1. Andrea S, Jacena LM, Patrick A, Rawi N, Tasleem C, John O, Randi H, David H. {{Electrocortical changes associated with minocycline treatment in fragile X syndrome}}. {J Psychopharmacol}. 2013.
Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). Human-targeted treatment trials with minocycline have shown benefits in behavioral measures and parent reports. Event-related potentials (ERPs) may provide a sensitive method of monitoring treatment response and changes in coordinated brain activity. Measurement of electrocortical changes due to minocycline was done in a double-blind, placebo-controlled crossover treatment trial in children with FXS. Children with FXS (Meanage 10.5 years) were randomized to minocycline or placebo treatment for 3 months then changed to the other treatment for 3 months. The minocycline dosage ranged from 25-100 mg daily, based on weight. Twelve individuals with FXS (eight male, four female) completed ERP studies using a passive auditory oddball paradigm. Current source density (CSD) and ERP analysis at baseline showed high-amplitude, long-latency components over temporal regions. After 3 months of treatment with minocycline, the temporal N1 and P2 amplitudes were significantly reduced compared with placebo. There was a significant amplitude increase of the central P2 component on minocycline. Electrocortical habituation to auditory stimuli improved with minocycline treatment. Our study demonstrated improvements of the ERP in children with FXS treated with minocycline, and the potential feasibility and sensitivity of ERPs as a cognitive biomarker in FXS treatment trials.
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2. Coskun MA, Loveland KA, Pearson DA, Papanicolaou AC, Sheth BR. {{Interaction of Finger Representations in the Cortex of Individuals with Autism: A Functional Window into Cortical Inhibition}}. {Autism Res}. 2013.
An established neural biomarker of autism spectrum disorder (ASD) has the potential to provide novel biological and pharmacological targets for treatment. Lower level of inhibition in brain circuits is a leading biomarker candidate. A physiological investigation of the functional levels of inhibition in the cortex of individuals with autism can provide a strong test of the hypothesis. The amplitude of cortical response to the stimulation of adjacent fingers is controlled by the level of cortical inhibition and provides just such a test. Using magnetoencephalography, we recorded the response of the somatosensory cortex to the passive tactile stimulation of the thumb (D1), and index finger (D2), and to the simultaneous stimulation of both fingers combined (D1,D2) of the dominant (right) hand of young subjects with and without autism. For each participant, we measured the response to the stimulation of both fingers combined (D1,D2) relative to the post hoc sum of the responses to the stimulation of each finger alone (D1+D2) in multiple different ways and linearly regressed the ASD and neurotypical (NT) groups’ responses. The resulting slopes were then compared: Smaller slope values imply attenuated response to paired finger stimulation, and enhanced levels of inhibition. The short-latency M40 and mid-latency M80 response slopes of the group with autism obtained in different ways were either significantly smaller, or statistically indistinguishable from NT. The result does not support reduced inhibition in the somatosensory cortex of individuals with autism, contrary to the seminal hypothesis of reduced inhibition. Implications are discussed including refinements of current theory. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Hamilton PJ, Campbell NG, Sharma S, Erreger K, Herborg Hansen F, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. {{De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder}}. {Mol Psychiatry}. 2013.
De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.Molecular Psychiatry advance online publication, 27 August 2013; doi:10.1038/mp.2013.102.
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4. Howlin P. {{Social disadvantage and exclusion: adults with autism lag far behind in employment prospects}}. {J Am Acad Child Adolesc Psychiatry}. 2013; 52(9): 897-9.
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5. Khatri N, Simpson KL, Lin RC, Paul IA. {{Lasting neurobehavioral abnormalities in rats after neonatal activation of serotonin 1A and 1B receptors: possible mechanisms for serotonin dysfunction in autistic spectrum disorders}}. {Psychopharmacology (Berl)}. 2013.
