1. Ayano G, Maravilla JC, Alati R. {{Risk of autistic spectrum disorder in offspring with parental mood disorders: A systematic review and meta-analysis}}. {Journal of affective disorders}. 2019; 248: 185-97.
BACKGROUND: The association between mood disorders in parents and autism spectrum disorder (ASD) risk in offspring has been investigated in several studies, but the evidence is inconclusive. This systematic review and meta-analysis will explore whether an association exists between parental mood disorders and ASD risk in offspring. METHODS: A literature search was performed using the electronic databases PubMed, EMBASE, PsycINFO, and Scopus. We also reviewed reference lists from retrieved articles. Meta-analysis was conducted, and combined effect values and their 95% confidence intervals were calculated. Study-specific risk ratios (RRs) were pooled using a random effect model. The risk of publication bias was assessed by funnel plot and Egger’s regression asymmetry test. RESULTS: Nine observational studies (two cohort and seven case-control studies) were included for analysis. Our meta-analysis found a greater risk of ASD in children exposed to parental affective, depressive, and bipolar disorders [(RRs 1.65 (95%CI 1.45-1.88); 1.37 (95%CI 1.04-1.81) and 1.87; 95%CI 1.69-2.07) respectively]. We also found increased ASD risk in children of mothers who experienced affective and depressive disorders [(RRs 1.67 (95%CI 1.34-2.09) and 1.62 (95%CI 1.32-1.99) respectively]. We found no increased risk of ASD in children exposed to paternal affective and depressive disorders. Subgroup and sensitivity analysis confirmed the robustness of our main analysis. CONCLUSION: The evidence from the present study suggests parental affective, depressive and bipolar, as well as maternal affective and depressive disorders increased the risk of ASD in offspring. Exposure to affective and depressive disorders in fathers only was not linked with ASD risk in children.
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2. Barone R, Spampinato C, Pino C, Palermo F, Scuderi A, Zavattieri A, Gulisano M, Giordano D, Rizzo R. {{Online comprehension across different semantic categories in preschool children with autism spectrum disorder}}. {PLoS One}. 2019; 14(2): e0211802.
BACKGROUND: Word comprehension across semantic categories is a key area of language development. Using online automated eye-tracking technology to reduce response demands during a word comprehension test may be advantageous in children with autism spectrum disorder (ASD). OBJECTIVES: To measure online accuracy of word recognition across eleven semantic categories in preschool children with ASD and in typically developing (TD) children matched for gender and developmental age. METHODS: Using eye-tracker methodology we measured the relative number of fixations on a target image as compared to a foil of the same category shown simultaneously on screen. This online accuracy measure was considered a measure of word understanding. We tested the relationship between online accuracy and offline word recognition and the effects of clinical variables on online accuracy. Twenty-four children with ASD and 21 TD control children underwent the eye-tracking task. RESULTS: On average, children with ASD were significantly less accurate at fixating on the target image than the TD children. After multiple comparison correction, no significant differences were found across the eleven semantic categories of the experiment between preschool children with ASD and younger TD children matched for developmental age. The ASD group showed higher intragroup variability consistent with greater variation in vocabulary growth rates. Direct effects of non-verbal cognitive levels, vocabulary levels and gesture productions on online word recognition in both groups support a dimensional view of language abilities in ASD. CONCLUSIONS: Online measures of word comprehension across different semantic categories show higher interindividual variability in children with ASD and may be useful for objectively monitor gains on targeted language interventions.
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3. Faber S, Fahrenholz T, Wolle MM, Kern JC, 2nd, Pamuku M, Miller L, Jamrom J, Skip Kingston HM. {{Chronic exposure to xenobiotic pollution leads to significantly higher total glutathione and lower reduced to oxidized glutathione ratio in red blood cells of children with autism}}. {Free radical biology & medicine}. 2019.
