1. Althaus M, Groen Y, Wijers AA, Noltes H, Tucha O, Hoekstra PJ. {{Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder}}. {Neuropsychologia}. 2015; 79(Pt A): 53-69.
OBJECTIVE: The study investigated the effects of nasally administered oxytocin on neurophysiological orienting to empathy-evoking pictures in normally intelligent male adults with and without an autism spectrum disorder (ASD). It further investigated whether these effects might be moderated by the individual’s approach and avoidance tendencies. METHODS: All subjects participated in a randomised double-blind placebo controlled crossover trial where either oxytocin (OXT) or placebo was administered preceding the viewing of affective pictures.The pictures, selected from the International Affective Picture System (IAPS), represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. Both cardiac (ECR) and cortical (LPP) evoked orienting responses were measured and both were enhanced for the pictures with humans, in particular for the unpleasant ones. RESULTS: No significant group differences were found, nor were there any treatment effects. Moderator analysis, however, demonstrated that OXT did enhance orienting to affective pictures with humansin male adults with ASD who are easily distressed when seeing others in stressful situations and in healthy males who are highly sensitive to anticipated punishment and criticism or have a low drive for goal achievement. CONCLUSION: Individual differences in stress-related avoidance tendencies should be taken into account when considering OXT as a treatment of social deficiencies in autism.
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2. Antonucci N, Cirillo A, Siniscalco D. {{Beneficial Effects of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Cases}}. {Case Rep Psychiatry}. 2015; 2015: 325061.
Introduction. Autism spectrum disorders are defined by behavioral and language atypias. Growing body of evidence indicates inflammatory mediators may contribute to the condition. Palmitoylethanolamide (PEA) is naturally occurring and has been available as a nonprescription medical food supplement in Europe since 2008. PEA has been tested in thousands of human subjects without any noted significant side effects. Here we report the first cases of the administration of PEA to two children with autism. Case Presentations. The first 13-year-old male child (Subject 1) presented with a total IgE of 572 IU/mL (nl < 200) and with low mature CD57(+) natural killer cell counts (32 cells/microL; nl = 60-300 cells/microL) and with significant eczema and allergic stigmata. Expressive language, as measured by mean length of utterance, and overall autism severity as measured by the Childhood Autism Rating Scale, Second Edition, improved significantly. Atopic symptoms diminished. No side effects were reported. The second male child, age 15 (Subject 2), also displayed noticeable and rapid improvements in cognitive, behaviors, and sociability. Conclusion. Currently, there is no definitive treatment for autism condition. Palmitoylethanolamide could be an effective treatment for autism syndrome. We propose appropriate double-blind clinical trials to further explore palmitoylethanolamide efficacy and safety. Lien vers le texte intégral (Open Access ou abonnement)
3. Bijl N, Thys C, Wittevrongel C, De la Marche W, Devriendt K, Peeters H, Van Geet C, Freson K. {{Platelet studies in autism spectrum disorder patients and first-degree relatives}}. {Mol Autism}. 2015; 6: 57.
BACKGROUND: Platelets have been proven to be a useful cellular model to study some neuropathologies, due to the overlapping biological features between neurons and platelets as granule secreting cells. Altered platelet dense granule morphology was previously reported in three autism spectrum disorder (ASD) patients with chromosomal translocations that disrupted ASD candidate genes NBEA, SCAMP5, and AMYSIN, but a systematic analysis of platelet function in ASD is lacking in contrast to numerous reports of elevated serotonin levels in platelets and blood as potential biomarker for ASD. METHODS: We explored platelet count, size, epinephrine-induced activation, and dense granule ATP secretion in a cohort of 159 ASD patients, their 289 first-degree relatives (103 unaffected siblings, 99 mothers, and 87 fathers), 45 adult controls, and 65 pediatric controls. For each of the responses separately, a linear mixed model with gender as a covariate was used to compare the level between groups. We next investigated the correlation between platelet function outcomes and severity of impairments in social behavior (social responsiveness score (SRS)). RESULTS: The average platelet count was increased in ASD patients and siblings vs. controls (ASD 320.3 x 10(9)/L, p = 0.003; siblings 332.0 x 10(9)/L, p < 0.001; controls 283.0 x 10(9)/L). The maximal platelet secretion-dependent aggregation response to epinephrine was not significantly lower for ASD patients. However, secondary wave responses following stimulation with epinephrine were more frequently delayed or absent compared to controls (ASD 52 %, siblings 45 %, parents 53 %, controls 22 %, p = 0.002). In addition, stimulated release of ATP from dense granules was reduced in ASD patients, siblings, and parents vs. controls following activation of platelets with either collagen (ASD 1.54 muM, p = 0.001; siblings 1.51 muM, p < 0.001; parents 1.67 muM, p = 0.021; controls 2.03 muM) or ADP (ASD 0.96 muM, p = 0.003; siblings 1.00 muM, p = 0.012; parents 1.17 muM, p = 0.21; controls 1.40 muM). Plasma serotonin levels were increased for ASD patients (n = 20, p = 0.005) and siblings (n = 20, p = 0.0001) vs. controls (n = 16). No significant correlations were found in the different groups between SRS scores and count, size, epinephrine aggregation, or ATP release. CONCLUSIONS: We report increased platelet counts, decreased platelet ATP dense granule secretion, and increased serotonin plasma levels not only in ASD patients but also in their first-degree relatives. This suggests that potential genetic factors associated with platelet counts and granule secretion can be associated with, but are not fully penetrant for ASD. Lien vers le texte intégral (Open Access ou abonnement)
4. Blumberg SJ, Zablotsky B, Avila RM, Colpe LJ, Pringle BA, Kogan MD. {{Diagnosis lost: Differences between children who had and who currently have an autism spectrum disorder diagnosis}}. {Autism}. 2015.
