Pubmed du 13/06/19

jeudi 13 juin 2019

1. Akobirshoev I, Mitra M, Dembo R, Lauer E. In-hospital mortality among adults with autism spectrum disorder in the United States : A retrospective analysis of US hospital discharge data. Autism ;2019 (Jun 12):1362361319855795.

A retrospective data analysis using 2004-2014 Healthcare Cost and Utilization Project Nationwide Inpatient Sample was conducted to examine in-hospital mortality among adults with autism spectrum disorders in the United States compared to individuals in the general population. We modeled logistic regressions to compare inpatient hospital mortality between adults with autism spectrum disorders (n = 34,237) and age-matched and sex-matched controls (n = 102,711) in a 1:3 ratio. Adults with autism spectrum disorders had higher odds for inpatient hospital mortality than controls (odds ratio = 1.44, 95% confidence interval : 1.29-1.61, p < 0.001). This risk remained high even after adjustment for age, sex, race/ethnicity, income, number of comorbidities, epilepsy and psychiatric comorbidities, hospital bed size, hospital region, and hospitalization year (odds ratio = 1.51, 95% confidence interval : 1.33-1.72, p < 0.001). Adults with autism spectrum disorders who experienced in-hospital mortality had a higher risk for having 10 out of 27 observed Elixhauser-based medical comorbidities at the time of death, including psychoses, other neurological disorders, diabetes, hypothyroidism, rheumatoid arthritis collagen vascular disease, obesity, weight loss, fluid and electrolyte disorders, deficiency anemias, and paralysis. The results from the interaction of sex and autism spectrum disorders status suggest that women with autism spectrum disorders have almost two times higher odds for in-hospital mortality (odds ratio = 1.95, p < 0.001) than men with autism spectrum disorders. The results from the stratified analysis also showed that women with autism spectrum disorders had 3.17 times higher odds (95% confidence interval : 2.50-4.01, p < 0.001) of in-hospital mortality compared to women from the non-autism spectrum disorders matched control group ; this difference persisted even after adjusting for socioeconomic, clinical, and hospital characteristics (odds ratio = 2.75, 95% confidence interval : 2.09-3.64, p < 0.001). Our findings underscore the need for more research to develop better strategies for healthcare and service delivery to people with autism spectrum disorders.

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2. Brito NH, Elliott AJ, Isler JR, Rodriguez C, Friedrich C, Shuffrey LC, Fifer WP. Neonatal EEG linked to individual differences in socioemotional outcomes and autism risk in toddlers. Dev Psychobiol ;2019 (Jun 11)

Research using electroencephalography (EEG) as a measure of brain function and maturation has demonstrated links between cortical activity and cognitive processes during infancy and early childhood. The current study examines whether neonatal EEG is correlated with later atypical socioemotional behaviors or neurocognitive delays. Parental report developmental assessments were administered to families with children ages 24 to 36 months who had previously participated in a neonatal EEG study (N = 129). Significant associations were found between neonatal EEG (higher frequencies in the frontal polar, temporal, and parietal brain regions) and BITSEA ASD risk scores. Infants with lower EEG power in these brain areas were more likely to have higher risk of socioemotional problems. When examining sex differences, significant links were found for males but not for females. These results demonstrate some promising associations between early neural biomarkers and later risk for atypical behaviors, which may shape early neurobehavioral development and could lead to earlier identification and intervention.

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3. Chen LC, Su WC, Ho TL, Lu L, Tsai WC, Chiu YN, Jeng SF. Postural Control and Interceptive Skills in Children With Autism Spectrum Disorder. Phys Ther ;2019 (Jun 11)

BACKGROUND : Increasing evidence shows common motor deficits associated with autism spectrum disorder (ASD) which may relate to impaired planning and control processes of the sensorimotor system. Catching is a fundamental motor skill that requires coordination between vision, posture, and arm movements. Although postural control and ball catching have been shown to be impaired in children with ASD, previous studies have not investigated how these components are integrated. OBJECTIVE : The objective of this study was to investigate the sensorimotor control of arm movements and postural adjustments during ball catching in children with and without ASD. DESIGN : This study employed a cross-sectional design. METHODS : Fifteen children with ASD (8.8 +/- 1.2 years of age, 12 boys) and 15 age- and gender-matched typically developing (TD) children participated in this study. Children were asked to catch a ball rolling down a ramp in 6 test conditions in which visual inputs and ramp direction were manipulated to provide different sensory conditions and postural demands. RESULTS : Compared to TD peers, children with ASD had increased difficulties catching the balls especially those from the lateral directions. They less used visual information to plan for catching motion, demonstrated less and delayed anticipatory postural adjustments, and exhibited increased corrective control. LIMITATIONS : The sample excluded children with intellectual disability and attention deficit and hyperactivity disorders that might reduce the generalizability to the whole ASD population. CONCLUSIONS : Our results suggest that motor difficulties present in children with ASD may result from compromised sensorimotor integration in planning and control of movements.

