Pubmed du 30/08/19

Pubmed du jour

2019-08-30 12:03:50

1. Boterberg S, Van Coster R, Roeyers H. {{Characteristics, Early Development and Outcome of Parent-Reported Regression in Autism Spectrum Disorder}}. {J Autism Dev Disord};2019 (Aug 28)

This study explored regression patterns in 100 children with ASD (3-11 years) using several approaches to enhance the validity of retrospective parent report. Both early development and outcome were examined in regression groups defined by 36 months age cut-off and two underlying empirical patterns based on type and onset age. Results over regression groups were generally consistent. During early development, children with regression showed a similar amount of social atypicalities and stereotyped behaviour as compared to children without regression. However, parents indicated less communication skills which could be a valuable predictor of regression. Development after regression was characterised by early language delay and more restricted and repetitive behaviour. The findings provide insight into the diagnosis and prognosis of regression in ASD.

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2. Dawson-Squibb JJ, de Vries PJ. {{Developing an Evaluation Framework for Parent Education and Training in Autism Spectrum Disorder: Results of a Multi-stakeholder Process}}. {J Autism Dev Disord};2019 (Aug 28)

Despite the need for parent education and training programmes in autism spectrum disorder (ASD), there is no generally-accepted evaluation framework to select programmes for different settings. Here we generated an evaluation framework using a multi-stakeholder, implementation science approach. Purposive sampling identified ASD experts, implementation/health systems experts, and parents/carers of individuals with ASD. A consensus-building stakeholder workshop with 14 stakeholders and thematic analysis was used to generate themes and components of the framework. Main themes included ‘Outcomes’ (parent, child, family and community), ‘Processes and Procedures’ (accessibility, acceptability, psychological process, and referral pathways) and ‘Implementation Landscape’ (sustainability, scalability, integration and coordination, and monitoring and evaluation). We propose that the evaluation framework and Evaluation Framework Checklist generated could guide clinicians, researchers and policy-makers.

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3. English MCW, Gignac GE, Visser TAW, Whitehouse AJO, Maybery MT. {{A comprehensive psychometric analysis of autism-spectrum quotient factor models using two large samples: Model recommendations and the influence of divergent traits on total-scale scores}}. {Autism Res};2019 (Aug 29)

The Autism-Spectrum Quotient (AQ) is a psychometric scale that is commonly used to assess autistic-like traits and behaviors expressed by neurotypical individuals. A potential strength of the AQ is that it provides subscale scores that are specific to certain dimensions associated with autism such as social difficulty and restricted interests. However, multiple psychometric evaluations of the AQ have led to substantial disagreement as to how many factors exist in the scale, and how these factors are defined. These challenges have been exacerbated by limitations in study designs, such as insufficient sample sizes as well as a reliance on Pearson, rather than polychoric, correlations. In addition, several proposed models of the AQ suggest that some factors are uncorrelated, or negatively correlated, which has ramifications for whether total-scale scores are meaningfully interpretable-an issue not raised by previous work. The aims of the current study were to provide: (a) guidance as to which models of the AQ are viable for research purposes, and (b) evidence as to whether total-scale scores are adequately interpretable for research purposes. We conducted a comprehensive series of confirmatory factor analyses on 11 competing AQ models using two large samples drawn from an undergraduate population (n = 1,702) and the general population (n = 1,280). Psychometric evidence largely supported using the three-factor model described by Russell-Smith et al. [Personality and Individual Differences 51(2), 128-132 (2011)], but did not support the use of total-scale scores. We recommend that researchers consider using AQ subscale scores instead of total-scale scores. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We examined 11 different ways of scoring subscales in the popular Autism-Spectrum Quotient (AQ) questionnaire in two large samples of participants (i.e., general population and undergraduate students). We found that a three-subscale model that used « Social Skill, » « Patterns/Details, » and « Communication/Mindreading » subscales was the best way to examine specific types of autistic traits in the AQ. We also found some weak associations between the three subscales-for example, being high on the « Patterns/Details » subscale was not predictive of scores on the other subscales. This means that meaningful interpretation of overall scores on the AQ is limited.

