1. Bennett TA, Szatmari P, Georgiades K, Hanna S, Janus M, Georgiades S, Duku E, Bryson S, Fombonne E, Smith IM, Mirenda P, Volden J, Waddell C, Roberts W, Vaillancourt T, Zwaigenbaum L, Elsabbagh M, Thompson A. {{Do reciprocal associations exist between social and language pathways in preschoolers with autism spectrum disorders?}}. {J Child Psychol Psychiatry};2014 (Nov 7)
BACKGROUND: Differences in how developmental pathways interact dynamically in children with autism spectrum disorder (ASD) likely contribute in important ways to phenotypic heterogeneity. This study aimed to model longitudinal reciprocal associations between social competence (SOC) and language (LANG) pathways in young children with ASD. METHODS: Data were obtained from 365 participants aged 2-4 years who had recently been diagnosed with an ASD and who were followed over three time points: baseline (time of diagnosis), 6- and 12 months later. Using structural equation modeling, a cross-lagged reciprocal effects model was developed that incorporated auto-regressive (stability) paths for SOC (using the Socialization subscale of the Vineland Adaptive Behavior Scales-2) and LANG (using the Preschool Language Scale-4 Auditory Comprehension subscale). Cross-domain associations included within-time correlations and lagged associations. RESULTS: SOC and LANG were highly stable over 12 months. Small reciprocal cross-lagged associations were found across most time points and within-time correlations decreased over time. There were no differences in strength of cross-lagged associations between SOC-LANG and LANG-SOC across time points. Few differences were found between subgroups of children with ASD with and without cognitive impairment. CONCLUSIONS: Longitudinal reciprocal cross-domain associations between social competence and language were small in this sample of young children with ASD. Instead, a pattern emerged to suggest that the two domains were strongly associated around time of diagnosis in preschoolers with ASD, and then appeared to become more independent over the ensuing 12 months.
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2. Bink M, van Boxtel GJ, Popma A, Bongers IL, Denissen AJ, van Nieuwenhuizen C. {{EEG theta and beta power spectra in adolescents with ADHD versus adolescents with ASD + ADHD}}. {Eur Child Adolesc Psychiatry};2014 (Nov 6)
Attention problems are common in youngsters with attention deficit hyperactivity disorder (ADHD) as well as in adolescents with combined autism spectrum disorder (ASD) and ADHD. However, it is unknown whether there is psychophysiological overlap and/or a difference in electroencephalogram (EEG) power spectra between ADHD and comorbid ASD and ADHD (ASD + ADHD), on and off stimulant medication. To explore potential differences and overlap, measures of theta and beta power in adolescents diagnosed with ADHD (n = 33) versus adolescents with combined ASD + ADHD (n = 20), categorized by stimulant medication use (57 % of the total sample), were compared. EEG measures were acquired in three conditions: (1) resting state, eyes closed (2) resting state, eyes open and (3) during an oddball task. In addition, performance on the d2 attention test was analyzed. Adolescents with ADHD displayed more absolute theta activity than adolescents with ASD + ADHD during the eyes open and task conditions, independent of stimulant medication use. In addition, only the adolescents with ADHD showed an association between diminished attention test performance and increased theta in the eyes open condition. Results of the current study suggest that although there is behavioral overlap between ADHD characteristics in adolescents with ADHD and adolescents with combined ASD + ADHD, the underlying psychophysiological mechanisms may be different. Adolescents with ASD + ADHD exhibited fewer of the EEG physiological signs usually associated with ADHD, although there was an overlap in attentional problems between the groups. This may indicate that treatments developed for ADHD work differently in some adolescents with ASD + ADHD and adolescents with ADHD only.
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3. Burke MM, Goldman SE. {{Identifying the Associated Factors of Mediation and Due Process in Families of Students with Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Nov 6)
Compared to families of students with other types of disabilities, families of students with autism spectrum disorder (ASD) are significantly more likely to enact their procedural safeguards such as mediation and due process. However, we do not know which school, child, and parent characteristics are associated with the enactment of safeguards. For this study, 507 parents of students with ASD responded to a national web-based survey. Parents who filed for due process or mediation were more likely to advocate for their child, have poor family-school partnerships, and have greater household incomes. Parents were also more likely to utilize their safeguards if their children were older, experiencing more internalizing behaviors, and educated in segregated placements. Implications for research and practice are discussed.
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4. Byars SG, Stearns SC, Boomsma JJ. {{Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects}}. {Proc Biol Sci};2014 (Nov 7);281(1794):20140604.
Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark’s roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean +/- 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory.
