1. Bolte S, Bartl-Pokorny KD, Jonsson U, Berggren S, Zhang D, Kostrzewa E, Falck-Ytter T, Einspieler C, Pokorny FB, Jones EJ, Roeyers H, Charman T, Marschik PB. {{How can clinicians detect and treat autism early? Methodological trends of technology use in research}}. {Acta Paediatr};2015 (Oct 19)
We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965- 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye-tracking were the most frequently used technologies. Conclusion The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention. This article is protected by copyright. All rights reserved.
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2. De Marco M, Iavarone A, Santoro G, Carlomagno S. {{Brief Report: Two Day-Date Processing Methods in an Autistic Savant Calendar Calculator}}. {J Autism Dev Disord};2015 (Oct 17)
Special ability in computing the day of week for given dates was observed in a 24 year-old male (FB) diagnosed with Asperger syndrome. FB performed almost flawlessly (98.2 %) both with past and future dates, over a span of 40 years. Response latency was slower as temporal remoteness of future dates increased. Within the future timespan, FB’s performance was consistent with the active use of calendar regularities. On the contrary, within the past timespan (for which no remoteness effect was seen), his performance was mainly linked to memory retrieval of personal events. The case presented here complements the existent literature on calendar calculators, as, for first time, two distinct day-date processing styles are described in the same individual.
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3. Hammer M, Krueger-Burg D, Tuffy LP, Cooper BH, Taschenberger H, Goswami SP, Ehrenreich H, Jonas P, Varoqueaux F, Rhee JS, Brose N. {{Perturbed Hippocampal Synaptic Inhibition and gamma-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism}}. {Cell Rep};2015 (Oct 20);13(3):516-523.
Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of gamma-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches.
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4. Hoffmann F, Koehne S, Steinbeis N, Dziobek I, Singer T. {{Preserved Self-other Distinction During Empathy in Autism is Linked to Network Integrity of Right Supramarginal Gyrus}}. {J Autism Dev Disord};2015 (Oct 17)
Autism spectrum disorder (ASD) shows deficits in self-other distinction during theory of mind (ToM). Here we investigated whether ASD patients also show difficulties in self-other distinction during empathy and if potential deficits are linked to dysfunctional resting-state connectivity patterns. In a first study, ASD patients and controls performed an emotional egocentricity paradigm and a ToM task. In the second study, resting-state connectivity of right temporo-parietal junction and right supramarginal gyrus (rSMG) were analysed using a large-scale fMRI data set. ASD patients exhibited deficient ToM but normal emotional egocentricity, which was paralleled by reduced connectivity of regions of the ToM network and unimpaired rSMG network connectivity. These results suggest spared self-other distinction during empathy and an intact rSMG network in ASD.
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5. Iourov IY, Vorsanova SG, Korostelev SA, Zelenova MA, Yurov YB. {{Long contiguous stretches of homozygosity spanning shortly the imprinted loci are associated with intellectual disability, autism and/or epilepsy}}. {Mol Cytogenet};2015;8:77.
BACKGROUND: Long contiguous stretches of homozygosity (LCSH) (regions/runs of homozygosity) are repeatedly detected by single-nucleotide polymorphism (SNP) chromosomal microarrays. Providing important clues regarding parental relatedness (consanguinity), uniparental disomy, chromosomal recombination or rearrangements, LCSH are rarely considered as a possible epigenetic cause of neurodevelopmental disorders. Additionally, despite being relevant to imprinting, LCSH at imprinted loci have not been truly addressed in terms of pathogenicity. In this study, we examined LCSH in children with unexplained intellectual disability, autism, congenital malformations and/or epilepsy focusing on chromosomal regions which harbor imprinted disease genes. RESULTS: Out of 267 cases, 14 (5.2 %) were found to have LCSH at imprinted loci associated with a clinical outcome. There were 5 cases of LCSH at 15p11.2, 4 cases of LCSH at 7q31.2, 3 cases of LCSH at 11p15.5, and 2 cases of LCSH at 7q21.3. Apart from a case of LCSH at 7q31.33q32.3 (~4 Mb in size), all causative LCSH were 1-1.5 Mb in size. Clinically, these cases were characterized by a weak resemblance to corresponding imprinting diseases (i.e., Silver-Russell, Beckwith-Wiedemann, and Prader-Willi/Angelman syndromes), exhibiting distinctive intellectual disability, autistic behavior, developmental delay, seizures and/or facial dysmorphisms. Parental consanguinity was detected in 8 cases (3 %), and these cases did not exhibit LCSH at imprinted loci. CONCLUSIONS: This study demonstrates that shorter LCSH at chromosomes 7q21.3, 7q31.2, 11p15.5, and 15p11.2 occur with a frequency of about 5 % in the children with intellectual disability, autism, congenital malformations and/or epilepsy. Consequently, this type of epigenetic mutations appears to be the most common one among children with neurodevelopmental diseases. Finally, since LCSH less than 2.5-10 Mb in size are generally ignored in diagnostic SNP microarray studies, one can conclude that an important epigenetic cause of intellectual disability, autism or epilepsy is actually overlooked.
