Pubmed du 15/09/19

dimanche 15 septembre 2019

1. Bertollo JR, Strang JF, Anthony LG, Kenworthy L, Wallace GL, Yerys BE. Adaptive Behavior in Youth with Autism Spectrum Disorder : The Role of Flexibility. J Autism Dev Disord ;2019 (Sep 13)

Cognitive and behavioral flexibility are important predictors of adaptive behavior in school-age autistic youth. While prior research has utilized broad measures of flexibility, the current study uses the multi-dimensional Flexibility Scale-Revised to examine which specific flexibility skills relate to adaptive functioning. Through parent-report measures on 216 autistic youth, flexibility explained 22.2% of variance in adaptive socialization skills (p < 0.001). Specifically, Social Flexibility accounted for significant variance in adaptive socialization skills, while Transitions/Change approached significance. In exploratory analyses, flexibility explained 11.5% of variance in Communication skills (p < 0.001). This pattern remained after controlling for co-occurring ADHD symptoms. The current study helps to refine the relationship between flexibility and adaptive behavior, which may ultimately help to inform more targeted interventions.

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2. Biag HMB, Potter LA, Wilkins V, Afzal S, Rosvall A, Salcedo-Arellano MJ, Rajaratnam A, Manzano-Nunez R, Schneider A, Tassone F, Rivera SM, Hagerman RJ. Metformin treatment in young children with fragile X syndrome. Mol Genet Genomic Med ;2019 (Sep 14):e956.

BACKGROUND : Metformin is a drug commonly used in individuals with type 2 diabetes, obesity, and impaired glucose tolerance. It has a strong safety profile in both children and adults. Studies utilizing the Drosophila model and knock out mouse model of fragile X syndrome (FXS) have found metformin to rescue memory, social novelty deficits, and neuroanatomical abnormalities. These studies provided preliminary evidence that metformin could be used as a targeted treatment for the cognitive and behavioral problems associated with FXS. Previously, a case series of children and adults with FXS treated with metformin demonstrated improvements in irritability, social responsiveness, language, and hyperactivity. METHODS : Here, we present nine children with FXS between 2 and 7 years of age who were treated clinically with metformin and monitored for behavioral and metabolic changes. RESULTS : Parent reports and developmental testing before and after metformin are presented. There were improvements in language development and behavior (such as lethargy and stereotypy) in most of the patients. CONCLUSION : These results support the need for a controlled trial of metformin in children with FXS under 7 years old whose brains are in a critical developmental window and thus may experience a greater degree of clinical benefit from metformin.

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3. Bradley EA, Ammash N, Martinez SC, Chin K, Hebson C, Singh HS, Aboulhosn J, Grewal J, Billadello J, Chakinala MM, Daniels CJ, Zaidi AN. "Treat-to-close" : Non-repairable ASD-PAH in the adult : Results from the North American ASD-PAH (NAAP) Multicenter Registry. Int J Cardiol ;2019 (Sep 15) ;291:127-133.

BACKGROUND : Adults presenting with an unrepaired atrial septal defect and pulmonary arterial hypertension (ASD-PAH) are typically classified as "correctable" or "non-correctable". The use of directed PAH medical therapy in non-correctable ASD-PAH leading to favorable closure candidacy, repair status and long-term follow-up is not well studied. We therefore sought to characterize response to PAH targeted therapy in ’non-correctable’ ASD-PAH. METHODS AND RESULTS : Nine North American tertiary care centers submitted retrospective data from adults with unrepaired ASD-PAH that did not meet recommendations for repair at initial presentation (1996-2017). Sixty-nine patients (women 51(74%), 40+/-15years, mean pulmonary artery pressure (mPA) 51+/-13mmHg, pulmonary vascular resistance (PVR) 8.7+/-4.9 Wood units, Qp:Qs 1.6+/-0.4) were enrolled. All patients were prescribed PAH targeted therapy and late shunt repair occurred in 19(28%) (Women 15(29%) vs. Men 4(22%), p=0.6). At late follow-up (4.4+/-2.9years) 6-minute walk test distance (6MWTD) was significantly better in the group that underwent repair (486+/-89m vs. 375+/-139m, p<0.05). Transthoracic echo showed significant improvement in right ventricular (RV) function (severe dysfunction in repaired 8(40%) vs. unrepaired groups 35(69%), p<0.05). Divergent survival curves suggest that with larger studies and more follow-up, differences in survival between repaired and unrepaired groups may be important. (repaired : 17(94%) vs. unrepaired : 32(81%), p=0.18). CONCLUSIONS : This is the first and largest multicenter study evaluating the "treat-to-close" approach in non-correctable ASD-PAH. Our new data supports further study of this strategy in patients who have reversibility of PAH in response to targeted therapy. We demonstrate that in the carefully selected patient with non-correctable ASD-PAH, successful shunt repair is possible if post-therapy PVR is </=6.5 Wood units. Patients who underwent repair had improved RV function following PAH targeted therapy. Divergent survival curves suggest that with further study, defect repair may affect medium-term to late survival.