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5. Casanova MF, Hensley MK, Sokhadze EM, El-Baz AS, Wang Y, Li X, Sears L. {{Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder}}. {Front Hum Neurosci};2014;8:851.
The term autism spectrum disorder (ASD) describes a range of conditions characterized by impairments in social interactions, communication, and by restricted and repetitive behaviors. Autism spectrum disorder may also present with symptoms suggestive of autonomic nervous system (ANS) dysfunction. The objective of this study was to determine the effect of 18 sessions of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) on autonomic function in children with ASD by recording electrocardiogram (ECG) and electrodermal activity (EDA) pre- post- and during each rTMS session. The autonomic measures of interest in this study were R-R cardiointervals in EKG (R-R), time and frequency domain measures of heart rate variability (HRV) and skin conductance level (SCL). Heart rate variability measures such as R-R intervals, standard deviation of cardiac intervals, pNN50 (percentage of cardiointervals >50 ms different from preceding interval), power of high frequency (HF) and LF components of HRV spectrum, LF/HF ratio, were then derived from the recorded EKG. We expected that the course of 18 weekly inhibitory LF rTMS applied to the dorsolateral prefrontal cortex (DLPFC) would enhance autonomic balance by facilitating frontal inhibition of limbic activity thus resulting in decreased overall heart rate (HR), increased HRV (in a form of increased HF power), decreased LF power (resulting in decreased LF/HF ratio), and decreased SCL. Behavioral evaluations post-18 TMS showed decreased irritability, hyperactivity, stereotype behavior and compulsive behavior ratings while autonomic measures indicated a significant increase in cardiac interval variability and a decrease of tonic SCL. The results suggest that 18 sessions of LF rTMS in ASD results in increased cardiac vagal control and reduced sympathetic arousal.
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6. Esan F, Chester V, Gunaratna IJ, Hoare S, Alexander RT. {{The Clinical, Forensic and Treatment Outcome Factors of Patients with Autism Spectrum Disorder Treated in a Forensic Intellectual Disability Service}}. {J Appl Res Intellect Disabil};2014 (Nov 7)
BACKGROUND: To describe the characteristics of those with autism spectrum disorder (ASD) treated within a forensic intellectual disability hospital and to compare them with those without ASD. METHOD: Service evaluation of a cohort of 138 patients treated over a 6-year period. RESULTS: Of the 138, 42 had an ASD. Personality disorders and harmful use or dependence on drugs were significantly lower in the ASD group. The ASD group was less likely to be subject to criminal sections or restriction orders. Self-harm was significantly higher in the ASD group. There were no differences in the length of stay and direction of care pathway. CONCLUSIONS: Although the ASD and non-ASD groups differ on clinical and forensic characteristics, their treatment outcomes appear similar. This suggests that the diagnostic category of ASD alone may be inadequate in predicting the treatment outcome. There is a case to identify distinct typologies within the ASD group.
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7. Finn L, Ramasamy R, Dukes C, Scott J. {{Using WatchMinder to Increase the On-Task Behavior of Students with Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Nov 7)
This study assessed the use of WatchMinder, a vibrating prompt watch, and self-graphing on the on-task behavior of students with autism spectrum disorder in an elementary special education setting. Using a multiple baseline across subjects design, results showed an immediate increase in on-task behavior when the intervention was introduced. Participants maintained high levels of on-task behavior during the follow-up phase. Implications for expanded self-monitoring treatment packages are discussed.
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8. Gong X, Wang Y, Zeng J, Li S, Luo Y. {{Computational Identification and Experimental Validation of MicroRNAs Binding to the Fragile X Syndrome Gene Fmr1}}. {Neurochem Res};2014 (Nov 7)
MicroRNAs (miRNAs) usually bind to their target mRNAs through imperfect base pairing in the 3′-untranslated regions (3′ UTRs) and regulate target gene expression via post-transcriptional suppression. In recent years, computational approaches to predict miRNA targets have facilitated the identification of potential target sites. In this study, we used three programs TargetScan, miRDB and miRanda to predict potential miRNA binding sites to the fragile X gene Fmr1 and picked out 61 miRNAs which were predicted by all three programs for further investigation. Excitingly, 5 out of these miRNAs, miR-23a, miR-32, miR-124, miR-335-5p and miR-350, were experimentally verified by luciferase reporter assays. Furthermore, overexpression of miR-124 in mouse embryonic neural progenitor cells (eNPC) could not only significantly reduce Fmr1 level, but also increase Cdk4 and cyclin D1 levels which coincidently promoted eNPC proliferation. Our results imply that miR-124 plays an important role in the proliferation of mouse embryonic stem cells by promoting Cdk4 and cyclin D1 expression through directly inhibiting Fmr1 expression.
