1. Abdallah MW, Pearce BD, Larsen N, Greaves-Lord K, Norgaard-Pedersen B, Hougaard DM, Mortensen EL, Grove J. {{Amniotic Fluid MMP-9 and Neurotrophins in Autism Spectrum Disorders: An Exploratory Study}}. {Autism Res}. 2012 Sep 24.
Evidence suggests that some developmental disorders, such as autism spectrum disorders (ASDs), are caused by errors in brain plasticity. Given the important role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in neuroplasticity, amniotic fluid samples for 331 ASD cases and 698 frequency-matched controls were analyzed for levels of MMP-9, brain-derived neurotrophic factor, NT-4 and transforming growth factor-beta utilizing a Danish historic birth cohort and Danish nationwide health registers. Laboratory measurements were performed using an in-house multiplex sandwich immunoassay Luminex xMAP method, and measurements were analyzed using tobit and logistic regression. Results showed elevated levels of MMP-9 in ASD cases compared with controls (crude and adjusted tobit regression P-values: 0.01 and 0.06). Our results highlight the importance of exploring the biologic impact of MMP-9 and potential therapeutic roles of its inhibitors in ASD and may indicate that neuroplastic impairments in ASD may present during pregnancy. Autism Res 2012, **: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Cascio C, Gribbin M, Gouttard S, Smith RG, Jomier M, Field S, Graves M, Hazlett HC, Muller K, Gerig G, Piven J. {{Fractional anisotropy distributions in 2- to 6-year-old children with autism}}. {J Intellect Disabil Res}. 2012 Sep 24.
Background Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. Methods A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating delta, the estimated mean and standard deviation of the approximating F for each distribution. Results The estimated delta parameter, , was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of was the driving force behind these results. Conclusions While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition.
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3. Dove D, Warren Z, McPheeters ML, Taylor JL, Sathe NA, Veenstra-Vanderweele J. {{Medications for Adolescents and Young Adults With Autism Spectrum Disorders: A Systematic Review}}. {Pediatrics}. 2012 Sep 24.
BACKGROUND AND OBJECTIVE:Although many treatments have been studied in children with autism spectrum disorders (ASDs), less attention has focused on interventions that may be helpful in adolescents and young adults with ASD. The goal of this study was to systematically review evidence regarding medication treatments for individuals between the ages of 13 and 30 years with ASD.METHODS:The Medline, PsycINFO, and ERIC databases were searched (1980-December 2011), as were reference lists of included articles. Two investigators independently assessed studies against predetermined inclusion/exclusion criteria. Two investigators independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength of evidence ratings on the basis of predetermined criteria.RESULTS:Eight studies of medications were identified that focused on 13- to 30-year-olds with ASD; 4 of the studies were of fair quality. The strength of evidence was insufficient for all outcomes associated with medications tested in this population; however, the 2 available studies of the atypical antipsychotic medication risperidone in this age range were consistent with the moderate evidence in children with ASD for treating problem behavior, including aggression, and high strength of evidence for adverse events, including sedation and weight gain.CONCLUSIONS:There is a marked lack of data on use of medication treatments for adolescents and young adults with ASD. The evidence on the use of risperidone in this age range is insufficient when considered alone but is consistent with the data in the population of children with ASD.
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4. Ghaleiha A, Asadabadi M, Mohammadi MR, Shahei M, Tabrizi M, Hajiaghaee R, Hassanzadeh E, Akhondzadeh S. {{Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial}}. {The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)}. 2012 Sep 24:1-7.
Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).
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5. Li H, Xue Z, Ellmore TM, Frye RE, Wong ST. {{Network-based analysis reveals stronger local diffusion-based connectivity and different correlations with oral language skills in brains of children with high functioning autism spectrum disorders}}. {Human brain mapping}. 2012 Sep 24.