Analyses of reduced glutathione (GSH), oxidized glutathione (GSSG), and total glutathione (tGSH) in red blood cell samples from 30 children diagnosed with autism and 30 age, gender, and socioeconomic status matched controls were undertaken. The children’s ages ranged from 2-9. Samples were obtained from subjects residing in Western Pennsylvania, an area of the United States greatly affected by high levels of mercury deposition and airborne PM 2.5 particulates. Liquid chromatography – mass spectrometry was utilized by following EPA Method 6800 for sample analyses. The children with autism had a significantly lower mean red blood cell (RBC) reduced to oxidized glutathione ratio (GSH/GSSG) compared to the control children (p=0.025). In addition, compared to the controls, the children with autism had significantly higher RBC tGSH values (p=0.0076) and GSH values (p=0.022). These results suggest that exposure to toxic elements may prompt compensatory increases in production of GSH in children with autism in environments higher in toxins. The compensation did not fully correct the anti-oxidant properties of exposure to xenobiotics as demonstrated by the significantly lower GSH/GSSG in children with autism compared to controls. Out of a set of glutathione biomarkers, GSH/GSSG may best determine the degree of compensation for oxidative stress in children with autism.
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4. Gong T, Lundholm C, Rejno G, Bolte S, Larsson H, D’Onofrio BM, Lichtenstein P, Almqvist C. {{Parental asthma and risk of autism spectrum disorder in offspring: a population and family based case-control study}}. {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}. 2019.
BACKGROUND: Associations between parental asthma and prenatal exposure to asthma medications with offspring autism spectrum disorder (ASD) have been reported. However, the associations might be confounded by unmeasured (genetic and shared environmental) familial factors. OBJECTIVE: We investigated the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to beta2-agonists, other asthma medications and offspring ASD using cases and controls selected from the population as well as biological relatives with different degrees of relatedness. METHODS: We included all children (N=1,579,263) born in Sweden 1992-2007. A nested case-control design was used to compare 22,894 ASD cases identified from the National Patient Register to (i) 228,940 age-, county- and sex-matched controls randomly selected from the population, (ii) their eligible full-siblings (n=1,267), (iii) half-siblings (n=1,323), (iv) full-cousins (n=11,477), and (v) half-cousins (n=3,337). Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for ASD in children differentially exposed to parental asthma or prenatal asthma medications. RESULTS: Maternal asthma was associated with increased risk of offspring ASD (OR 1.43, 95% CI 1.38-1.49); there was a weaker association for paternal asthma (OR 1.17, 95% CI 1.11-1.23). The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings (OR 1.20, 95% CI 0.80-1.81), full-cousins (OR 1.28, 95% CI 1.16-1.41), and half-cousins (OR 1.30, 95% CI 1.10-1.54), albeit with wider confidence intervals. Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD. CONCLUSIONS AND CLINICAL RELEVANCE: In this large observational study, parental asthma was associated with slightly elevated risk of ASD in offspring. More specifically, the increased risk by maternal asthma did not seem to be confounded by familial factors. There was no evidence of an association between asthma medications during pregnancy and offspring ASD. This article is protected by copyright. All rights reserved.
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5. Guerini FR, Bolognesi E, Sotgiu S, Carta A, Clerici C, Chiappedi M, Ghezzo A, Zanette M, Martina Mensi M, Paola Canevini M, Zanzottera M, Agliardi C, Saul Costa A, Balottin U, Clerici M. {{HLA-G allelic distribution in Sardinian children with Autism Spectrum Disorders: a replication study}}. {Brain, behavior, and immunity}. 2019.
Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present. Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population. One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers, and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele, associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both ASD groups compared to controls (pc=1×10(-3); OR:3.5, 95%CI: 1.8-6.8). However, given the lack of data on HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect. These data confirm an association of HLA-G locus with ASD development, particularly with those alleles linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations.
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6. Hamad AF, Alessi-Severini S, Mahmud SM, Brownell M, Kuo IF. {{Annual trends in prevalence and incidence of autism spectrum disorders in Manitoba preschoolers and toddlers: 2004-2015}}. {Canadian journal of public health = Revue canadienne de sante publique}. 2019.