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6. Jeffries T, Crosland K, Miltenberger R. {{Evaluating a tablet application and differential reinforcement to increase eye contact in children with autism}}. {J Appl Behav Anal};2015 (Oct 19)
We tested the effectiveness of a tablet application and differential reinforcement to increase eye contact in 3 children with autism. The application required the child to look at a picture of a person’s face and identify the number displayed in the person’s eyes. Eye contact was assessed immediately after training, 1 hr after training, and in a playroom. The tablet application was not effective; however, differential reinforcement was effective for all participants.
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7. Kadak MT, Cetin I, Tarakcioglu MC, Ozer OF, Kacar S, Cimen B. {{Low Serum Level alpha-Synuclein and Tau Protein in Autism Spectrum Disorder Compared to Controls}}. {Neuropediatrics};2015 (Oct 19)
alpha-Synuclein (alpha-syn) and tau proteins are thought to be related with the synaptic loss and cell death underlying several important neurodegenerative diseases. The aim of our study was to investigate serum alpha-syn and tau levels in autism. Serum levels of alpha-syn and tau were measured, and autism spectrum disorder (ASD) severity was assessed at admission using the Childhood Autism Rating Scale (CARS) total score. The mean CARS score of the autism group on admission was 47.91 points (SD: 5.97). The results indicated that the mean serum alpha-syn and serum tau levels were significantly (p < 0.001) lower in children with ASD as compared with normal cases (33.01 +/- 20.78 and 55.19 +/- 15.34 ng/mL and 241.23 +/- 290.5 and 509.78 +/- 269.25 ng/mL, respectively). There was a significant positive correlation between serum alpha-syn levels and serum levels of tau identified by Pearson correlation analysis (r = 0.922, n = 28, p < 0.001). Synaptic abnormality in autism may result from microglial activity. Furthermore, alpha-syn and tau aggregation may lead to synaptic dysfunction, and this may contribute to either neuronal or synaptic dysfunction or neurodegeneration. Our preliminary study suggests that low levels of serum alpha-syn and tau may be implicated in the relationship between synaptic activity and autism.
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8. Kucukkal TG, Yang Y, Uvarov O, Cao W, Alexov E. {{Impact of Rett Syndrome Mutations on MeCP2 MBD Stability}}. {Biochemistry};2015 (Oct 20);54(41):6357-6368.
Rett syndrome causing missense mutations in the methyl-CpG-binding domain (MBD) of methyl CpG-binding protein 2 (MeCP2) were investigated both in silico and in vitro to reveal their effect on protein stability. It is demonstrated that the vast majority of frequently occurring mutations in the human population indeed alter the MBD folding free energy by a fraction of a kcal/mol up to more than 1 kcal/mol. While the absolute magnitude of the change of the free energy is small, the effect on the MBD functionality may be substantial since the folding free energy of MBD is about 2 kcal/mol only. Thus, it is emphasized that the effect of mutations on protein integrity should be evaluated with respect to the wild-type folding free energy but not with the absolute value of the folding free energy change. Furthermore, it was observed that the magnitude of the effect is correlated neither with the burial of the mutation sites nor with the basic amino acid physicochemical property change. Mutations that strongly perturb the immediate structural features were found to have little effect on folding free energy, while very conservative mutations resulted in large changes of the MBD stability. This observation was attributed to the protein’s ability to structurally relax and reorganize to reduce the effect of mutation. Comparison between in silico and in vitro results indicated that some Web servers perform relatively well, while the free energy perturbation approach frequently overpredicts the magnitude of the free energy change especially when a charged amino acid is involved.