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4. Flygare O, Andersson E, Ringberg H, Hellstadius AC, Edbacken J, Enander J, Dahl M, Aspvall K, Windh I, Russell A, Mataix-Cols D, Ruck C. Adapted cognitive behavior therapy for obsessive-compulsive disorder with co-occurring autism spectrum disorder : A clinical effectiveness study. Autism ;2019 (Jun 12):1362361319856974.

Obsessive-compulsive disorder and autism spectrum disorder commonly co-occur. Adapted cognitive behavior therapy for obsessive-compulsive disorder in adults with autism spectrum disorder has not previously been evaluated outside the United Kingdom. In this study, 19 adults with obsessive-compulsive disorder and autism spectrum disorder were treated using an adapted cognitive behavior therapy protocol that consisted of 20 sessions focused on exposure with response prevention. The primary outcome was the clinician-rated Yale-Brown Obsessive-Compulsive Scale. Participants were assessed up to 3 months after treatment. There were significant reductions on the Yale-Brown Obsessive-Compulsive Scale at post-treatment (d = 1.5), and improvements were sustained at follow-up (d = 1.2). Self-rated obsessive-compulsive disorder and depressive symptoms showed statistically significant reductions. Improvements in general functioning and quality of life were statistically non-significant. Three participants (16%) were responders at post-treatment and four (21%) were in remission from obsessive-compulsive disorder. At follow-up, three participants (16%) were responders and one (5%) was in full remission. Adapted cognitive behavior therapy for obsessive-compulsive disorder in adults with co-occurring autism spectrum disorder is associated with reductions in obsessive-compulsive symptoms and depressive symptoms. However, outcomes are modest ; few patients were completely symptom free, and treatment engagement was low with few completed exposures and low adherence to homework assignments. We identify and discuss the need for further treatment refinement for this vulnerable group.

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5. Garfunkel D, Anagnostou EA, Aman MG, Handen BL, Sanders KB, Macklin EA, Chan J, Veenstra-VanderWeele J. Pharmacogenetics of Metformin for Medication-Induced Weight Gain in Autism Spectrum Disorder. J Child Adolesc Psychopharmacol ;2019 (Jun 12)

Objectives : We recently found that metformin attenuated weight gain due to mixed dopamine and serotonin receptor antagonists, commonly termed atypical antipsychotics, in children and adolescents with autism spectrum disorder (ASD). Previous studies have found that genetic variation predicts response to metformin in diabetes. In this study, we aimed to assess whether response to metformin for weight gain in this population is associated with variants in five genes previously implicated in metformin response in diabetes. Methods : Youth with ASD who experienced significant weight gain while taking mixed receptor antagonist medications were randomly assigned to metformin or placebo for 16 weeks, followed by open-label metformin treatment for 16 weeks. In the 53 participants with available DNA samples, we used a linear, mixed model analysis to assess response in the first 16 weeks of metformin treatment, whether in the randomized or open-label period, based upon genotypes at polymorphisms in five genes previously associated with metformin response in diabetes : ATM, SLC2A2, MATE1, MATE2, and OCT1. Results : In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin. No other polymorphism showed a significant difference. Conclusion : As has been shown for metformin treatment in diabetes, genetic variation may predict response to metformin for weight gain in youth with ASD treated with mixed receptor antagonists. Further work is needed to replicate these findings and evaluate whether they can be used prospectively to improve outcomes.

