1. Au-Yeung SK, Kaakinen JK, Liversedge SP, Benson V. {{Processing of Written Irony in Autism Spectrum Disorder: An Eye-Movement Study}}. {Autism Res};2015 (May 11)
Previous research has suggested that individuals with Autism Spectrum Disorders (ASD) have difficulties understanding others communicative intent and with using contextual information to correctly interpret irony. We recorded the eye movements of typically developing (TD) adults ASD adults when they read statements that could either be interpreted as ironic or non-ironic depending on the context of the passage. Participants with ASD performed as well as TD controls in their comprehension accuracy for speaker’s statements in both ironic and non-ironic conditions. Eye movement data showed that for both participant groups, total reading times were longer for the critical region containing the speaker’s statement and a subsequent sentence restating the context in the ironic condition compared to the non-ironic condition. The results suggest that more effortful processing is required in both ASD and TD participants for ironic compared with literal non-ironic statements, and that individuals with ASD were able to use contextual information to infer a non-literal interpretation of ironic text. Individuals with ASD, however, spent more time overall than TD controls rereading the passages, to a similar degree across both ironic and non-ironic conditions, suggesting that they either take longer to construct a coherent discourse representation of the text, or that they take longer to make the decision that their representation of the text is reasonable based on their knowledge of the world. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Demopoulos C, Lewine JD. {{Audiometric Profiles in Autism Spectrum Disorders: Does Subclinical Hearing Loss Impact Communication?}}. {Autism Res};2015 (May 11)
Rates of hearing impairment in individuals with Autism Spectrum Disorders (ASD) are higher than those reported in the general population. Although ASD is not caused by hearing impairment, it may exacerbate symptomatology. Participants with ASD (N = 60) and typically developing peers (N = 16) aged 5-18 years underwent a comprehensive audiological screening (pure tone audiometry, uncomfortable loudness level, tympanometry, acoustic reflexes, distortion product otoacoustic emissions, and auditory brainstem response) and assessment of communication abilities (expressive/receptive language, articulation, phonological awareness, and vocal affect recognition). Incidence of abnormal findings on at least one measure of audiological functioning was higher for the ASD group (55%) than controls (14.9%) or the general population estimate (6%). The presence of sound sensitivity was also considerably higher for the ASD group (37%) compared with controls (0%) or general population estimates (8-15%). When participants with ASD were dichotomized into groups with and without evidence of clinical audiological abnormality, no significant differences were identified on measures of communication; however, results of correlational analyses indicated that variability in hearing thresholds at middle range frequencies (2000 Hz) was significantly related to performance on all measures of speech articulation and language after correction for multiple comparisons (r = -0.48 to r = -0.53, P < 0.0045). These findings suggest that dichotomized classification of clinical audiology may not be sufficient to understand the role of subclinical hearing loss in ASD symptomatology and that treatment studies for mild/subclinical hearing loss in this population may be worthwhile. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Duan G, Chen J, Zhang W, Yu B, Jin Y, Wang Y, Yao M. {{Physical maltreatment of children with autism in Henan province in China: A cross-sectional study}}. {Child Abuse Negl};2015 (May 6)
The aim of this study was to investigate the frequency of child physical maltreatment (CPM) in children with autism aged 2-5 years in Henan province (China), and to explore the risk factors for severe CPM in these children. This cross-sectional study was performed at the Psychology Clinic of the Third Affiliated Hospital of Zhengzhou University between September 2012 and September 2013 with 180 parents of children with autism. Children and parents had no history of any cognitive therapy. The childhood autism rating scale (CARS) was used to evaluate the severity of autism in children. Data on parental CPM during the past 3 months were collected from parental self-reporting. Logistic regression was used to investigate the risk factors of severe CPM. CPM was self-reported by 88% of the parents of children with autism. One hundred and fifty four of these cases were in the minor CPM group (86%) and 64 in the severe CPM group (36%). Most cases of severe CPM were unlikely to have caused injury. Univariate analyses showed that child’s age (p=.018), age started to speak (p=.043) and CARS score (p=.048) were associated with severe CPM. Child’s age (p=.011) and CARS score (p=.041) were independently associated with severe CPM. The risk of severe CPM increased with age and CARS score. Our findings showed that CPM is widespread in families of children with autism in Central China and more knowledge should be provided to parents of children with autism, particularly in cases of severe autism (those with high CARS scores).