OBJECTIVES: Autism spectrum disorders (ASD) are among the leading causes of disabilities in children. We examined the annual prevalence and incidence rate of ASD between 2004 and 2015 in children aged 1 to 5 years residing in Manitoba. METHODS: A population-based study was conducted using the Manitoba Population Research Data Repository. The study included children aged 1 to 5 years residing in Manitoba between 2004 and 2015. Standard identification algorithm was used to identify ASD cases from hospital abstracts and medical claims. Annual prevalence and incidence rates were calculated for the overall population and then stratified according to sex, region, and socio-economic status (SES). Multivariable negative binomial regression models, adjusted for sex, region, and SES, were used to examine changes in prevalence and incidence over study years. RESULTS: Among children aged 1 to 5 years, 1685 ASD cases were diagnosed between 2004 and 2015. The crude ASD prevalence increased from 0.46% in 2004 to 0.97% in 2015 (p = 0.002). The crude incidence rate increased from 0.16% in 2004 to 0.39% in 2015 (p = 0.002). The increase in ASD prevalence and incidence was observed in all subgroups based on sex, region, and SES. The adjusted negative binomial model showed an annual relative risk increase, since 2004, for both prevalence and incidence of 1.69 (95% CI 1.56-1.83) and 1.84 (95% CI 1.62-2.09), respectively. CONCLUSION: During the period from 2004 to 2015, both prevalence and incidence rates of diagnosed ASD in preschoolers and toddlers residing in Manitoba increased significantly.
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7. Levy SE, Rescorla LA, Chittams JL, Kral TJ, Moody EJ, Pandey J, Pinto-Martin JA, Pomykacz AT, Ramirez A, Reyes N, Rosenberg CR, Schieve L, Thompson A, Young L, Zhang J, Wiggins L. {{ASD Screening with the Child Behavior Checklist/1.5-5 in the Study to Explore Early Development}}. {J Autism Dev Disord}. 2019.
We analyzed CBCL/1(1/2)-5 Pervasive Developmental Problems (DSM-PDP) scores in 3- to 5-year-olds from the Study to Explore Early Development (SEED), a multi-site case control study, with the objective to discriminate children with ASD (N = 656) from children with Developmental Delay (DD) (N = 646), children with Developmental Delay (DD) plus ASD features (DD-AF) (N = 284), and population controls (POP) (N = 827). ASD diagnosis was confirmed with the ADOS and ADI-R. With a cut-point of T >/= 65, sensitivity was 80% for ASD, with specificity varying across groups: POP (0.93), DD-noAF (0.85), and DD-AF (0.50). One-way ANOVA yielded a large group effect (eta(2) = 0.50). Our results support the CBCL/1(1/2)-5’s as a time-efficient ASD screener for identifying preschoolers needing further evaluation.
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8. Lord C. {{Taking Sleep Difficulties Seriously in Children With Neurodevelopmental Disorders and ASD}}. {Pediatrics}. 2019.
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9. Randell E, McNamara R, Delport S, Busse M, Hastings RP, Gillespie D, Williams-Thomas R, Brookes-Howell L, Romeo R, Boadu J, Ahuja AS, McKigney AM, Knapp M, Smith K, Thornton J, Warren G. {{Sensory integration therapy versus usual care for sensory processing difficulties in autism spectrum disorder in children: study protocol for a pragmatic randomised controlled trial}}. {Trials}. 2019; 20(1): 113.
BACKGROUND: Autism spectrum disorder (ASD) is a common lifelong condition affecting 1 in 100 people. ASD affects how a person relates to others and the world around them. Difficulty responding to sensory information (noise, touch, movement, taste, sight) is common, and might include feeling overwhelmed or distressed by loud or constant low-level noise (e.g. in the classroom). Affected children may also show little or no response to these sensory cues. These ‘sensory processing difficulties’ are associated with behaviour and socialisation problems, and affect education, relationships, and participation in daily life. Sensory integration therapy (SIT) is a face-to-face therapy or treatment provided by trained occupational therapists who use play-based sensory-motor activities and the just-right challenge to influence the way the child responds to sensation, reducing distress, and improving motor skills, adaptive responses, concentration, and interaction with others. With limited research into SIT, this protocol describes in detail how the intervention will be defined and evaluated. METHODS: This is a two-arm pragmatic individually 1:1 randomised controlled trial with an internal pilot of SIT versus usual care for primary school aged children (aged 4 to 11 years) with ASD and sensory processing difficulties; 216 children will be recruited from multiple sources. Therapy will be delivered in clinics meeting full fidelity criteria for manualised SIT over 26 weeks (face-to-face sessions: two per week for 10 weeks, two per month for 2 months; telephone call: one per month for 2 months). Follow-up assessments will be completed at 6 and 12 months post-randomisation. Prior to recruitment, therapists will be invited to participate in focus groups/interviews to explore what is delivered as usual care in trial regions; carers will be invited to complete an online survey to map out their experience of services. Following recruitment, carers will be given diaries to record their contact with services. Following intervention, carer and therapist interviews will be completed. DISCUSSION: Results of this trial will provide high-quality evidence on the clinical and cost effectiveness of SIT aimed at improving behavioural, functional, social, educational, and well-being outcomes for children and well-being outcomes for carers and families. TRIAL REGISTRATION: ISRCTN14716440 . Registered on 8 November 2016.
