Pubmed du 22/06/19

samedi 22 juin 2019

1. Baghdadli A, Miot S, Rattaz C, Akbaraly T, Geoffray MM, Michelon C, Loubersac J, Traver S, Mortamais M, Sonie S, Pottelette J, Robel L, Speranza M, Vesperini S, Maffre T, Falissard B, Picot MC. Investigating the natural history and prognostic factors of ASD in children : the multicEntric Longitudinal study of childrEN with ASD - the ELENA study protocol. BMJ Open ;2019 (Jun 19) ;9(6):e026286.

INTRODUCTION : There is global concern about the increasing prevalence of autism spectrum disorders (ASDs), which are early-onset and long-lasting disorders. Although ASDs are considered to comprise a unique syndrome, their clinical presentation and outcome vary widely. Large-scale and long-term cohort studies of well-phenotyped samples are needed to better understand the course of ASDs and their determinants. The primary objective of the multicEntric Longitudinal study of childrEN with ASD (ELENA) study is to understand the natural history of ASD in children and identify the risk and prognostic factors that affect their health and development. METHODS AND ANALYSIS : This is a multicentric, longitudinal, prospective, observational cohort in which 1000 children with ASD diagnosed between 2 and 16 years of age will be recruited by 2020 and followed over 6 years. The baseline follow-up starts with the clinical examination to establish the ASD diagnosis. A battery of clinical tools consisting of the Autism Diagnostic Observation Schedule, the revised version of the Autism Diagnostic Interview, measures of intellectual functioning, as well as large-scale behavioural and developmental measurements will allow us to study the heterogeneity of the clinical presentation of ASD subtypes. Subsequent follow-up at 18 months and at 3, 4.5 and 6 years after the baseline examination will allow us to explore the developmental trajectories and variables associated with the severity of ASD. In addition to the children’s clinical and developmental examinations, parents are invited to complete self-reported questionnaires concerning perinatal and early postnatal history, congenital anomalies, genetic factors, lifestyle factors, medical and psychiatric comorbidities, and the socioeconomic environment. As of 1 November 2018, a total of 766 participants have been included. ETHICS AND DISSEMINATION : Ethical approval was obtained through the Marseille Mediterranean Ethics Committee (ID RCB : 2014-A01423-44), France. We aim to disseminate the findings through national and international conferences, international peer-reviewed journals, and social media. TRIAL REGISTRATION NUMBER : NCT02625116 ; Pre-results.

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2. Boutrus M, Gilani SZ, Alvares GA, Maybery MT, Tan DW, Mian A, Whitehouse AJO. Increased facial asymmetry in autism spectrum conditions is associated with symptom presentation. Autism Res ;2019 (Jun 21)

A key research priority in the study of autism spectrum conditions (ASC) is the discovery of biological markers that may help to identify and elucidate etiologically distinct subgroups. One physical marker that has received increasing research attention is facial structure. Although there remains little consensus in the field, findings relating to greater facial asymmetry (FA) in ASC exhibit some consistency. As there is growing recognition of the importance of replicatory studies in ASC research, the aim of this study was to investigate the replicability of increased FA in autistic children compared to nonautistic peers. Using three-dimensional photogrammetry, this study examined FA in 84 autistic children, 110 typically developing children with no family history of the condition, and 49 full siblings of autistic children. In support of previous literature, significantly greater depth-wise FA was identified in autistic children relative to the two comparison groups. As a further investigation, increased lateral FA in autistic children was found to be associated with greater severity of ASC symptoms on the Autism Diagnostic Observation Schedule, second edition, specifically related to repetitive and restrictive behaviors. These outcomes provide an important and independent replication of increased FA in ASC, as well as a novel contribution to the field. Having confirmed the direction and areas of increased FA in ASC, these findings could motivate a search for potential underlying brain dysmorphogenesis. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : This study looked at the amount of facial asymmetry (FA) in autistic children compared to typically developing children and children who have siblings with autism. The study found that autistic children, compared to the other two groups, had greater FA, and that increased FA was related to greater severity of autistic symptoms. The face and brain grow together during the earliest stages of development, and so findings of facial differences in autism might inform future studies of early brain differences associated with the condition.