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4. Gotham K, Marvin AR, Taylor JL, Warren Z, Anderson CM, Law PA, Law JK, Lipkin PH. {{Characterizing the daily life, needs, and priorities of adults with autism spectrum disorder from Interactive Autism Network data}}. {Autism};2015 (May 11)
Using online survey data from a large sample of adults with autism spectrum disorder and legal guardians, we first report outcomes across a variety of contexts for participants with a wide range of functioning, and second, summarize these stakeholders’ priorities for future research. The sample included n = 255 self-reporting adults with autism spectrum disorder aged 18-71 years (M = 38.5 years, standard deviation = 13.1 years) and n = 143 adults with autism spectrum disorder aged 18-58 years (M = 25.0 years, standard deviation = 8.2 years) whose information was provided by legal guardians. Although the self-reporting subsample had much higher rates of employment, marriage/partnership, and independent living than are typically seen in autism spectrum disorder outcome studies, they remained underemployed and had strikingly high rates of comorbid disorders. Data on both descriptive outcomes and rated priorities converged across subsamples to indicate the need for more adult research on life skills, treatments, co-occurring conditions, and vocational and educational opportunities. Stakeholders also placed priority on improving public services, health care access, and above all, public acceptance of adults with autism spectrum disorder. Findings must be interpreted in light of the self-reporting subsample’s significant proportion of females and of later-diagnosed individuals. This study underscores the need for lifespan research; initiatives will benefit from incorporating information from the unique perspectives of adults with autism spectrum disorder and their families.
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5. Haq SS, Kodak T, Kurtz-Nelson E, Porritt M, Rush K, Cariveau T. {{Comparing the effects of massed and distributed practice on skill acquisition for children with autism}}. {J Appl Behav Anal};2015 (May 11)
We replicated and extended the findings of Haq and Kodak (2015) by evaluating the efficiency of massed and distributed practice for teaching tacts and textual and intraverbal behavior to 3 children with autism. Massed practice included all practice opportunities conducted on 1 day during each week, and distributed practice included practice opportunities conducted across several days during the week. The results indicated that distributed practice was more efficient for all participants. Suggested areas for future research and implications for practice are discussed.
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6. Jonsson U, Choque Olsson N, Bolte S. {{Can findings from randomized controlled trials of social skills training in autism spectrum disorder be generalized? The neglected dimension of external validity}}. {Autism};2015 (May 11)
Systematic reviews have traditionally focused on internal validity, while external validity often has been overlooked. In this study, we systematically reviewed determinants of external validity in the accumulated randomized controlled trials of social skills group interventions for children and adolescents with autism spectrum disorder. We extracted data clustered into six overarching themes: source population, included population, context, treatment provider, treatment intervention, and outcome. A total of 15 eligible randomized controlled trials were identified. The eligible population was typically limited to high-functioning school-aged children with autism spectrum disorder, and the included population was predominantly male and Caucasian. Scant information about the recruitment of participants was provided, and details about treatment providers and settings were sparse. It was not evident from the trials to what extent acquired social skills were enacted in everyday life and maintained over time. We conclude that the generalizability of the accumulated evidence is unclear and that the determinants of external validity are often inadequately reported. At this point, more effectiveness-oriented randomized controlled trials of equally high internal and external validity are needed. More attention to the determinants of external validity is warranted when this new generation of randomized controlled trials are planned and reported. We provide a tentative checklist for this purpose.
