Pubmed du 04/10/19

vendredi 4 octobre 2019

1. Abruzzo PM, Matte A, Bolotta A, Federti E, Ghezzo A, Guarnieri T, Marini M, Posar A, Siciliano A, De Franceschi L, Visconti P. Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder. J Transl Med ;2019 (Oct 2) ;17(1):332.

BACKGROUND : It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. METHODS : We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another-comparable-group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. RESULTS : The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. CONCLUSIONS : Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

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2. Fraguas D, Diaz-Caneja CM, Pina-Camacho L, Moreno C, Duran-Cutilla M, Ayora M, Gonzalez-Vioque E, de Matteis M, Hendren RL, Arango C, Parellada M. Dietary Interventions for Autism Spectrum Disorder : A Meta-analysis. Pediatrics ;2019 (Oct 4)

CONTEXT : Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial. OBJECTIVE : To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach. DATA SOURCES : Ovid Medline, PsycINFO, Embase databases. STUDY SELECTION : We selected placebo-controlled, double-blind, randomized clinical trials assessing the efficacy of dietary interventions in ASD published from database inception through September 2017. DATA EXTRACTION : Outcome variables were subsumed under 4 clinical domains and 17 symptoms and/or functions groups. Hedges’ adjusted g values were used as estimates of the effect size of each dietary intervention relative to placebo. RESULTS : In this meta-analysis, we examined 27 double-blind, randomized clinical trials, including 1028 patients with ASD : 542 in the intervention arms and 486 in the placebo arms. Participant-weighted average age was 7.1 years. Participant-weighted average intervention duration was 10.6 weeks. Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains. Effect sizes were small (mean Hedges’ g for significant analyses was 0.31), with low statistical heterogeneity and low risk of publication bias. LIMITATIONS : Methodologic heterogeneity among the studies in terms of the intervention, clinical measures and outcomes, and sample characteristics. CONCLUSIONS : This meta-analysis does not support nonspecific dietary interventions as treatment of ASD but suggests a potential role for some specific dietary interventions in the management of some symptoms, functions, and clinical domains in patients with ASD.

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3. Getahun D, Fassett MJ, Jacobsen SJ, Xiang AH, Takhar HS, Wing DA, Peltier MR. Autism Spectrum Disorders in Children Exposed in Utero to Hyperemesis Gravidarum. Am J Perinatol ;2019 (Oct 3)

OBJECTIVE : This study aimed to determine if hyperemesis gravidarum (HG) is associated with autism spectrum disorder (ASD) risk, and how this association is influenced by race, ethnicity, sex, exposure timing, and medication used to treat it. STUDY DESIGN : This is a retrospective cohort study using records from 469,789 mother-child pairs who delivered at Kaiser Permanente Southern California (KPSC) hospital (1991-2014). Singleton-born children were followed longitudinally from 2 to 17 years of age. Clinical records were used to determine the diagnosis of HG and specialist-confirmed diagnosis of ASD. RESULTS : Children exposed to HG in-utero had higher rates of ASD than unexposed children (2.87 vs. 1.71/1,000 person-years ; adjusted hazard ratio [adj.HR] : 1.53 ; 95% confidence interval [CI] : 1.37-1.70). Children exposed at first and second trimester of pregnancies were more likely to develop ASD ; 1.58-fold (95% CI : 1.40-1.79), and 1.36-fold (95% CI : 1.05-1.75), respectively, compared with unexposed children. HG was associated with ASD for boys (adj.HR : 1.50 ; 95% CI : 1.33-1.70) and girls (adj.HR : 1.62 ; 95% CI : 1.28-2.05). HG was significantly associated with ASD risk in white and Hispanic children. The medications used to treat HG did not contribute to ASD risk. CONCLUSION : HG diagnosis is associated with ASD risk and may be helpful in identifying at-risk children who could benefit from enhanced surveillance and earlier diagnosis and intervention.

