1. Aan Het Rot M, Hogenelst K. {{The influence of affective empathy and autism spectrum traits on empathic accuracy}}. {PLoS One};2014;9(6):e98436.
Autism spectrum disorder is characterized by interpersonal deficits and has been associated with limited cognitive empathy, which includes perspective taking, theory of mind, and empathic accuracy (EA). The capacity for affective empathy may also be impaired. In the present study we aimed to determine if EA in normally developing individuals with varying levels of autism spectrum traits is moderated by trait affective empathy. Fifty male and fifty female participants (‘perceivers’) completed the Autism-Spectrum Quotient and the Balanced Emotional Empathy Scale to assess autism spectrum traits and trait affective empathy, respectively. EA was assessed using a Dutch-language version of a previously developed task and involved rating the feelings of others (‘targets’) verbally recounting autobiographical emotional events. Targets varied in trait emotional expressivity, assessed using the Berkeley Expressivity Questionnaire. Perceivers with more autism spectrum traits performed worse on the EA task, particularly when their trait affective empathy was relatively low. Interpersonal deficits in autism spectrum disorder may be partially explained by low cognitive empathy. Further, they might be aggravated by a limited capacity for affective empathy.
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2. Blumenthal I, Ragavendran A, Erdin S, Klei L, Sugathan A, Guide JR, Manavalan P, Zhou JQ, Wheeler VC, Levin JZ, Ernst C, Roeder K, Devlin B, Gusella JF, Talkowski ME. {{Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex and multiplex autism families}}. {Am J Hum Genet};2014 (Jun 5);94(6):870-883.
Reciprocal copy-number variation (CNV) of a 593 kb region of 16p11.2 is a common genetic cause of autism spectrum disorder (ASD), yet it is not completely penetrant and can manifest in a wide array of phenotypes. To explore its molecular consequences, we performed RNA sequencing of cerebral cortex from mouse models with CNV of the syntenic 7qF3 region and lymphoblast lines from 34 members of 7 multiplex ASD-affected families harboring the 16p11.2 CNV. Expression of all genes in the CNV region correlated well with their DNA copy number, with no evidence of dosage compensation. We observed effects on gene expression outside the CNV region, including apparent positional effects in cis and in trans at genomic segments with evidence of physical interaction in Hi-C chromosome conformation data. One of the most significant positional effects was telomeric to the 16p11.2 CNV and includes the previously described « distal » 16p11.2 microdeletion. Overall, 16p11.2 CNV was associated with altered expression of genes and networks that converge on multiple hypotheses of ASD pathogenesis, including synaptic function (e.g., NRXN1, NRXN3), chromatin modification (e.g., CHD8, EHMT1, MECP2), transcriptional regulation (e.g., TCF4, SATB2), and intellectual disability (e.g., FMR1, CEP290). However, there were differences between tissues and species, with the strongest effects being consistently within the CNV region itself. Our analyses suggest that through a combination of indirect regulatory effects and direct effects on nuclear architecture, alteration of 16p11.2 genes disrupts expression networks that involve other genes and pathways known to contribute to ASD, suggesting an overlap in mechanisms of pathogenesis.
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3. Brodhead MT, Higbee TS, Pollard JS, Akers JS, Gerencser KR. {{The use of linked activity schedules to teach children with autism to play hide-and-seek}}. {J Appl Behav Anal};2014 (Jun 6)
Linked activity schedules were used to establish appropriate game play in children with autism during a game of hide-and-seek. All 6 participants demonstrated acquisition of appropriate play skills in the presence of the activity schedules and maintained responding during subsequent phases. When the schedules were removed, responding decreased to baseline levels, demonstrating that the schedules controlled responding. Implications for future research on the use of activity schedules to teach social behavior are discussed.
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4. Dere E, Dahm L, Lu D, Hammerschmidt K, Ju A, Tantra M, Kastner A, Chowdhury K, Ehrenreich H. {{Heterozygous ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender}}. {Front Behav Neurosci};2014;8:181.
Autism-spectrum disorders (ASD) are heterogeneous, highly heritable neurodevelopmental conditions affecting around 0.5% of the population across cultures, with a male/female ratio of approximately 4:1. Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g., through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar phenotypical consequences. Ambra1, strongly expressed in cortex, hippocampus, and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1 (+/-) females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups, which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1 (+/-) mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1 (+/-) females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation.