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7. Kana RK, Patriquin MA, Black BS, Channell MM, Wicker B. {{Altered Medial Frontal and Superior Temporal Response to Implicit Processing of Emotions in Autism}}. {Autism Res};2015 (May 11)
Interpreting emotional expressions appropriately poses a challenge for individuals with autism spectrum disorder (ASD). In particular, difficulties with emotional processing in ASD are more pronounced in contexts where emotional expressions are subtle, automatic, and reflexive-that is, implicit. In contrast, explicit emotional processing, which requires the cognitive evaluation of an emotional experience, appears to be relatively intact in individuals with ASD. In the present study, we examined the brain activation and functional connectivity differences underlying explicit and implicit emotional processing in age- and IQ-matched adults with (n = 17) and without (n = 15) ASD. Results indicated: (1) significantly reduced levels of brain activation in participants with ASD in medial prefrontal cortex (MPFC) and superior temporal gyrus (STG) during implicit emotion processing; (2) significantly weaker functional connectivity in the ASD group in connections of the MPFC with the amygdala, temporal lobe, parietal lobe, and fusiform gyrus; (3) No group difference in performance accuracy or reaction time; and (4) Significant positive relationship between empathizing ability and STG activity in ASD but not in typically developing participants. These findings suggest that the neural mechanisms underlying implicit, but not explicit, emotion processing may be altered at multiple levels in individuals with ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K, Raja A, Coe BP, Stessman HA, He ZX, Leal SM, Bernier R, Eichler EE. {{Excess of rare, inherited truncating mutations in autism}}. {Nat Genet};2015 (May 11)
To assess the relative impact of inherited and de novo variants on autism risk, we generated a comprehensive set of exonic single-nucleotide variants (SNVs) and copy number variants (CNVs) from 2,377 families with autism. We find that private, inherited truncating SNVs in conserved genes are enriched in probands (odds ratio = 1.14, P = 0.0002) in comparison to unaffected siblings, an effect involving significant maternal transmission bias to sons. We also observe a bias for inherited CNVs, specifically for small (<100 kb), maternally inherited events (P = 0.01) that are enriched in CHD8 target genes (P = 7.4 x 10-3). Using a logistic regression model, we show that private truncating SNVs and rare, inherited CNVs are statistically independent risk factors for autism, with odds ratios of 1.11 (P = 0.0002) and 1.23 (P = 0.01), respectively. This analysis identifies a second class of candidate genes (for example, RIMS1, CUL7 and LZTR1) where transmitted mutations may create a sensitized background but are unlikely to be completely penetrant.
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9. Mahajan R, Dirlikov B, Crocetti D, Mostofsky SH. {{Motor Circuit Anatomy in Children with Autism Spectrum Disorder With or Without Attention Deficit Hyperactivity Disorder}}. {Autism Res};2015 (May 11)
This study examined the morphology of frontal-parietal regions relevant to motor functions in children with autism spectrum disorder (ASD) with or without attention deficit hyperactivity disorder (ADHD). We also explored its associations with autism severity and motor skills, and the impact of comorbid ADHD on these associations. Participants included 126 school-age children: 30 had ASD only, 33 had ASD with ADHD, and 63 were typically developing. High resolution 3T MPRAGE images were acquired to examine the cortical morphology (gray matter volume, GMV, surface area, SA, and cortical thickness, CT) in three regions of interest (ROI): precentral gyrus (M1), postcentral gyrus (S1), and inferior parietal cortex (IPC). Children with ASD showed abnormal increases in GMV and SA in all three ROIs: (a) increased GMV in S1 bilaterally and in right M1 was specific to children with ASD without ADHD; (b) all children with ASD (with or without ADHD) showed increases in the left IPC SA. Furthermore, on measures of motor function, impaired praxis was associated with increased GMV in right S1 in the ASD group with ADHD. Children with ASD with ADHD showed a positive relationship between bilateral S1 GMV and manual dexterity, whereas children with ASD without ADHD showed a negative relationship. Our findings suggest that (a) ASD is associated with abnormal morphology of cortical circuits crucial to motor control and learning; (b) anomalous overgrowth of these regions, particularly S1, may contribute to impaired motor skill development, and (c) functional and morphological differences are apparent between children with ASD with or without ADHD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Talbott EO, Arena VC, Rager JR, Clougherty JE, Michanowicz DR, Sharma RK, Stacy SL. {{Fine particulate matter and the risk of autism spectrum disorder}}. {Environ Res};2015 (May 6);140:414-420.
The causes of autism spectrum disorder (ASD) are not well known. Recent investigations have suggested that air pollution, including PM2.5, may play a role in the onset of this condition. The objective of the present work was to investigate the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD. A population-based case-control study was conducted in children born between January 1, 2005 and December 31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited from specialty autism clinics, local pediatric practices, and school-based special needs services. ASD cases were children who scored 15 or above on the Social Communication Questionnaire (SCQ) and had written documentation of an ASD diagnosis. Controls were children without ASD recruited from a random sample of births from the Pennsylvania state birth registry and frequency matched to cases on birth year, gender, and race. A total of 217 cases and 226 controls were interviewed. A land use regression (LUR) model was used to create person- and time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one through three, pregnancy, years one and two of life) and cumulative (starting from pre-pregnancy) key developmental time periods. Logistic regression was used to investigate the association between estimated exposure to PM2.5 during key developmental time periods and risk of ASD, adjusting for mother’s age, education, race, and smoking. Adjusted odds ratios (AOR) were elevated for specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We also examined the effect of cumulative pregnancy periods; noting that starting with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46-1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01-2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are associated with increased risk of ASD. Future research should include multiple pollutant models and the elucidation of the biological mechanism for PM2.5 and ASD.
