1. Abdallah MW, Larsen N, Grove J, Norgaard-Pedersen B, Thorsen P, Mortensen EL, Hougaard DM. {{Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish Historic Birth Cohort}}. {Brain Behav Immun}. 2011.
INTRODUCTION: Elevated levels of chemokines have been reported in plasma and brain tissue of individuals with Autism Spectrum Disorders (ASD). The aim of this study was to examine chemokine levels in amniotic fluid (AF) samples of individuals diagnosed with ASD and their controls. MATERIAL AND METHODS: A Danish Historic Birth Cohort (HBC) kept at Statens Serum Institute, Copenhagen was utilized. Using data from Danish nation-wide health registers, a case-control study design of 414 cases and 820 controls was adopted. Levels of MCP-1, MIP-1alpha and RANTES were analyzed using Luminex xMAP technology. Case-control differences were assessed as dichotomized at below the 10th percentile or above the 90th percentile cut-off points derived from the control biomarker distributions (logistic regression) or continuous measures (tobit regression). RESULTS AND CONCLUSION: AF volume for 331 cases and 698 controls was sufficient for Luminex analysis. Including all individuals in the cohort yielded no significant differences in chemokine levels in cases versus controls. Logistic regression analyses, performed on individuals diagnosed using ICD-10 only, showed increased risk for ASD with elevated MCP-1 (elevated 90th percentile adjusted OR: 2.32 [95% CI: 1.17-4.61]) compared to controls. An increased risk for infantile autism with elevated MCP-1 was also found (adjusted OR: 2.28 [95% CI: 1.16-4.48]). Elevated levels of MCP-1 may decipher an etiologic immunologic dysfunction or play rather an indirect role in the pathophysiology of ASD. Further studies to confirm its role and to identify the potential pathways through which MCP-1 may contribute to the development of ASD are necessary.
Lien vers le texte intégral (Open Access ou abonnement)
2. Green SA, Ben-Sasson A, Soto TW, Carter AS. {{Anxiety and Sensory Over-Responsivity in Toddlers with Autism Spectrum Disorders: Bidirectional Effects Across Time}}. {J Autism Dev Disord}. 2011.
This report focuses on the emergence of and bidirectional effects between anxiety and sensory over-responsivity (SOR) in toddlers with autism spectrum disorders (ASD). Participants were 149 toddlers with ASD and their mothers, assessed at 2 annual time points. A cross-lag analysis showed that anxiety symptoms increased over time while SOR remained relatively stable. SOR positively predicted changes in anxiety over and above child age, autism symptom severity, NVDQ, and maternal anxiety, but anxiety did not predict changes in SOR. Results suggest that SOR emerges earlier than anxiety, and predicts later development of anxiety.
Lien vers le texte intégral (Open Access ou abonnement)
3. Gross M. {{Copy numbers count for autism}}. {Curr Biol}. 2011; 21(15): R571-3.
4. Guiraud JA, Kushnerenko E, Tomalski P, Davies K, Ribeiro H, Johnson MH. {{Differential habituation to repeated sounds in infants at high risk for autism}}. {Neuroreport}. 2011.
It has been suggested that poor habituation to stimuli might explain atypical sensory behaviours in autism. We investigated habituation to repeated sounds using an oddball paradigm in 9-month-old infants with an older sibling with autism and hence at high risk for developing autism. Auditory-evoked responses to repeated sounds in control infants (at low risk of developing autism) decreased over time, demonstrating habituation, and their responses to deviant sounds were larger than responses to standard sounds, indicating discrimination. In contrast, neural responses in infants at high risk showed less habituation and a reduced sensitivity to changes in frequency. Reduced sensory habituation may be present at a younger age than the emergence of autistic behaviour in some individuals, and we propose that this could play a role in the over responsiveness to some stimuli and undersensitivity to others observed in autism.
Lien vers le texte intégral (Open Access ou abonnement)
5. Hambly C, Fombonne E. {{The Impact of Bilingual Environments on Language Development in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2011.