Autism spectrum disorder diagnoses sometimes change due to misdiagnosis, maturation, or treatment. This study uses a probability-based national survey-the Survey of Pathways to Diagnosis and Services-to compare currently diagnosed (n = 1420) and previously diagnosed (n = 187) children aged 6-17 years based on retrospective parental reports of early concerns about their children’s development, responses to those concerns by doctors and other healthcare providers, the type of provider who made the first autism spectrum disorder diagnosis, and the autism spectrum disorder subtype diagnoses received (if any). Propensity score matching was used to control for differences between the groups on children’s current level of functioning and other current characteristics that may have been related to diagnosis loss. Approximately 13% of the children ever diagnosed with autism spectrum disorder were estimated to have lost the diagnosis, and parents of 74% of them believed it was changed due to new information. Previously diagnosed children were less likely to have parents with early concerns about verbal skills, nonverbal communication, learning, and unusual gestures or movements. They were also less likely to have been referred to and diagnosed by a specialist. Previously diagnosed children were less likely to have ever received a diagnosis of Asperger’s disorder or autistic disorder.
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5. Cheslack-Postava K, Susser E, Liu K, Bearman PS. {{Can Sibling Sex Ratios Be Used as a Valid Test for the Prenatal Androgen Hypothesis of Autism Spectrum Disorders?}}. {PLoS One}. 2015; 10(10): e0141338.
BACKGROUND: Sibling sex ratios have been applied as an indirect test of a hypothesized association between prenatal testosterone levels and risk for autism, a developmental disorder disproportionately affecting males. Differences in sibling sex ratios between those with and without autism would provide evidence of a shared risk factor for autism and offspring sex. Conclusions related to prenatal testosterone, however, require additional assumptions. Here, we used directed acyclic graphs (DAGs) to clarify the elements required for a valid test of the hypothesis that sibling sex ratios differ between children with and without autism. We then conducted such a test using a large, population-based sample of children. METHODS: Over 1.1 million subjects, born in California from 1992-2007, and identified through birth records, were included. The association between autism diagnosis, determined using the administrative database of the California Department of Developmental Services, and the sex of the subsequent sibling was examined using generalized estimating equations. Sources of potential bias identified using DAGs were addressed. RESULTS: Among male children with autism, 52.2% of next-born siblings were brothers, versus 51.0% for unaffected males. For females with autism, 50.2% of following siblings were brothers versus 51.2% among control females. The relative risk of a subsequent male sibling associated with autism diagnosis was 1.02 (95% confidence interval: 0.99, 1.04). CONCLUSIONS: In a large, population-based sample we failed to find evidence suggesting an excess of brothers among children with autism while controlling for several threats to validity. This test cannot rule out a role of any given exposure, including prenatal testosterone, in either risk of autism or offspring sex ratio, but suggests against a common cause of both.
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6. Floris DL, Lai MC, Auer T, Lombardo MV, Ecker C, Chakrabarti B, Wheelwright SJ, Bullmore ET, Murphy DG, Baron-Cohen S, Suckling J. {{Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay}}. {Hum Brain Mapp}. 2015.
In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl’s gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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7. Grant N, Rodger S, Hoffmann T. {{Intervention decision-making processes and information preferences of parents of children with autism spectrum disorders}}. {Child Care Health Dev}. 2015.
