1. Al-Ayadhi LY. {{Relationship between sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders}}. {Neurochem Res};2012 (Feb);37(2):394-400.
The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders.
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2. Aldridge FJ, Gibbs VM, Schmidhofer K, Williams M. {{Investigating the Clinical Usefulness of the Social Responsiveness Scale (SRS) in a Tertiary Level, Autism Spectrum Disorder Specific Assessment Clinic}}. {J Autism Dev Disord};2012 (Feb);42(2):294-300.
The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems.
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3. Allison C, Auyeung B, Baron-Cohen S. {{Toward brief « red flags » for autism screening: the short autism spectrum quotient and the short quantitative checklist in 1,000 cases and 3,000 controls}}. {J Am Acad Child Adolesc Psychiatry};2012 (Feb);51(2):202-212 e207.
OBJECTIVE: Frontline health professionals need a « red flag » tool to aid their decision making about whether to make a referral for a full diagnostic assessment for an autism spectrum condition (ASC) in children and adults. The aim was to identify 10 items on the Autism Spectrum Quotient (AQ) (Adult, Adolescent, and Child versions) and on the Quantitative Checklist for Autism in Toddlers (Q-CHAT) with good test accuracy. Method: A case sample of more than 1,000 individuals with ASC (449 adults, 162 adolescents, 432 children and 126 toddlers) and a control sample of 3,000 controls (838 adults, 475 adolescents, 940 children, and 754 toddlers) with no ASC diagnosis participated. Case participants were recruited from the Autism Research Centre’s database of volunteers. The control samples were recruited through a variety of sources. Participants completed full-length versions of the measures. The 10 best items were selected on each instrument to produce short versions. Results: At a cut-point of 6 on the AQ-10 adult, sensitivity was 0.88, specificity was 0.91, and positive predictive value (PPV) was 0.85. At a cut-point of 6 on the AQ-10 adolescent, sensitivity was 0.93, specificity was 0.95, and PPV was 0.86. At a cut-point of 6 on the AQ-10 child, sensitivity was 0.95, specificity was 0.97, and PPV was 0.94. At a cut-point of 3 on the Q-CHAT-10, sensitivity was 0.91, specificity was 0.89, and PPV was 0.58. Internal consistency was >0.85 on all measures. Conclusions: The short measures have potential to aid referral decision making for specialist assessment and should be further evaluated.
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4. Baird G. {{2.64% of South Korean children aged 7 to 12 have autism spectrum disorders}}. {Evid Based Ment Health};2012 (Feb);15(1):11.
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5. Bohlander AJ, Orlich F, Varley CK. {{Social skills training for children with autism}}. {Pediatr Clin North Am};2012 (Feb);59(1):165-174.
This article summarizes the current literature on social skills training for children and adolescents with autism spectrum disorders. The article describes several different methods of social skills training, along with a summary of research findings on effectiveness. Interventions described include social skills groups, peer mentoring/training, social stories, and video modeling. The article also describes information about accessing social skills training services, and concludes with future directions and recommendations for pediatricians.
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6. Boucher J. {{Putting theory of mind in its place: psychological explanations of the socio-emotional-communicative impairments in autistic spectrum disorder}}. {Autism};2012 (Feb 1)
In this review, the history of the theory of mind (ToM) theory of autistic spectrum disorder (ASD) is outlined (in which ToM is indexed by success on false belief tasks), and the explanatory power and psychological causes of impaired ToM in ASD are critically discussed. It is concluded that impaired ToM by itself has only limited explanatory power, but that explorations of the psychological precursors of impaired ToM have been fruitful in increasing understanding of mindreading impairments in ASD (where ‘mindreading’ refers those abilities that underlie triadic interaction as well as ToM). It is argued that early explanations of impaired mindreading are untenable for various reasons, but that impairments of dyadic interaction in ASD that could lead to impaired ability to represent others’ mental states may be the critical psychological cause, or causes, of impaired ToM. The complexity of causal routes to impaired ToM is emphasized.
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7. Cappadocia MC, Weiss JA, Pepler D. {{Bullying experiences among children and youth with autism spectrum disorders}}. {J Autism Dev Disord};2012 (Feb);42(2):266-277.
Few studies have investigated bullying experiences among children diagnosed with autism spectrum disorders (ASD); however, preliminary research suggests that children with ASD are at greater risk for being bullied than typically developing peers. The aim of the current study was to build an understanding of bullying experiences among children with ASD based on parent reports by examining rates of various forms of bullying, exploring the association between victimization and mental health problems, and investigating individual and contextual variables as correlates of victimization. Victimization was related to child age, internalizing and externalizing mental health problems, communication difficulties, and number of friends at school, as well as parent mental health problems. Bullying prevention and intervention strategies are discussed.
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8. Carlson GC. {{Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders}}. {Pharmacol Biochem Behav};2012 (Feb);100(4):850-854.