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4. Guo BQ, Li HB, Zhai DS, Ding SB. {{Association of maternal prenatal folic acid intake with subsequent risk of autism spectrum disorder in children: A systematic review and meta-analysis}}. {Prog Neuropsychopharmacol Biol Psychiatry};2019 (Aug 30);94:109650.

BACKGROUND: A number of studies have explored the link of antenatal folic acid (FA) intake with autism spectrum disorder (ASD) in children, with inconsistent findings. Therefore, we conducted a systematic review and meta-analysis of relevant studies to elucidate the actual association between maternal FA intake during the prenatal period and the risk of ASD in offspring. METHODS: PubMed, EMBASE, PsycINFO, Scopus, Web of Science, and Cochrane Library were searched up to June 7, 2018, without language restriction. The random-effects model was applied to summarize results. The adjusted odds ratios (ORs) and hazard ratios (HRs) were pooled separately. RESULTS: Eight observational studies (a total of 13 reports; 840,776 children and 7127 cases) were included. FA intake was mainly estimated from self-report of mothers or available databases. The results of overall analysis from 6 studies (9 reports) combined by OR and 2 studies (4 reports) presenting HR showed that the likelihoods of ASD in offspring whose mothers were prenatally exposed to FA did not vary significantly compared with those in offspring of mothers without such exposure (OR=0.91, 95% CI: 0.73-1.13 and HR=0.66, 95% CI: 0.38-1.17, respectively). Further analysis revealed that the primary outcome of the meta-analysis was stable regardless of the study design, and not unduly affected by any single report. Additionally, no publication bias was observed, and the findings of overall analysis were in agreement with those of subgroup analyses. CONCLUSIONS: This study does not provide support for the association between maternal FA intake during the prenatal period and the reduced risk of ASD in children. However, in view of the types and limited number of studies in the literature, more investigation is needed to confirm the findings of this meta-analysis.

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5. Guo X, Simas T, Lai MC, Lombardo MV, Chakrabarti B, Ruigrok ANV, Bullmore ET, Baron-Cohen S, Chen H, Suckling J. {{Enhancement of indirect functional connections with shortest path length in the adult autistic brain}}. {Hum Brain Mapp};2019 (Aug 29)

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi-metric) connectivity of the functional connectome associated with autism. Resting-state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi-metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi-metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer-distance edges in the majority between networks. However, no significant diagnosis-by-sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.

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6. Hamad AF, Alessi-Severini S, Mahmud SM, Brownell M, Kuo IF. {{Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study}}. {PLoS One};2019;14(8):e0221921.

BACKGROUND: Prenatal antibiotic exposure induces changes in infants’ gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD. METHODS: This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort. RESULTS: Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings’ cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant. CONCLUSIONS: Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.

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7. Hao Z, Wu Q, Li Z, Li Y, Li Q, Lai X, Liu H, Zhang M, Yang T, Chen J, Tang Y, Miao J, Xu H, Li T, Hu R. {{Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders}}. {Cell Res};2019 (Aug 28)

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8. Kalkbrenner AE, Meier SM, Madley-Dowd P, Ladd-Acosta C, Fallin MD, Parner E, Schendel D. {{Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring}}. {Autism Res};2019 (Aug 29)

Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991-2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism – no ADHD, 2,205 autism + ID, and 11,342 autism – no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13-1.22]) but attenuated in the maternal cluster (0.98 [0.88-1.09]) and sibling (0.86 [0.64-1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Smoking during pregnancy has many harmful impacts, which may include harming the baby’s developing brain. However, in a study of thousands of families in Denmark, it does not appear that smoking in pregnancy leads to autism or autism in combination with intellectual problems or attention deficits, once you account for the way smoking patterns and developmental disabilities run in families.

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9. Kinnaird E, Norton C, Pimblett C, Stewart C, Tchanturia K. {{Eating as an autistic adult: An exploratory qualitative study}}. {PLoS One};2019;14(8):e0221937.