RATIONALE: Perinatal exposure of rats to selective serotonin reuptake inhibitors (SSRIs) produces sensory and social abnormalities paralleling those seen in autistic spectrum disorders (ASDs). However, the possible mechanism(s) by which this exposure produces behavioral abnormalities is unclear. OBJECTIVE: We hypothesized that the lasting effects of neonatal SSRI exposure are a consequence of abnormal stimulation of 5-HT1A and/or 5-HT1B receptors during brain development. We examined whether such stimulation would result in lasting sensory and social deficits in rats in a manner similar to SSRIs using both direct agonist stimulation of receptors as well as selective antagonism of these receptors during SSRI exposure. METHODS: Male and female rat pups were treated from postnatal days 8 to 21. In Experiment 1, pups received citalopram (20 mg/kg/day), saline, (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT; 0.5 mg/kg/day) or 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline dimaleate (CGS-12066B; 10 mg/kg/day). In Experiment 2, a separate cohort of pups received citalopram (20 mg/kg/day), or saline which was combined with either N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo-hexanecarboxami de maleate (WAY-100635; 0.6 mg/kg/day) or N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadi azol-3-yl)-1-1′-biphenyl-4-carboxamide (GR-127935; 6 mg/kg/day) or vehicle. Rats were then tested in paradigms designed to assess sensory and social response behaviors at different time points during development. RESULTS: Direct and indirect neonatal stimulation of 5-HT1A or 5-HT1B receptors disrupts sensory processing, produces neophobia, increases stereotypic activity, and impairs social interactions in manner analogous to that observed in ASD. CONCLUSION: Increased stimulation of 5-HT1A and 5-HT1B receptors plays a significant role in the production of lasting social and sensory deficits in adult animals exposed as neonates to SSRIs.
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6. Lin PI, Kuo PH, Chen CH, Wu JY, Gau SS, Wu YY, Liu SK. {{Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model}}. {PLoS One}. 2013; 8(8): e72056.
Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected p = 1.73×10(-8)). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (p = 0.037; combinatorial analysis Stouffer’s z trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions.
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7. Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X. {{Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism}}. {J Transl Med}. 2013; 11(1): 196.
BACKGROUND: Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism. METHODS: 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment. RESULTS: There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05). CONCLUSIONS: Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period.Trial registration: ClinicalTrials.gov: NCT01343511, Title « Safety and Efficacy of Stem Cell Therapy in Patients with Autism ».
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8. Meador KJ, Loring DW. {{Prenatal valproate exposure is associated with autism spectrum disorder and childhood autism}}. {J Pediatr}. 2013; 163(3): 922-6.
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9. Nakai Y, Takashima R, Takiguchi T, Takada S. {{Speech intonation in children with autism spectrum disorder}}. {Brain Dev}. 2013.
Objective: The prosody of children with autism spectrum disorder (ASD) has several abnormal features. We assessed the speech tone of children with ASD and of children with typical development (TD) by using a new quantitative acoustic analysis. Methods: Our study participants consisted of 63 children (26 with ASD and 37 with TD). The participants were divided into 4 groups based on their developmental features and age. We assessed the variety of the fundamental frequency (F0) pattern quantitatively, using pitch coefficient of variation (CV), considering the different F0 mean for each word. Results: (1) No significant difference was observed between the ASD and TD group at pre-school age. However, the TD group exhibited significantly greater pitch CV than the ASD group at school age. (2) In pitch CV, range and standard deviation of the whole speech of each participant, no significant differences were observed between the type of participants and age. (3) No significant correlation was found between the pitch CV of each word and the Japanese Autism Screening Questionnaire total score, or between the pitch CV of each word and the intelligence quotient levels in the ASD group. A significant correlation was observed between the pitch CV of each word and social reciprocal interaction score. Conclusions: We assessed the speech tone of children with ASD by using a new quantitative method. Monotonous speech in school-aged children with ASD was detected. The extent of monotonous speech was related to the extent of social reciprocal interaction in children with ASD.
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10. Roux AM, Shattuck PT, Cooper BP, Anderson KA, Wagner M, Narendorf SC. {{Postsecondary employment experiences among young adults with an autism spectrum disorder}}. {J Am Acad Child Adolesc Psychiatry}. 2013; 52(9): 931-9.
OBJECTIVE: We examined postsecondary employment experiences of young adults with an autism spectrum disorder (ASD) and compared these outcomes with those of young adults with different disabilities. METHOD: Data were from Wave 5 of the National Longitudinal Transition Study-2 (NLTS2), a nationally representative survey of young adults who had received special education services during high school. We examined the prevalence of ever having had, and currently having, a paid job at 21 to 25 years of age. We analyzed rates of full-time employment, wages earned, number of jobs held since high school, and job types. RESULTS: Approximately one-half (53.4%) of young adults with an ASD had ever worked for pay outside the home since leaving high school, the lowest rate among disability groups. Young adults with an ASD earned an average of $8.10 per hour, significantly lower than average wages for young adults in the comparison groups, and held jobs that clustered within fewer occupational types. Odds of ever having had a paid job were higher for those who were older, from higher-income households, and with better conversational abilities or functional skills. CONCLUSIONS: Findings of worse employment outcomes for young adults with an ASD suggest that this population is experiencing particular difficulty in successfully transitioning into employment. Research is needed to determine strategies for improving outcomes as these young adults transition into adulthood.
