1. Benson PR. {{Coping and Psychological Adjustment Among Mothers of Children with ASD: An Accelerated Longitudinal Study}}. {J Autism Dev Disord};2014 (Mar 6)
Utilizing a cohort sequential design and multilevel modeling on a sample of 113 mothers, the effects of four coping strategies (engagement, disengagement, distraction, and cognitive reframing) on multiple measures of maternal adjustment were assessed over a 7 years period when children with autism spectrum disorders in the study were approximately 7-14 years old. Findings indicated increased use of disengagement and distraction to be related to increased maternal maladjustment over time, while increased use of cognitive reframing was linked to improved maternal outcomes (findings regarding engagement’s effects on adjustment measures were mixed). In addition, results indicated that use of different coping strategies at times moderated the effects of child behavior on maternal adjustment. Study findings are discussed in light of prior research and study limitations and clinical implications are highlighted.
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2. Blaser E, Eglington L, Carter AS, Kaldy Z. {{Pupillometry Reveals a Mechanism for the Autism Spectrum Disorder (ASD) Advantage in Visual Tasks}}. {Sci Rep};2014;4:4301.
Research on the neural underpinnings of Autism Spectrum Disorder (ASD) has focussed primarily on impairments of social interaction and communication. Less is known though about the second diagnostic criterion of restricted behaviors and interests. Uniquely in this domain, alongside impairments stands an ‘ASD advantage’ characterised by superior performance on many visual tasks. We recently found that 2-year-olds with ASD dramatically outperform age-matched, typically developing controls on visual search. Here we use task-evoked, phasic pupil responses – a sensitive, involuntary measure of effort and a biomarker of the locus coeruleus-norepinephrine (LC-NE) system’s modulation of attention – to isolate a causal factor: a ‘hyperphasic’ LC-NE system compels (here, advantageously) focussed attention. However, this focussed attention in other contexts may contribute to restricted behaviors and interests.
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3. Bolte S. {{The power of words: is qualitative research as important as quantitative research in the study of autism?}}. {Autism};2014 (Feb);18(2):67-68.
4. Bouvet L, Donnadieu S, Valdois S, Caron C, Dawson M, Mottron L. {{Veridical mapping in savant abilities, absolute pitch, and synesthesia: an autism case study}}. {Front Psychol};2014;5:106.
An enhanced role and autonomy of perception are prominent in autism. Furthermore, savant abilities, absolute pitch, and synesthesia are all more commonly found in autistic individuals than in the typical population. The mechanism of veridical mapping has been proposed to account for how enhanced perception in autism leads to the high prevalence of these three phenomena and their structural similarity. Veridical mapping entails functional rededication of perceptual brain regions to higher order cognitive operations, allowing the enhanced detection and memorization of isomorphisms between perceptual and non-perceptual structures across multiple scales. In this paper, we present FC, an autistic individual who possesses several savant abilities in addition to both absolute pitch and synesthesia-like associations. The co-occurrence in FC of abilities, some of them rare, which share the same structure, as well as FC’s own accounts of their development, together suggest the importance of veridical mapping in the atypical range and nature of abilities displayed by autistic people.
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5. Carayol J, Schellenberg GD, Dombroski B, Amiet C, Genin B, Fontaine K, Rousseau F, Vazart C, Cohen D, Frazier TW, Hardan AY, Dawson G, Rio Frio T. {{A scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism}}. {Front Genet};2014;5:33.