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4. Case L, Yun J. The Effect of Different Intervention Approaches on Gross Motor Outcomes of Children With Autism Spectrum Disorder : A Meta-Analysis. Adapt Phys Activ Q ;2019 (Sep 13):1-26.

Despite the rising interest in intervention for children with autism spectrum disorder, the extent to which interventions are effective on gross motor outcomes is currently unknown. The purpose of this study was to analyze the effect of different intervention approaches on gross motor outcomes among children with autism spectrum disorder using meta-analysis. A total of 18 studies met the inclusion criteria for quantitative analysis. Pre- and posttest means and SDs were extracted to calculate effect sizes. Potential moderator variables were chosen based on important intervention characteristics. The results suggest that interventions have a large effect on gross motor outcomes among children with autism spectrum disorder (delta = 0.99, SE = 0.19, p < .001, 95% confidence interval [0.62, 1.36]). The interventions that were 16 total hours or longer had a significantly larger effect than those less than 16 hr. In addition, the interventions in experimental settings had significantly larger effects than the interventions in practical settings. Future interventions should consider intensity, including not only the duration of the intervention but also the intensity in which specific intervention goals are targeted.

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5. Gabard-Durnam LJ, Wilkinson C, Kapur K, Tager-Flusberg H, Levin AR, Nelson CA. Longitudinal EEG power in the first postnatal year differentiates autism outcomes. Nat Commun ;2019 (Sep 13) ;10(1):4188.

An aim of autism spectrum disorder (ASD) research is to identify early biomarkers that inform ASD pathophysiology and expedite detection. Brain oscillations captured in electroencephalography (EEG) are thought to be disrupted as core ASD pathophysiology. We leverage longitudinal EEG power measurements from 3 to 36 months of age in infants at low- and high-risk for ASD to test how and when power distinguishes ASD risk and diagnosis by age 3-years. Power trajectories across the first year, second year, or first three years postnatally were submitted to data-driven modeling to differentiate ASD outcomes. Power dynamics during the first postnatal year best differentiate ASD diagnoses. Delta and gamma frequency power trajectories consistently distinguish infants with ASD diagnoses from others. There is also a developmental shift across timescales towards including higher-frequency power to differentiate outcomes. These findings reveal the importance of developmental timing and trajectory in understanding pathophysiology and classifying ASD outcomes.

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6. Hare-Harris AE, Mitchel MW, Myers SM, Mitchel AD, King BR, Ruocco BG, Martin CL, Flax JF, Brzustowicz LM. Within-task variability on standardized language tests predicts autism spectrum disorder : a pilot study of the Response Dispersion Index. J Neurodev Disord ;2019 (Sep 13) ;11(1):21.

BACKGROUND : Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD. METHODS : Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Participants were divided into four diagnostic groups : unaffected, ASD-only, LI-only, and ASD + LI. For each language measure, RDI was defined as the product of the total number of test items and the sum of the weight (based on item difficulty) of test items missed. Group differences in RDI were assessed, and the relationship between RDI and ASD diagnosis among individuals with LI was investigated for each language assessment. RESULTS : Although standard scores were unable to distinguish the LI-only and ASD/ASD + LI groups, the ASD/ASD + LI groups had higher RDI scores compared to LI-only group across all measures of expressive, pragmatic, and metalinguistic language. RDI was positively correlated with quantitative ASD traits across all subgroups and was an effective predictor of ASD diagnosis among individuals with LI. CONCLUSIONS : The RDI is an effective quantitative metric of developmental deviance/difference that correlates with ASD traits, supporting previous associations between ASD and non-sequential skill acquisition. The RDI can be adapted to other clinical measures to investigate the degree of difference that is not captured by standard performance summary scores.