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10. Reynolds AM, Soke GN, Sabourin KR, Hepburn S, Katz T, Wiggins LD, Schieve LA, Levy SE. {{Sleep Problems in 2- to 5-Year-Olds With Autism Spectrum Disorder and Other Developmental Delays}}. {Pediatrics}. 2019.
: media-1vid110.1542/5984243260001PEDS-VA_2018-0492Video Abstract BACKGROUND: Sleep problems can impact daytime behavior, quality of life, and overall health. We compared sleep habits in young children with autism spectrum disorder (ASD) and other developmental delays and disorders and in children from the general population (POP). METHODS: We included 2- to 5-year-old children whose parent completed all items on the Children’s Sleep Habits Questionnaire (CSHQ) in a multisite case-control study: 522 children with ASD; 228 children with other developmental delays and disorders with autism spectrum disorder characteristics (DD w/ASD); 534 children with other developmental delays and disorders without autism spectrum disorder characteristics (DD w/o ASD); and 703 POP. Multivariable analysis of variance compared CSHQ mean total score (TS) and subscale scores between groups. Logistic regression analysis examined group differences by using TS cutoffs of 41 and 48. Analyses were adjusted for covariates. RESULTS: Mean CSHQ TS for children in each group: ASD (48.5); DD w/ASD (50.4); DD w/o ASD (44.4); and POP (43.3). Differences between children with ASD and both children with DD w/o ASD and POP were statistically significant. Using a TS cutoff of 48, the proportion of children with sleep problems was significantly higher in children in the ASD group versus DD w/o ASD and POP groups (adjusted odds ratios [95% confidence intervals]: 2.12 [1.57 to 2.87] and 2.37 [1.75 to 3.22], respectively). CONCLUSIONS: Sleep problems are more than twice as common in young children with ASD and DD w/ASD. Screening for sleep problems is important in young children to facilitate provision of appropriate interventions.
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11. Shanok NA, Jones NA, Lucas NN. {{The Nature of Facial Emotion Recognition Impairments in Children on the Autism Spectrum}}. {Child Psychiatry Hum Dev}. 2019.
This study examined socio-emotional skills, utilizing a facial emotion recognition (FER) task featuring unfamiliar and familiar faces, in children with autism spectrum disorders (ASD) compared to typically developing (TD) children. Results showed that the TD children were more proficient on the FER overall whereas ASD children recognized familiar expressions more precisely than unfamiliar ones. Further, ASD children did not differ from TD children in recognizing happy expressions but ASD children were less skilled with recognizing negative expressions. Findings suggest that ASD children possess more adept FER abilities than previously thought especially for important social others. Ultimately, a task featuring an array of positive and negative familiar and unfamiliar expressions may provide a more comprehensive assessment of socio-emotional abilities in ASD children.
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12. Tillmann J, San Jose Caceres A, Chatham CH, Crawley D, Holt R, Oakley B, Banaschewski T, Baron-Cohen S, Bolte S, Buitelaar JK, Durston S, Ham L, Loth E, Simonoff E, Spooren W, Murphy DG, Charman T. {{Investigating the factors underlying adaptive functioning in autism in the EU-AIMS Longitudinal European Autism Project}}. {Autism Res}. 2019.