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5. Grow LL, Kodak T, Carr JE. {{A comparison of methods for teaching receptive labeling to children with autism spectrum disorders: A systematic replication}}. {J Appl Behav Anal};2014 (Jun 6)
Previous research has demonstrated that the conditional-only method (starting with a multiple-stimulus array) is more efficient than the simple-conditional method (progressive incorporation of more stimuli into the array) for teaching receptive labeling to children with autism spectrum disorders (Grow, Carr, Kodak, Jostad, & Kisamore, ). The current study systematically replicated the earlier study by comparing the 2 approaches using progressive prompting with 2 boys with autism. The results showed that the conditional-only method was a more efficient and reliable teaching procedure than the simple-conditional method. The results further call into question the practice of teaching simple discriminations to facilitate acquisition of conditional discriminations.
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6. Hasegawa C, Kikuchi M, Yoshimura Y, Hiraishi H, Munesue T, Nakatani H, Higashida H, Asada M, Oi M, Minabe Y. {{The broader autism phenotype in mothers predicts social responsiveness in young children with autism spectrum disorders}}. {Psychiatry Clin Neurosci};2014 (Jun 6)
AIMS: The aim of this study was to identify phenotypes in mothers and fathers that are specifically associated with disturbances in reciprocal social interactions and communication in their young children with autism spectrum disorder (ASD) in a Japanese sample. METHOD: Autistic traits in parents were evaluated using the autism spectrum quotient (AQ), the empathy quotient (EQ) and the systemizing quotient (SQ) in 88 parents (44 mothers and corresponding fathers) of children with ASD and in 60 parents (30 mothers and corresponding fathers) of TD (typically development) children. For the measurement of autistic traits in children, we employed the Social Responsiveness Scale (SRS). RESULTS: In two of the five AQ subscales (social skills and communication), the parents of ASD children scored significantly higher than did the parents of TD children, regardless of whether the parent was a mother or a father. In addition, in mothers of ASD children, there were significant positive correlations between two of the five AQ subscales (attention switching and communication) and the SRS T-score in their children. CONCLUSIONS: This is the first study to demonstrate that the social skills and communication subscales in the AQ are more sensitive as autism traits in a Japanese sample and to demonstrate that some autistic traits in mothers are specifically associated with disturbances in the social ability of their young children with ASD, as measured by the SRS score. Further study is necessary to determine whether these results were caused by genetic or environmental factors.
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7. Isomura T, Ogawa S, Yamada S, Shibasaki M, Masataka N. {{Preliminary evidence that different mechanisms underlie the anger superiority effect in children with and without Autism Spectrum Disorders}}. {Front Psychol};2014;5:461.
Previous studies have demonstrated that angry faces capture humans’ attention more rapidly than emotionally positive faces. This phenomenon is referred to as the anger superiority effect (ASE). Despite atypical emotional processing, adults and children with Autism Spectrum Disorders (ASD) have been reported to show ASE as well as typically developed (TD) individuals. So far, however, few studies have clarified whether or not the mechanisms underlying ASE are the same for both TD and ASD individuals. Here, we tested how TD and ASD children process schematic emotional faces during detection by employing a recognition task in combination with a face-in-the-crowd task. Results of the face-in-the-crowd task revealed the prevalence of ASE both in TD and ASD children. However, the results of the recognition task revealed group differences: In TD children, detection of angry faces required more configural face processing and disrupted the processing of local features. In ASD children, on the other hand, it required more feature-based processing rather than configural processing. Despite the small sample sizes, these findings provide preliminary evidence that children with ASD, in contrast to TD children, show quick detection of angry faces by extracting local features in faces.
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8. Kerns CM, Kendall PC, Berry L, Souders MC, Franklin ME, Schultz RT, Miller J, Herrington J. {{Traditional and Atypical Presentations of Anxiety in Youth with Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Jun 6)
We assessed anxiety consistent (i.e., « traditional ») and inconsistent (i.e., « atypical ») with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were explored. Fifty-nine participants (7-17 years, Mage = 10.48 years; IQ > 60) with ASD and parents completed semi-structured interviews, self- and parent-reports. Seventeen percent of youth presented with traditional anxiety, 15 % with atypical anxiety, and 31 % with both. Language ability, anxious cognitions and hypersensitivity predicted traditional anxiety, whereas traditional anxiety and ASD symptoms predicted atypical anxiety. Findings suggest youth with ASD express anxiety in ways similar and dissimilar to DSM definitions. Similarities support the presence of comorbid anxiety disorders in ASD. Whether dissimilarities are unique to ASD requires further examination.
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9. Lau WY, Gau SS, Chiu YN, Wu YY. {{Autistic Traits in Couple Dyads as a Predictor of Anxiety Spectrum Symptoms}}. {J Autism Dev Disord};2014 (Jun 7)
The link between parental autistic tendency and anxiety symptoms was studied in 491 Taiwanese couples raising biological children with autism spectrum disorders (ASDs). Parental autistic tendency as measured by Autism Spectrum Quotient (AQ) was associated with anxiety symptoms across all domains. Large effect sizes were found in social phobia and post traumatic stress disorders for both parents, and in general anxiety disorder and agoraphobia for mothers. These associations were irrespective of child’s autistic tendency, spouse’s AQ scores and the couples’ compatibility in their autistic tendency. Perceived family support and parental education moderated the link but not child’s autistic severity. Research and clinical implications regarding psychiatric vulnerability of parents of children with ASD were drawn and discussed.
