1. Bernardino I, Mouga S, Almeida J, van Asselen M, Oliveira G, Castelo-Branco M. {{A Direct Comparison of Local-Global Integration in Autism and other Developmental Disorders: Implications for the Central Coherence Hypothesis}}. {PLoS One}. 2012; 7(6): e39351.
The weak central coherence hypothesis represents one of the current explanatory models in Autism Spectrum Disorders (ASD). Several experimental paradigms based on hierarchical figures have been used to test this controversial account. We addressed this hypothesis by testing central coherence in ASD (n = 19 with intellectual disability and n = 20 without intellectual disability), Williams syndrome (WS, n = 18), matched controls with intellectual disability (n = 20) and chronological age-matched controls (n = 20). We predicted that central coherence should be most impaired in ASD for the weak central coherence account to hold true. An alternative account includes dorsal stream dysfunction which dominates in WS. Central coherence was first measured by requiring subjects to perform local/global preference judgments using hierarchical figures under 6 different experimental settings (memory and perception tasks with 3 distinct geometries with and without local/global manipulations). We replicated these experiments under 4 additional conditions (memory/perception*local/global) in which subjects reported the correct local or global configurations. Finally, we used a visuoconstructive task to measure local/global perceptual interference. WS participants were the most impaired in central coherence whereas ASD participants showed a pattern of coherence loss found in other studies only in four task conditions favoring local analysis but it tended to disappear when matching for intellectual disability. We conclude that abnormal central coherence does not provide a comprehensive explanation of ASD deficits and is more prominent in populations, namely WS, characterized by strongly impaired dorsal stream functioning and other phenotypic traits that contrast with the autistic phenotype. Taken together these findings suggest that other mechanisms such as dorsal stream deficits (largest in WS) may underlie impaired central coherence.
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2. Desai MU, Divan G, Wertz FJ, Patel V. {{The discovery of autism: Indian parents’ experiences of caring for their child with an autism spectrum disorder}}. {Transcult Psychiatry}. 2012.
The current study investigated the lived experience of 12 parents of children with an Autism Spectrum Disorder in everyday cultural contexts in Goa, India. Narratives from parents collected between 2009 and 2010 were analyzed using the procedures of phenomenological psychology. Four temporal phases of parents’ experience emerged from these data. Findings showed that the earliest phase of the child’s life was a period of relative normalcy and social cohesion. In the second phase, the child’s behaviors began to disrupt the everyday social order, but parents viewed these unexpected behaviors as temporary. In the third phase, parents’ observations in public situations, along with assessments of others, led to a qualitative shift in which parents began to perceive that there was a persisting problem interfering with their child’s social and practical activities. In the fourth phase, parents grappled with developing their child’s capacities to meet existing practical opportunities in the local society, while attempting to reshape the social world to accommodate the abilities and limits of children like their own. Parents’ fundamental concerns throughout their journey were: learning to meet new and unfamiliar challenges as parents, caring for their child’s basic needs, and finding an engaging niche with a sense of belonging for their child in the everyday milieu. Both culture-specific and potentially universal levels of experience are delineated in the overall findings. Implications for culturally sensitive research and practice in India and other low- and middle-income countries are discussed.
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3. Gowen E, Hamilton A. {{Motor Abilities in Autism: A Review Using a Computational Context}}. {J Autism Dev Disord}. 2012.
Altered motor behaviour is commonly reported in Autism Spectrum Disorder, but the aetiology remains unclear. Here, we have taken a computational approach in order to break down motor control into different components and review the functioning of each process. Our findings suggest abnormalities in two areas-poor integration of information for efficient motor planning, and increased variability in basic sensory inputs and motor outputs. In contrast, motor learning processes are relatively intact and there is inconsistent evidence for deficits in predictive control. We suggest future work on motor abilities in autism should focus on sensorimotor noise and on higher level motor planning, as these seem to have a significant role in causing motor difficulties for autistic individuals.
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4. Hammock E, Veenstra-Vanderweele J, Yan Z, Kerr TM, Morris M, Anderson GM, Carter CS, Cook EH, Jacob S. {{Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(7): 712-21 e1.
OBJECTIVE: Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to ASD. Plasma oxytocin (OT) and whole-blood serotonin (5-HT) levels are consistently altered in some individuals with ASD. Reciprocal relationships have been described between brain oxytocin and serotonin systems during development. We therefore investigated the relationship between these peripheral biomarkers as well as their relationships with age. METHOD: In our first study, we analyzed correlations between these two biomarkers in 31 children and adolescents who were diagnosed with autism and were not on medications. In our second study, we explored whether whole-blood 5-HT levels are altered in mice lacking the oxytocin receptor gene Oxtr. RESULTS: In humans, OT and 5-HT were negatively correlated with each other (p < .05) and this relationship was most prominent in children less than 11 years old. Paralleling human findings, mice lacking Oxtr showed increased whole-blood 5-HT levels (p = .05), with this effect driven exclusively by mice less than 4 months old (p < .01). CONCLUSIONS: Identifying relationships between identified ASD biomarkers may be a useful approach to connect otherwise disparate findings that span multiple systems in this heterogeneous disorder. Using neurochemical biomarkers to perform parallel studies in animal and human populations within a developmental context is a plausible approach to probe the root causes of ASD and to identify potential interventions.
