1. Bock I, Nemeth K, Pentelenyi K, Balicza P, Balazs A, Molnar MJ, Roman V, Nagy J, Levay G, Kobolak J, Dinnyes A. {{Targeted next generation sequencing of a panel of autism-related genes identifies an EHMT1 mutation in a Kleefstra syndrome patient with autism and normal intellectual performance}}. {Gene};2016 (Dec 31);595(2):131-141.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with unknown genetic and environmental causation in most of the affected individuals. On the other hand, there are a growing number of ASD-associated syndromes, where the exact genetic origin can be revealed. Here we report a method, which included the targeted next generation sequencing (NGS) and filtering of 101 ASD associated genes, followed by database search. Next, RNA sequencing was used to study the region of interest at the transcriptional level. Using this workflow, we identified a de novo mutation in the euchromatic histone-lysine N-methyltransferase 1 gene (EHMT1) of an autistic patient with dysmorphisms. Sequencing of EHMT1 transcripts showed that the premature termination codon (Trp1138Ter) created by a single nucleotide change elicited nonsense-mediated mRNA decay, which led to haploinsufficiency already at the transcriptional level. Database and literature search provided evidence that this mutation caused Kleefstra syndrome (KS), which was confirmed by the presence of the disorder-specific phenotype in the patient. We provide a proof of principle that the implemented method is capable to elucidate the genetic etiology of individuals with syndromic autism. The novel mutation detected in the EHMT1 gene is responsible for KS’s symptoms. In addition, further genetic factors might be involved in the ASD pathogenesis of the patient including a missense DPP6 mutation (Arg322Cys), which segregated with the autistic phenotype within the family.
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2. Brown LS. {{The Influence of Music on Facial Emotion Recognition in Children with Autism Spectrum Disorder and Neurotypical Children}}. {J Music Ther};2016 (Dec 31)
BACKGROUND: Children with autism spectrum disorder (ASD) often struggle with social skills, including the ability to perceive emotions based on facial expressions. Research evidence suggests that many individuals with ASD can perceive emotion in music. Examining whether music can be used to enhance recognition of facial emotion by children with ASD would inform development of music therapy interventions. OBJECTIVE: The purpose of this study was to investigate the influence of music with a strong emotional valance (happy; sad) on children with ASD’s ability to label emotions depicted in facial photographs, and their response time. METHODS: Thirty neurotypical children and 20 children with high-functioning ASD rated expressions of happy, neutral, and sad in 30 photographs under two music listening conditions (sad music; happy music). During each music listening condition, participants rated the 30 images using a 7-point scale that ranged from very sad to very happy. Response time data were also collected across both conditions. RESULTS: A significant two-way interaction revealed that participants’ ratings of happy and neutral faces were unaffected by music conditions, but sad faces were perceived to be sadder with sad music than with happy music. Across both conditions, neurotypical children rated the happy faces as happier and the sad faces as sadder than did participants with ASD. Response times of the neurotypical children were consistently shorter than response times of the children with ASD; both groups took longer to rate sad faces than happy faces. Response times of neurotypical children were generally unaffected by the valence of the music condition; however, children with ASD took longer to respond when listening to sad music. CONCLUSIONS: Music appears to affect perceptions of emotion in children with ASD, and perceptions of sad facial expressions seem to be more affected by emotionally congruent background music than are perceptions of happy or neutral faces.
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3. Cabibihan JJ, Javed H, Aldosari M, Frazier TW, Elbashir H. {{Sensing Technologies for Autism Spectrum Disorder Screening and Intervention}}. {Sensors (Basel)};2016 (Dec 27);17(1)
This paper reviews the state-of-the-art in sensing technologies that are relevant for Autism Spectrum Disorder (ASD) screening and therapy. This disorder is characterized by difficulties in social communication, social interactions, and repetitive behaviors. It is diagnosed during the first three years of life. Early and intensive interventions have been shown to improve the developmental trajectory of the affected children. The earlier the diagnosis, the sooner the intervention therapy can begin, thus, making early diagnosis an important research goal. Technological innovations have tremendous potential to assist with early diagnosis and improve intervention programs. The need for careful and methodological evaluation of such emerging technologies becomes important in order to assist not only the therapists and clinicians in their selection of suitable tools, but to also guide the developers of the technologies in improving hardware and software. In this paper, we survey the literatures on sensing technologies for ASD and we categorize them into eye trackers, movement trackers, electrodermal activity monitors, tactile sensors, vocal prosody and speech detectors, and sleep quality assessment devices. We assess their effectiveness and study their limitations. We also examine the challenges faced by this growing field that need to be addressed before these technologies can perform up to their theoretical potential.