Neuroimaging has uncovered both long-range and short-range connectivity abnormalities in the brains of individuals with autism spectrum disorders (ASD). However, the precise connectivity abnormalities and the relationship between these abnormalities and cognition and ASD symptoms have been inconsistent across studies. Indeed, studies find both increases and decreases in connectivity, suggesting that connectivity changes in the ASD brain are not merely due to abnormalities in specific connections, but rather, due to changes in the structure of the network in which the brain areas interact (i.e., network topology). In this study, we examined the differences in the network topology between high-functioning ASD patients and age and gender matched typically developing (TD) controls. After quantitatively characterizing the whole-brain connectivity network using diffusion tensor imaging (DTI) data, we searched for brain regions with different connectivity between ASD and TD. A measure of oral language ability was then correlated with the connectivity changes to determine the functional significance of such changes. Whole-brain connectivity measures demonstrated greater local connectivity and shorter path length in ASD as compared to TD. Stronger local connectivity was found in ASD, especially in regions such as the left superior parietal lobule, the precuneus and angular gyrus, and the right supramarginal gyrus. The relationship between oral language ability and local connectivity within these regions was significantly different between ASD and TD. Stronger local connectivity was associated with better performance in ASD and poorer performance in TD. This study supports the notion that increased local connectivity is compensatory for supporting cognitive function in ASD. Hum Brain Mapp, 2012. (c) 2012 Wiley Periodicals, Inc.
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6. Mari Bauset S, Zazpe I, Mari Sanchis A, Llopis Gonzalez A, Suarez-Varela MM. {{Are There Anthropometric Differences Between Autistic and Healthy Children?}}. {Journal of child neurology}. 2012 Sep 24.
Anthropometric development and growth were assessed in 2 groups of 6- to 9-year-olds: children with autism spectrum disorders and typically developing children. In a case-control study conducted in Valencia, Spain, we compared the body mass index (kg/m(2)) of 40 children with autism spectrum disorders (cases) and 113 typically developing children (controls) from the same area of residence. The sex- and age-adjusted odds ratios for being underweight in cases was 2.41 compared to controls. Furthermore, the body mass index distribution of the cases was significantly offset to lower values with respect to that of the controls (P = .024). In particular, 20% of the cases had a body mass index below the fifth percentile versus just 8.85% of the controls. Our data suggest that the anthropometric development of children with autism spectrum disorders should be monitored as part of routine care.
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7. Nightingale S. {{Autism spectrum disorders}}. {Nature reviews Drug discovery}. 2012 Sep 24.
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8. Richman DM, Barnard-Brak L, Bosch A, Thompson S, Grubb L, Abby L. {{Predictors of self-injurious behaviour exhibited by individuals with autism spectrum disorder}}. {J Intellect Disabil Res}. 2012 Sep 24.
BACKGROUND: Presence of an autism spectrum disorder is a risk factor for development of self-injurious behaviour (SIB) exhibited by individuals with developmental disorders. The most salient SIB risk factors historically studied within developmental disorders are level of intellectual disability, communication deficits and presence of specific genetic disorders. Recent SIB research has expanded the search for risk factors to include less commonly studied variables for people with developmental disorders: negative affect, hyperactivity and impulsivity. METHOD: A heterogeneous sample of 617 individuals with autism spectrum disorder diagnoses was derived from the National Database of Autism Research. Latent constructs were estimated from items of the community version of the Aberrant Behaviour Checklist. Structural equation modelling was used to assess whether impulsivity, hyperactivity, negative affect, severity of stereotypy, intellectual functioning or severity of autism symptoms predicted severity of SIB. RESULTS: Impulsivity (beta = 0.46), followed by intellectual functioning (beta = -0.39), and stereotypy (beta = 0.23) were the variables most highly predictive of increased SIB; impulsivity and stereotypy remained significant predictors of SIB after severity of autism symptoms and intelligence quotient (IQ) were controlled for. CONCLUSIONS: High levels of impulsivity and stereotypy were significant predictors of SIB in a large and diverse sample of people with confirmed autism diagnoses. Future research is needed on the effects of reducing impulsivity and stereotypy on the outcomes of treatment, early intervention and attempts to prevent the development of SIB.