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4. Guo H, Li Y, Shen L, Wang T, Jia X, Liu L, Xu T, Ou M, Hoekzema K, Wu H, Gillentine MA, Liu C, Ni H, Peng P, Zhao R, Zhang Y, Phornphutkul C, Stegmann APA, Prada CE, Hopkin RJ, Shieh JT, McWalter K, Monaghan KG, van Hasselt PM, van Gassen K, Bai T, Long M, Han L, Quan Y, Chen M, Li K, Zhang Q, Tan J, Zhu T, Liu Y, Pang N, Peng J, Scott DA, Lalani SR, Azamian M, Mancini GMS, Adams DJ, Kvarnung M, Lindstrand A, Nordgren A, Pevsner J, Osei-Owusu IA, Romano C, Calabrese G, Galesi O, Gecz J, Haan E, Ranells J, Racobaldo M, Nordenskjold M, Madan-Khetarpal S, Sebastian J, Ball S, Zou X, Zhao J, Hu Z, Xia F, Liu P, Rosenfeld JA, de Vries BBA, Bernier RA, Xu ZD, Li H, Xie W, Hufnagel RB, Eichler EE, Xia K. Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. Sci Adv ;2019 (Sep) ;5(9):eaax2166.

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

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5. Oakley BFM, Brewer R, Bird G, Catmur C. No evidence for an opposite pattern of cognitive performance in autistic individuals with and without alexithymia : A response to Rodgaard et al. (2019). J Abnorm Psychol ;2019 (Oct) ;128(7):738-739.

Rodgaard and colleagues (2019) confirmed our finding of a negative relationship between performance on the Reading the Mind in the Eyes Test and alexithymia, regardless of autism diagnosis. In their analysis of our cognitive Theory of Mind data, however, they did not control for autistic traits, which covary with alexithymia. Here we demonstrate that when autistic traits are controlled for, there is no significant association between alexithymia and cognitive theory of mind performance in participants with autism. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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6. Rodgaard EM, Jensen K, Mottron L. An opposite pattern of cognitive performance in autistic individuals with and without alexithymia. J Abnorm Psychol ;2019 (Oct) ;128(7):735-737.

Oakley, Brewer, Bird, and Catmur (2016) investigated whether the Reading the Minds in the Eyes Test (RMET) measures emotion recognition rather than theory of mind (ToM). To explore this, 19 participants with autism and 23 controls, matched on alexithymia traits, were tested with the RMET, as well as the ToM Movie for Assessment of Social Cognition (MASC). The authors found a significant difference between the two groups on the MASC but not on the RMET, but dividing the groups based on alexithymia resulted in a significantly lower performance on the RMET but not on the MASC for the alexithymia group. Therefore, they conclude that difficulties on the RMET are associated with alexithymia, not autism, while difficulties on the MASC are associated with autism, not alexithymia. Here we investigated what seems to be opposite patterns of performance on the two cognitive tasks within the autism group, which modified the authors’ interpretation of their data. This was examined by correlating the alexithymia scores with the RMET and a subscale of the MASC scores, referred to as the cognitive MASC. We found a negative correlation between the alexithymia score and the RMET score while also finding a positive correlation between the alexithymia score and the cognitive MASC score in the autism group. Such an opposite pattern of performance suggests the presence of distinct patterns of ToM difficulties within the autism group. This also indicates that, contrary to what is reported by Oakley et al., there is an association between alexithymia and the MASC within the autism group. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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7. Stahlhut M, Downs J, Wong K, Bisgaard AM, Nordmark E. Feasibility and Effectiveness of an Individualized 12-Week "Uptime" Participation (U-PART) Intervention in Girls and Women With Rett Syndrome. Phys Ther ;2019 (Oct 4)