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4. Chahboun S, Vulchanov V, Saldana D, Eshuis H, Vulchanova M. {{Can You Play with Fire and Not Hurt Yourself? A Comparative Study in Figurative Language Comprehension between Individuals with and without Autism Spectrum Disorder}}. {PLoS One};2016;11(12):e0168571.
Individuals with High functioning autism (HFA) are distinguished by relative preservation of linguistic and cognitive skills. However, problems with pragmatic language skills have been consistently reported across the autistic spectrum, even when structural language is intact. Our main goal was to investigate how highly verbal individuals with autism process figurative language and whether manipulation of the stimuli presentation modality had an impact on the processing. We were interested in the extent to which visual context, e.g., an image corresponding either to the literal meaning or the figurative meaning of the expression may facilitate responses to such expressions. Participants with HFA and their typically developing peers (matched on intelligence and language level) completed a cross-modal sentence-picture matching task for figurative expressions and their target figurative meaning represented in images. We expected that the individuals with autism would have difficulties in appreciating the non-literal nature of idioms and metaphors, despite intact structural language skills. Analyses of accuracy and reaction times showed clearly that the participants with autism performed at a lower level than their typically developing peers. Moreover, the modality in which the stimuli were presented was an important variable in task performance for the more transparent expressions. The individuals with autism displayed higher error rates and greater reaction latencies in the auditory modality compared to the visual stimulus presentation modality, implying more difficulty. Performance differed depending on type of expression. Participants had more difficulty understanding the culturally-based expressions, but not expressions grounded in human experience (biological idioms). This research highlights the importance of stimulus presentation modality and that this can lead to differences in figurative language comprehension between typically and atypically developing individuals. The current study also contributes to current debates on the role of structural language in figurative language comprehension in autism.
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5. Chirumbolo S, Bjorklund G, Urbina MA. {{May traffic air pollution be involved in autism spectrum disorder?}}. {Environ Res};2016 (Dec 27);154:57-59.
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6. Hatfield M, Falkmer M, Falkmer T, Ciccarelli M. {{Evaluation of the effectiveness of an online transition planning program for adolescents on the autism spectrum: trial protocol}}. {Child Adolesc Psychiatry Ment Health};2016;10:48.
BACKGROUND: The transition from high school to post-secondary education and work is difficult for adolescents on the autism spectrum. Transition planning can be an effective way of supporting adolescents on the autism spectrum to prepare for leaving school and to succeed in obtaining employment; however, there is a need for an autism-specific transition planning program with proven effectiveness. This paper describes a trial protocol for evaluating the Better OutcOmes & Successful Transitions for Autism (BOOST-A); an online interactive program that empowers adolescents on the autism spectrum to plan their transition from school to further study, training, or employment. METHODS: The trial will involve adolescents on the autism spectrum in high school and their parents, who will be alternately assigned to a control group (regular practice) or an intervention group (using the BOOST-A). The BOOST-A was developed using the PRECEDE-PROCEED model, and is based on the self-determination model, and the strengths- and technology-based approaches. It involves participants completing a series of online modules. The primary outcome will be self-determination, because high self-determination has been linked to successful transition to employment among adolescents on the autism spectrum. Secondary outcomes will include domain-specific self-determination, career planning and exploration, quality of life, and environmental support. Data will be obtained from questionnaires completed by the adolescent on the autism spectrum and their parent/s. Data collection will take place at baseline (Time point 1) and 12 months later (Time point 2). DISCUSSION AND CONCLUSIONS: This trial will provide evidence of the effectiveness of the BOOST-A to assist adolescents on the autism spectrum to successfully transition from school. Trial registration #ACTRN12615000119594.
