese population. Experimental and therapeutic medicine. 2018 ; 15(6) : 4749-54.

Abnormal apolipoprotein E (APOE) methylation has been demonstrated to be associated with Alzheimer’s disease, which may have overlapping mechanisms with autism spectrum disorder (ASD). Thus, the purpose of the present study was to assess the possible link between APOE methylation and ASD. Genomic DNA was extracted from peripheral blood and subjected to a methylation assay. SYBR green-based quantitative methylation-specific polymerase chain reaction analysis was used to measure APOE methylation in 62 pediatric patients with ASD and 73 age-matched healthy subjects. The APOE methylation in each sample was expressed as a percentage of methylation of a reference (PMR). The results indicated that APOE methylation in pediatric patients with ASD was significantly higher than that in the healthy controls (median PMR, 33 vs. 11% ; P=2.36x10(-10)). Receiver operating characteristic curve demonstrated that PMR of 15.4% was the optimal cut-off for predicting ASD (area under curve, 0.817 ; sensitivity, 93.5% ; specificity, 72.6% ; P=2.36x10(-10)). In summary, the present results indicated that APOE hypermethylation in peripheral blood DNA may be used as a diagnostic biomarker for ASD.

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9. Hwang-Gu SL, Lin HY, Chen YC, Tseng YH, Hsu WY, Chou MC, Chou WJ, Wu YY, Gau SS. Symptoms of ADHD Affect Intrasubject Variability in Youths with Autism Spectrum Disorder : An Ex-Gaussian Analysis. J Clin Child Adolesc Psychol. 2018 : 1-14.

Increased intrasubject variability in reaction times (RT-ISV) is frequently found in individuals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in individuals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.

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10. Jones RM, Tarpey T, Hamo A, Carberry C, Brouwer G, Lord C. Statistical Learning is Associated with Autism Symptoms and Verbal Abilities in Young Children with Autism. J Autism Dev Disord. 2018.

Statistical learning-extracting regularities in the environment-may underlie complex social behavior. 124 children, 56 with autism and 68 typically developing, ages 2-8 years, completed a novel visual statistical learning task on an iPad. Averaged together, children with autism demonstrated less learning on the task compared to typically developing children. However, multivariate classification analyses characterized individual behavior patterns, and demonstrated a subset of children with autism had similar learning patterns to typically developing children and that subset of children had less severe autism symptoms. Therefore, statistically averaging data resulted in missing critical heterogeneity. Variability in statistical learning may help to understand differences in autism symptoms across individuals and could be used to tailor and inform treatment decisions.

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11. Miao Z, Liu X, Li W, He Q, Liu X. Assessment of efficacy of prenatal genetic diagnosis for fragile X syndrome using nested PCR. Experimental and therapeutic medicine. 2018 ; 15(6) : 5107-12.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and the leading monogenic cause of autism spectrum disorder. It has previously been demonstrated that prenatal genetic diagnosis is efficient for the diagnosis of FXS. The present study investigated the diagnostic effects of nested polymerase chain reaction (PCR) for fragile X mental retardation 1 (FMR1) and expanded CGG repeats. It was demonstrated that the nested PCR assay rapidly measured the multi-copies of the FMR1 gene in individual samples. The nested PCR assay detected normal CGG repeat lengths and expanded CGG repeat lengths with a low occurrence of false positives. In addition, the nested PCR assay resulted in increased sensitivity and specificity for patients with FXS. Furthermore, the nested PCR assay identified the mutation and generated conclusive cases for FXS, indicating that this assay is beneficial for the diagnosis of FXS patients. In conclusion, these outcomes indicate that nested PCR assay is a reliable and easier method for diagnosis of FXS, which may be used for the diagnosis of FXS patients.

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12. Rhee J, Park K, Kim KC, Shin CY, Chung C. Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression. Molecules and cells. 2018 ; 41(5) : 486-94.

Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphory-lated CaMKIIalpha were significantly decreased while the expression level of CaMKIIalpha was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.