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7. Jameel L, Vyas K, Bellesi G, Crawford S, Channon S. Thinking about other’s mistakes : contrasting patterns of performance in groups high or low in autistic or psychopathic traits. Cogn Neuropsychiatry ;2019 (Sep 15):1-17.

Introduction : Counterfactual thinking refers to thoughts such as, "What if ... ?" or "If only ... " that hypothesise about how past events might have turned out differently. It is a functional process, allowing us to reflect upon and solve problems, and to evoke appropriate responses. It is thought to involve both cognitive and emotional processes, and is linked to the development of false belief and moral emotions. Methods : The present study compared responses to a novel task, "Counterfactual Judgments", in students who scored high or low on self-report measures of autistic or psychopathic traits, two conditions putatively associated with deficits in empathy. Results : Contrasting patterns of performance were revealed : those with high versus low autistic traits gave harsher ratings of blame for others’ mistakes and showed reduced sensitivity to punitive counterfactual alternatives, whereas those with high versus low psychopathic traits gave lower ratings for moral judgments of regret and guilt. A self-report questionnaire measure of empathy also provided some evidence of reduced empathic processing in both the high trait groups. Conclusions : The findings are considered in the light of the possible contributions of cognitive versus emotional processes to counterfactual thinking. The possible implications for managing social dysfunction in clinical populations are also discussed.

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8. Ku B, Heinonen GA, MacDonald M, Hatfield B. An inquiry into how parents of children with autism spectrum disorder interact with their children in a motor skill-based play setting. Res Dev Disabil ;2019 (Sep 11) ;94:103494.

BACKGROUND : Most studies examining parental behaviors of parents of young children with autism spectrum disorder (ASD) and typically developing (TD) children have taken place in free play settings and have primarily focused on examining social behaviors. Motor skill-based play settings, which are distinctly different from free play settings, have not been explicitly studied as it relates to parental behaviors in these environments. AIMS : The purpose of this study was to examine parental behaviors of parents of children with and without ASD in two distinctly different play settings. METHODS : Parental behaviors of eighteen parents of children with (n=9) and without ASD (n=9) were examined by observation in different play settings (free play [a social-play/traditional play based setting] and a motor skill-based play setting). The examined parental behaviors included parental encouragement, negativity, sensitivity, detachment, and intrusiveness. A 2 x 2 (group x play setting) repeated measures of ANOVA was conducted to examine the main effect of group (TD vs ASD) and play setting (a social-play based setting and a motor skill-based setting) and the interaction effect between group and play setting on parental behaviors. Post-hoc independent t-tests between groups in each setting were conducted to follow-up on significant interactions indicated in the repeated measures of ANOVA RESULTS : The repeated measures ANOVA revealed that parental encouragement showed a significant interaction effect, suggesting that the effect of group on parental encouragement depended on play setting. A post-hoc analysis revealed that parents of children with ASD showed statistically significant lower parental encouragement in a motor skill-based play setting but not in a social-play based setting compared to parents of TD children. Moreover, there was a main effect of group (parents of children with ASD vs. parents of TD children) on parental intrusiveness indicating that the mean parental intrusiveness on children with ASD was significantly higher than parents of TD children across both play settings. There were no statistically significant main or interaction effects on the other parental behaviors (parental negativity, sensitivity, and detachment) between groups. CONCLUSIONS AND IMPLICATIONS : The current study indicated parental encouragement differences between parents of children with ASD and parents of TD children varied based on the play setting. These results identify a need to examine parental behaviors, especially parental encouragement and parental intrusiveness across various types of play settings. Furthermore, as parents of children with ASD displayed lower parental encouragement in a motor skill-based play setting compared to parents of TD children, future studies are warranted to improve parental encouragement of parents of children with ASD in a motor skill-based play setting.

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9. Li S, Zhao H, Huang R, He L, Tian C, Huang H, Han X, Tang F, Lin Z, Deng S, Zhou J, Li Z. Generation of iPSC line (GIBHi001-A) from a patient with autism spectrum disorder. Stem Cell Res ;2019 (Sep 6) ;40:101571.