The impact of bilingual exposure on language learning has not been systematically studied in children with Autism Spectrum Disorders. This study compared the social abilities and language levels of children (mean age = 56 months) with ASDs from bilingual (n = 45) and monolingual (n = 30) environments. Bilingually-exposed children were subgrouped based on simultaneous bilingual exposure from infancy (SIM, n = 24) versus sequential post-infancy bilingual exposure (SEQ, n = 21). Despite significantly different amounts of bilingual exposure across all groups (p = <0.001) and significantly stronger social interaction scores in the SIM group compared to the SEQ group on the Vineland Adaptive Behavior Scales-II Interpersonal subdomain (p = 0.025), there were no significant group differences in language level. Bilingually-exposed children with ASDs did not experience additional delays in language development.
Lien vers le texte intégral (Open Access ou abonnement)
6. Kuwano Y, Kamio Y, Kawai T, Katsuura S, Inada N, Takaki A, Rokutan K. {{Autism-Associated Gene Expression in Peripheral Leucocytes Commonly Observed between Subjects with Autism and Healthy Women Having Autistic Children}}. {PLoS One}. 2011; 6(9): e24723.
Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder.
Lien vers le texte intégral (Open Access ou abonnement)
7. Morita T, Kosaka H, Saito DN, Ishitobi M, Munesue T, Itakura S, Omori M, Okazawa H, Wada Y, Sadato N. {{Emotional responses associated with self-face processing in individuals with autism spectrum disorders: An fMRI study}}. {Soc Neurosci}. 2011.
Individuals with autism spectrum disorders (ASD) show impaired emotional responses to self-face processing, but the underlying neural bases are unclear. Using functional magnetic resonance imaging, we investigated brain activity when 15 individuals with high-functioning ASD and 15 controls rated the photogenicity of self-face images and photographs of others’ faces. Controls showed a strong correlation between photogenicity ratings and extent of embarrassment evoked by self-face images; this correlation was weaker among ASD individuals, indicating a decoupling between the cognitive evaluation of self-face images and emotional responses. Individuals with ASD demonstrated relatively low self-related activity in the posterior cingulate cortex (PCC), which was related to specific autistic traits. There were significant group differences in the modulation of activity by embarrassment ratings in the right insular (IC) and lateral orbitofrontal cortices. Task-related activity in the right IC was lower in the ASD group. The reduced activity in the right IC for self-face images was associated with weak coupling between cognitive evaluation and emotional responses to self-face images. The PCC is responsible for self-referential processing, and the IC plays a role in emotional experience. Dysfunction in these areas could contribute to the lack of self-conscious behaviors in response to self-reflection in ASD individuals.
Lien vers le texte intégral (Open Access ou abonnement)
8. Paluszkiewicz SM, Martin BS, Huntsman MM. {{Fragile X Syndrome: The GABAergic System and Circuit Dysfunction}}. {Dev Neurosci}. 2011.
Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, sensory hypersensitivity, and high incidences of autism spectrum disorders and epilepsy. These phenotypes are suggestive of defects in neural circuit development and imbalances in excitatory glutamatergic and inhibitory GABAergic neurotransmission. While alterations in excitatory synapse function and plasticity are well-established in Fmr1 knockout (KO) mouse models of FXS, a number of recent electrophysiological and molecular studies now identify prominent defects in inhibitory GABAergic transmission in behaviorally relevant forebrain regions such as the amygdala, cortex, and hippocampus. In this review, we summarize evidence for GABAergic system dysfunction in FXS patients and Fmr1 KO mouse models alike. We then discuss some of the known developmental roles of GABAergic signaling, as well as the development and refinement of GABAergic synapses as a framework for understanding potential causes of mature circuit dysfunction. Finally, we highlight the GABAergic system as a relevant target for the treatment of FXS.
Lien vers le texte intégral (Open Access ou abonnement)
9. Warner J. {{Autism’s lone wolf: Simon Baron-Cohen wants to know, Are ‘autistic’ traits a predictable outcome of new marriage patterns?}}. {Time}. 2011; 178(8): 44-7.
10. Ziats MN, Rennert OM. {{Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways}}. {PLoS One}. 2011; 6(9): e24691.
The Autism Spectrum Disorders (ASD) represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFkappaB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia-in addition to neurons-deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.