BACKGROUND: When a child is diagnosed with autism, parents are faced with the task of choosing from many different intervention options. To find information about the options available, parents turn to a number of different sources. This study explores parents’ (n = 23) intervention decision-making processes and information preferences following the diagnosis of ASD for their child. METHODS: Qualitative thematic analysis of verbatim transcripts from interviews and focus groups involving parents of children with an autism diagnosis was undertaken. RESULTS: Analysis of the results revealed that there are concurrent emotional and pragmatic intervention ‘journeys’ undertaken by parents post diagnosis, which encompass the primary themes of: (1) information sources used, (2) parents’ information preferences and (3) factors influencing intervention decision making. Parents described a journey from the point of diagnosis that involved seeking information on ASD interventions from multiple sources, with the Internet being the primary source. They were overwhelmed by the sheer volume of information available, and their preferences for information varied according to their stage in the journey post diagnosis. Parents had a ‘trial and error’ approach to choosing ASD interventions, with confidence increasing as they became more familiar with their child’s condition, and had opportunities to explore numerous information sources about their child’s diagnosis. While confidence increased over time, consideration of the effectiveness or evidence supporting interventions remained largely absent throughout the journey. CONCLUSION: This study highlights the need for parents of children with ASD to be supported to make informed intervention decisions, particularly with consideration for research evidence.
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8. Guillon Q, Afzali MH, Roge B, Baduel S, Kruck J, Hadjikhani N. {{The Importance of Networking in Autism Gaze Analysis}}. {PLoS One}. 2015; 10(10): e0141191.
Visual scanning of faces in individuals with Autism Spectrum Disorder (ASD) has been intensively studied using eye-tracking technology. However, most of studies have relied on the same analytic approach based on the quantification of fixation time, which may have failed to reveal some important features of the scanning strategies employed by individuals with ASD. In the present study, we examined the scanning of faces in a group of 20 preschoolers with ASD and their typically developing (TD) peers, using both classical fixation time approach and a new developed approach based on transition matrices and network analysis. We found between group differences in the eye region in terms of fixation time, with increased right eye fixation time for the ASD group and increased left eye fixation time for the TD group. Our complementary network approach revealed that the left eye might play the role of an anchor in the scanning strategies of TD children but not in that of children with ASD. In ASD, fixation time on the different facial parts was almost exclusively dependent on exploratory activity. Our study highlights the importance of developing innovative measures that bear the potential of revealing new properties of the scanning strategies employed by individuals with ASD.
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9. Han B, Tijus C, Le Barillier F, Nadel J. {{Morphing technique reveals intact perception of object motion and disturbed perception of emotional expressions by low-functioning adolescents with Autism Spectrum Disorder}}. {Res Dev Disabil}. 2015; 47: 393-404.
A morphing procedure has been designed to compare directly the perception of emotional expressions and of moving objects. Morphing tasks were presented to 12 low-functioning teenagers with Autism Spectrum Disorder (LF ASD) compared to 12 developmental age-matched typical children and a group presenting ceiling performance. In a first study, when presented with morphed stimuli of objects and emotional faces, LF ASD showed an intact perception of object change of state together with an impaired perception of emotional facial change of state. In a second study, an eye-tracker recorded visual exploration of morphed emotional stimuli displayed by a human face and a robotic set-up. Facing the morphed robotic stimuli, LF ASD displayed equal duration of fixations toward emotional regions and toward mechanical sources of motion, while the typical groups tracked the emotional regions only. Altogether the findings of the two studies suggest that individuals with ASD process motion rather than emotional signals when facing facial expressions.
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10. McDuffie A, Oakes A, Machalicek W, Ma M, Bullard L, Nelson S, Abbeduto L. {{Early language intervention using distance video-teleconferencing: A pilot study of young males with fragile X syndrome and their mothers}}. {Am J Speech Lang Pathol}. 2015.
Purpose: This study examined the effects of a naturalistic parent-implemented language intervention on the use of verbally responsive language by mothers of six young males with fragile X syndrome (FXS). The intervention included parent education sessions and clinician coaching delivered onsite and by distance video-teleconferencing. Method: A single-case multiple baseline across participants was used to examine intervention effects on maternal use of language support strategies. A nonparametric analysis was used to evaluate the relative effectiveness of onsite compared to distance coaching sessions. Results: Mothers increased their use of utterances that followed into their child’s focus of attention and prompted child communication acts. Intervention effects were not observed for maternal contingent responses to child communication possibly due to the limited number of spontaneous communication acts children produced. Children showed moderate increases in the use of prompted communication acts while intervention effects on spontaneous communication acts were more modest and variable. Comparable increases in maternal strategy use were observed during onsite and distance sessions. Conclusion: No previous study has examined a distance-delivered parent-implemented language intervention for young males with FXS. Mothers were able to increase their use of verbally responsive language. Intervention efficacy might be enhanced by incorporating an AAC device for some children and a more concerted focus on increasing the frequency of child communication acts. Findings provide preliminary support for the efficacy of the distance delivery format.