BACKGROUND: Although eating difficulties are known to be common in children on the autism spectrum, there is a lack of research on whether these behaviours persist or change into adulthood. Emerging evidence suggests that autistic adults may experience higher levels of disordered eating than the general population, indicating the impact of autism on eating in this adult population warrants further exploration. METHOD: This study interviewed 12 autistic adults about their eating habits, with a focus on the continuing or changing presence of behaviours often seen in autistic children such as sensory sensitivity or a preference for routines. Interviews were transcribed and analysed using thematic analysis. RESULTS: Overall, participants suggested that autism did continue to impact their eating into adulthood, particularly in the areas of sensory sensitivity, medical difficulties, executive functioning difficulties, and rigidity, but that they had learned to adapt so that these issues no longer represented a problem. However, a minority of participants did feel that their autism had a negative effect on their eating, particularly those diagnosed with eating disorders. Additionally, eating behaviours associated with autism were identified as potentially contributing to having an unhealthy body weight. CONCLUSIONS: Certain traits associated with autism, such as cognitive rigidity and sensory sensitivity, could potentially continue to influence the eating behaviours of autistic adults. These traits are typically experienced as differences which can be adapted around and managed, rather than specific problems. However, these traits can potentially contribute to difficulties such as disordered eating and weight gain, and the implications of these should be explored by future research.

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10. Kinnear D, Rydzewska E, Dunn K, Hughes-McCormack LA, Melville C, Henderson A, Cooper SA. {{Relative influence of intellectual disabilities and autism on mental and general health in Scotland: a cross-sectional study of a whole country of 5.3 million children and adults}}. {BMJ Open};2019 (Aug 27);9(8):e029040.

OBJECTIVES: To determine the relative extent that autism and intellectual disabilities are independently associated with poor mental and general health, in children and adults. DESIGN: Cross-sectional study. For Scotland’s population, logistic regressions investigated odds of intellectual disabilities and autism predicting mental health conditions, and poor general health, adjusted for age and gender. PARTICIPANTS: 1 548 819 children/youth aged 0-24 years, and 3 746 584 adults aged more than 25 years, of whom 9396/1 548 819 children/youth had intellectual disabilities (0.6%), 25 063/1 548 819 children/youth had autism (1.6%); and 16 953/3 746 584 adults had intellectual disabilities (0.5%), 6649/3 746 584 adults had autism (0.2%). These figures are based on self-report. MAIN OUTCOME MEASURES: Self-reported general health status and mental health. RESULTS: In children/youth, intellectual disabilities (OR 7.04, 95% CI 6.30 to 7.87) and autism (OR 25.08, 95% CI 23.08 to 27.32) both independently predicted mental health conditions. In adults, intellectual disabilities (OR 3.50, 95% CI 3.20 to 3.84) and autism (OR 5.30, 95% CI 4.80 to 5.85) both independently predicted mental health conditions. In children/youth, intellectual disabilities (OR 18.34, 95% CI 17.17 to 19.58) and autism (OR 8.40, 95% CI 8.02 to 8.80) both independently predicted poor general health. In adults, intellectual disabilities (OR 7.54, 95% CI 7.02 to 8.10) and autism (OR 4.46, 95% CI 4.06 to 4.89) both independently predicted poor general health. CONCLUSIONS: Both intellectual disabilities and autism independently predict poor health, intellectual disabilities more so for general health and autism more so for mental health. Intellectual disabilities and autism are not uncommon, and due to their associated poor health, sufficient services/supports are needed. This is not just due to coexistence of these conditions or just to having intellectual disabilities, as the population with autism is independently associated with substantial health inequalities compared with the general population, across the entire life course.

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11. Manelis L, Meiri G, Ilan M, Flusser H, Michaelovski A, Faroy M, Kerub O, Dinstein I, Menashe I. {{Language regression is associated with faster early motor development in children with autism spectrum disorder}}. {Autism Res};2019 (Aug 30)