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5. Harfterkamp M, van de Loo-Neus G, Minderaa RB, van der Gaag RJ, Escobar R, Schacht A, Pamulapati S, Buitelaar JK, Hoekstra PJ. {{A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(7): 733-41.
OBJECTIVE: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. METHOD: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. RESULTS: Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p < .001). The CTRS-R:S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo, but not the other CTRS-R:S subscores. However, there were not significantly more patients on atomoxetine (20.9%) who improved much, or very much according to the CGI-I, than on placebo (8.7%; p = 0.14). Adverse events (mostly nausea, decrease in appetite, fatigue, and early morning awakening) were reported in 81.3% of atomoxetine patients and 65.3% of placebo patients (p > .1). There were no serious adverse events. CONCLUSIONS: Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. Clinical trial registration information-A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692.
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6. Hus V, Lord C. {{Effects of Child Characteristics on the Autism Diagnostic Interview-Revised: Implications for Use of Scores as a Measure of ASD Severity}}. {J Autism Dev Disord}. 2012.
The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained from this interview is used. The current study examines how algorithm totals reflecting past (ADI-Diagnostic) and current (ADI-Current) behaviors are influenced by child characteristics, such as demographics, behavioral problems and developmental level. Children with less language at the time of the interview had higher ADI-Diagnostic and ADI-Current. ADI-Diagnostic totals were also associated with age; parents of older children reported more severe past behaviors. Recommendations are provided regarding the use of the ADI-R as a measure of ASD severity, taking language and age into account.
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7. Kang-Yi CD, Grinker RR, Mandell DS. {{Korean Culture and Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2012.
This paper reviews the literature on early child development among Koreans, with a focus on autism spectrum disorders (ASD). The literature review of 951 abstracts in English, 101 abstracts in Korean and 27 full articles published from 1994 to 2011 was performed to understand the presentation of and response to ASD in Korean culture. Based on research to date on the identification, description, and treatment of ASD in Korean populations, we argue that at both conceptual and practical levels, early child development and interventions must be understood within cultural context. Culturally informed research on ASD is vital for increasing awareness of the importance of early intervention and the need for educational and psychological services in countries in which autism is stigmatized, misdiagnosed or undiagnosed.
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8. Theoharides TC, Asadi S. {{Unwanted Interactions Among Psychotropic Drugs and Other Treatments for Autism Spectrum Disorders}}. {J Clin Psychopharmacol}. 2012.
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9. Tse MT. {{Neurodevelopmental disorders: Exploring the links between SHANK2 and autism}}. {Nat Rev Drug Discov}. 2012.
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10. Weiss HR, Liu X, Grewal P, Chi OZ. {{Reduced effect of stimulation of AMPA receptors on cerebral O(2) consumption in a rat model of autism}}. {Neuropharmacology}. 2012.
Previous work demonstrated that basal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activity did not contribute to the elevated regional cerebral O(2) consumption in the brains of Eker rat (an autism-tuberous sclerosis model). We tested the hypothesis that increased stimulation of AMPA receptors also would not augment cerebral O(2) consumption in the Eker rat. Three cortical sites were prepared for administration of saline, 10(-4) and 10(-3) M AMPA in young (4 weeks) male control Long Evans and Eker rats (70-100 g). Cerebral blood flow ((14)C-iodoantipyrine) and O(2) consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. Receptor levels were studied through Western analysis of the GLuR1 subunit of the AMPA receptor. We found significantly increased cortical O(2) consumption (+33%) after 10(-4) M AMPA in control rats. The higher dose of AMPA did not further increase consumption. In the Eker rats, neither dose led to a significant increase in cortical O(2) consumption. Regional blood flow followed a similar pattern to oxygen consumption but cortical O(2) extraction did not differ. Cortical AMPA receptor protein levels were significantly reduced (-21%) in the Eker compared to control rats. Both O(2) consumption and blood flow were significantly elevated in the pons of the Eker rats compared to control. These data demonstrate a reduced importance of AMPA receptors in the control of cortical metabolism, related to reduced AMPA receptor protein, in the Eker rat. This suggests that increasing AMPA receptor activity may not be an effective treatment for children with autism spectrum disorders as they also have reduced AMPA receptor number.