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7. Logan K, Iacono T, Trembath D. {{A systematic review of research into aided AAC to increase social-communication functions in children with autism spectrum disorder}}. {Augment Altern Commun};2016 (Dec 31):1-14.
Augmentative and alternative communication (AAC) interventions have been shown to be effective in supporting children with autism spectrum disorder (ASD) to communicate, particularly to request preferred items and activities. The aim of this systematic review was to examine the effectiveness of AAC interventions in supporting children to produce a broader range of communicative functions and determine the extent to which these interventions have been evaluated beyond immediate effectiveness to address maintenance, generalization, and social validity. A systematic search and application of inclusion criteria yielded 30 interventions that focused on communication functions beyond object requests. In many of the studies, flaws detracted from the certainty of evidence, and maintenance, generalization, and/or social validity were not addressed. Further research is needed to evaluate the extent to which AAC interventions can support children with ASD to communicate using a variety of communication functions, as well as to demonstrate sustained, transferable, and meaningful change.
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8. Melancia F, Servadio M, Schiavi S, Campolongo P, Giusti-Paiva A, Trezza V. {{Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring}}. {Behav Brain Res};2016 (Dec 26)
Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated. To address this issue, we used a validated animal model of prenatal hypothyroidism based on the administration of the thyroid peroxidase inhibitor methimazole (MMI, 0.02g/100ml in tap water) to rat dams from gestational day 9 up to delivery. The offspring was tested in behavioral tasks during infancy (PNDs 5,9, 13) and adolescence (PND 35-40) to capture some of the core and associated symptoms of ASD. MMI-exposed pups were able to vocalize as controls when separated from the nest, and showed intact social discrimination abilities in the homing behavior test. At adolescence, the offspring from both sexes did not show an anxious-phenotype in the elevated plus maze and showed intact object recognition. However, MMI-exposed male rats showed increased novelty-directed exploratory behaviors: they solicited their partner to play more and showed more interest for novel rather than familiar objects compared to control rats. Our results show that prenatal MMI-induced hypothyroidism does not cause in the rat offspring behaviors that resemble core and associated ASD symptoms, like deficits in communication and social interaction and anxiety.
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9. Nadeem A, Ahmad SF, Bakheet SA, Al-Harbi NO, Al-Ayadhi LY, Attia SM, Ma Zoheir K. {{Toll-like receptor 4 signaling is associated with upregulated NADPH oxidase expression in peripheral T cells of children with autism}}. {Brain Behav Immun};2016 (Dec 26)
Autismspectrum disorders (ASD) affect millions of children worldwide, and are characterized by impairment in social interaction and communication, and specific repetitive behavioral patterns. Growing evidence highlights a role of toll-like receptors (TLRs) in the pathogenesis of ASD. Specifically, TLR-4 activation has been shown to be associated with increased pro-inflammatory cytokines as well as autistic symptoms in offspring. NADPH oxidase (NOX-2) derived reactive oxygen species (ROS) have also been shown to play pathogenic role under inflammatory conditions. However, the role of TLR-4 in the regulation of NOX-2 derived ROS has not been explored in ASD, particularly in T cells. Therefore, this study explored TLR-4 and NOX-2 related signaling in peripheral T cells of ASD patients (n=35) and age-matched typically developing children (n=30). In this study, we find that ASD individuals have increased TLR-4 expression on T cells which is associated with increased NOX-2 expression and ROS generation as compared to typically developing children. Moreover, activation of TLR-4 on T cells by lipopolysaccharide (LPS) in vitro leads to enhanced generation of NOX-2 derived ROS via nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB) pathway. These data support a link between T cell TLR-4 activation and NOX-2/ROS upregulation in ASD patients. Our study has implications in the context of neuroinflammation observed in ASD patients as ROS may lead to amplification and perpetuation of inflammation both in the periphery and central nervous system. Our data also suggest that therapeutic targeting of TLR-4 signaling may lead to reduction in inflammation of ASD patients.