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11. McMahon CM, Henderson HA, Newell L, Jaime M, Mundy P. {{Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions.
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12. Philippe A, Craus Y, Rio M, Bahi-Buisson N, Boddaert N, Malan V, Bonnefont JP, Robel L. {{Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder}}. {BMC Psychiatry}. 2015; 15(1): 256.
BACKGROUND: Deletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD). Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling. CASE PRESENTATION: Here, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3. The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder. CONCLUSION: Our present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.
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13. Suganya V, Geetha A, Sujatha S. {{Urine proteome analysis to evaluate protein biomarkers in children with autism}}. {Clin Chim Acta}. 2015; 450: 210-9.
BACKGROUND: Autism is a complex developmental disability for which no specific diagnostic markers have been identified so far. The present study aimed to evaluate whether there is any abnormal protein(s) excreted in the urine of autistic children by proteome analysis which may act as diagnostic marker. METHODS: Urine proteome analysis was carried out in first void urine samples of autistic and normal children (n=30) in the age group of 4-12years by 2D-PAGE followed by MALDI-TOF-MS analysis. RESULTS: Comparison of 2D-PAGE gels revealed that many urinary proteins are expressed differentially in autistic children. Total numbers of spots observed were 250 and 159 in autism and normal samples respectively, out of which 95 matches were observed. In addition, 3 spots of abnormally expressed peptides were selected, excised and analyzed. Peptide sequence with significant match score was for kininogen-1 (KNG-1)-50 (spot-1), IgG1 heavy chain variable region-35(spot-2) and mannan-binding lectin serine protease-2 isoform-2 precursor-45(spot-3). All the autistic children showed significant increase (p<0.001) in urinary kininogen level measured quantitatively by ELISA, when compared to normal children. CONCLUSION: Increased urinary kininogen-1 level in all the autistic children and the possibility of this protein as a diagnostic marker need further investigation. Lien vers le texte intégral (Open Access ou abonnement)
14. Wang P, Lin M, Pedrosa E, Hrabovsky A, Zhang Z, Guo W, Lachman HM, Zheng D. {{CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment}}. {Mol Autism}. 2015; 6: 55.
BACKGROUND: Disruptive mutation in the CHD8 gene is one of the top genetic risk factors in autism spectrum disorders (ASDs). Previous analyses of genome-wide CHD8 occupancy and reduced expression of CHD8 by shRNA knockdown in committed neural cells showed that CHD8 regulates multiple cell processes critical for neural functions, and its targets are enriched with ASD-associated genes. METHODS: To further understand the molecular links between CHD8 functions and ASD, we have applied the CRISPR/Cas9 technology to knockout one copy of CHD8 in induced pluripotent stem cells (iPSCs) to better mimic the loss-of-function status that would exist in the developing human embryo prior to neuronal differentiation. We then carried out transcriptomic and bioinformatic analyses of neural progenitors and neurons derived from the CHD8 mutant iPSCs. RESULTS: Transcriptome profiling revealed that CHD8 hemizygosity (CHD8 (+/-)) affected the expression of several thousands of genes in neural progenitors and early differentiating neurons. The differentially expressed genes were enriched for functions of neural development, beta-catenin/Wnt signaling, extracellular matrix, and skeletal system development. They also exhibited significant overlap with genes previously associated with autism and schizophrenia, as well as the downstream transcriptional targets of multiple genes implicated in autism. Providing important insight into how CHD8 mutations might give rise to macrocephaly, we found that seven of the twelve genes associated with human brain volume or head size by genome-wide association studies (e.g., HGMA2) were dysregulated in CHD8 (+/-) neural progenitors or neurons. CONCLUSIONS: We have established a renewable source of CHD8 (+/-) iPSC lines that would be valuable for investigating the molecular and cellular functions of CHD8. Transcriptomic profiling showed that CHD8 regulates multiple genes implicated in ASD pathogenesis and genes associated with brain volume.
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15. Wu JY. {{Autism, an area that needs public attention and investment}}. {Sci China Life Sci}. 2015; 58(10): 931-2.
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16. Yu L, Wu Y, Wu BL. {{Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism}}. {Sci China Life Sci}. 2015; 58(10): 958-67.
Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.