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11. Ruble LA, Toland MD, Birdwhistell JL, McGrew JH, Usher EL. {{Preliminary Study of the Autism Self-Efficacy Scale for Teachers (ASSET)}}. {Res Autism Spectr Disord}. 2013; 7(9): 1151-9.
The purpose of the current study was to evaluate a new measure, the Autism Self-Efficacy Scale for Teachers (ASSET) for its dimensionality, internal consistency, and construct validity derived in a sample of special education teachers (N = 44) of students with autism. Results indicate that all items reflect one dominant factor, teachers’ responses to items were internally consistent within the sample, and compared to a 100-point scale, a 6-point response scale is adequate. ASSET scores were found to be negatively correlated with scores on two subscale measures of teacher stress (i.e., self-doubt/need for support and disruption of the teaching process) but uncorrelated with teacher burnout scores. The ASSET is a promising tool that requires replication with larger samples.
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12. Scherff A, Taylor M, Eley TC, Happe F, Charman T, Ronald A. {{What Causes Internalising Traits and Autistic Traits to Co-occur in Adolescence? A Community-Based Twin Study}}. {J Abnorm Child Psychol}. 2013.
Autism shows a high degree of comorbidity with anxiety disorders. Adolescence is a time of increased stress and vulnerability to internalising problems. This study addresses for the first time the degree of genetic and environmental overlap between autistic traits (total measure and subscales) and internalising traits in a community-based adolescent twin sample. Parents of 12-14-year-old twins (N = 3,232 pairs; 3,460 males, 3,004 females) reported on the twins’ internalising and autistic traits. Autistic trait subscales were created using principal component analysis. Bivariate twin model-fitting was conducted. Autistic and internalising traits correlated moderately (r = 0.30). Genetic influences on individual traits were substantial but genetic overlap between traits was moderate (genetic correlation: males = 0.30, females = 0.12). Shared environmental influences were low for internalising traits and moderate for autistic traits, and showed considerable overlap (shared environmental correlation: males = 0.53, females = 1). Nonshared environmental influences were moderate for internalising traits and low for autistic traits and showed low overlap. A multiple component solution was found for autistic traits and of the derived subscales, autistic-like ‘Social Unease’ showed the most phenotypic and genetic overlap with internalising traits.
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13. Scott FJ, Baron-Cohen S. {{Imagining real and unreal things: evidence of a dissociation in autism}}. {J Cogn Neurosci}. 1996; 8(4): 371-82.
Current theories of visual imagery hold that the same neural processes govern both the representation of real objects and the representation of imagined (but real) objects. Here we test whether the representation of imagined (real) objects and the representation of imagined (but unreal) objects depend on the same or different neurocognitive processes. A likely clinical group for a dissociation between these two types of imagination are children with autism, since they show deficits in imaginative play, impoverished imagination is part of their diagnosis, but they can search for hidden objects. The present study explored imagination in autism using experimental methods. Experiment 1 investigated if children with autism could introduce changes to their representations of people and houses, using Karmiloff-Smith’s (1989) technique of asking children to draw « impossible » people or houses. Results showed that children with autism were significantly worse than matched controls in their ability to introduce « unreal » changes to their representations of people and houses. Instead, they tended to draw real people or objects. Experiment 2 investigated whether the performance in Experiment 1 by children with autism was due to an inability to disengage from « real world » representations, as executive dysfunction theorists would argue. To do this, the experimenter instructed them on what to draw and how to draw it. Results showed that even when executive control passed to the experimenter in this way, the children with autism were still significantly impaired in their ability to draw imaginary but unreal things relative to the matched controls. Experiment 3 investigated whether the results from Experiments 1 and 2 arose because of a generativity deficit in autism, which might be the executive dysfunction theorists’ alternative account. To test this, the same subjects were given a test of Verbal Fluency and a test of imagining multiple functions of a brick. Results showed that the children with autism were no worse than clinical controls in their ability to generate ideas about real objects, suggesting that a global generativity deficit cannot explain the previous findings. Rather, these results point to a specific impairment in the ability to imagine unreal objects. This is discussed in terms of its possible neural dissociability from other kinds of imagery, and in terms of its possible relationship to theory of mind.
