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 (Sep 10)
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.
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2. Adler K, Moore JK, Filippov G, Wu S, Carmichael J, Schermer M. {{A Novel Assay for Evaluating Fragile X Locus Repeats}}. {J Mol Diagn};2011 (Jul 26)
We have developed a novel fragile X locus repeat assay that is a simple and high-throughput method that, with clinical validation, may be suitable for screening. It uses amplification of the FMR1 trinucleotide repeat region, followed by a hybridization assay to quantify the number of repeats in the amplicons. To our knowledge, this is the first repeat-counting assay that uses fluorescent signals rather than electrophoresis or mass spectrometry as the signaling mechanism. We also report the development of a simple microfluidic electrophoresis reflex test that uses the same amplicons and reduces the need for Southern blots to differentiate homozygous female normal samples from full mutations. The new assay, which is based on a suspension-array hybridization method, was tested on a series of male and female reference samples spanning the range from normal to full mutations. It was also tested on DNA from 1008 dried blood spot samples from pregnant women in their first trimester. The hybridization assay identified 51 of those as potentially expanded alleles of >/=45 repeats or as intermediate or higher in FMR1 repeat classification. Of these screen-positive samples, eight were confirmed by microfluidic electrophoresis as premutations consisting of >/=55 repeats. The FMR1 repeat assay is straightforward to run in high throughput, and the results are in the form of numerical ratios for ease of initial interpretation.
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3. Coury DL. {{Review: little evidence of clear benefit for most medical treatments for children with autism spectrum disorders}}. {Evid Based Ment Health};2011 (Sep 30)
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4. Hawkes N. {{Local autism strategy groups should be set up, NICE recommends}}. {BMJ};2011;343:d6263.
5. Lord C. {{Unweaving the autism spectrum}}. {Cell};2011 (Sep 30);147(1):24-25.
Although genes associated with human autism spectrum disorders have been identified, bridging the gap between genetics and the patchwork of behavioral deficits associated with the disease remains an enormous challenge. Penagarikano et al. (2011) now show that mice lacking CNTNAP2, a gene that causes a rare form of epilepsy associated with autistic features and language impairment, display similar phenotypes to their human counterparts, raising hopes that such models may speed the identification of neuronal circuitries underlying the core features of autism.
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6. Patricia H. {{Review: possible benefits from early intensive behavioural and developmental interventions in children with autism spectrum disorders, but more research needed}}. {Evid Based Ment Health};2011 (Sep 30)
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7. Penagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, Sonnenblick LI, Gruver R, Almajano J, Bragin A, Golshani P, Trachtenberg JT, Peles E, Geschwind DH. {{Absence of CNTNAP2 Leads to Epilepsy, Neuronal Migration Abnormalities, and Core Autism-Related Deficits}}. {Cell};2011 (Sep 30);147(1):235-246.
Although many genes predisposing to autism spectrum disorders (ASD) have been identified, the biological mechanism(s) remain unclear. Mouse models based on human disease-causing mutations provide the potential for understanding gene function and novel treatment development. Here, we characterize a mouse knockout of the Cntnap2 gene, which is strongly associated with ASD and allied neurodevelopmental disorders. Cntnap2(-/-) mice show deficits in the three core ASD behavioral domains, as well as hyperactivity and epileptic seizures, as have been reported in humans with CNTNAP2 mutations. Neuropathological and physiological analyses of these mice before the onset of seizures reveal neuronal migration abnormalities, reduced number of interneurons, and abnormal neuronal network activity. In addition, treatment with the FDA-approved drug risperidone ameliorates the targeted repetitive behaviors in the mutant mice. These data demonstrate a functional role for CNTNAP2 in brain development and provide a new tool for mechanistic and therapeutic research in ASD. PAPERFLICK:
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8. Salomon RG, Hong L, Hollyfield JG. {{Discovery of Carboxyethylpyrroles (CEPs): Critical Insights into AMD, Autism, Cancer, and Wound Healing from Basic Research on the Chemistry of Oxidized Phospholipids}}. {Chem Res Toxicol};2011 (Oct 3)
Basic research, exploring the hypothesis that 2-(omega-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modification of protein lysyl epsilon-amino groups by gamma-hydroxyalkenal phospholipids that are formed by oxidative cleavage of docosahexaenate-containing phospholipids. Chemical synthesis of CEP-modified proteins and the production of highly specific antibodies that recognize them preceded and facilitated their detection in vivo and enabled exploration of their biological occurrence and activities. This investigational approach, from the chemistry of biomolecules to disease phenotype, is proving to be remarkably productive.
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9. Siniscalco D, Sapone A, Giordano C, Cirillo A, de Novellis V, de Magistris L, Rossi F, Fasano A, Maione S, Antonucci N. {{The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients}}. {J Autism Dev Disord};2011 (Oct 4)
Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and neurons, autistic children also show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the activation of caspases, cysteinyl aspartate-specific proteases involved in apoptosis and several other cell functions in PBMCs from 15 ASD children compared to age-matched normal healthy developing controls. The mRNA levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also increased in ASD patients. Our data are suggestive of a possible role of the capsase pathway in ASD clinical outcome and of the use of caspase as potential diagnostic and/or therapeutic tools in ASD management.
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10. Taylor JL, Warren ZE. {{Maternal Depressive Symptoms Following Autism Spectrum Diagnosis}}. {J Autism Dev Disord};2011 (Oct 1)
The current study examined depressive symptoms, concerning the week following autism spectrum diagnosis and an average of 1.4 years later, in mothers (n = 75) of young children diagnosed with an autism spectrum disorder (ASD). Over three-quarters of mothers (78.7%) provided retrospective reports of clinically significant depressive symptoms regarding the week following their child’s ASD diagnosis, with some 37.3% continuing to report clinically significant levels of depressive symptoms at follow-up. Depressive symptoms immediately following diagnosis were not related to initial global characteristics of child functioning, but were related to reported child problem behaviors and financial barriers at follow-up. Results of this study underscore the importance of attention to caregiver distress and depression within models of autism detection and intervention.
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11. Vissers ME, Cohen MX, Geurts HM. {{Brain connectivity and high functioning autism: A promising path of research that needs refined models, methodological convergence, and stronger behavioral links}}. {Neurosci Biobehav Rev};2011 (Sep 24)
Here we review findings from studies investigating functional and structural brain connectivity in high functioning individuals with autism spectrum disorders (ASDs). The dominant theory regarding brain connectivity in people with ASD is that there is long distance under-connectivity and local over-connectivity of the frontal cortex. Consistent with this theory, long-range cortico-cortical functional and structural connectivity appears to be weaker in people with ASD than in controls. However, in contrast to the theory, there is less evidence for local over-connectivity of the frontal cortex. Moreover, some patterns of abnormal functional connectivity in ASD are not captured by current theoretical models. Taken together, empirical findings measuring different forms of connectivity demonstrate complex patterns of abnormal connectivity in people with ASD. The frequently suggested pattern of long-range under-connectivity and local over-connectivity is in need of refinement.