There is strong evidence that metabotropic and ionotropic glutamate receptors are affected in autism spectrum disorders (ASD), but there are few candidate genes indicating involvement of these receptors. This suggests that glutamate receptor dysregulation may primarily be involved in the expression of ASD, but is an uncommon etiology. Directly implicated in models of fragile-X with ASD phenotypes is metabotropic glutamate receptor type 5 (mGluR5), which appears to be an effective pharmacologic target in a number of models of ASD. The review of other ASD models demonstrates that there is also evidence of a role for kainate, NMDA, and AMPA receptors in the neuropathophysiology of ASD, though the relationship between dysfunction in those receptors and ASD-associated phenotypes is not well understood. Current models indicate a way forward to delineate the role of glutamate receptors in ASD. Further development of preclinical models focusing on glutamate receptors may provide tools to target a clinically important subset of ASD symptoms.
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9. Chien YL, Wu YY, Chen CH, Gau SS, Huang YS, Chien WH, Hu FC, Chao YL. {{Association of HLA-DRB1 alleles and neuropsychological function in autism}}. {Psychiatr Genet};2012 (Feb);22(1):46-49.
Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRbeta1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.
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10. Choudhury PR, Lahiri S, Rajamma U. {{Glutamate mediated signaling in the pathophysiology of autism spectrum disorders}}. {Pharmacol Biochem Behav};2012 (Feb);100(4):841-849.
Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD.
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11. Christakou A, Murphy CM, Chantiluke K, Cubillo AI, Smith AB, Giampietro V, Daly E, Ecker C, Robertson D, Murphy DG, Rubia K. {{Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism}}. {Mol Psychiatry};2012 (Jan 31)
Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD.Molecular Psychiatry advance online publication, 31 January 2012; doi:10.1038/mp.2011.185.
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12. Chugani DC. {{Neuroimaging and Neurochemistry of Autism}}. {Pediatr Clin North Am};2012 (Feb);59(1):63-73.
Positron emission tomography, single-photon emission tomography, and magnetic resonance spectroscopy (MRS) are powerful tools for the monitoring of diverse neurochemical functions. Neuroimaging studies targeting neurotransmitter systems in autism have provided clues about how differences in development of these systems might lead to new intervention approaches. Direct measurement of diverse neurochemicals with MRS provides unique probes of neuronal integrity in vivo. Future directions include the combination of imaging modalities made possible by advances in software and hardware. Many tracers have not been applied in autism, and new molecules and signaling pathways might be targeted as genes associated with autism are identified.
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13. Clayton TA. {{Metabolic differences underlying two distinct rat urinary phenotypes, a putative role for gut microbial metabolism of phenylalanine and a possible connection to autism}}. {FEBS Lett};2012 (Feb 1)
A novel explanation is proposed for the metabolic differences underlying two distinct rat urinary compositional phenotypes i.e. that these may arise from differences in the gut microbially-mediated metabolism of phenylalanine. As part of this hypothesis, it is further suggested that elements of the mammalian gut microbiota may convert phenylalanine to cinnamic acid, either by means of an ammonia lyase-type reaction or by means of a three step route via phenylpyruvate and phenyllactate. The wider significance of such conversions is discussed with similar metabolism of tryptophan and subsequent glycine conjugation potentially explaining the origin of trans-indolylacryloylglycine, a postulated marker for autism.
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14. Close HA, Lee LC, Kaufmann CN, Zimmerman AW. {{Co-occurring Conditions and Change in Diagnosis in Autism Spectrum Disorders}}. {Pediatrics};2012 (Feb);129(2):e305-316.
OBJECTIVE: This study aimed to investigate descriptive characteristics and co-occurring neurodevelopmental and psychiatric conditions in young children, children, and adolescents with a current and consistent or past but not current (PBNC) diagnosis of autism spectrum disorder (ASD) and how such characteristics and conditions may engender a change in diagnosis of an ASD. METHODS: Cross-sectional data of 1366 children with a parent-reported current or PBNC ASD diagnosis were obtained from the National Survey of Children’s Health 2007 data set across 3 developmental stages: young children (aged 3-5 years), children (aged 6-11 years), and adolescents (aged 12-17 years). Multinomial logistic regression was used to examine demographic characteristics and co-occurring conditions that differentiate the groups with a current ASD from groups with a PBNC ASD. RESULTS: Results indicated the co-occurring conditions that distinguish groups currently diagnosed with an ASD from groups with a PBNC ASD diagnosis. In young children, current moderate/severe learning disability, and current moderate/severe developmental delay; in children, past speech problem, current moderate/severe anxiety, and past hearing problem; and in adolescents, current moderate/severe speech problem, current mild seizure/epilepsy, and past hearing problem. CONCLUSIONS: These findings suggest that the presence of co-occurring psychiatric and neurodevelopmental conditions are associated with a change in ASD diagnosis. Questions remain as to whether changes in diagnosis of an ASD are due to true etiologic differences or shifts in diagnostic determination.