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C>T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

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10. Peyroux E, Franck N. Is social cognitive training efficient in autism ? A pilot single-case study using the RC2S+ program. Neurocase ;2019 (Sep 15):1-8.

In high-functioning autism, deficits in emotional processing and theory of mind are relevant to understanding the particularities of social functioning. Here we used a multiple baseline and ABA single-case design to assess the efficacy of an individualized social cognitive training program using both pen-and-paper and computerized materials for an 18-year old patient. After the treatment phase, we found significant improvement in both emotional processes and theory of mind. These results provide further significant data showing that therapeutic tools based on digital relational simulation are a promising way for helping people with autism to compensate for their impaired social functioning.

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11. Stewart GR, Wallace GL, Cottam M, Charlton RA. Theory of mind performance in younger and older adults with elevated autistic traits. Autism Res ;2019 (Sep 14)

Little is known about the impact of aging with Autism Spectrum Disorder on theory of mind (ToM). While ToM difficulties appear to abate with age in older autistic populations, this has yet to be explored in the Broad Autism Phenotype (BAP). The current study examined ToM performance among younger (n = 49, aged 18-46) and older adults (n = 47, aged 60-91) who were classified as on the BAP (younger n = 18 ; older n = 21) or not (younger n = 31 ; older n = 26) using the BAP Questionnaire. ToM was assessed using the ecologically valid Strange Stories Film Task (SSFT) and the dynamic Happe-Frith Triangle Animations task (TA). A 2 x 2 analysis of variance examined the effects of autistic traits (BAP vs. non-BAP) and age (young vs. old). For both SSFT and TA, results showed autistic trait main effects on task performance (non-BAP > BAP). Age main effects were observed for some but not all metrics on TA (younger better than older), with no differences in SSFT. An interaction of autistic traits and age was observed in TA Intentionality, with younger non-BAP and younger BAP performing similarly but older non-BAP performing better than older BAP. Results show that younger and older adults with elevated autistic traits show poorer ToM performance. Despite ToM difficulties being common in later life in the general population, this effect was not observed when using a ToM task designed to reflect real-world scenarios. However, results suggest that autistic traits and age could interact to increase risk for poor ToM performance in older adults who endorse elevated autistic traits. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The behaviors and characteristics commonly found in autism spectrum disorders have been linked to differences in understanding social situations. Similar difficulties have also been found in older age. We assessed social understanding in younger and older adults from the general population. Both younger and older adults who report more autism-like characteristics experience more difficulties with social understanding. However, few differences were found between younger and older adults.

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12. Wall CA, Hogan AL, Will EA, McQuillin S, Kelleher BL, Roberts JE. Early negative affect in males and females with fragile X syndrome : implications for anxiety and autism. J Neurodev Disord ;2019 (Sep 13) ;11(1):22.

BACKGROUND : Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD ; however, these relations remain poorly understood in FXS. METHODS : The present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD. RESULTS : Results indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS. CONCLUSIONS : The current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females.

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13. Wang ZJ, Zhong P, Ma K, Seo JS, Yang F, Hu Z, Zhang F, Lin L, Wang J, Liu T, Matas E, Greengard P, Yan Z. Correction : Amelioration of autism-like social deficits by targeting histone methyltransferases EHMT1/2 in Shank3-deficient mice. Mol Psychiatry ;2019 (Sep 13)

A correction to this paper has been published and can be accessed via a link at the top of the paper.

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14. Wieckowski AT, White SW. Attention Modification to Attenuate Facial Emotion Recognition Deficits in Children with Autism : A Pilot Study. J Autism Dev Disord ;2019 (Sep 13)

Diminished attending to faces may contribute to the impairments in emotion recognition and expression in autism spectrum disorder (ASD). The current study evaluated the acceptability, feasibility, and preliminary efficacy of an attention modification intervention designed to attenuate deficits in facial emotion recognition (FER). During the 10-session experimental treatment, children (n = 8) with ASD watched dynamic videos of people expressing different emotions with the facial features highlighted to guide children’s attention. Children and their parents generally rated the treatment as acceptable and helpful. Although FER improvement was not apparent on task-based measures, parents reported slight improvements and decreased socioemotional problems following treatment. Results suggest that further research on visual attention retraining for ASD, within an experimental therapeutic program, may be promising.

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