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14. Sprenger L, Buhler E, Poustka L, Bach C, Heinzel-Gutenbrunner M, Kamp-Becker I, Bachmann C. {{Impact of ADHD symptoms on autism spectrum disorder symptom severity}}. {Res Dev Disabil}. 2013; 34(10): 3545-52.
Despite the official exclusion criteria for autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) in the DSM-IV and ICD-10, patients with ASD often show ADHD symptoms. We aimed to examine the potential influence of ADHD symptoms on autistic psychopathology in a large sample of patients with ASD. We tested the hypothesis that patients with ASD and an additional ADHD (ASD+) would show a higher severity of autistic symptoms than those with ASD only (ASD-). We measured autistic symptoms using the autism diagnostic observation schedule (ADOS-G), the autism diagnostic interview (ADI-R), and the social responsiveness scale (SRS). To measure overall psychopathology and ADHD symptoms, we used the child behavior checklist (CBCL) and the ADHD rating scale (FBB-ADHS), respectively. Group differences between the ASD+ and the ASD- group (group division was conducted according to the results of the FBB-ADHS) were calculated using a univariate analysis of variance (ANOVA). The ASD+ group showed a greater severity of autistic symptoms than the ASD- group, measured by the SRS and the ADI-R. Especially in the social interaction subscale (ADI-R), a significantly higher symptom severity was found in the ASD+ group. No significant group differences were found regarding autistic symptoms measured by the ADOS-G. Patients with ASD and an additional ADHD expressed a stronger severity of autistic symptoms than patients with ASD only. According to our results, the possibility of a co-diagnosis of ADS and ADHD, as is being planned in the DSM-5, is in line with earlier studies, is highly reasonable, will simplify research, and have therapeutic implications.
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15. Tenyi T, Jeges S, Halmai T, Csabi G. {{[Minor physical anomalies in autism]}}. {Ideggyogy Sz}. 2013; 66(7-8): 269-72.
BACKGROUND AND PURPOSE: Minor physical anomalies are mild, clinically and cosmetically insignificant errors of morphogenesis which have a prenatal origin and may bear major informational value for diagnostic, prognostic and epidemiological purposes. Since both the central nervous system and the skin are derived from the same ectodermal tissue in utero, minor physical anomalies can be external markers of abnormal brain development and they appear more commonly in neurodevelopmental disorders. In a recently published meta-analysis Ozgen et al. have published the results of seven studies–all have used the Waldrop Scale which contains 18 minor physical anomalies–and reported on the higher prevalence of minor physical anomalies among patients with autism. There are only a very few data on the individual analysis of the prevalence of minor physical anomalies in autism. METHODS: In our study we have studied the prevalence of 57 minor physical anomalies in 20 patients with autism and in 20 matched control subjects by the use of the Mehes Scale. RESULTS: The prevalence of minor physical anomalies was significantly higher in the autism group (p < 0.001). The individual analysis of the 57 minor physical anomalies showed the significantly more frequent apperance of four signs (primitive shape of ear p = 0.047, abnormal philtrum p = 0.001, clinodactylia p = 0.002, wide distance between toes 1 and 2 p = 0.003). No correlation was found between the four significantly more common minor physical anomalies. CONCLUSION: The higher prevalence of minor physical anomalies in autism supports the neurodevelopmental hypothesis of the disorder and the individual analysis of minor physical anomalies can help to understand the nature of the neurodevelopmental defect.
16. Tordjman S, Anderson GM, Cohen D, Kermarrec S, Carlier M, Touitou Y, Saugier-Veber P, Lagneaux C, Chevreuil C, Verloes A. {{Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome}}. {Mol Autism}. 2013; 4(1): 29.
BACKGROUND: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized. METHODS: Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. RESULTS: The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. CONCLUSIONS: Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism.
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17. Webb SJ, Bernier R, Henderson HA, Johnson MH, Jones EJ, Lerner MD, McPartland JC, Nelson CA, Rojas DC, Townsend J, Westerfield M. {{Guidelines and Best Practices for Electrophysiological Data Collection, Analysis and Reporting in Autism}}. {J Autism Dev Disord}. 2013.