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6. Nygaard KR, Maloney SE, Dougherty JD. Erroneous inference based on a lack of preference within one group : Autism, mice, and the social approach task. Autism Res ;2019 (Jun 11)

The Social Approach Task is commonly used to identify sociability deficits when modeling liability factors for autism spectrum disorder (ASD) in mice. It was developed to expand upon existing assays to examine distinct aspects of social behavior in rodents and has become a standard component of mouse ASD-relevant phenotyping pipelines. However, there is variability in the statistical analysis and interpretation of results from this task. A common analytical approach is to conduct within-group comparisons only, and then interpret a difference in significance levels as if it were a group difference, without any direct comparison. As an efficient shorthand, we named this approach EWOCs : Erroneous Within-group Only Comparisons. Here, we examined the prevalence of EWOCs and used simulations to test whether this approach could produce misleading inferences. Our review of Social Approach studies of high-confidence ASD genes revealed 45% of papers sampled used only this analytical approach. Through simulations, we then demonstrate how a lack of significant difference within one group often does not correspond to a significant difference between groups, and show this erroneous interpretation increases the rate of false positives up to 25%. Finally, we define a simple solution : use an index, like a social preference score, with direct statistical comparisons between groups to identify significant differences. We also provide power calculations to guide sample size in future studies. Overall, elimination of EWOCs and adoption of direct comparisons should result in more accurate, reliable, and reproducible data interpretations from the Social Approach Task across ASD liability models. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The Social Approach Task is widely used to assess social behavior in mice and is frequently used in studies modeling autism. However, reviewing published studies showed nearly half do not use correct comparisons to interpret these data. Using simulated and original data, we argue the correct statistical approach is a direct comparison of scores between groups. This simple solution should reduce false positives and improve consistency of results across studies.

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7. Parlade MV, Weinstein A, Garcia D, Rowley AM, Ginn NC, Jent JF. Parent-Child Interaction Therapy for children with autism spectrum disorder and a matched case-control sample. Autism ;2019 (Jun 12):1362361319855851.

Parent-Child Interaction Therapy is an empirically based, behavioral parent training program for young children exhibiting disruptive behaviors. Parent-Child Interaction Therapy shows promise for treating disruptive behaviors in children with autism spectrum disorder. Treatment processes (i.e. treatment length and homework compliance), parenting skills, parenting stress, and behavioral outcomes (i.e. disruptive and externalizing behaviors and executive functioning) were compared in 16 children with autism spectrum disorder and 16 children without autism spectrum disorder matched on gender, age, and initial intensity of disruptive behaviors. Samples were statistically similar in terms of child receptive language, child race and ethnicity, parent age, gender and education, and number of two-parent families in treatment. Families received standard, mastery-based Parent-Child Interaction Therapy. Both groups demonstrated significant and clinically meaningful improvements in child disruptive and externalizing behavior and executive functioning, parenting skills, and parenting stress. Length of treatment, homework compliance, and parent and child outcomes did not differ significantly between groups. A subset of children with autism spectrum disorder also showed significant improvements in social responsiveness, adaptive skills, and restricted/repetitive behaviors. This study replicates and extends prior research by demonstrating that children with and without autism spectrum disorder experience similar benefits following Parent-Child Interaction Therapy. Findings may expand the availability and dissemination of time-limited, evidence-based interventions for autism spectrum disorder and comorbid disruptive behaviors.

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8. Patel SP, Kim JH, Larson CR, Losh M. Mechanisms of voice control related to prosody in autism spectrum disorder and first-degree relatives. Autism Res ;2019 (Jun 12)

Differences in prosody (e.g., intonation, rhythm) are among the most obvious language-related impairments in autism spectrum disorder (ASD), and significantly impact communication. Subtle prosodic differences have also been identified in a subset of clinically unaffected first-degree relatives of individuals with ASD, and may reflect genetic liability to ASD. This study investigated the neural basis of prosodic differences in ASD and first-degree relatives through analysis of feedforward and feedback control involved in the planning, production, self-monitoring, and self-correction of speech by using a pitch-perturbed auditory feedback paradigm during sustained vowel and speech production. Results revealed larger vocal response magnitudes to pitch-perturbed auditory feedback across tasks in ASD and ASD parent groups, with differences in sustained vowel production driven by parents who displayed subclinical personality and language features associated with ASD (i.e., broad autism phenotype). Both ASD and ASD parent groups exhibited increased response onset latencies during sustained vowel production, while the ASD parent group exhibited decreased response onset latencies during speech production. Vocal response magnitudes across tasks were associated with prosodic atypicalities in both individuals with ASD and their parents. Exploratory event-related potential (ERP) analyses in a subgroup of participants during the sustained vowel task revealed reduced P1 ERP amplitudes in the ASD group, with similar trends observed in parents. Overall, results suggest underdeveloped feedforward systems and neural attenuation in detecting audio-vocal feedback may contribute to ASD-related prosodic atypicalities. Importantly, results implicate atypical audio-vocal integration as a marker of genetic risk to ASD, evident in ASD and among clinically unaffected relatives. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Previous research has identified atypicalities in prosody (e.g., intonation) in individuals with ASD and a subset of their first-degree relatives. In order to better understand the mechanisms underlying prosodic differences in ASD, this study examined how individuals with ASD and their parents responded to unexpected differences in what they heard themselves say to modify control of their voice (i.e., audio-vocal integration). Results suggest that disruptions to audio-vocal integration in individuals with ASD contribute to ASD-related prosodic atypicalities, and the more subtle differences observed in parents could reflect underlying genetic liability to ASD.

