1. Ghalichi F, Ghaemmaghami J, Malek A, Ostadrahimi A. {{Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: a randomized clinical trial}}. {World J Pediatr};2016 (Jun 10)
BACKGROUND: Genetic and environmental factors are both responsible for the etiology of autism spectrum disorders (ASD). Although epidemiological studies have been conducted to clarify the association between restriction diets and ASD, the conclusion remains unclear. This study was undertaken to investigate the effect of gluten free diet (GFD) on gastrointestinal symptoms and behavioral indices in children with ASD. METHODS: In this randomized clinical trial, 80 children diagnosed with ASD by the Autism Diagnostic Interview-Revised (ADI-R) were assigned into GFD (n=40) and regular diet (RD) (n=40) groups for 6 weeks. At the beginning and end of the intervention, the ROME capital SHA, Cyrillic questionnaire for evaluating gastrointestinal symptoms and Gilliam Autism Rating Scale 2 questionnaire (GARS-2) for assessing psychometric properties were completed. RESULTS: Of the 80 children, 53.9% had gastrointestinal abnormalities. In the GFD group, the prevalence of gastrointestinal symptoms decreased significantly (P<0.05) after intake of GFD (40.57% vs. 17.10%) but increased insignificantly in the RD group (42.45% vs. 44.05%). GFD intervention resulted in a significant decrease in behavioral disorders (80.03+/-14.07 vs. 75.82+/-15.37, P<0.05) but an insignificant increase in the RD group (79.92+/-15.49 vs. 80.92+/-16.24). CONCLUSION: This study suggested that GFD may be effective in controlling gastrointestinal symptoms and ASD behaviors. Lien vers le texte intégral (Open Access ou abonnement)
2. Jiang HY, Xu LL, Shao L, Xia RM, Yu ZH, Ling ZX, Yang F, Min D, Ruan B. {{Maternal Infection during Pregnancy and Risk of Autism Spectrum Disorders: A Systematic Review and Meta-analysis}}. {Brain Behav Immun};2016 (Jun 7)
Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR = 1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR = 1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.
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3. Kerr DJ, Marsillo A, Guariglia SR, Budylin T, Sadek R, Menkes S, Chauhan A, Wen GY, McCloskey DP, Wieraszko A, Banerjee P. {{Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior}}. {Biochim Biophys Acta};2016 (Jun 7)
Type IV ATPases are putative aminophospholipid translocases (APLTs), more commonly known as flippases. A pronounced induction of the flippase Atp8a1 was observed in post-mortem tissue homogenates from the hippocampus and temporal lobe of juvenile autistic subjects compared to age-matched controls. In order to simulate the human data, C57BL/6 mice were allowed to develop after intra-hippocampal injection of recombinant lentivirus expressing Atp8a1 at the early developmental stage of postnatal day 6 (P6). Transmission electron microscopy (TEM) analysis of the lentivirus-Atp8a1 treated (Atp8a1+) mice in adulthood revealed fewer and weaker excitatory synapses in the hippocampal CA1 region compared to mice injected with empty virus. Significant inhibition of the Schaffer collateral pathway was observed in the Atp8a1+ mice in paired-pulse recording (PPR) at 20-ms inter-stimulus interval. In the three-chambered sociability test, the Atp8a1+ mice displayed no preference for an encaged stranger mouse over a novel object, which is a characteristic autistic-like behavior. In sharp contrast, Atp8a1 (-/-) mice displayed a preference for a stranger mouse over the novel object, which is characteristic of neurotypical mouse behavior. However, similar to the Atp8a1+ mice, the Atp8a1 (-/-) mice harbored fewer and weaker excitatory synapses in CA1 compared to wild-type controls, and displayed inhibition at 20-ms inter-stimulus interval in PPR. These findings suggest that both elevated and diminished levels of Atp8a1 during early development are detrimental to brain connectivity, but only elevated Atp8a1 is associated with aberrant social behavior. Mice with augmented levels of Atp8a1 may therefore serve as a potential model in autism research.