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15. Daniels AM, Rosenberg RE, Anderson C, Law JK, Marvin AR, Law PA. {{Verification of parent-report of child autism spectrum disorder diagnosis to a web-based autism registry}}. {J Autism Dev Disord};2012 (Feb);42(2):257-265.
Growing interest in autism spectrum disorder (ASD) research requires increasingly large samples to uncover epidemiologic trends; such a large dataset is available in a national, web-based autism registry, the Interactive Autism Network (IAN). The objective of this study was to verify parent-report of professional ASD diagnosis to the registry’s database via a medical record review on a sample of IAN Research participants. Sixty-one percent of families agreed to participate; 98% (n = 116) of whom provided documentation verifying a professionally diagnosed ASD. Results of this study suggest that information collected from parents participating in IAN Research is valid, participants can be authenticated, and that scientists can both confidently use IAN data and recruit participants for autism research.
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16. Dichter GS, Richey JA, Rittenberg AM, Sabatino A, Bodfish JW. {{Reward circuitry function in autism during face anticipation and outcomes}}. {J Autism Dev Disord};2012 (Feb);42(2):147-160.
The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary outcomes, participants with ASDs showed hyperactivation in left midfrontal and anterior cingulate gyrus. Groups did not differ in nucleus accumbens responses to faces. The ASD group demonstrated hyperactivation in bilateral amygdala during face anticipation that predicted social symptom severity and in bilateral insular cortex during face outcomes. These results add to the growing body of evidence that autism is characterized by altered functioning of reward circuitry. Additionally, atypical amygdala activation during the processing of social rewards may contribute to the development or expression of autistic features.
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17. Duchan E, Patel DR. {{Epidemiology of autism spectrum disorders}}. {Pediatr Clin North Am};2012 (Feb);59(1):27-43.
Epidemiologic data gathered over the last 40 years report that the conservative estimate of autistic spectrum disorder prevalence is 27.5 per 10,000 individuals; however, the prevalence estimate based on newer surveys is 60 per 10,000 individuals. Several factors are considered in various epidemiologic surveys of autism, especially the evolution of the concept of autism and changing criteria for diagnosis. This article reviews the incidence, prevalence, and risk factors for autism.
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18. Eldevik S, Hastings RP, Jahr E, Hughes JC. {{Outcomes of behavioral intervention for children with autism in mainstream pre-school settings}}. {J Autism Dev Disord};2012 (Feb);42(2):210-220.
We evaluated outcomes for 31 children with autism (2-6 years of age at intake) who received behavioral intervention in mainstream pre-school settings and a comparison group of 12 children receiving treatment as usual. After 2 years, children receiving behavioral intervention had higher IQ scores (Hedges g = 1.03 (95% CI = .34, 1.72) and adaptive behavior composite scores (Hedges g = .73 (95% CI = .05, 1.36). Despite probably fewer intervention hours, these group level outcomes were comparable to studies providing more intensive intervention. Individual child data also showed positive results with 19.4% achieving change at a reliable level for IQ; but a lower percentage than found in recent meta-analysis research. Strengths and weaknesses of the mainstream pre-school delivery model are discussed.
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19. Evans TL, Blice-Baum AC, Mihailescu MR. {{Analysis of the Fragile X mental retardation protein isoforms 1, 2 and 3 interactions with the G-quadruplex forming semaphorin 3F mRNA}}. {Mol Biosyst};2012 (Feb);8(2):642-649.
Fragile X syndrome, the most prevalent inheritable mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP) expression. FMRP is an RNA-binding protein with nucleo-cytoplasmic shuttle activity, proposed to act as a translation regulator of specific mRNAs in the brain. It has been shown that FMRP uses its arginine-glycine-glycine (RGG) box domain to bind a subset of mRNA targets that form a G-quadruplex structure. FMRP has also been shown to undergo the post-translational modifications of arginine methylation and phosphorylation, as well as alternative splicing, resulting in multiple isoforms. The alternative splice isoforms investigated in this study, isoform 1 (ISO1), isoform 2 (ISO2), and isoform 3 (ISO3), are created by the alternative splicing acceptor site at exon 15. FMRP ISO2 and ISO3 are truncated by 12 and 13 residues, respectively, relative to the longest FMRP isoform ISO1. These truncations, which are in the close proximity of the RGG box domain, preserve the integrity of the RGG box in all three isoforms, but eliminate the in vivo phosphorylation sites, present only on FMRP ISO1. We have expressed and purified recombinant FMRP ISO1, ISO2 and ISO3 in Escherichia coli, free of post-translational modifications, and by using fluorescence spectroscopy, we show that each FMRP isoform binds G-quadruplex RNA, albeit with different binding affinities, suggesting that naturally occurring sequence modifications in the proximity of the RGG box modulate its G-quadruplex RNA binding ability.