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9. Lazenby DC, Sideridis GD, Huntington N, Prante M, Dale PS, Curtin S, Henkel L, Iverson JM, Carver L, Dobkins K, Akshoomoff N, Tagavi D, Nelson CA, 3rd, Tager-Flusberg H. {{Language Differences at 12 Months in Infants Who Develop Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Oct 17)
Little is known about early language development in infants who later develop autism spectrum disorder (ASD). We analyzed prospective data from 346 infants, some of whom were at high risk for developing ASD, to determine if language differences could be detected at 12 months of age in the infants who later were diagnosed with ASD. Analyses revealed lower receptive and expressive language scores in infants who later were diagnosed with ASD. Controlling for overall ability to understand and produce single words, a Rasch analysis indicated that infants who later developed ASD had a higher degree of statistically unexpected word understanding and production. At 12 months of age, quantitative and qualitative language patterns distinguished infants who later developed ASD from those who did not.
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10. McHale SM, Updegraff KA, Feinberg ME. {{Siblings of Youth with Autism Spectrum Disorders: Theoretical Perspectives on Sibling Relationships and Individual Adjustment}}. {J Autism Dev Disord};2015 (Oct 17)
A burgeoning research literature investigates the sibling relationships of youth with autism spectrum disorder (ASD) and their implications for individual adjustment. Focusing on four relationship domains-behaviors, emotions, cognitions and involvement-and toward advancing this generally atheoretical literature, we review and apply tenets from a range of theoretical perspectives in an effort to illuminate the mechanisms underlying sibling relationship experiences and their adjustment implications. Our review suggests new directions for research to test theoretically-grounded hypotheses about how sibling relationships develop and are linked to individual adjustment. In addition, we consider how identifying underlying bio-psycho-social processes can aid in the development of interventions to promote warm and involved sibling relationships and positive youth development.
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11. Miron O, Ari-Even Roth D, Gabis LV, Henkin Y, Shefer S, Dinstein I, Geva R. {{Prolonged auditory brainstem responses in infants with autism}}. {Autism Res};2015 (Oct 19)
Numerous studies have attempted to identify early physiological abnormalities in infants and toddlers who later develop autism spectrum disorder (ASD). One potential measure of early neurophysiology is the auditory brainstem response (ABR), which has been reported to exhibit prolonged latencies in children with ASD. We examined whether prolonged ABR latencies appear in infancy, before the onset of ASD symptoms, and irrespective of hearing thresholds. To determine how early in development these differences appear, we retrospectively examined clinical ABR recordings of infants who were later diagnosed with ASD. Of the 118 children in the participant pool, 48 were excluded due to elevated ABR thresholds, genetic aberrations, or old testing age, leaving a sample of 70 children: 30 of which were tested at 0-3 months, and 40 were tested at toddlerhood (1.5-3.5 years). In the infant group, the ABR wave-V was significantly prolonged in those who later developed ASD as compared with case-matched controls (n = 30). Classification of infants who later developed ASD and case-matched controls using this measure enabled accurate identification of ASD infants with 80% specificity and 70% sensitivity. In the group of toddlers with ASD, absolute and interpeak latencies were prolonged compared to clinical norms. Findings indicate that ABR latencies are significantly prolonged in infants who are later diagnosed with ASD irrespective of their hearing thresholds; suggesting that abnormal responses might be detected soon after birth. Further research is needed to determine if ABR might be a valid marker for ASD risk. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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12. Namasivayam AK, Yan T, Wong WY, van Lieshout P. {{Quality of statistical reporting in developmental disability journals}}. {Int J Rehabil Res};2015 (Oct 16)
Null hypothesis significance testing (NHST) dominates quantitative data analysis, but its use is controversial and has been heavily criticized. The American Psychological Association has advocated the reporting of effect sizes (ES), confidence intervals (CIs), and statistical power analysis to complement NHST results to provide a more comprehensive understanding of research findings. The aim of this paper is to carry out a sample survey of statistical reporting practices in two journals with the highest h5-index scores in the areas of developmental disability and rehabilitation. Using a checklist that includes critical recommendations by American Psychological Association, we examined 100 randomly selected articles out of 456 articles reporting inferential statistics in the year 2013 in the Journal of Autism and Developmental Disorders (JADD) and Research in Developmental Disabilities (RDD). The results showed that for both journals, ES were reported only half the time (JADD 59.3%; RDD 55.87%). These findings are similar to psychology journals, but are in stark contrast to ES reporting in educational journals (73%). Furthermore, a priori power and sample size determination (JADD 10%; RDD 6%), along with reporting and interpreting precision measures (CI: JADD 13.33%; RDD 16.67%), were the least reported metrics in these journals, but not dissimilar to journals in other disciplines. To advance the science in developmental disability and rehabilitation and to bridge the research-to-practice divide, reforms in statistical reporting, such as providing supplemental measures to NHST, are clearly needed.
