1. Benson PR. {{Network Characteristics, Perceived Social Support, and Psychological Adjustment in Mothers of Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (Apr 7)
This study examined the characteristics of the support networks of 106 mothers of children with ASD and their relationship to perceived social support, depressed mood, and subjective well-being. Using structural equation modeling, two competing sets of hypotheses were assessed: (1) that network characteristics would impact psychological adjustment directly, and (2) that network effects on adjustment would be indirect, mediated by perceived social support. Results primarily lent support to the latter hypotheses, with measures of network structure (network size) and function (proportion of network members providing emotional support) predicting increased levels of perceived social support which, in turn, predicted decreased depressed mood and increased well-being. Results also indicated that increased interpersonal strain in the maternal network was directly and indirectly associated with increased maternal depression, while being indirectly linked to reduced well-being. Study limitations and implications are discussed.
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2. Bhakar AL, Dolen G, Bear MF. {{The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)}}. {Annu Rev Neurosci};2012 (Apr 5)
Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way. Expected final online publication date for the Annual Review of Neuroscience Volume 35 is June 17, 2012. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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3. Bible E. {{Neurodevelopmental disorders: Transplantation therapy in a mouse model of Rett syndrome}}. {Nat Rev Neurol};2012 (Apr 10)
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4. Brunelle F, Bargiacchi A, Chabane N, Saitovitch A, Grevent D, Zilbovicius M, Boddaert N. {{[Brain imaging of infantile autism.]}}. {Arch Pediatr};2012 (Apr 5)
Understanding of brain structural anomalies seen in children with autism has considerably progressed since the apparition of MRI and functional imaging. All the results are converging toward the description of anatomical and functional anomalies in the regions of the so-called « social brain ». Statistical analyses show diminution of gray matter in the region of the superior temporal sulcus (STS). Functional studies with PET shows a diminution of brain blood flow at rest in the same region. Brain activation studies show absence of activation of the specialized region in processing human voice and hypoactivation of « social brain » regions in complex tasks of social cognition. At last, abnormal connectivity between the frontal and temporal regions has been showed. Those regions are implicated in processing sensorial inputs necessary for normal social life. All those anomalies could be responsible of the abnormal social behaviour pattern of children with autism.
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5. Dufault R, Lukiw WJ, Crider R, Schnoll R, Wallinga D, Deth R. {{A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States}}. {Clin Epigenetics};2012 (Apr 10);4(1):6.
ABSTRACT: The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91 % between 2005 to 2010 while the number of children receiving special education services overall declined by 5 %. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.
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6. Egawa J, Endo T, Tamura R, Masuzawa N, Fukui N, Sugai T, Someya T. {{Influence of the 5-HTR1A C-1019G polymorphism on clinical phenotypes of autism spectrum disorders}}. {Psychiatry Res};2012 (Apr 5)
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7. Key AP, Stone WL. {{Processing of novel and familiar faces in infants at average and high risk for autism}}. {Dev Cogn Neurosci};2012 (Apr);2(2):244-255.
The study investigated whether infant siblings of children with autism (sibs-ASD) process familiar and novel faces differently from typical infants and whether sensitivity to face familiarity is associated with infants’ social and communicative behaviors. Visual event-related potentials (ERPs) were recorded in 35 infants, age 9 months+/-15 days (20 typical infants, 15 sibs-ASD) using an oddball paradigm presenting photographs of infants’ mothers (70% of trials) and an unfamiliar female (30% of trials). Eye tracking responses to a different unfamiliar face were recorded to determine whether differences in gaze patterns might account for any ERP differences found. There were no group differences in the distribution, number or duration of fixations. Both infant groups differentiated between mothers and strangers, as reflected in amplitude modulations of posterior N290/P400 and frontal/central Nc responses. Group differences were present in the latency of the P400 response, where a delayed response to the stranger face was observed only in typical infants. Across both groups, shorter Nc latency to mother’s face was associated with parental reports of stronger interpersonal skills. Individual differences in the speed of processing for novel vs. familiar faces may be an informative early marker of risk for atypical social development.
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8. Lee HY, Jan LY. {{Fragile X syndrome: mechanistic insights and therapeutic avenues regarding the role of potassium channels}}. {Curr Opin Neurobiol};2012 (Apr 5)
Fragile X syndrome (FXS) is a common form of mental disability and one of the known causes of autism. The mutation responsible for FXS is a large expansion of the trinucleotide CGG repeats that leads to DNA methylation of the fragile X mental retardation gene 1 (FMR1) and transcriptional silencing, resulting in the absence of fragile X mental retardation protein (FMRP), an mRNA binding protein. Although it is widely known that FMRP is critical for metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), which has provided a general theme for developing pharmacological drugs for FXS, specific downstream targets of FMRP may also be of therapeutic value. Since alterations in potassium channel expression level or activity could underlie neuronal network defects in FXS, here we describe recent findings on how these channels might be altered in mouse models of FXS and the possible therapeutic avenues for treating FXS.
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9. Lubs HA, Stevenson RE, Schwartz CE. {{Fragile x and x-linked intellectual disability: four decades of discovery}}. {Am J Hum Genet};2012 (Apr 6);90(4):579-590.