Language regression (LR) is a consistent and reproducible phenomenon that is reported by ~25% of parents who have children with autism spectrum disorder (ASD). However, there is controversy regarding the etiological and clinical significance of this phenomenon. Here, we examined data from a cohort of 218 children with ASD from the Negev Autism Center in Israel. We identified 36 children with ASD who were reported to exhibit clear LR by their parent on three independent occasions and compared them to 104 children whose parents did not report any concern of regression (NR). We compared a variety of key developmental characteristics across these two groups. We found that the age at which children with ASD in the LR group achieve key developmental milestones of crawling, walking, and use of first words is significantly younger than the age of children in the NR group, and comparable to the age of typically developing children. In contrast, no differences were observed in physical growth characteristics such as head circumference, weight, or height between the groups. Furthermore, almost all children with LR were born close to full term (>35 weeks) and none had a history of hypotonia. Notably, despite their apparently typical early development, children with LR were diagnosed with more severe symptoms of ASD than children with NR. These results strengthen the motivation to continue and study LR among children with ASD and suggest that early detection and intervention studies of ASD may benefit from stratifying children into LR and NR groups. Autism Res 2019, 1-12. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The presence of language regression (LR) among children with autism is still a matter of scientific debate. Here, we show that children with autism and reported LR start to crawl, talk, and walk at the same age as other typically developing children and significantly earlier than other children with autism. These findings, along with other medical differences between these groups, suggest that children who experienced LR comprise a distinct subgroup within the autism spectrum.

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12. Manicacci M, Bouteyre E, Despax J, Brejard V. {{Involvement of Emotional Intelligence in Resilience and Coping in Mothers of Autistic Children}}. {J Autism Dev Disord};2019 (Aug 28)

In a context described as a challenge in parenting (having an autistic child), we sought to highlight the emotional skills that mothers gain as a result of interacting with their child, and how they then use these skills. Mothers of autistic children (n = 136) and mothers of non-autistic children (n = 139) responded to emotional intelligence, resilience, and coping scales. Comparisons revealed smaller differences between groups than expected. Nevertheless, mothers of autistic children showed greater resilience abilities than mothers of non-autistic children. Moreover, we noted differences between both groups regarding their use of emotional skills. Emotional intelligence is a resource that deserves to be explored in terms of its clinical implications, especially among the parents of autistic children.

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13. Nijhof AD, Bird G. {{Self-processing in individuals with autism spectrum disorder}}. {Autism Res};2019 (Aug 30)

Research attempting to explain the social difficulties observed in autism spectrum disorder has focused predominantly on difficulties understanding others, but there are indications that self-referential processing is also atypical in autism. For example, infants who later get an autism diagnosis show a reduced response when hearing their own name. In addition, research suggests that the self-bias (the tendency to preferentially process information when self-relevant) is smaller or absent in autism. However, findings are mixed: researchers are yet to clarify exactly those aspects of self-processing which are atypical in autism and in what way they are atypical. To gain further insight into these issues, future studies should focus on whether and how different aspects of self-processing are related in both neurotypical and autistic individuals. Furthermore, the (a)typical development of different aspects of the self, as well as the impact of the self on different domains of cognitive processing, deserves further attention, requiring studies with participants in a wide age range. Finally, the use of neural measures of self-processing will be invaluable, given the recent hypothesis that autistic individuals may learn to compensate for difficulties by relying on neural pathways which differ from those utilised by neurotypical individuals. Autism Res 2019, 1-5. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Research has indicated that individuals with autism spectrum disorder show differences in the processing of self-relevant information. However, as yet, exactly how self-processing differs in autism remains unknown. To further our understanding of the self in autism, future studies should focus on the relationship between different aspects of self-processing, investigating brain activity as well as behaviour, across a wide range of ages.

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14. Ouyang Q, Kavanaugh BC, Joesch-Cohen L, Dubois B, Wu Q, Schmidt M, Baytas O, Pastore SF, Harripaul R, Mishra S, Hussain A, Kim KH, Holler-Managan YF, Ayub M, Mir A, Vincent JB, Liu JS, Morrow EM. {{GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates}}. {Hum Genet};2019 (Aug 30)