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20. Faja S, Webb SJ, Jones E, Merkle K, Kamara D, Bavaro J, Aylward E, Dawson G. {{The effects of face expertise training on the behavioral performance and brain activity of adults with high functioning autism spectrum disorders}}. {J Autism Dev Disord};2012 (Feb);42(2):278-293.
The effect of expertise training with faces was studied in adults with ASD who showed initial impairment in face recognition. Participants were randomly assigned to a computerized training program involving either faces or houses. Pre- and post-testing included standardized and experimental measures of behavior and event-related brain potentials (ERPs), as well as interviews after training. After training, all participants met behavioral criteria for expertise with the specific stimuli on which they received training. Scores on standardized measures improved after training for both groups, but only the face training group showed an increased face inversion effect behaviorally and electrophysiological changes to faces in the P100 component. These findings suggest that individuals with ASD can gain expertise in face processing through training.
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21. Farber JM. {{Autism, cognition, and parent counseling-part 2}}. {J Dev Behav Pediatr};2012 (Feb);33(2):161-162.
As the incidence of autism has risen, many neurodevelopmental pediatricians have been omitting a consideration of cognitive level in their evaluation of children, and in communicating with parents. This is a disservice to families, who should be given pertinent information, both in verbal and written forms, about their child and the prognosis. A template is presented for a letter that can be provided to parents, highlighting the basic information they need after a diagnosis has been made.
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22. Felce D, Kerr M. {{Investigating low adaptive behaviour and presence of the triad of impairments characteristic of autistic spectrum disorder as indicators of risk for challenging behaviour among adults with intellectual disabilities}}. {J Intellect Disabil Res};2012 (Feb 1)
Background Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of impairments characteristic of autism and level of adaptive behaviour were independently associated with level of challenging behaviour among adults with intellectual disabilities. Methods Five datasets were merged to produce information on challenging behaviour, adaptive behaviour, presence of the triad of impairments, gender and age of 818 adults. Variables were entered into a multivariate linear regression, which also tested the interaction between the presence of the triad of impairments and level of adaptive behaviour. Results Presence of the triad of impairments, level of adaptive behaviour, their interaction, and age, but not gender, significantly and independently contributed to the prediction of challenging behaviour. Presence/absence of the triad of impairments moderated the effect of adaptive behaviour on challenging behaviour. The inverse relationship found in the absence of the triad of impairments was virtually removed when present. Conclusions This study has shown that it is necessary to control for intercorrelation between potential risk factors for challenging behaviour and to explore how interaction between them might moderate associations.
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23. Finestack LH, Palmer M, Abbeduto L. {{Macrostructural narrative language of adolescents and young adults with down syndrome or fragile x syndrome}}. {Am J Speech Lang Pathol};2012 (Feb);21(1):29-46.
PURPOSE: To gain a better understanding of language abilities, the expressive macrostructural narrative language abilities of verbally expressive adolescents and young adults with Down syndrome (DS) and those with fragile X syndrome (FXS) were examined. METHOD: The authors evaluated 24 adolescents and young adults with DS, 12 male adolescents and young adults with FXS, and 21 younger children with typical development (TD). Narrative samples were assessed at the macrostructural level using the narrative scoring scheme (Heilmann, Miller, Nockerts, & Dunaway, 2010). Three group comparisons were made using (a) the full sample matched on nonverbal mental age, (b) a subset of the participants individually matched on nonverbal mental age, and (c) a subset of participants individually matched on mean length of utterance. RESULTS: Study analyses revealed that the DS and FXS groups significantly outperformed the TD group on a limited number of narrative scoring scheme measures. No significant differences emerged between the DS and FXS groups. CONCLUSIONS: The study’s results suggest that some aspects of macrostructural narrative language may be relative strengths for adolescents and young adults with DS and those with FXS. These results can be used to create more nuanced and informed approaches to assessment and intervention for these populations.
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24. Fraser R, Cotton S, Gentle E, Angus B, Allott K, Thompson A. {{Non-expert clinicians’ detection of autistic traits among attenders of a youth mental health service}}. {Early Interv Psychiatry};2012 (Feb);6(1):83-86.
Aims: The aims of this study were to determine the point prevalence of autism spectrum disorders and to estimate the prevalence of autistic traits in a youth mental health service. Methods: Following three educational sessions on autism spectrum disorders, treating clinicians were interviewed to determine whether the clients on their caseloads had (i) a confirmed prior diagnosis of autism spectrum disorder; (ii) were felt to exhibit autistic traits; or (iii) were not felt to exhibit autistic traits. Results: Information on autism spectrum disorder status was obtained for 476 patients. Of the included patients, 3.4% (n = 16) had a confirmed diagnosis of autism spectrum disorder and 7.8% (n = 37) were reported by treating clinicians to exhibit autistic traits. Conclusions: The rate of autism spectrum disorder was higher in this population than that in community samples with twice as many again being identified as having autistic traits by their treating clinicians. This has implications for correct diagnosis and appropriate management in these settings.