Autism spectrum disorders (ASD) are highly heritable complex neurodevelopmental disorders with a 4:1 male: female ratio. Common genetic variation could explain 40-60% of the variance in liability to autism. Because of their small effect, genome-wide association studies (GWASs) have only identified a small number of individual single-nucleotide polymorphisms (SNPs). To increase the power of GWASs in complex disorders, methods like convergent functional genomics (CFG) have emerged to extract true association signals from noise and to identify and prioritize genes from SNPs using a scoring strategy combining statistics and functional genomics. We adapted and applied this approach to analyze data from a GWAS performed on families with multiple children affected with autism from Autism Speaks Autism Genetic Resource Exchange (AGRE). We identified a set of 133 candidate markers that were localized in or close to genes with functional relevance in ASD from a discovery population (545 multiplex families); a gender specific genetic score (GS) based on these common variants explained 1% (P = 0.01 in males) and 5% (P = 8.7 x 10(-7) in females) of genetic variance in an independent sample of multiplex families. Overall, our work demonstrates that prioritization of GWAS data based on functional genomics identified common variants associated with autism and provided additional support for a common polygenic background in autism.
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6. Francesco B, Riccardo LR, Francesco G, Clementina CG, Anna G, Charlotte KN, Nicoletta L. {{Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action}}. {Neurosci Biobehav Rev};2014 (Mar 1)
Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.
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7. Frazier TW, Thompson L, Youngstrom EA, Law P, Hardan AY, Eng C, Morris N. {{A Twin Study of Heritable and Shared Environmental Contributions to Autism}}. {J Autism Dev Disord};2014 (Mar 7)
The present study examined genetic and shared environment contributions to quantitatively-measured autism symptoms and categorically-defined autism spectrum disorders (ASD). Participants included 568 twins from the Interactive Autism Network. Autism symptoms were obtained using the Social Communication Questionnaire and Social Responsiveness Scale. Categorically-defined ASD was based on clinical diagnoses. DeFries-Fulker and liability threshold models examined etiologic influences. Very high heritability was observed for extreme autism symptom levels ([Formula: see text]). Extreme levels of social and repetitive behavior symptoms were strongly influenced by common genetic factors. Heritability of categorically-defined ASD diagnosis was comparatively low (.21, 95 % CI 0.15-0.28). High heritability of extreme autism symptom levels confirms previous observations of strong genetic influences on autism. Future studies will require large, carefully ascertained family pedigrees and quantitative symptom measurements.
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8. Geurts HM, van den Bergh SF, Ruzzano L. {{Prepotent Response Inhibition and Interference Control in Autism Spectrum Disorders: Two Meta-Analyses}}. {Autism Res};2014 (Mar 4)
There is a substantial amount of data providing evidence for, but also against the hypothesis that individuals with autism spectrum disorders (ASD) encounter inhibitory control deficits. ASD is often associated with interference control deficits rather than prepotent response inhibition. Moreover, the developmental trajectory for these inhibitory control processes is hypothesized to differ in ASD as compared to typical development. In efforts to gain a more comprehensive perspective of inhibition in ASD, separate quantitative analysis for prepotent response inhibition studies and interference control studies were conducted. Together, these two meta-analyses included 41 studies with a combined sample size of 1,091 people with ASD (M age 14.8 years), and 1,306 typically developing (TD) controls (M age 13.8 years).The meta-analyses indicated that individuals with ASD show increased difficulties in prepotent response inhibition (effect size 0.55) and in interference control (effect size 0.31). In addition, age was a relevant moderator for prepotent response inhibition but not for interference control. Exploratory analyses revealed that when IQ was taken into account, heterogeneity considerably decreased among interference control studies but not among prepotent response inhibition. In contrast to the general belief, both prepotent response inhibition and interference control problems were observed in individuals with ASD. However, a large variation between studies was also found. Therefore, there remain factors beyond inhibition type, age, or IQ that significantly influence inhibitory control performance among individuals with ASD. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Hao G, Layton TL, Zou XB, Li DY. {{Evaluating autism in a Chinese population: the Clinical Autism Diagnostic Scale}}. {World J Pediatr};2014 (Mar 6)
BACKGROUND: The purpose of this study was to report on the psychometric measures and discriminatory function of a new diagnostic test for autism spectrum disorders, the Clinical Autism Diagnostic Scale (CADS). METHODS: The CADS was used to test 216 children in the study, including 86 with low-functioning autism specturm disorders (ASD), 16 children with highfunctioning ASD, 16 with pervasive developmental disorder, not otherwise specified, 7 with Asperger syndrome, 65 with typical development, 11 children with language impairments and 15 with intellectual disabilities. Ages ranged from 38-73 months. Behaviors for the groups were compared across seven domains. RESULTS: The results indicated the instrument was reliable, valid, and successfully differentiated the different groups of children with and without autism. All ASD groups were found to display difficulties in the domains of sensory behaviors and stereotyped behaviors. The play and social domains were found to measure similar underlying concepts of behaviors, while the receptive language and expressive language domains were also found to measure similar underlying-language concepts. The group of children diagnosed as having low-functioning autism performed less well on all tested domains in the instrument than did the other three groups of children with ASD, and these other three groups each also presented unique patterns of behaviors and differed on individual domains. CONCLUSIONS: CADS is a reliable and valid test. It successfully differentiates the abilities of children with ASD at different levels of functioning.