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9. Lange N, Travers BG, Bigler ED, Prigge MB, Froehlich AL, Nielsen JA, Cariello AN, Zielinski BA, Anderson JS, Fletcher PT, Alexander AA, Lainhart JE. {{Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6-35 Years}}. {Autism Res};2014 (Nov 7)
Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter-scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8-year period. This initial analysis includes between one and three high-quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Meilleur AA, Jelenic P, Mottron L. {{Prevalence of Clinically and Empirically Defined Talents and Strengths in Autism}}. {J Autism Dev Disord};2014 (Nov 6)
Outstanding skills, including special isolated skills (SIS) and perceptual peaks (PP) are frequent features of autism. However, their reported prevalence varies between studies and their co-occurrence is unknown. We determined the prevalence of SIS in a large group of 254 autistic individuals and searched for PP in 46 of these autistic individuals and 46 intelligence and age-matched typically developing controls. The prevalence of SIS among autistic individuals was 62.5 % and that of PP was 58 % (13 % in controls). The prevalence of SIS increased with intelligence and age. The existence of an SIS in a particular modality was not associated with the presence of a PP in the same modality. This suggests that talents involve an experience-dependent component in addition to genetically defined alterations of perceptual encoding.
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11. Nakao S, Scott JM, Masterson EE, Chi DL. {{Non-traumatic Dental Condition-Related Emergency Department Visits and Associated Costs for Children and Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord};2014 (Nov 6)
We analyzed 2010 US National Emergency Department Sample data and ran regression models to test the hypotheses that individuals with ASD are more likely to have non-traumatic dental condition (NTDC)-related emergency department (ED) visits and to incur greater costs for these visits than those without ASD. There were nearly 2.3 million NTDC-related ED visits in 2010. Less than 1.0 % (children) and 2.1 % (adults) of all ED visits were for NTDC. There was no significant difference in NTDC-related ED visits or costs for children by ASD status. Adults with ASD had significantly lower odds of NTDC-related ED visits (OR 0.39; 95 % CI 0.29, 0.52; p < 0.001) but incurred significantly greater mean costs for NTDC-related ED visits (p < 0.006) than did adults without ASD.
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12. Padmanabhan A, Garver K, O’Hearn K, Nawarawong N, Liu R, Minshew N, Sweeney J, Luna B. {{Developmental Changes in Brain Function Underlying Inhibitory Control in Autism Spectrum Disorders}}. {Autism Res};2014 (Nov 7)
The development of inhibitory control-the ability to suppress inappropriate actions in order to make goal-directed responses-is often impaired in autism spectrum disorders (ASD). In the present study, we examined whether the impairments in inhibitory control evident in ASD reflect-in part-differences in the development of the neural substrates of inhibitory control from adolescence into adulthood. We conducted a functional magnetic resonance imaging (fMRI) study on the anti-saccade task, a probe of inhibitory control, in high-functioning adolescents and adults with ASD compared to a matched group of typically developing (TD) individuals. The ASD group did not show the age-related improvements in behavioral performance from adolescence to adulthood evident in the typical group, consistent with previous behavioral work. The fMRI results indicated that much of the circuitry recruited by the ASD group was similar to the TD group. However, the ASD group demonstrated some unique patterns, including: (a) a failure to recruit the frontal eye field during response preparation in adolescence but comparable recruitment in adulthood; (b) greater recruitment of putamen in adolescence and precuneus in adolescence and adulthood than the TD group; and (c) decreased recruitment in the inferior parietal lobule relative to TD groups. Taken together, these results suggest that brain circuitry underlying inhibitory control develops differently from adolescence to adulthood in ASD. Specifically, there may be relative underdevelopment of brain processes underlying inhibitory control in ASD, which may lead to engagement of subcortical compensatory processes. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Schaaf RC, Lane AE. {{Toward a Best-Practice Protocol for Assessment of Sensory Features in ASD}}. {J Autism Dev Disord};2014 (Nov 6)
Sensory difficulties are a commonly occurring feature of autism spectrum disorders and are now included as one manifestation of the ‘restricted, repetitive patterns of behavior, interests, or activities’ diagnostic criteria of the DSM5 necessitating guidelines for comprehensive assessment of these features. To facilitate the development of such guidelines, this paper provides an overview of the literature on sensory features in autism spectrum disorder. We summarize the literature pertaining to: terminology, current assessment practices, sensory development, and the relationship of sensory features to core symptoms of autism. The paper concludes with recommendations for clinical assessment of sensory features in Autism.