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25. Frazier TW. {{Friends not foes: combined risperidone and behavior therapy for irritability in autism}}. {J Am Acad Child Adolesc Psychiatry};2012 (Feb);51(2):129-131.
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26. Froehlich AL, Anderson JS, Bigler ED, Miller JS, Lange NT, Dubray MB, Cooperrider JR, Cariello A, Nielsen JA, Lainhart JE. {{Intact Prototype Formation but Impaired Generalization in Autism}}. {Res Autism Spectr Disord};2012 (Spring);6(2):921-930.
Cognitive processing in autism has been characterized by a difficulty with the abstraction of information across multiple stimuli or situations and subsequent generalization to new stimuli or situations. This apparent difficulty leads to the suggestion that prototype formation, a process of creating a mental summary representation of multiple experienced stimuli that go together in a category, may be impaired in autism. Adults with high functioning autism and a typically developing comparison group matched on age and IQ completed a random dot pattern categorization task. Participants with autism demonstrated intact prototype formation in all four ways it was operationally defined, and this performance was not significantly different from that of control participants. However, participants with autism categorized dot patterns that were more highly distorted from the category prototypes less accurately than did control participants. These findings suggest, at least within the constraints of the random dot pattern task, that although prototype formation may not be impaired in autism, difficulties may exist with the generalization of what has been learned about a category to novel stimuli, particularly as they become less similar to the category’s prototype.
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27. Geluk CA, Jansen LM, Vermeiren R, Doreleijers TA, van Domburgh L, de Bildt A, Twisk JW, Hartman CA. {{Autistic symptoms in childhood arrestees: longitudinal association with delinquent behavior}}. {J Child Psychol Psychiatry};2012 (Feb);53(2):160-167.
Background: To compare childhood arrestees with matched comparison groups on levels of autistic symptoms and to assess the unique predictive value of autistic symptoms for future delinquent behavior in childhood arrestees. Methods: Childhood first-time arrestees (n = 308, baseline age 10.7 +/- 1.5 years) were followed up for 2 years. Autistic symptoms, externalizing disorders and delinquent behavior were assessed yearly. Childhood arrestees were compared on autistic symptoms with matched (age, gender) general population and clinical autism spectrum disorder samples. The predictive value of autistic symptoms for delinquent behavior was analyzed using generalized estimating equations. Results: At each assessment, levels of autistic symptoms in childhood arrestees were in between levels found in the general population and autism spectrum disorder samples. Autistic symptoms were positively associated with delinquent behavior in childhood arrestees, even after adjustment for externalizing disorders: IRR (incidence rate ratio) 1.23; 95% CI 1.11-1.36 and IRR 1.29; 95% CI 1.15-1.45 for core autistic symptoms and total symptom score, respectively. Conclusions: Autistic symptoms are more prevalent in childhood arrestees compared to the general population and are uniquely associated with future delinquent behavior. Attention should, therefore, be given to the possible presence of autism related symptomatology in these children. Implications for diagnostic assessment and intervention need further investigation.
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28. Ghanizadeh A. {{Acetaminophen may mediate oxidative stress and neurotoxicity in autism}}. {Med Hypotheses};2012 (Feb);78(2):351.
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29. Gillespie-Lynch K, Sepeta L, Wang Y, Marshall S, Gomez L, Sigman M, Hutman T. {{Early childhood predictors of the social competence of adults with autism}}. {J Autism Dev Disord};2012 (Feb);42(2):161-174.
Longitudinal research into adult outcomes in autism remains limited. Unlike previous longitudinal examinations of adult outcome in autism, the twenty participants in this study were evaluated across multiple assessments between early childhood (M = 3.9 years) and adulthood (M = 26.6 years). In early childhood, responsiveness to joint attention (RJA), language, and intelligence were assessed. In adulthood, the parents of participants responded to interviews assessing the adaptive functioning, autistic symptomology and global functioning of their children. RJA and early childhood language predicted a composite measure of adult social functioning and independence. Early childhood language skills and intelligence predicted adult adaptive behaviors. RJA predicted adult non-verbal communication, social skills and symptoms. Adaptive behaviors changed with development, but symptoms of autism did not. Additional factors associated with adult outcomes are discussed.
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30. Greydanus DE, Toledo-Pereyra LH. {{Historical perspectives on autism: its past record of discovery and its present state of solipsism, skepticism, and sorrowful suspicion}}. {Pediatr Clin North Am};2012 (Feb);59(1):1-11.