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3. Buro A, Gray H. Gender Differences in Nutrient Intake, Diet Quality, and Mealtime Behaviors Among Children with Autism Spectrum Disorder (P11-105-19). Curr Dev Nutr ;2019 (Jun) ;3(Suppl 1)

Objectives : As ASD is more frequently diagnosed in males than females, research findings in ASD behaviors such as diet can be biased towards male-dominant features. Gender differences needed to be further explored to develop an intervention based on gender-specific needs, if there are any. This preliminary analysis aims to investigate gender differences in nutrient intake, diet quality, and mealtime behaviors among children with ASD. Methods : A cross-sectional analysis of dietary intake and mealtime behavior was conducted in 39 children (26 males, 13 females) aged 2 to 17 with ASD. A parent of each child completed a 24-hour recall phone call and a mealtime behavior survey. Energy and nutrient intake data were analyzed with NDSR Pilot-Pack software. Diet quality was assessed using the Healthy Eating Index-2015 (HEI-2015). Descriptive statistics were generated in SPSS for nutrient intake and mealtime behaviors and in SAS for diet quality. Independent t-tests were performed to examine gender differences for nutrient intake and diet quality data ; chi-square tests were performed for mealtime behavior outcomes. Results : There were no gender differences in energy or nutrient intake. Males exhibited significantly higher HEI component scores for whole grains (P = 0.029), fatty acids (P = 0.039), and saturated fats (P = 0.049). Total HEI score was higher in males, but the difference was not statistically significant. There was no difference in total mealtime behavior score by gender. However, males showed greater difficulty eating at home (P = 0.028) and preference for certain food temperatures (P = 0.008), while females had greater parent-reported binge eating behavior (P = 0.048). Conclusions : Boys in this study had higher diet quality in some categories and exhibited greater prevalence of certain problematic mealtime behaviors. Further research is needed to examine gender-specific needs in children with ASD that should be considered when implementing nutrition interventions. Funding Sources : This work was supported by the University of South Florida Research and Innovation Internal Awards Program under Grant No. 0128126.

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4. Diop H, Cabral H, Gopal D, Cui X, Stern JE, Kotelchuck M. Early Autism Spectrum Disorders in Children Born to Fertile, Subfertile, and ART-Treated Women. Matern Child Health J ;2019 (Jun 20)

INTRODUCTION : We examined the prevalence of autism spectrum disorders (ASDs) in Massachusetts (MA) comparing children born via assisted reproductive technology (ART) and children born to women with indicators of subfertility but no ART (Subfertile), to children born to women with neither ART nor indicators of subfertility (Fertile). We assessed the direct, indirect, and total effects of ART and subfertility on ASD among singletons. METHODS : This study included 10,147 ART, 8072 Subfertile and 441,898 Fertile MA resident births from the MA Outcome Study of ART (MOSART) database linked with Early Intervention program participation data. ART included fresh in vitro fertilization (IVF), fresh intracytoplasmic sperm injection (ICSI), and frozen embryo transfer. We estimated the prevalence of ASD by fertility group. We used logistic regression to assess the natural direct effect (NDE), natural indirect effect (NIE) through preterm birth, and total effects of each fertility group on ASD. RESULTS : The NDE indicated that, compared to the Fertile group, the odds of ASD were not statistically higher in the ART (ORNDE 1.07 ; 95% CI 0.88-1.30), Subfertile (ORNDE 1.11 ; 95% CI 0.89-1.38), IVF (ORNDE 0.91 ; 95% CI 0.68-1.22), or ICSI (ORNDE 1.13 ; 95% CI 0.84-1.51) groups, even if the rate of preterm birth was the same across all groups. The total effect (product of NDE and NIE) was not significant for ART (ORTotal Effect 1.08 ; 95% CI 0.89-1.30), Subfertile (ORTotal Effect 1.11 ; 95% CI 0.89-1.38), IVF (ORTotal Effect 0.92 ; 95% CI 0.69-1.23), or ICSI (ORTotal Effect 1.13 ; 95% CI 0.84-1.52). CONCLUSION : Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.

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5. DiStefano C, Dickinson A, Baker E, Jeste SS. EEG Data Collection in Children with ASD : The Role of State in Data Quality and Spectral Power. Res Autism Spectr Disord ;2019 (Jan) ;57:132-144.