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9. Pecukonis M, Plesa Skwerer D, Eggleston B, Meyer S, Tager-Flusberg H. Concurrent Social Communication Predictors of Expressive Language in Minimally Verbal Children and Adolescents with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Jun 11)

Numerous studies have investigated the predictors of language in pre-verbal toddlers and verbally fluent children with autism spectrum disorder (ASD). The present study investigated the concurrent relations among expressive language and a set of empirically-selected social communication variables-joint attention, imitation, and play-in a unique sample of 37 minimally verbal (MV) children and adolescents with ASD. Results revealed that imitation and play were significantly correlated with expressive language, even when controlling for non-verbal IQ, but joint attention was not. Imitation was the only predictor variable to reach significance within the regression model. Findings demonstrate that predictors of expressive language vary for subpopulations of the autism spectrum, and have broader implications for intervention design for older, MV individuals with ASD.

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10. Riordan NH, Hincapie ML, Morales I, Fernandez G, Allen N, Leu C, Madrigal M, Paz Rodriguez J, Novarro N. Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autism Spectrum Disorder in Children : Safety Profile and Effect on Cytokine Levels. Stem Cells Transl Med ;2019 (Jun 11)

Individuals with autism spectrum disorder (ASD) suffer from developmental disabilities that impact communication, behavior, and social interaction. Immune dysregulation and inflammation have been linked to children with ASD, the latter manifesting in serum levels of macrophage-derived chemokine (MDC) and thymus, and activation-regulated chemokine (TARC). Mesenchymal stem cells derived from umbilical cord tissue (UC-MSCs) have immune-modulatory and anti-inflammatory properties, and have been safely used to treat a variety of conditions. This study investigated the safety and efficacy of UC-MSCs administered to children diagnosed with ASD. Efficacy was evaluated with the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS), and with measurements of MDC and TARC serum levels. Twenty subjects received a dose of 36 million intravenous UC-MSCs every 12 weeks (four times over a 9-month period), and were followed up at 3 and 12 months after treatment completion. Adverse events related to treatment were mild or moderate and short in duration. The CARS and ATEC scores of eight subjects decreased over the course of treatment, placing them in a lower ASD symptom category when compared with baseline. MDC and TARC inflammatory cytokine levels also decreased for five of these eight subjects. The mean MDC, TARC, ATEC, and CARS values attained their lowest levels 3 months after the last administration. UC-MSC administration in children with ASD was therefore determined to be safe. Although some signals of efficacy were observed in a small group of children, possible links between inflammation levels and ASD symptoms should be further investigated. Stem Cells Translational Medicine 2019.

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11. Verma V, Paul A, Amrapali Vishwanath A, Vaidya B, Clement JP. Understanding intellectual disability and autism spectrum disorders from common mouse models : synapses to behaviour. Open Biol ;2019 (Jun 28) ;9(6):180265.

Normal brain development is highly dependent on the timely coordinated actions of genetic and environmental processes, and an aberration can lead to neurodevelopmental disorders (NDDs). Intellectual disability (ID) and autism spectrum disorders (ASDs) are a group of co-occurring NDDs that affect between 3% and 5% of the world population, thus presenting a great challenge to society. This problem calls for the need to understand the pathobiology of these disorders and to design new therapeutic strategies. One approach towards this has been the development of multiple analogous mouse models. This review discusses studies conducted in the mouse models of five major monogenic causes of ID and ASDs : Fmr1, Syngap1, Mecp2, Shank2/3 and Neuroligins/Neurnexins. These studies reveal that, despite having a diverse molecular origin, the effects of these mutations converge onto similar or related aetiological pathways, consequently giving rise to the typical phenotype of cognitive, social and emotional deficits that are characteristic of ID and ASDs. This convergence, therefore, highlights common pathological nodes that can be targeted for therapy. Other than conventional therapeutic strategies such as non-pharmacological corrective methods and symptomatic alleviation, multiple studies in mouse models have successfully proved the possibility of pharmacological and genetic therapy enabling functional recovery.

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