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10. Liu T, Wan RP, Tang LJ, Liu SJ, Li HJ, Zhao QH, Liao WP, Sun XF, Yi YH, Long YS. {{A MicroRNA Profile in Fmr1 Knockout Mice Reveals MicroRNA Expression Alterations with Possible Roles in Fragile X Syndrome}}. {Mol Neurobiol};2014 (Jun 7)
Fragile X syndrome (FXS), a common form of inherited mental retardation, is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is involved in brain functions by interacting with mRNAs and microRNAs (miRNAs) that selectively control gene expression at translational level. However, little is known about the role of FMRP in regulating miRNA expression. Here, we found a development-dependant dynamic expression of Fmr1 gene (encoding FMRP) in mouse hippocampus with a small peak at postnatal day 7 (P7). MiRNA microarray analysis showed that the levels of 38 miRNAs showed a significant increase with about 15 ~ 250-folds and the levels of 26 miRNAs showed a significant decrease with only about 2 ~ 4-folds in the hippocampus of P7 Fmr1 knockout (KO) mice. The qRT-PCR assay showed that nine of the most increased miRNAs (>100-folds in microarrays) increased about 40 ~ 70-folds and their pre-miRNAs increased about 5 ~ 10-folds, but no significant difference in their pri-miRNA levels was observed, suggesting that the alterations of partial miRNAs are an indirect consequence of FMRP lacking. We further demonstrated that a set of protein-coding mRNAs, potentially targeted by the nine miRNAs, were down-regulated in the hippocampus of Fmr1 KO mice. Finally, luciferase assays demonstrated that miR-34b, miR-340, and miR-148a could down-regulate the reporter gene expression by interacting with the Met 3′ UTR. Taken together, these findings suggest that the miRNA expression alterations resulted from the absence of FMRP might contribute to molecular pathology of FXS.
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11. Raff M. {{Open questions: What has genetics told us about autism spectrum disorders?}}. {BMC Biol};2014;12(1):45.
Some of the most interesting questions in biology today, in my view, derive from the real advances in neuropsychiatry that have come largely from human genetics. Research in autism spectrum disorders (ASDs) has been leading the way, mainly because it has become especially well funded and has recently attracted many outstanding scientists. (I must make it clear that I am an outsider in this field, as I have never worked on any neuropsychiatric disorder).
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12. Slaughter V, Ong SS. {{Social Behaviors Increase More When Children With ASD Are Imitated by Their Mother vs. an Unfamiliar Adult}}. {Autism Res};2014 (Jun 5)
Previous research suggests that being imitated by an adult increases the social behaviors of children with an autism spectrum disorder (ASD). In the current study, we examined whether familiarity with the imitating social partner modulates this effect. Ten children with ASD and their mothers participated. The children’s social behaviors were observed prior to and following a 3-min period in which an adult social partner imitated everything they did. In one condition the partner was the child’s mother, and in the other condition the partner was an unfamiliar experimenter. The results revealed significant increases in distal social behaviors (gazes toward the adult, vocalizing) following imitation by both partners. There was a significantly greater increase in proximal social behaviors (including approach, being physically close, and touching) and a greater decrease in playing alone when the imitator was the child’s mother as opposed to the experimenter. The findings suggest that the experience of being imitated creates an atmosphere of mutuality and rapport between children with ASD and their social partners, which increases their sociability even in interactions with already familiar adults. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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13. Stevenson RA, Segers M, Ferber S, Barense MD, Wallace MT. {{The impact of multisensory integration deficits on speech perception in children with autism spectrum disorders}}. {Front Psychol};2014;5:379.
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14. Stoodley CJ. {{Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia}}. {Front Syst Neurosci};2014;8:92.