Individuals with autism spectrum disorder (ASD) exhibit significant impairments in adaptive functioning that impact on their ability to meet the demands of everyday life. A recurrent finding is that there is a pronounced discrepancy between level of cognitive ability and adaptive functioning, and this is particularly prominent among higher-ability individuals. However, the key clinical and demographic associations of these discrepancies remain unclear. This study included a sample of 417 children, adolescents, and adults with ASD as part of the EU-AIMS LEAP cohort. We examined how age, sex, IQ, levels of ASD symptom and autistic trait severity and psychiatric symptomatology are associated with adaptive functioning as measured by the Vineland Adaptive Behavior Scales-Second Edition and IQ-adaptive functioning discrepancies. Older age, lower IQ and higher social-communication symptoms were associated with lower adaptive functioning. Results also demonstrate that older age, higher IQ and higher social-communication symptoms are associated with greater IQ-adaptive functioning discrepancy scores. By contrast, sensory ASD symptoms, repetitive and restricted behaviors, as well as symptoms of attention deficit/hyperactivity disorder (ADHD), anxiety and depression, were not associated with adaptive functioning or IQ-adaptive functioning discrepancy scores. These findings suggest that it is the core social communication problems that define ASD that contribute to adaptive function impairments that people with ASD experience. They show for the first time that sensory symptoms, repetitive behavior and associated psychiatric symptoms do not independently contribute to adaptive function impairments. Individuals with ASD require supportive interventions across the lifespan that take account of social-communicative ASD symptom severity. Autism Res 2019, 00: 1-13. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: This study investigated key clinical and demographic associations of adaptive functioning impairments in individuals with autism. We found that older age, lower IQ and more severe social-communicative symptoms, but not sensory or repetitive symptoms or co-occurring psychiatric symptoms, are associated with lower adaptive functioning and greater ability-adaptive function discrepancies. This suggests that interventions targeting adaptive skills acquisition should be flexible in their timing and intensity across developmental periods, levels of cognitive ability and take account of social-communicative ASD symptom severity.
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13. Togo S, Itahashi T, Hashimoto R, Cai C, Kanai C, Kato N, Imamizu H. {{Fourth finger dependence of high-functioning autism spectrum disorder in multi-digit force coordination}}. {Sci Rep}. 2019; 9(1): 1737.
A number of studies have reported that the digit ratio 2D:4D (length of the second finger divided by length of the fourth finger) is smaller (longer fourth digit) in autism spectrum disorder (ASD) than in typically developed (TD) controls. Because form and function are closely related in biological systems, we hypothesized that the 4D dominance occurs in not only finger morphology but also physical performance in ASD. Individuals with ASD and TD controls participated in a multi-digit force-producing task. Individuals with ASD showed a significant 4D dependence compared to TD controls in the task. We found a significant correlation between 4D dependence and scores of the standard diagnostic instrument across individuals with ASD. Our analysis of functional connectivity in resting-state functional MRI suggests that connectivity between the visual cortex and the cerebellum contributes to the 4D dependence. Collectively, these results extend the 2D:4D ratio beyond being a morphological marker to being involved in motor functions in the form of 4D dependence in a multi-digit force task.
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14. Wadge H, Brewer R, Bird G, Toni I, Stolk A. {{Communicative misalignment in Autism Spectrum Disorder}}. {Cortex}. 2019; 115: 15-26.
Communication deficits are a defining feature of Autism Spectrum Disorder (ASD), manifest during social interactions. Previous studies investigating communicative deficits have largely focused on the perceptual biases, social motivation, cognitive flexibility, or mentalizing abilities of isolated individuals. By embedding autistic individuals in live non-verbal interactions, we characterized a novel cause for their communication deficits. Adults with ASD matched neurotypical individuals in their ability and propensity to generate and modify intelligible behaviors for a communicative partner. However, they struggled to align the meaning of those behaviors with their partner when meaning required referencing their recent communicative history. This communicative misalignment explains why autistic individuals are vulnerable in everyday interactions, which entail fleeting ambiguities, but succeed in social cognition tests involving stereotyped contextual cues. These findings illustrate the cognitive and clinical importance of considering social interaction as a communicative alignment challenge, and how ineffective human communication is without this key interactional ingredient.