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4. Prince EB, Kim ES, Wall CA, Gisin E, Goodwin MS, Simmons ES, Chawarska K, Shic F. {{The relationship between autism symptoms and arousal level in toddlers with autism spectrum disorder, as measured by electrodermal activity}}. {Autism};2016 (Jun 10)
Electrodermal activity was examined as a measure of physiological arousal within a naturalistic play context in 2-year-old toddlers (N = 27) with and without autism spectrum disorder. Toddlers with autism spectrum disorder were found to have greater increases in skin conductance level than their typical peers in response to administered play activities. In the autism spectrum disorder group, a positive relationship was observed between restrictive and repetitive behaviors and skin conductance level increases in response to mechanical toys, whereas the opposite pattern was observed for passive toys. This preliminary study is the first to examine electrodermal activity levels in toddlers with autism spectrum disorder during play-based, naturalistic settings, and it highlights the potential for electrodermal activity as a measure of individual variability within autism spectrum disorder and early development.
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5. Satoh M, Obara T, Nishigori H, Ooba N, Morikawa Y, Ishikuro M, Metoki H, Kikuya M, Mano N. {{Prescription trends in children with pervasive developmental disorders (PDD): A claims data-based study in Japan}}. {World J Pediatr};2016 (Jun 10)
BACKGROUND: The only drug approved for pervasive developmental disorders (PDD) in Japan is pimozide. Several psychotropic drugs are also prescribed for offlabel use in Japan, but details regarding their prescription and use are largely unknown. The purpose of this study was to clarify the use of drug treatment in Japanese children with PDD. METHODS: Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD (International Classification of Diseases version 10 codes: F84) from 2005 to 2010 (total of 3276 patients as of 2010). The prescription rates were presented as the percentage of PDD patients who were prescribed each drug. RESULTS: Prior to 2010, the prescription rates for atypical antipsychotics, other antipsychotics, psychostimulants, all other central nervous system drugs, anticovnvulsants, non-barbiturates, and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the « nervous system » (trend P=0.02). The prescription rate for risperidone consistently increased, reaching 6.9% in 2010 (trend P<0.0001), the highest rate of the surveyed drugs among the antipsychotics. The prescription rate for aripiprazole also increased (trend P<0.0001), reaching 1.9% in 2010. The prescription rate for pimozide showed no annual changes, with a low rate of 0.4% in 2010. CONCLUSIONS: Compared with pimozide, the prescription rates for risperidone, aripiprazole and other psychotropic drugs have increased. Because safety data for these drugs in Japanese children are sparse, there is a need for future safety evaluations of these drugs in Japanese children. Lien vers le texte intégral (Open Access ou abonnement)
6. Zhou J, Zhang X, Ren J, Wang P, Zhang J, Wei Z, Tian Y. {{Validation of reference genes for quantitative real-time PCR in valproic acid rat models of autism}}. {Mol Biol Rep};2016 (Jun 10)
Autism is a neurodevelopmental disorder, and embryonic exposure to valproic acid (VPA) in rodents is the most frequently studied environmentally triggered autism models. Valproic acid can affect gene transcription as a histone deacetylase inhibitor, and thus may alter the expression of the most genes including reference genes. The aim of the current study is to validate suitable reference genes for quantitative real-time PCR (qPCR) quantification in prefrontal cortex and hippocampus of VPA rat models of autism. Female rats received a single intraperitoneal injection of 400 mg/kg sodium VPA at day 12.5 post-conception and controls were injected with saline. Male offspring were used to observe the expression of nine commonly used reference genes by qPCR, and the data were analyzed by four commonly used reference selection program including geNorm, BestKeeper, NormFinder and RefFinder. The results showed that VPA affected the expression of these commonly used reference genes in prefrontal cortex and hippocampus on postnatal 3, 5 weeks and 80 days, Gapdh and Actin, two very frequently used reference genes, were identified as the least stable genes in VPA group. Hprt1 was selected as the most stable gene, and Hmbs and Tbp were the optimum gene pair in prefrontal cortex and hippocampus across all VPA and controls. Problematically, the use of unstable reference genes results in calculation of different PGRN mRNA expression levels. The results suggest that selection of suitable references is critical for accurate mRNA quantification, and specifically in VPA induced rat models of autism.