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10. Huguet G, Nava C, Lemiere N, Patin E, Laval G, Ey E, Brice A, Leboyer M, Szepetowski P, Gillberg C, Depienne C, Delorme R, Bourgeron T. {{Heterogeneous Pattern of Selective Pressure for PRRT2 in Human Populations, but No Association with Autism Spectrum Disorders}}. {PLoS One};2014;9(3):e88600.
Inherited and de novo genomic imbalances at chromosome 16p11.2 are associated with autism spectrum disorders (ASD), but the causative genes remain unknown. Among the genes located in this region, PRRT2 codes for a member of the synaptic SNARE complex that allows the release of synaptic vesicles. PRRT2 is a candidate gene for ASD since homozygote mutations are associated with intellectual disability and heterozygote mutations cause benign infantile seizures, paroxysmal dyskinesia, or hemiplegic migraine. Here, we explored the contribution of PRRT2 mutations in ASD by screening its coding part in a large sample of 1578 individuals including 431 individuals with ASD, 186 controls and 961 individuals from the human genome Diversity Panel. We detected 24 nonsynonymous variants, 1 frameshift (A217PfsX8) and 1 in-frame deletion of 6 bp (p.A361_P362del). The frameshift mutation was observed in a control with no history of neurological or psychiatric disorders. The p.A361_P362del was observed in two individuals with autism from sub-Saharan African origin. Overall, the frequency of PRRT2 deleterious variants was not different between individuals with ASD and controls. Remarkably, PRRT2 displays a highly significant excess of nonsynonymous (pN) vs synonymous (pS) mutations in Asia (pN/pS = 4.85) and Europe (pN/pS = 1.62) compared with Africa (pN/pS = 0.26; Asia vs Africa: P = 0.000087; Europe vs Africa P = 0.00035; Europe vs Asia P = P = 0.084). We also showed that whole genome amplification performed through rolling cycle amplification could artificially introduce the A217PfsX8 mutation indicating that this technology should not be performed prior to PRRT2 mutation screening. In summary, our results do not support a role for PRRT2 coding sequence variants in ASD, but provide an ascertainment of its genetic variability in worldwide populations that should help researchers and clinicians to better investigate the role of PRRT2 in human diseases.
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11. Li J, Zhu L, Gummerum M. {{The relationship between moral judgment and cooperation in children with high-functioning autism}}. {Sci Rep};2014;4:4314.
This study investigated moral judgment in children with high-functioning autism and their cooperation in prisoner’s dilemma game with partners of different moralities. Thirty-eight 6- to 12-year-old high-functioning autistic (HFA) children and 31 typically developing (TD) children were recruited. Children were asked to judge story protagonists’ morality. After making this moral judgment correctly, they were asked to play with the morally nice and the morally naughty child in a repeated prisoner’s dilemma game. Results showed that both HFA and TD children made correct moral judgments, and that HFA children might even have more rigid criteria for what constitutes morally naughty acts. HFA children’s cooperation did not differ depending on the morality of the interaction partner, while TD children showed higher cooperation when interacting with the morally nice than the morally naughty child did. Thus, partner’s morality did influence TD children’s but not HFA children’s subsequent cooperation.