Background : Electroencephalography can elucidate neurobiological mechanisms underlying heterogeneity in ASD. Studying the full range of children with ASD introduces methodological challenges stemming from participants’ difficulties tolerating the data collection process, leading to diminished EEGdataretentionandincreasedvariabilityin participant ’state’ during the recording. Quantifying state will improve data collection methods and aide in interpreting results. Objectives : Observationally quantify participant state during the EEG recording ; examine its relationship to child characteristics, data retention and spectral power. Methods : Participants included 5-11 year-old children with D (N=39) and age-matched TD children (N=16). Participants were acclimated to the EEG environment using behavioral strategies. EEG was recorded while participants watched a video of bubbles. Participant ’state’ was rated using a Likert scale (Perceived State Rating : PSR). Results : Participants with ASD had more elevated PSR than TD participants. Less EEG data were retained in participants with higher PSR scores, but this was not related to age or IQ. TD participants had higher alpha power compared with the ASD group. Within the ASD group, participants with high PSR had decreased frontal alpha power. Conclusions : Given supportive strategies, EEG data was collected from children with ASD across cognitive levels. Participant state influenced both EEG data retention and alpha spectral power. Alpha suppression is linked to attention and vigilance, suggesting that these participants were less ’at rest’. This highlights the importance of considering state when conducting EEG studies with challenging participants, both to increase data retention rates and to quantify the influence of state on EEG variables.

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6. Goodwin MS, Mazefsky CA, Ioannidis S, Erdogmus D, Siegel M. Predicting aggression to others in youth with autism using a wearable biosensor. Autism Res ;2019 (Jun 21)

Unpredictable and potentially dangerous aggressive behavior by youth with Autism Spectrum Disorder (ASD) can isolate them from foundational educational, social, and familial activities, thereby markedly exacerbating morbidity and costs associated with ASD. This study investigates whether preceding physiological and motion data measured by a wrist-worn biosensor can predict aggression to others by youth with ASD. We recorded peripheral physiological (cardiovascular and electrodermal activity) and motion (accelerometry) signals from a biosensor worn by 20 youth with ASD (ages 6-17 years, 75% male, 85% minimally verbal) during 69 independent naturalistic observation sessions with concurrent behavioral coding in a specialized inpatient psychiatry unit. We developed prediction models based on ridge-regularized logistic regression. Our results suggest that aggression to others can be predicted 1 min before it occurs using 3 min of prior biosensor data with an average area under the curve of 0.71 for a global model and 0.84 for person-dependent models. The biosensor was well tolerated, we obtained useable data in all cases, and no users withdrew from the study. Relatively high predictive accuracy was achieved using antecedent physiological and motion data. Larger trials are needed to further establish an ideal ratio of measurement density to predictive accuracy and reliability. These findings lay the groundwork for the future development of precursor behavior analysis and just-in-time adaptive intervention systems to prevent or mitigate the emergence, occurrence, and impact of aggression in ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Unpredictable aggression can create a barrier to accessing community, therapeutic, medical, and educational services. The present study evaluated whether data from a wearable biosensor can be used to predict aggression to others by youth with autism spectrum disorder (ASD). Results demonstrate that aggression to others can be predicted 1 min before it occurs with high accuracy, laying the groundwork for the future development of preemptive behavioral interventions and just-in-time adaptive intervention systems to prevent or mitigate the emergence, occurrence, and impact of aggression to others in ASD.

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7. LaGasse AB, Manning RCB, Crasta JE, Gavin WJ, Davies PL. Assessing the Impact of Music Therapy on Sensory Gating and Attention in Children With Autism : A Pilot and Feasibility Study. J Music Ther ;2019 (Jun 21)

Children with autism spectrum disorder (ASD) frequently demonstrate atypical processing of sensory information and deficits in attentional abilities. These deficits may impact social and academic functioning. Although music therapy has been used to address sensory and attentional needs, there are no studies including physiologic indicators of sensory processing to determine the impact of music therapy. The objective of this study was to determine the feasibility of conducting study protocols, determine the adequacy of electroencephalography (EEG) and behavioral measures in identifying attentional differences in children with ASD compared with typically developing (TD) children, and to gather preliminary evidence of intervention effects on brain responses and attention outcomes. Seven children with high functioning ASD ages 5 -12 and seven age- and gender-matched TD completed procedures measuring brain responses (EEG) and behaviors (the Test of Everyday Attention for Children). Children with ASD then completed a 35-min individual music therapy attention protocol delivered by a board-certified music therapist ten times over 5 weeks. Children with ASD completed measures of brain responses and behavior post-intervention to determine pre- to post-test differences. Consent and completion rates were 100% for children who met the study criteria. Feasibility measures indicated that measures of brain responsivity could be used to determine attentional differences between children with ASD and typical children. Initial outcome data for brain responses and behavior indicated positive trends for the impact of music therapy on selective attention skills.