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature. GPT2 loss-of-function mutations were identified in four families, nine patients total, including: a homozygous mutation in one child [c.775T>C (p.C259R)]; compound heterozygous mutations in two siblings [c.812A>C (p.N271T)/c.1432_1433delGT (p.V478Rfs*73)]; a novel homozygous, putative splicing mutation [c.1035C>T (p.G345=)]; and finally, a recurrent mutation, previously identified in a distinct family [c.1210C>T (p.R404*)]. All patients were diagnosed with IDD. A majority of patients had remarkably small stature throughout development, many < 1st percentile for height and weight. Given the potential biological function of GPT2 in cellular growth, this phenotype is strongly suggestive of a newly identified clinical susceptibility. Further, homozygous GPT2 mutations manifested in at least 2 of 176 families with IDD (approximately 1.1%) in a Pakistani cohort, thereby representing a relatively common cause of recessive IDD in this population, with recurrence of the p.R404* mutation in this population. Based on variants in the ExAC database, we estimated that approximately 1 in 248 individuals are carriers of moderately or severely deleterious variants in GPT2. Lien vers le texte intégral (Open Access ou abonnement)

15. Pecora LA, Hancock GI, Mesibov GB, Stokes MA. {{Characterising the Sexuality and Sexual Experiences of Autistic Females}}. {J Autism Dev Disord};2019 (Aug 28)

Current understandings of the sexuality of autistic females have been predominantly drawn from qualitative studies. This study aimed to quantitatively examine the sexual functioning of autistic females (N = 135), by comparing these to the sexual interest, behaviours, and experiences to 96 autistic males and 161 typically developing females. Autistic females reported less sexual interest, yet more experiences than autistic males. More autistic females also reported engaging in sexual behaviours that were later regretted, unwanted, or receiving unwanted sexual advances. Differences between autistic and typically developing females were significant. Results indicate that due to a mismatch between less sexual interest, yet increased sexual behaviours, autistic women are at greater risk of negative sexual experiences including victimisation and abuse than autistic men.

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16. Shic F, Wang Q, Macari SL, Chawarska K. {{The role of limited salience of speech in selective attention to faces in toddlers with autism spectrum disorders}}. {J Child Psychol Psychiatry};2019 (Aug 30)

BACKGROUND: Impaired attention to faces of interactive partners is a marker for autism spectrum disorder (ASD) in early childhood. However, it is unclear whether children with ASD avoid faces or find them less salient and whether the phenomenon is linked with the presence of eye contact or speech. METHODS: We investigated the impacts of speech (SP) and direct gaze (DG) on attention to faces in 22-month-old toddlers with ASD (n = 50) and typically developing controls (TD, n = 47) using the Selective Social Attention 2.0 (SSA 2.0) task. The task consisted of four conditions where the presence (+) and absence (-) of DG and SP were systematically manipulated. The severity of autism symptoms, and verbal and nonverbal skills were characterized concurrently with eye tracking at 22.4 (SD = 3.2) months and prospectively at 39.8 (SD = 4.3) months. RESULTS: Toddlers with ASD looked less than TD toddlers at face and mouth regions only when the actress was speaking (direct gaze absence with speech, DG-SP+: d = 0.99, p < .001 for face, d = 0.98, p < .001 for mouth regions; direct gaze present with speech, DG+SP+, d = 1.47, p < .001 for face, d = 1.01, p < .001 for mouth regions). Toddlers with ASD looked less at the eye region only when both gaze and speech cues were present (d = 0.46, p = .03). Salience of the combined DG and SP cues was associated concurrently and prospectively with the severity of autism symptoms, and the association remained significant after controlling for verbal and nonverbal levels. CONCLUSIONS: The study links poor attention to faces with limited salience of audiovisual speech and provides no support for the face avoidance hypothesis in the early stages of ASD. These results are consequential for research on early discriminant and predictive biomarkers as well as identification of novel treatment targets. Lien vers le texte intégral (Open Access ou abonnement)

17. Tandon R, Pradhan S. {{Autistic features in Unverricht-Lundborg disease}}. {Epilepsy Behav Rep};2019;12:100323.

We studied three patients with Unverricht-Lundborg disease for autistic features along with other clinical features associated with progressive myoclonus epilepsy. We diagnosed this disease based on noise and touch sensitive myoclonus, ataxia, cognitive decline, typical EEG features, normal MRI of the brain and applied Children’s Global Assessment Scale and Childhood Autism Spectrum Test to these children. The CGAS score was 35 in two and 50 in one of them. CAST scores were above 15 in all of three of them. Autistic features may be an important clinical feature of this disease. History and physical examination for myoclonus should probably be taken in autistic children.