Differences in cerebellar structure have been identified in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental dyslexia. However, it is not clear if different cerebellar regions are involved in each disorder, and thus whether cerebellar anatomical differences reflect a generic developmental vulnerability or disorder-specific characteristics. To clarify this, we conducted an anatomic likelihood estimate (ALE) meta-analysis on voxel-based morphometry (VBM) studies which compared ASD (17 studies), ADHD (10 studies), and dyslexic (10 studies) participants with age-matched typically-developing (TD) controls. A second ALE analysis included studies in which the cerebellum was a region of interest (ROI). There were no regions of significantly increased gray matter (GM) in the cerebellum in ASD, ADHD, or dyslexia. Data from ASD studies revealed reduced GM in the inferior cerebellar vermis (lobule IX), left lobule VIIIB, and right Crus I. In ADHD, significantly decreased GM was found bilaterally in lobule IX, whereas participants with developmental dyslexia showed GM decreases in left lobule VI. There was no overlap between the cerebellar clusters identified in each disorder. We evaluated the functional significance of the regions revealed in both whole-brain and cerebellar ROI ALE analyses using Buckner and colleagues’ 7-network functional connectivity map available in the SUIT cerebellar atlas. The cerebellar regions identified in ASD showed functional connectivity with frontoparietal, default mode, somatomotor, and limbic networks; in ADHD, the clusters were part of dorsal and ventral attention networks; and in dyslexia, the clusters involved ventral attention, frontoparietal, and default mode networks. The results suggest that different cerebellar regions are affected in ASD, ADHD, and dyslexia, and these cerebellar regions participate in functional networks that are consistent with the characteristic symptoms of each disorder.
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15. Tenenbaum EJ, Amso D, Abar B, Sheinkopf SJ. {{Attention and word learning in autistic, language delayed and typically developing children}}. {Front Psychol};2014;5:490.
Previous work has demonstrated that patterns of social attention hold predictive value for language development in typically developing infants. The goal of this research was to explore how patterns of attention in autistic, language delayed, and typically developing children relate to early word learning and language abilities. We tracked patterns of eye movements to faces and objects while children watched videos of a woman teaching them a series of new words. Subsequent test trials measured participants’ recognition of these novel word-object pairings. Results indicated that greater attention to the speaker’s mouth was related to higher scores on standardized measures of language development for autistic and typically developing children (but not for language delayed children). This effect was mediated by age for typically developing, but not autistic children. When effects of age were controlled for, attention to the mouth among language delayed participants was negatively correlated with standardized measures of language learning. Attention to the speaker’s mouth and eyes while she was teaching the new words was also predictive of faster recognition of those words among autistic children. These results suggest that language delays among children with autism may be driven in part by aberrant social attention, and that the mechanisms underlying these delays may differ from those in language delayed participants without autism.
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16. Uutela M, Lindholm J, Rantamaki T, Umemori J, Hunter K, Voikar V, Castren ML. {{Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome}}. {Front Cell Neurosci};2014;8:150.
Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD), including Fragile X syndrome (FXS). The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO) mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild-type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test. In Fmr1 KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced brain-derived neurotrophic factor (BDNF) and increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmr1 KO mice when compared with wild-type controls. The postnatal mRNA expression of serotonin transporter (SERT) was reduced in the thalamic nuclei of Fmr1 KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild-type and Fmr1 mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD.
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17. Wilson CE, Happe F, Wheelwright SJ, Ecker C, Lombardo MV, Johnston P, Daly E, Murphy CM, Spain D, Lai MC, Chakrabarti B, Sauter DA, Baron-Cohen S, Murphy DG. {{The Neuropsychology of Male Adults With High-Functioning Autism or Asperger Syndrome}}. {Autism Res};2014 (Jun 5)
Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P’s < 0.05). To investigate cognitive profiles, 12 variables were entered into a support vector machine (SVM), which achieved good classification accuracy (81%) at a level significantly better than chance (P < 0.0001). After correcting for multiple correlations, there were no significant associations between cognitive performance and severity of either autistic or comorbid symptomatology. There were no significant differences between AS and HFA groups on the cognitive tasks. Cognitive classification models could be a useful aid to the diagnostic process when used in conjunction with other data sources-including clinical history. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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18. Zoder-Martell KA, Dufrene BA, Tingstrom DH, Olmi DJ, Jordan SS, Biskie EM, Sherman JC. {{Training direct care staff to increase positive interactions with individuals with developmental disabilities}}. {Res Dev Disabil};2014 (Jun 7);35(9):2180-2189.
This study tested the effects of direct training on direct care staff’s initiation of positive interactions with individuals with developmental disabilities who resided in an intermediate care facility. Participants included four direct care staff and their residents. Direct training included real-time prompts delivered via a one-way radio, and data were collected for immediate and sustained increases in rates of direct care staff’s positive interactions. Additionally, this study evaluated the link between increased rates of positive interactions and concomitant decreases in residents’ challenging behaviors. A multiple baseline design across participants was used and results indicated that all direct care staff increased their rates of positive interactions during direct training. Moreover, all but one participant continued to engage residents in positive interactions at levels above the criterion during the maintenance phase and follow-up phases. The direct care staff member who did not initially meet the criterion improved to adequate levels following one brief performance feedback session. With regard to residents’ challenging behaviors, across phases, residents engaged in low levels of challenging behaviors making those results difficult to evaluate. However, improvements in residents’ rate of positive interactions were noted.