Concepts of autism have evolved over the twentieth century after Bleuler coined the term to refer to symptoms of self-absorption in those with schizophrenia. Autism nosology changed to the current sesquipedalian constellation of autism spectrum disorders with a confusing archipelago of 5 conditions that often serve as islands of confusion to both the general public and professionals. This article reviews historical links that have led to the current confusing and controversial situation that is encouraging some people to return to magic, mysticism, and mantics for health care, despite the amazing accumulation of progress in vaccinology over the past 2 centuries.
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31. Guo W, Murthy AC, Zhang L, Johnson EB, Schaller EG, Allan AM, Zhao X. {{Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome}}. {Hum Mol Genet};2012 (Feb 1);21(3):681-691.
Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates the adult neural stem cell fate through the translational regulation of glycogen synthase kinase 3beta (GSK3beta), we investigated the effects of a GSK3beta inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3beta could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3beta inhibition as a potential treatment for the learning deficits seen in FXS.
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32. Hagebeuk EE, Bijlmer RP, Koelman JH, Poll-The BT. {{Respiratory Disturbances in Rett Syndrome: Don’t Forget to Evaluate Upper Airway Obstruction}}. {J Child Neurol};2012 (Jan 30)
Rett syndrome is characterized by loss of motor and social functions, development of stereotypic hand movements, seizures, and breathing disturbances. This study evaluates the presence of overnight respiratory disturbances. Polysomnography in combination with a questionnaire (the Sleep Disturbance Scale for Children) was performed in 12 Dutch patients with Rett. Respiratory disturbances were present in all, clinically relevant in 10 (apnea hypopnea per hour 1.0-14.5). In 8 children, central apneas were present during the day often with obstructive apneas at night. In 6, obstructive sleep apnea syndrome was diagnosed, in 3 severe, with frequent oxygen desaturations. Significant respiratory complaints were present in 3 patients, all had obstructive sleep apnea syndrome. Of the 12 patients with Rett, 8 (67%) snored, and in 5 obstructive sleep apnea syndrome was present. In children, hypertrophied tonsils and adenoids are a common cause of obstructive sleep apnea syndrome, which may benefit from therapeutic intervention. We recommend performing polysomnography in patients with Rett syndrome and respiratory complaints.
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33. Halbach NS, Smeets EE, van den Braak N, van Roozendaal KE, Blok RM, Schrander-Stumpel CT, Frijns JP, Maaskant MA, Curfs LM. {{Genotype-phenotype relationships as prognosticators in Rett syndrome should be handled with care in clinical practice}}. {Am J Med Genet A};2012 (Feb);158A(2):340-350.
Rett syndrome (RTT; OMIM 312750) is an X-linked dominant neurodevelopmental disorder leading to cognitive and motor impairment, epilepsy, and autonomic dysfunction in females. Since the discovery that RTT is caused by mutations in MECP2, large retrospective genotype-phenotype correlation studies have been performed. A number of general genotype-phenotype relationships were confirmed and specific disorder profiles were described. Nevertheless, conflicting results are still under discussion, partly due to the variability in classification of mutations, assessment tools, and structure of the data sets. The aim of this study was to investigate relationships between genotype and specific clinical data collected by the same experienced physician in a well-documented RTT cohort, and evaluate its prognostic value in counseling young parents with a newly diagnosed RTT girl regarding her future outcome. The Maastricht-Leuven Rett Syndrome Database is a register of 137 molecularly confirmed clinical RTT cases, containing both molecular and clinical data on examination and follow up by the same experienced physician. Although the general genotype-phenotype relationships were confirmed, the clinical severity was still found to be very variable. We therefore recommend caution in using genotype-phenotype data in the prognosis of outcome for children in Rett syndrome. Early diagnosis, early intervention, and preventive management are imperative for better outcomes and better quality of daily life for RTT females and their families. (c) 2011 Wiley Periodicals, Inc.
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34. Hampson DR, Gholizadeh S, Pacey LK. {{Pathways to drug development for autism spectrum disorders}}. {Clin Pharmacol Ther};2012 (Feb);91(2):189-200.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders whose prevalence has risen over the past two decades. Current drug treatments for ASDs and the related disorders-fragile X syndrome (FXS) and Rett syndrome-target specific symptoms but do not address the basic underlying etiologies. However, based partly on an improved understanding of the neurochemical underpinnings of FXS, pharmacotherapy for this syndrome has progressed to the point of clinical trials of several novel drug treatments. By contrast, our overall understanding of the neuropathophysiology of ASDs is still rudimentary. There is hope in the field that knowledge and experience gained in the study of fragile X and Rett syndromes may be applicable to the larger autism patient population. In this review, we discuss how recent advances in our understanding of the biochemistry and neuropathology of these disorders could lead to new more effective treatments for ASDs.