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14. Smoot Reinert S, Jackson K, Bigelow K. {{Using Posturography to Examine the Immediate Effects of Vestibular Therapy for Children with Autism Spectrum Disorders: A Feasibility Study}}. {Phys Occup Ther Pediatr};2014 (Nov 6)
ABSTRACT Aims: The primary objective of this study was to determine the feasibility of using posturography to monitor acute changes in postural control induced by a Sensory Integration (SI) therapy intervention. A secondary objective was to identify which posturography outcome parameters, tests conditions and data analysis methods might be most useful in identifying post-intervention changes. Methods: Five children with Autism Spectrum Disorder (ASD) and five children with typical development (TD) participated in a 10 min vestibular swing activity and had their postural stability evaluated pre- and post-intervention under four different sensory testing conditions. Sway ranges, mean sway velocity, sway root mean square (RMS), and sample entropy were calculated from center of pressure (COP) data. Results: All five children with ASD demonstrated decreased mean sway velocity in the eyes open/flat plate condition post-intervention with an average decrease of 5.87 +/- 2.69 mm/s. Four of the five children with ASD demonstrated an increase in RMS and a decrease in anterior/posterior sample entropy post-intervention in the eyes closed, foam pad condition and eyes open, flat plate condition respectively. Conclusion: Posturography may be useful for assessing acute physiologic responses to an SI therapy intervention and warrants further investigation.
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15. Tsheringla S, Minju KA, Russell S, Mammen P, Russell PS, Nair MK. {{A Meta-analysis of the Diagnostic Accuracy of Autism Diagnostic Observation Schedule Module-1 for Autism Spectrum Disorders}}. {Indian J Pediatr};2014 (Nov 7)
OBJECTIVE: Autism Diagnostic Observation Schedule (ADOS) is considered gold standard for the diagnosis of Autism Spectrum Disorders (ASD). The authors evaluated the cumulative diagnostic accuracy of ADOS-Module 1 (ADOSM1) using the original diagnostic algorithm with meta-analysis and meta-regression. METHODS: The authors, electronically and manually searched for studies from 1999 to 2013 that evaluated the accuracy of ADOSM1 using the original diagnostic algorithm in detecting ASD. Primary results of Sensitivity (Sn), Specificity (Sp) and Diagnostic Odds Ratio (DOR) for ADOSM1 were summarized using random-effects model. Summary Receiver Operating characteristic Curves and its Area Under the Curve (SROC-AUC) were used to summarize overall diagnostic accuracy of ADOSM1. The modifying effects of quality of study and sample size, on the diagnostic odds ratio, were investigated using meta-regression. RESULTS: A total of 7 cross-sectional studies provided data on 4,057 children. The pooled Sn, Sp, DOR and SROC-AUC for the overall diagnostic accuracy of ADOSM1 were: 0.91 (95 % CI = 0.88 to 0.93), 0.27 (95 % CI = 0.24 to 0.30), 5.40 (95 % CI = 1.51 to 19.23) and 0.52 respectively. Meta-regression analysis showed a non-significant relationship between ADOSM1 and study quality as well as sample size. There were subgroup differences in the DOR. CONCLUSIONS: The authors conclude that ADOSM1 with the original diagnostic algorithm lacks overall diagnostic accuracy and pooled specificity to confirm the diagnosis of Autism Spectrum Disorders. ADOSM1 with the revised diagnostic algorithm should be used instead for the diagnosis of this group of disorders.
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16. West PR, Amaral DG, Bais P, Smith AM, Egnash LA, Ross ME, Palmer JA, Fontaine BR, Conard KR, Corbett BA, Cezar GG, Donley EL, Burrier RE. {{Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children}}. {PLoS One};2014;9(11):e112445.
BACKGROUND: The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. OBJECTIVES: To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment. METHODS: Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD. RESULTS: A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set. CONCLUSIONS: This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.
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17. Yoshimura S, Sato W, Uono S, Toichi M. {{Impaired Overt Facial Mimicry in Response to Dynamic Facial Expressions in High-Functioning Autism Spectrum Disorders}}. {J Autism Dev Disord};2014 (Nov 6)
Previous electromyographic studies have reported that individuals with autism spectrum disorders (ASD) exhibited atypical patterns of facial muscle activity in response to facial expression stimuli. However, whether such activity is expressed in visible facial mimicry remains unknown. To investigate this issue, we videotaped facial responses in high-functioning individuals with ASD and controls to dynamic and static facial expressions of anger and happiness. Visual coding of facial muscle activity and the subjective impression ratings showed reduced congruent responses to dynamic expressions in the ASD group. Additionally, this decline was related to social dysfunction. These results suggest that impairment in overt facial mimicry in response to others’ dynamic facial expressions may underlie difficulties in reciprocal social interaction among individuals with ASD.