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12. Liang S, Wang XL, Zou MY, Wang H, Zhou X, Sun CH, Xia W, Wu LJ, Fujisawa TX, Tomoda A. {{Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population}}. {J Zhejiang Univ Sci B};2014 (Mar);15(3):264-271.
Objective: A study in a Caucasian population has identified two single-nucleotide polymorphisms (SNPs) in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population. Methods: We performed a similar association study using families with three individuals (one autistic child and two unaffected parents). A family-based transmission disequilibrium test (TDT) was used to analyze the results. Results: There were significant associations between autism and the two SNPs of ZNF533 gene (rs11885327: chi(2)=4.5200, P=0.0335; rs1964081: chi(2)=4.2610, P=0.0390) and the SNP of DOCK4 gene (rs2217262: chi(2)=5.3430, P=0.0208). Conclusions: Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.
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13. Moul C, Cauchi A, Hawes DJ, Brennan J, Dadds MR. {{Differentiating Autism Spectrum Disorder and Overlapping Psychopathology with a Brief Version of the Social Responsiveness Scale}}. {Child Psychiatry Hum Dev};2014 (Mar 7)
The Social Responsiveness Scale (SRS) is a well-established measure of autism spectrum disorder (ASD), yet it is known to suffer reduced specificity in samples of children with comorbid emotional or behavioural problems. This research examined the specificity of the SRS in children with mixed presentations of internalising and externalising psychopathology and ASD. Participants were 522 (397 male) children aged between 4 and 16 years. The associations between SRS total scores and diagnoses were determined using partial correlations and analyses of variance. A subsample of participants with a single diagnosis was used to identify a subset of questions that distinguished between ASD and all other diagnoses. These items were used to create the 16-item SRS-brief. The SRS was found to have good reliability and sensitivity but poor specificity. The SRS-brief had good psychometric properties and was found to be a more accurate tool for the screening of ASD than the original SRS.
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14. Stachnik J, Gabay M. {{Emerging role of aripiprazole for treatment of irritability associated with autistic disorder in children and adolescents}}. {Adolesc Health Med Ther};2010;1:105-114.
Autistic disorder is a largely misunderstood and difficult to treat neurodevelopmental disorder. Three core domains of functioning are affected by autistic disorder, ie, socialization, communication, and behavior. Signs of autistic disorder may be present early, but are frequently overlooked, resulting in a delay in its diagnosis and a subsequent delay in treatment. No one definitive therapy is available, and treatment consists of early educational and behavioral interventions, as well as drug therapy. Atypical antipsychotics have often been used in the treatment of autistic disorder to target irritability, aggression, and self-injurious behavior, all of which can interfere with other aspects of treatment. One atypical antipsychotic, aripiprazole, has recently been approved for treatment of irritability associated with autistic disorder. Based on the results from two randomized, controlled trials, with efficacy data from nearly 300 patients, treatment with aripiprazole was associated with reductions in irritability, global improvements in behavior, and improvements in quality of life from both the patient and caregiver perspectives. Dosage of aripiprazole ranged from 5 mg to 15 mg per day. Aripiprazole was well tolerated during clinical trials, with most adverse events considered mild or moderate. Clinically relevant weight gain occurred in about 30% of patients given aripiprazole, although when compared with other atypical antipsychotics, aripiprazole appears to have fewer metabolic effects and a lower risk of weight gain. However, pediatric patients taking any atypical antipsychotic should be carefully monitored for potential adverse events, because the long-term effects of antipsychotic therapy in this population are not well known. When used appropriately, aripiprazole has the potential to be an effective treatment for children with autistic disorder to improve irritability and aggressive behavior and improve quality of life.