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35. Heyer NJ, Echeverria D, Woods JS. {{Disordered Porphyrin Metabolism: A Potential Biological Marker for Autism Risk Assessment}}. {Autism Res};2012 (Feb 1)
Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger’s syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl (penta) and coproporphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and coproporphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS, and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (P < 0.006) and copro (P < 0.006) concentrations compared with same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic curve analysis, we evaluated the sensitivity and specificity of penta, copro, and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS, and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic. Autism Res 2012,**: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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36. Huerta M, Lord C. {{Diagnostic evaluation of autism spectrum disorders}}. {Pediatr Clin North Am};2012 (Feb);59(1):103-111.
Research on the identification and evaluation of autism spectrum disorders is reviewed, and best practices for clinical work are discussed. The latest research on diagnostic tools, and their recommended use, is also reviewed. Recommendations include the use of instruments designed to assess multiple domains of functioning and behavior, the inclusion of parents and caregivers as active partners, and the consideration of developmental factors throughout the diagnostic process.
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37. Jones RM, Wheelwright S, Farrell K, Martin E, Green R, Di Ceglie D, Baron-Cohen S. {{Brief report: female-to-male transsexual people and autistic traits}}. {J Autism Dev Disord};2012 (Feb);42(2):301-306.
The ‘extreme male brain’ theory suggests females with Autism Spectrum Conditions are hyper-masculinized in certain aspects of behavior. We predicted that females with Gender Identity Disorder (who are masculinized) would have elevated Autism Spectrum Quotient (AQ) scores. AQ scores from five groups were compared: (1) n = 61 transmen (female-to-male transsexual people); (2) n = 198 transwomen (male-to-female transsexual people); (3) n = 76 typical males; (4) n = 98 typical females; and (5) n = 125 individuals with Asperger Syndrome (AS). Transmen had a higher mean AQ than typical females, typical males and transwomen, but lower than individuals with AS. Transmen have more autistic traits and may have had difficulty socializing with female peers and thus found it easier to identify with male peer groups.
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38. Kaluzna-Czaplinska J, Blaszczyk S. {{The level of arabinitol in autistic children after probiotic therapy}}. {Nutrition};2012 (Feb);28(2):124-126.
OBJECTIVE: The level of D-arabinitol (DA) and the ratio of D-/L-arabinitol (DA/LA) in the urine of children with autism were investigated. The changes in DA/LA after probiotic treatment in urine samples of children with autism were studied. METHODS: DA and LA and the DA/LA ratio were identified by capillary gas chromatography/mass spectrometry in urine before and after the probiotic therapy. RESULTS: The level of DA is significantly higher (P < 0.05) in the urine of autistic children before (A) and after probiotic supplementation (A1) (160.04 +/- 22.88 mumol/mmol creatinine and 89.53 +/- 37.41 mumol/mmol creatinine, respectively). Nonetheless, the probiotic supplementation let to a significant decrease in DA and DA/LA and to a significant improvement in ability of concentration and carrying out orders. CONCLUSION: The use of probiotics seems to be helpful in reducing the level of DA and the ratio of DA/LA in the urine of children with autism.
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39. Kaplan G, McCracken JT. {{Psychopharmacology of autism spectrum disorders}}. {Pediatr Clin North Am};2012 (Feb);59(1):175-187.
At present, no evidence-based effective pharmacologic options are available for treating the core deficits of autism spectrum disorders (ASDs), which are best addressed by behavioral and educational interventions. However, such evidence exists for several of the frequently associated/comorbid symptoms such as aggression and severe irritability, hyperactivity, and repetitive behaviors, which can become a major source of additional distress and interference in functioning. This article offers information on the psychopharmacology of ASD that is current, relevant, and organized in a user-friendly manner, to form a concise but informative reference guide for primary pediatric clinicians.
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40. Kim SH, Lord C. {{Combining information from multiple sources for the diagnosis of autism spectrum disorders for toddlers and young preschoolers from 12 to 47 months of age}}. {J Child Psychol Psychiatry};2012 (Feb);53(2):143-151.
Background: Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms. Methods: Single and combined use of the ADI-R and ADOS algorithms were compared to clinical best estimate diagnoses for 435 children with autism spectrum disorders (ASD), 113 children with nonspectrum disorders, and 47 children with typical development from 12 to 47 months of age. Sequential strategies to reach a diagnostic decision by prioritizing administrations of instruments were also evaluated. Results: Well-balanced sensitivities and specificities above 80% were obtained for ASD diagnoses using both instruments. Specificities significantly improved when both instruments were used compared to one. Scores that can be used to systematically prioritize administrations of instruments were identified. Conclusions: The ADI-R and ADOS make independent, additive contributions to more accurate diagnostic decisions for clinicians evaluating toddlers and young preschoolers with ASD. Sequential assessment strategies using the scores identified may be appropriate for some children.
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41. Kirkland A. {{The legitimacy of vaccine critics: what is left after the autism hypothesis?}}. {J Health Polit Policy Law};2012 (Feb);37(1):69-97.