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13. Pennisi P, Tonacci A, Tartarisco G, Billeci L, Ruta L, Gangemi S, Pioggia G. {{Autism and social robotics: A systematic review}}. {Autism Res};2015 (Oct 20)
Social robotics could be a promising method for Autism Spectrum Disorders (ASD) treatment. The aim of this article is to carry out a systematic literature review of the studies on this topic that were published in the last 10 years. We tried to address the following questions: can social robots be a useful tool in autism therapy? We followed the PRISMA guidelines, and the protocol was registered within PROSPERO database (CRD42015016158). We found many positive implications in the use of social robots in therapy as for example: ASD subjects often performed better with a robot partner rather than a human partner; sometimes, ASD patients had, toward robots, behaviors that TD patients had toward human agents; ASDs had a lot of social behaviors toward robots; during robotic sessions, ASDs showed reduced repetitive and stereotyped behaviors and, social robots manage to improve spontaneous language during therapy sessions. Therefore, robots provide therapists and researchers a means to connect with autistic subjects in an easier way, but studies in this area are still insufficient. It is necessary to clarify whether sex, intelligence quotient, and age of participants affect the outcome of therapy and whether any beneficial effects only occur during the robotic session or if they are still observable outside the clinical/experimental context. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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14. Reiner O, Karzburn E, Kshirsagar A, Kaibuchi K. {{Regulation of Neuronal Migration, an Emerging Topic in Autism Spectrum Disorders (ASD)}}. {J Neurochem};2015 (Oct 20)
Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental diseases that demonstrate strong heritability, however the inheritance is not simple and many genes have been associated with these disorders. ASD is regarded as a neurodevelopmental disorder, and abnormalities at different developmental stages are part of the disease etiology. This review provides a general background on neuronal migration during brain development and discusses recent advancements in the field connecting ASD and aberrant neuronal migration. This article is protected by copyright. All rights reserved.
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15. Urbain C, Vogan VM, Ye AX, Pang EW, Doesburg SM, Taylor MJ. {{Desynchronization of fronto-temporal networks during working memory processing in autism}}. {Hum Brain Mapp};2015 (Oct 20)
BACKGROUND: Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). METHODS: We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. RESULTS: We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps < 0.04 corrected) previously associated with challenging high-level conditions (i.e. the left insula and the anterior cingulate cortex (ACC)) and memory encoding and/or recognition (i.e. the right middle temporal gyrus and the right fusiform gyrus). Additionally, we found that reduced connectivity processes related to the right fusiform were correlated with the severity of symptoms in children with ASD, suggesting that such atypicalities could be directly related to the behavioural deficits observed. DISCUSSION: This study provides new evidence of atypical long-range synchronization in children with ASD in fronto-temporal areas that crucially contribute to challenging WM tasks, but also emotion regulation and social cognition processes. Thus, these results support the network disorder hypothesis of ASD and argue for a specific pathophysiological contribution of brain processes related to working memory and executive functions on the symptomatology of autism. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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16. Wang Y, Zhao X, Ju W, Flory M, Zhong J, Jiang S, Wang P, Dong X, Tao X, Chen Q, Shen C, Zhong M, Yu Y, Brown WT, Zhong N. {{Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder}}. {Transl Psychiatry};2015;5:e660.
A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.