X-Linked intellectual disability (XLID) accounts for 5%-10% of intellectual disability in males. Over 150 syndromes, the most common of which is the fragile X syndrome, have been described. A large number of families with nonsyndromal XLID, 95 of which have been regionally mapped, have been described as well. Mutations in 102 X-linked genes have been associated with 81 of these XLID syndromes and with 35 of the regionally mapped families with nonsyndromal XLID. Identification of these genes has enabled considerable reclassification and better understanding of the biological basis of XLID. At the same time, it has improved the clinical diagnosis of XLID and allowed for carrier detection and prevention strategies through gamete donation, prenatal diagnosis, and genetic counseling. Progress in delineating XLID has far outpaced the efforts to understand the genetic basis for autosomal intellectual disability. In large measure, this has been because of the relative ease of identifying families with XLID and finding the responsible mutations, as well as the determined and interactive efforts of a small group of researchers worldwide.
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10. Macari SL, Campbell D, Gengoux GW, Saulnier CA, Klin AJ, Chawarska K. {{Predicting Developmental Status from 12 to 24 Months in Infants at Risk for Autism Spectrum Disorder: A Preliminary Report}}. {J Autism Dev Disord};2012 (Apr 7)
The study examined whether performance profiles on individual items of the Toddler Module of the Autism Diagnostic Observation Schedule at 12 months are associated with developmental status at 24 months in infants at high and low risk for developing Autism Spectrum Disorder (ASD). A nonparametric decision-tree learning algorithm identified sets of 12-month predictors of developmental status at 24 months. Results suggest that identification of infants who are likely to exhibit symptoms of ASD at 24 months is complicated by variable patterns of symptom emergence. Fine-grained analyses linking specific profiles of strengths and deficits with specific patterns of symptom emergence will be necessary for further refinement of screening and diagnostic instruments for ASD in infancy.
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11. Moss J, Howlin P, Magiati I, Oliver C. {{Characteristics of autism spectrum disorder in Cornelia de Lange syndrome}}. {J Child Psychol Psychiatry};2012 (Apr 10)
Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in comparison to a matched group of individuals with ASD. Method: The Autism Diagnostic Observation Schedule (ADOS) was administered to 20 individuals with CdLS (mean age = 11.34; range = 6-13 years) and 20 individuals with idiopathic ASD (mean age = 10.42; range = 8-11 years). Participants were matched according to adaptive behaviour and receptive language skills. Results: Sixty-five percent (N = 13) of individuals with CdLS met the cut-off score for autism on the total ADOS score. Further analysis at domain and item level indicated that individuals with CdLS showed significantly less repetitive behaviour, (specifically sensory interests); more eye contact, more gestures and less stereotyped speech than the ASD group. The CdLS group also showed higher levels of anxiety. Conclusions: The comparison between CdLS and idiopathic ASD indicates subtle group differences in the profile of ASD symptomatology that are not accounted for by degree of intellectual disability or receptive language skills. These differences may not be evident when relying solely upon clinical and domain level scores, but may be distinguishing features of the ASD presentations in the two disorders. The findings have implications for the conceptualisation and assessment of ASD in individuals with genetic syndromes.
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12. Rahbar MH, Samms-Vaughan M, Loveland KA, Ardjomand-Hessabi M, Chen Z, Bressler J, Shakespeare-Pellington S, Grove ML, Bloom K, Pearson DA, Lalor GC, Boerwinkle E. {{Seafood Consumption and Blood Mercury Concentrations in Jamaican Children With and Without Autism Spectrum Disorders}}. {Neurotox Res};2012 (Apr 10)
Mercury is a toxic metal shown to have harmful effects on human health. Several studies have reported high blood mercury concentrations as a risk factor for autism spectrum disorders (ASDs), while other studies have reported no such association. The goal of this study was to investigate the association between blood mercury concentrations in children and ASDs. Moreover, we investigated the role of seafood consumption in relation to blood mercury concentrations in Jamaican children. Based on data for 65 sex- and age-matched pairs (2-8 years), we used a General Linear Model to test whether there is an association between blood mercury concentrations and ASDs. After controlling for the child’s frequency of seafood consumption, maternal age, and parental education, we did not find a significant difference (P = 0.61) between blood mercury concentrations and ASDs. However, in both cases and control groups, children who ate certain types of seafood (i.e., salt water fish, sardine, or mackerel fish) had significantly higher (all P < 0.05) geometric means blood mercury concentration which were about 3.5 times that of children living in the US or Canada. Our findings also indicate that Jamaican children with parents who both had education up to high school are at a higher risk of exposure to mercury compared to children with at least one parent who had education beyond high school. Based on our findings, we recommend additional education to Jamaican parents regarding potential hazards of elevated blood mercury concentrations, and its association with seafood consumption and type of seafood.
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13. Ramaekers VT, Quadros EV, Sequeira JM. {{Role of folate receptor autoantibodies in infantile autism}}. {Mol Psychiatry};2012 (Apr 10)
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14. Smith DG, Ehlers MD. {{Mining and modeling human genetics for autism therapeutics}}. {Curr Opin Neurobiol};2012 (Apr 4)
A growing understanding of the genetic origins of autism spectrum disorders (ASDs) and the impact of ASD risk genes on synaptic function presents new opportunities for drug discovery. Large-scale human genetics studies have begun to reveal molecular pathways and potential therapeutic drug targets. Subsequent validation and characterization of ASD risk genes in mouse models holds promise for defining relevant cellular mechanisms and brain circuits associated with the core behavioral symptoms of autism. Here we review recent advances in the molecular therapeutics in ASDs and discuss opportunities and obstacles for converting emerging biology into new medicines. We present emerging concepts on the impact of risk genes during development and adulthood that define points of intervention. We further highlight ongoing clinical trials in patients with syndromic forms of autism. These clinical studies will be an important test of the utility of human genetics as a starting point for drug discovery in ASDs.