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8. Nordahl-Hansen A. Regression in Autism is Far More Common Than Once Thought. Neurosci Biobehav Rev ;2019 (Jun 18)

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9. Panjwani A, Ji Y, Fahey J, Palmer A, Wang G, Hong X, Wang X. Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids (BCAAs), and Offspring ASD : Evidence of Sex Difference (P11-141-19). Curr Dev Nutr ;2019 (Jun) ;3(Suppl 1)

Objectives : Previous studies have consistently reported on the association between maternal metabolic conditions, like obesity and diabetes, and a higher risk of offspring ASD. However, the underlying mechanisms remain elusive. Branched-chain amino acids (BCAAs) are known to be involved in the inflammatory pathways underpinning obesity and diabetes, and studies have also shown associations between BCAAs and ASD. We sought to examine the joint associations of maternal metabolic conditions and maternal plasma BCAAs with offspring risk of ASD and explore whether the associations differ by child sex. Methods : This study was comprised of 864 mother-child pairs, a subset of the Boston Birth Cohort (BBC). Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry (LC-MS) in samples collected 24-72 hours postpartum. A composite BCAA score was created using principal components, and obesity and diabetes (ob/DM) were combined into one variable (none vs any). Logistic regression was used to explore the role of BCAAs as risk factors, mediators, or effect modifiers, along with maternal ob/DM and other covariables. BCAA, ob/DM, and sex interactions were also examined. Results : Maternal plasma BCAAs alone were not associated with child ASD and did not mediate the path between maternal ob/DM and ASD. However, in the presence of maternal ob/DM, maternal BCAA score was significantly associated with ASD (adjusted OR 2.35, 95% CI 1.21 - 4.55). Maternal BCAA score was also significantly associated with ASD in males compared to females (adjusted OR 4.91, 95% CI 2.48 - 9.69). There were significant interactions of leucine and valine with ob/DM and of leucine and isoleucine with male sex on the risk of offspring ASD. Finally, compared to females without maternal metabolic risk factors, males with both maternal ob/DM and high maternal BCAA score had over eight times higher risk of ASD. Conclusions : While male sex and maternal ob/DM were known risk factors of child ASD, our study showed that elevated levels of maternal plasma BCAAs further increased the risk of ASD under these conditions. Additional studies are warranted to clarify the role of BCAAs in ASD ; if confirmed, BCAAs have potential as early biomarkers of future risk of ASD, especially in the presence of maternal metabolic disorders and/or a male fetus. Funding Sources : Health Resources and Services Administration grant. Supporting Tables Images and/or Graphs :

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10. Stahmer A, Brookman-Frazee L. Utilizing Community-Based Implementation Trials to Advance Understanding of Service Disparities in Autism Spectrum Disorder. Glob Pediatr Health ;2019 ;6:2333794x19854939.

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11. Theoharides TC, Kavalioti M. Effect of stress on learning and motivation-relevance to autism spectrum disorder. Int J Immunopathol Pharmacol ;2019 (Jan-Dec) ;33:2058738419856760.

Learning and motivation are critical in the development of children, and to their acquisition of knowledge and skills. A case in point is autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impaired social interactions and communication, as well as by stereotypic movements. Maternal stress has been strongly associated with increased risk of developing ASD. Children experience multiple stressors such as separation anxiety, fear of the unknown, physical and/or emotional trauma, bullying, as well as environmental exposures. Stress is well known to affect learning and motivation. However, patients with ASD have aggrevated tresponses to stress, especially fear response. There is extensive literature connecting the amygdala to social behavior and to pathophysiologic responses to stress. The amygdala regulate the responses to stress, and anatomical changes in amygdala have been reported in ASD. In particular, corticotropin-releasing hormone (CRH), which is secreted under stress, is high in children with ASD and stimulates both mast cells and microglia, thus providing possible targets for therapy. Factors and/or circumstances that could interfere with the neurodevelopmental pathways involved in learning and motivation are clearly important and should be recognized early.

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