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13. Schiariti V, Mahdi S, Bolte S. International Classification of Functioning, Disability and Health Core Sets for cerebral palsy, autism spectrum disorder, and attention-deficit-hyperactivity disorder. Dev Med Child Neurol. 2018.

AIM : Capturing functional information is crucial in childhood disability. The International Classification of Functioning, Disability and Health (ICF) Core Sets promote assessments of functional abilities and disabilities in clinical practice regarding circumscribed diagnoses. However, the specificity of ICF Core Sets for childhood-onset disabilities has been doubted. This study aimed to identify content commonalities and differences among the ICF Core Sets for cerebral palsy (CP), and the newly developed Core Sets for autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD). METHOD : The categories within each Core Set were aggregated at the ICF component and chapter levels. Content comparison was conducted using descriptive analyses. RESULTS : The activities and participation component of the ICF was the most covered across all Core Sets. Main differences included representation of ICF components and coverage of ICF chapters within each component. CP included all ICF components, while ADHD and ASD predominantly focused on activities and participation. Environmental factors were highly represented in the ADHD Core Sets (40.5%) compared to the ASD (28%) and CP (27%) Core Sets. INTERPRETATION : International Classification of Functioning, Disability and Health Core Sets for CP, ASD, and ADHD capture both common but also unique functional information, showing the importance of creating condition-specific, ICF-based tools to build functional profiles of individuals with childhood-onset disabilities. WHAT THIS PAPER ADDS : The International Classification of Functioning, Disability and Health (ICF) Core Sets for cerebral palsy (CP), autism spectrum disorder (ASD), and attention-deficit-hyperactivity disorder (ADHD) include unique functional information. The ICF-based tools for CP, ASD, and ADHD differ in terms of representation and coverage of ICF components and ICF chapters. Representation of environmental factors uniquely influences functioning and disability across ICF Core Sets for CP, ASD and ADHD.

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14. Walters FP, Gray SH. Addressing sexual and reproductive health in adolescents and young adults with intellectual and developmental disabilities. Current opinion in pediatrics. 2018.

PURPOSE OF REVIEW : This review provides support for promoting the sexual health of adolescents and young adults with developmental disabilities, and particularly those with intellectual disabilities. It offers guidance for pediatricians on incorporating counseling on sexuality and reproductive healthcare, socially appropriate behavior, and sexual abuse prevention for adolescents and young adults with developmental disabilities into healthcare visits. Additionally, it provides resources for developmentally appropriate sexuality education in the home and community to allow access to the comprehensive sexual and reproductive healthcare patients deserve. RECENT FINDINGS : Adolescents and young adults with developmental disabilities often do not receive developmentally appropriate sexual health education, and this is associated with poor sexual health outcomes and increased rates of sexual abuse in this population. SUMMARY : Pediatricians should discuss sexual health with all patients, including adolescents and young adults with developmental disabilities. They are well suited to provide sexual health education and inform families about appropriate sexual health resources.

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15. Wise JM, Cepeda SL, Ordaz DL, McBride NM, Cavitt MA, Howie FR, Scalli L, Ehrenreich-May J, Wood JJ, Lewin AB, Storch EA. Open Trial of Modular Cognitive-Behavioral Therapy in the Treatment of Anxiety Among Late Adolescents with Autism Spectrum Disorder. Child Psychiatry Hum Dev. 2018.

Given the high rates of comorbid anxiety and autism spectrum disorder (ASD) in the adolescent and young adult population, effective treatment protocols to address anxiety symptoms are of importance to help promote greater independence across settings. While research supports the use of cognitive-behavioral therapy (CBT) across younger age groups with ASD, the literature is limited on interventions benefitting adolescents and young adults with comorbid anxiety disorders and ASD. Therefore, this open trial utilized a modified CBT manual for seven participants between the ages of 16 and 20 years, consisting of a 16-week modularized CBT treatment, including psychoeducation, cognitive therapy, and exposure therapy. Measures of anxiety and depression were completed at baseline and post-treatment. Findings demonstrated significant reductions on clinician-rated measures of anxiety. While findings are encouraging, additional studies examining the efficacy of CBT for this population with ASD and clinical anxiety are necessary to further identify beneficial treatment components.

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