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11. Weiss JA, Cappadocia MC, Tint A, Pepler D. {{Bullying Victimization, Parenting Stress, and Anxiety among Adolescents and Young Adults with Autism Spectrum Disorder}}. {Autism Res};2015 (May 11)
Bullying victimization is commonly associated with anxiety among individuals with and without Autism Spectrum Disorder (ASD), and both bullying victimization and anxiety are more prevalent among youth with ASD than in the general population. We explored individual and contextual factors that relate to anxiety in adolescents and young adults with ASD who also experience bullying victimization. Participants included 101 mothers of adolescents and young adults diagnosed with ASD. Hierarchical multiple regression analyses were conducted to investigate the relationship between bullying victimization and anxiety in children with ASD, as well as parenting stress as a potential moderator of that relationship. Findings indicate that parenting stress moderates the association between bullying victimization and anxiety. The severity of anxiety was most strongly associated with bullying victimization when mothers reported high levels of stress. Implications for interventions that assist parents with coping and address bullying victimization are discussed. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Wood AG, Nadebaum C, Anderson V, Reutens D, Barton S, O’Brien TJ, Vajda F. {{Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy}}. {Epilepsia};2015 (May 11)
PURPOSE: The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well-characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. METHODS: Participants were 105 Australian children aged 6-8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS). RESULTS: Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores. SIGNIFICANCE: Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low-dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.
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13. Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata KI, Iwamoto S, Yamagata T. {{Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients}}. {Brain Dev};2015 (May 6)
BACKGROUND: The genetic background of autism spectrum disorder (ASD) is considered a multi-genetic disorder with high heritability. Autistic children present with a higher prevalence of sleep disorders than has been observed in children with normal development. Some circadian-relevant genes have been associated with ASD (e.g., PER1, PER2, NPAS2, MTNR1A, and MTNR1B). METHODS: We analyzed 28 ASD patients (14 with sleep disorders and 14 without) and 23 control subjects of Japanese descent. The coding regions of 18 canonical clock genes and clock-controlled genes were sequenced. Detected mutations were verified by direct sequencing analysis, and additional control individuals were screened. RESULTS: Thirty-six base changes with amino acid changes were detected in 11 genes. Six missense changes were detected only in individuals with ASD with sleep disturbance: p.F498S in TIMELESS, p.S20R in NR1D1, p.R493C in PER3, p.H542R in CLOCK, p.L473S in ARNTL2, and p.A325V in MTNR1B. Six missense changes were detected only in individuals with ASD without sleep disturbance: p.S1241N in PER1, p.A325T in TIMELESS, p.S13T in ARNTL, p.G24E in MTNR1B, p.G24E in PER2, and p.T1177A in PER3. The p.R493C mutation in PER3 was detected in both groups. One missense change, p.P932L in PER2, was detected only in the control group. Mutations in NR1D1, CLOCK, and ARNTL2 were detected only in individuals with ASD with sleep disorder. The prevalence of the mutations detected only single time differed significantly among all ASD patients and controls (p=0.003). Two kinds of mutations detected only in individuals with ASD with sleep disorder, p.F498S in TIMELESS and p.R366Q in PER3, were considered to affect gene function by three different methods: PolyPhen-2, scale-invariant feature transform (SIFT) prediction, and Mutation Taster (www.mutationtaster.org). The mutations p.S20R in NR1D1, p.H542R in CLOCK, p.L473S in ARNTL2, p.A325T in TIMELESS, p.S13T in ARNTL, and p.G24E in PER2 were diagnosed to negatively affect gene function by more than one of these methods. CONCLUSION: Mutations in circadian-relevant genes affecting gene function are more frequent in patients with ASD than in controls. Circadian-relevant genes may be involved in the psychopathology of ASD.