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18. Topuz C, Ulke-Kurkcuoglu B. {{Increasing Verbal Interaction in Children with Autism Spectrum Disorders Using Audio Script Procedure}}. {J Autism Dev Disord};2019 (Aug 29)

This study aimed at investigating the effectiveness of audio script and script-fading procedure in teaching initiation to children with ASD. Three children with ASD and a parent of each child participated in the study. A nonconcurrent multiple baseline design across children was used. The findings showed that the initiation emitted by the children increased during audio script and script-fading procedure. Children also generalized initiation across different conditions and maintained the acquired skills. Finally, the social validity findings showed that the opinions of the parents regarding the procedure were overall positive. Results were discussed in terms of recommendations for practitioners and future research.

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19. Viswanathan SA, Russell PSS. {{Predictive components in the structure of an intensive, parent mediated, early intervention for children with autism spectrum disorders in India}}. {J Family Med Prim Care};2019 (Jul);8(7):2218-2222.

Introduction: The predictive factors of parent mediated, Early Intervention (EI) for children with Autism Spectrum Disorders (ASD) have not been studied in India; we document the structural therapeutic factors, which predict the EI outcome. Methods: Data of 77 children with an ICD 10 diagnosis of Pervasive Developmental Disorder (ASD in DSM 5), and completed a 12-week EI with proven effectiveness was collected from the database of a teaching hospital. We studied the structural therapeutic factors associated with EI outcome, as measured by Psycho-Educational Profile-Revised (PEP-R), while controlling the confounders with multiple linear regression analyses. Results: The Fine-motor skills improved in residential patients (t = 2.54, P = 0.02; 15 units). As the duration of intervention decreased at home per day, there was a significant decrease in Gross-motor skills (t = -2.67, P = 0.02; -15 units). With increase in duration of intervention in hospital per day, there was a significant increase (t = 2.86, P = 0.01; 30 units) in the Eye-hand integration. Cognitive-verbal skills acquisition decreased (t = -2.90, P = 0.01; 33 units) as the duration of intervention decreased at hospital. The use of medication did not predict any of the outcome factors. Conclusion: The above mentioned predictive factors should be monitored and titrated in the family context when children with ASD undergo parent mediated, EI programme. It is important to that the multidisciplinary family medicine teams reinforce these parents, who are the main column of support in primary-care settings for children with neuro-developmental disabilities in India.

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20. Wang Q, Wall CA, Barney EC, Bradshaw JL, Macari SL, Chawarska K, Shic F. {{Promoting Social Attention in 3-Year-Olds with ASD through Gaze-Contingent Eye Tracking}}. {Autism Res};2019 (Aug 30)

Young children with autism spectrum disorder (ASD) look less toward faces compared to their non-ASD peers, limiting access to social learning. Currently, no technologies directly target these core social attention difficulties. This study examines the feasibility of automated gaze modification training for improving attention to faces in 3-year-olds with ASD. Using free-viewing data from typically developing (TD) controls (n = 41), we implemented gaze-contingent adaptive cueing to redirect children with ASD toward normative looking patterns during viewing of videos of an actress. Children with ASD were randomly assigned to either (a) an adaptive Cue condition (Cue, n = 16) or (b) a No-Cue condition (No-Cue, n = 19). Performance was examined at baseline, during training, and post-training, and contrasted with TD controls (n = 23). Proportion of time looking at the screen (%Screen) and at actresses’ faces (%Face) was analyzed. At Pre-Training, Cue and No-Cue groups did not differ in %Face (P > 0.1). At Post-Training, the Cue group had higher %Face than the No-Cue group (P = 0.015). In the No-Cue group %Face decreased Pre- to Post-Training; no decline was observed in the Cue group. These results suggest gaze-contingent training effectively mitigated decreases of attention toward the face of onscreen social characters in ASD. Additionally, larger training effects were observed in children with lower nonverbal ability, suggesting a gaze-contingent approach may be particularly relevant for children with greater cognitive impairment. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions. Autism Res 2019, 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we leverage a new technology that combines eye tracking and automatic computer programs to help very young children with ASD look at social information in a more prototypical way. In a randomized controlled trial, we show that the use of this technology prevents the diminishing attention toward social information normally seen in children with ASD over the course of a single experimental session. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions.