The last dozen years have seen a massive transnational mobilization of the legal, political, and research communities in response to the worrisome hypothesis that vaccines could have a link to childhood autism and other developmental conditions. Vaccine critics, some already organized and some composed of newly galvanized parents, developed an alternate world of internally legitimating studies, blogs, conferences, publications, and spokespeople to affirm a connection. When the consensus turned against the autism hypothesis, these structures and a committed membership base unified all the organizations in resistance. This article examines the relationship between mobilization based on science and the trajectory of legitimacy vaccine criticism has taken. I argue that vaccine critics have run up against the limits of legitimate scientific argument and are now in the curious position of both doubling down on credibility-depleting stances and innovating new and possibly resonant formulations.
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42. Koh HC, Milne E. {{Evidence for a cultural influence on field-independence in autism spectrum disorder}}. {J Autism Dev Disord};2012 (Feb);42(2):181-190.
Field-independence, or weak central coherence, is a recognised phenotype of autism spectrum disorder (ASD). There is also evidence of cultural variation in this perceptual style, as neurotypical individuals from Western nations are more field-independent than neurotypical individuals from East-Asian nations. The majority of research on perceptual style in those with ASD has been carried out in Western nations therefore it is unclear whether increased field-independence in ASD is a culturally universal phenotype. Here, we assessed perceptual style in children with and without ASD from England and Singapore using the Children’s Embedded Figures Test and the Framed-Line Test. We found increased field-independence in the English participants with ASD only, suggesting that weak central coherence in ASD is not culturally universal.
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43. Konopka G, Wexler E, Rosen E, Mukamel Z, Osborn GE, Chen L, Lu D, Gao F, Gao K, Lowe JK, Geschwind DH. {{Modeling the functional genomics of autism using human neurons}}. {Mol Psychiatry};2012 (Feb);17(2):202-214.
Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD.
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44. Kornhuber J. {{[Autism spectrum disorders]}}. {Fortschr Neurol Psychiatr};2012 (Feb);80(2):71.
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45. Kourkoulou A, Leekam SR, Findlay JM. {{Implicit learning of local context in autism spectrum disorder}}. {J Autism Dev Disord};2012 (Feb);42(2):244-256.
Although previous research has reported impairments in implicit learning in individuals with ASD, research using one implicit learning paradigm, the contextual cueing task (Chun and Jiang in Cognitive Psychol 36:28-71, 1998), shows evidence of intact ability to integrate spatial contextual information. Using an adaptation of this paradigm, we replicated earlier findings showing that contextual cueing facilitates learning in ASD. Nevertheless, we found that exposure to repeated contexts that biased attention to local rather than global displays rendered it difficult for individuals with ASD to adapt to new trials. Thus, adaptive processes that allow one to respond flexibly and rapidly to new situations appear diminished in ASD when exposed to local spatial contexts. These findings have implications for practical learning strategies used in educational settings.
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46. Kramer JM, Coster WJ, Kao YC, Snow A, Orsmond GI. {{A New Approach to the Measurement of Adaptive Behavior: Development of the PEDI-CAT for Children and Youth with Autism Spectrum Disorders}}. {Phys Occup Ther Pediatr};2012 (Feb);32(1):34-47.
ABSTRACT. The use of current adaptive behavior measures in practice and research is limited by their length and need for a professional interviewer. There is a need for alternative measures that more efficiently assess adaptive behavior in children and youth with autism spectrum disorders (ASDs). The Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) is a computer-based assessment of a child’s ability to perform activities required for personal self-sufficiency and engagement in the community. This study evaluated the applicability, representativeness, and comprehensiveness of the Daily Activity, Social/Cognitive, and Responsibility domains for children and youth with an ASD. Twenty professionals and 18 parents provided feedback via in-person or virtual focus groups and cognitive interviews. Items were perceived to represent relevant functional activities within each domain. Child factors and assessment characteristics influenced parents’ ratings. In response to feedback, 15 items and additional directions were added to ensure the PEDI-CAT is a meaningful measure when used with this population.
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47. Lai G, Pantazatos SP, Schneider H, Hirsch J. {{Neural systems for speech and song in autism}}. {Brain};2012 (Feb 1)
Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal-posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls.
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48. Langen M, Leemans A, Johnston P, Ecker C, Daly E, Murphy CM, Dell’acqua F, Durston S, Murphy DG. {{Fronto-striatal circuitry and inhibitory control in autism: Findings from diffusion tensor imaging tractography}}. {Cortex};2012 (Feb);48(2):183-193.
INTRODUCTION: Repetitive behaviour and inhibitory control deficits are core features of autism; and it has been suggested that they result from differences in the anatomy of striatum; and/or the ‘connectivity’ of subcortical regions to frontal cortex. There are few studies, however, that have measured the micro-structural organisation of white matter tracts connecting striatum and frontal cortex. AIMS: To investigate differences in bulk volume of striatum and micro-structural organisation of fronto-striatal white matter in people with autism; and their association with