BACKGROUND : Girls and women with Rett Syndrome (RTT) have low levels of daily physical activity and high levels of sedentary time. Reducing sedentary time and enhancing "uptime" activities such as standing and walking could be an important focus for interventions to address long-term health and quality of life in RTT. OBJECTIVE : The aim of the study was to evaluate the feasibility and health-related effects of an individualized 12-week uptime participation (U-PART) intervention in girls and women with RTT. DESIGN : The study used a single-group pretest-posttest design with 4 assessments (2 baseline, postintervention, and follow-up). METHODS : A participation-based intervention using a whole-day approach was used. During a 12-week intervention period, individualized programs focused on participation in enjoyable uptime activities in home, school/day center, and community settings. Feasibility was assessed with a study-specific questionnaire. Primary outcome measures were sedentary time and daily step count. Secondary outcomes were gross motor skills, walking capacity, quality of life, and goal attainment scaling. RESULTS : Fourteen girls and women who were 5 to 48 years old and had RTT participated. The U-PART intervention was perceived as feasible by caregivers. Similar scores were observed at baseline assessments in all outcomes. Positive effects with small to medium effect sizes (0.27-0.54) were seen in sedentary time (-4%), daily step count (+689 steps per day), walking capacity (+18.8 m), quality of life (+2.75 points), and goal attainment scaling after the intervention. Positive effects were maintained in sedentary time (-3.2%) and walking capacity (+12.1 m) at short-term follow-up. LIMITATIONS : This study was limited by the lack of control group. However, participants acted as their own control, and the stable baseline period partially mitigated this issue. CONCLUSIONS : The U-PART intervention was found to be feasible and effective in the short term in girls and women with RTT.

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8. Topuz C, Ulke-Kurkcuoglu B. Correction to : Increasing Verbal Interaction in Children with Autism Spectrum Disorders Using Audio Script Procedure. J Autism Dev Disord ;2019 (Oct 1)

The original version of the article contains an error in table and figures. The corrected Table 1 and Figs. 1, 2, and 3 are given below. The original version of this article was revised.

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9. Wang M, Hossain F, Sulaiman R, Ren X. Exposure to Inorganic Arsenic and Lead and Autism Spectrum Disorder in Children : A Systematic Review and Meta-Analysis. Chem Res Toxicol ;2019 (Oct 4)

Inorganic arsenic (iAs) and lead (Pb) rank first and second on the U.S. Environmental Protection Agency’s priority list of hazardous substances. Both are known neurotoxic metals that cause detrimental effects on brain development and lead to deficits in cognitive function and behavioral performance in children. Studies have indicated a potential link between iAs and Pb exposure and a higher risk for autism spectrum disorder (ASD). To provide further insight into whether developmental exposure to iAs or Pb is associated with ASD, we conducted a systematic review and combined data into a meta-analysis to evaluate the available human evidence on the relationships. We systematically reviewed relevant studies published through December 30, 2018 and identified 14 studies on iAs and 37 studies on Pb exposure and their respective associations with ASD. Among them, 8 (53.3%) and 19 (51.3%) studies reported a positive association for iAs and Pb, respectively, and none reported a sole inverse association. In the following meta-analysis, we found statistically significant higher iAs concentrations, in hair and in blood, for children diagnosed with ASD compared with controls across studies. However, the findings on Pb exposure were inconsistent, with a significant association for hair Pb, no association for urinary Pb, and an inverse association for blood Pb. After considering strengths and limitations of the body of research, we concluded that there is consistent evidence supporting a positive association between early life iAs exposure and diagnosis of ASD and inconsistent evidence for Pb exposure and ASD risk. We believe it is in the best interest of policy makers and the public to reduce exposures to iAs and Pb among pregnant women and children. Further, our research supports the need for large perspective human studies with accurate measurement and determination of the long-term body burden of iAs and Pb exposures to assess the impact of iAs and Pb exposures on ASD risk.

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10. Weitlauf AS, Goode RH, Warren Z. Do We Have Evidence for Dietary and Nutritional Interventions for Autism Spectrum Disorder ?. Pediatrics ;2019 (Oct 4)

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11. Williams ZJ. Additional psychometric properties of the WHODAS-II in individuals with autism spectrum disorder. Autism Res ;2019 (Oct 4)

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