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21. Zhang Y, Xiang Z, Jia Y, He X, Wang L, Cui W. {{The Notch signaling pathway inhibitor Dapt alleviates autism-like behavior, autophagy and dendritic spine density abnormalities in a valproic acid-induced animal model of autism}}. {Prog Neuropsychopharmacol Biol Psychiatry};2019 (Aug 30);94:109644.

Autism spectrum disorders (ASDs) comprise a number of heterogeneous neurodevelopmental diseases. Recent studies suggest that the abnormal transmission of neural signaling pathways is associated with the pathogenesis of autism. The aim of this study was to identify a link between the Notch signaling pathway and the pathogenesis of autism. In this study, we demonstrated that prenatal exposure to valproic acid (VPA) resulted in autistic-like behaviors in offspring rats and that the expression of the Notch signaling pathway-related molecules Notch1, Jagged1, Notch intracellular domain (NICD) and Hes1 increased in the prefrontal cortex (PFC), hippocampus (HC) and cerebellum (CB) of VPA rats compared to those of controls. However, inhibiting the Notch pathway with (3,5-Difluorophenacetyl)-L-alanyl-S-phenylglycine-2-butyl Ester (Dapt) reduced the overexpression of Notch pathway-related molecules in offspring rats. Notably, Dapt improved autistic-like behaviors in a VPA-exposed rat model of autism. Furthermore, we investigated whether Dapt improved autistic-like behavior in a VPA rat model by regulating autophagy and affecting the morphology of dendritic spines. We found that the expression of the autophagy-related proteins Beclin 1, LC3B and phospho-p62 in the PFC, HC and CB of VPA model rats increased after Notch signal activation and was inhibited by Dapt compared to those of controls. Moreover, postsynaptic density-95 (PSD-95) protein expression also increased significantly compared to that of VPA model rats. The density of dendritic spines decreased in the PFC of VPA rats treated with Dapt compared to that of VPA model rats. Our present results suggest that VPA induces an abnormal activation of the Notch signaling pathway. The inhibition of excessive Notch signaling activation by Dapt can alleviate autistic-like behaviors in VPA rats. Our working model suggests that the Notch signaling pathway participates in the pathogenesis of autism by regulating autophagy and affecting dendritic spine growth. The results of this study may help to elucidate the mechanism underlying autism and provide a potential strategy for treating autism.

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22. Zuo C, Wang D, Tao F, Wang Y. {{Changes in the development of subcortical structures in autism spectrum disorder}}. {Neuroreport};2019 (Aug 27)

Many studies have reported abnormalities in the volume of subcortical structures in individuals with autism spectrum disorder (ASD), and many of these change with age. However, most studies that have investigated subcortical structures were cross-sectional and did not accurately segment the subcortical structures. In this study, we used volBrain, an automatic and reliable quantitative analysis tool, and a longitudinal design to examine developmental changes in the volume of subcortical structures in ASD, and quantified the relation between subcortical volume development and clinical correlates. Nineteen individuals with ASD (16 males; age: 12.53 +/- 2.34 years at baseline; interval: 2.33 years) and 14 typically developing controls (TDC; 12 males; age: 13.50 +/- 1.77 years at baseline; interval: 2.31 years) underwent T1-weighted MRI at two time points. Bilaterally, hippocampus volume increased from baseline to follow-up in both ASD and TDC, with no difference between groups. Left caudate and right thalamus volume decreased in ASD, but did not change in TDC. The decreases in left caudate and right thalamus volume were related to ASD social score. Right amygdala volume was larger in ASD than in TDC at baseline but not at follow-up. These results confirm previous cross-sectional findings regarding the development of subcortical structures in ASD. The association between developmental changes in left caudate and right thalamus volume and ASD social score offers an explanation for the social deficits in ASD. Results also captured the different abnormality of amygdala volume between childhood and late adolescence.

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