The EEG reflects the activation of large populations of neurons that act in synchrony and propagate to the scalp surface. This activity reflects both the brain’s background electrical activity and when the brain is being challenged by a task. Despite strong theoretical and methodological arguments for the use of EEG in understanding the neural correlates of autism, the practice of collecting, processing and evaluating EEG data is complex. Scientists should take into consideration both the nature of development in autism given the life-long, pervasive course of the disorder and the disability of altered or atypical social, communicative, and motor behaviors, all of which require accommodations to traditional EEG environments and paradigms. This paper presents guidelines for the recording, analyzing, and interpreting of EEG data with participants with autism. The goal is to articulate a set of scientific standards as well as methodological considerations that will increase the general field’s understanding of EEG methods, provide support for collaborative projects, and contribute to the evaluation of results and conclusions.
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18. Wentz E, Vujic M, Karrstedt EL, Erlandsson A, Gillberg C. {{A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism}}. {Eur Child Adolesc Psychiatry}. 2013.
Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.
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19. Wong HS, Huertas-Ceballos A, Cowan FM, Modi N. {{Evaluation of Early Childhood Social-Communication Difficulties in Children Born Preterm Using the Quantitative Checklist for Autism in Toddlers}}. {J Pediatr}. 2013.
OBJECTIVES: To characterize early childhood social-communication skills and autistic traits in children born very preterm using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) and explore neonatal and sociodemographic factors associated with Q-CHAT scores. STUDY DESIGN: Parents of children born before 30 weeks gestation and enrolled in a study evaluating routinely collected neurodevelopmental data between the post-menstrual ages of 20 and 28 months were invited to complete the Q-CHAT questionnaire. Children with severe neurosensory disabilities and cerebral palsy were excluded. Participants received neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development, 3rdedition (Bayley-III). Q-CHAT scores of this preterm cohort were compared with published general population scores. The association between Bayley-III cognitive and language scores and neonatal and sociodemographic factors with Q-CHAT scores were examined. RESULTS: Q-CHAT questionnaires were completed from 141 participants. At a mean post-menstrual age of 24 months, the Q-CHAT scores of the preterm cohort (mean 33.7, SD 8.3) were significantly higher than published general population scores (mean 26.7; SD 7.8), indicating greater social-communication difficulty and autistic behavior. Preterm children received higher scores, particularly in the categories of restricted, repetitive, stereotyped behavior, communication, and sensory abnormalities. Lower Bayley-III language scores and non-white ethnicity were associated with higher Q-CHAT scores. CONCLUSIONS: Preterm children display greater social-communication difficulty and autistic behavior than the general population in early childhood as assessed by the Q-CHAT. The implications for longer-term outcome will be important to assess.
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20. You X, Norr M, Murphy E, Kuschner ES, Bal E, Gaillard WD, Kenworthy L, Vaidya CJ. {{Atypical modulation of distant functional connectivity by cognitive state in children with Autism Spectrum Disorders}}. {Front Hum Neurosci}. 2013; 7: 482.
We examined whether modulation of functional connectivity by cognitive state differed between pre-adolescent children with Autism Spectrum Disorders (ASD) and age and IQ-matched control children. Children underwent functional magnetic resonance imaging (fMRI) during two states, a resting state followed by a sustained attention task. A voxel-wise method was used to characterize functional connectivity at two levels, local (within a voxel’s 14 mm neighborhood) and distant (outside of the voxel’s 14 mm neighborhood to the rest of the brain) and regions exhibiting Group x State interaction were identified for both types of connectivity maps. Distant functional connectivity of regions in the left frontal lobe (dorsolateral [BA 11, 10]; supplementary motor area extending into dorsal anterior cingulate [BA 32/8]; and premotor [BA 6, 8, 9]), right parietal lobe (paracentral lobule [BA 6]; angular gyrus [BA 39/40]), and left posterior middle temporal cortex (BA 19/39) showed a Group x State interaction such that relative to the resting state, connectivity reduced (i.e., became focal) in control children but increased (i.e., became diffuse) in ASD children during the task state. Higher state-related increase in distant connectivity of left frontal and right angular gyrus predicted worse inattention in ASD children. Two graph theory measures (global efficiency and modularity) were also sensitive to Group x State differences, with the magnitude of state-related change predicting inattention in the ASD children. Our results indicate that as ASD children transition from an unconstrained to a sustained attentional state, functional connectivity of frontal and parietal regions with the rest of the brain becomes more widespread in a manner that may be maladaptive as it was associated with attention problems in everyday life.
