1. Fridenson-Hayo S, Berggren S, Lassalle A, Tal S, Pigat D, Bolte S, Baron-Cohen S, Golan O. {{Basic and complex emotion recognition in children with autism: cross-cultural findings}}. {Mol Autism};2016;7:52.
BACKGROUND: Children with autism spectrum conditions (ASC) have emotion recognition deficits when tested in different expression modalities (face, voice, body). However, these findings usually focus on basic emotions, using one or two expression modalities. In addition, cultural similarities and differences in emotion recognition patterns in children with ASC have not been explored before. The current study examined the similarities and differences in the recognition of basic and complex emotions by children with ASC and typically developing (TD) controls across three cultures: Israel, Britain, and Sweden. METHODS: Fifty-five children with high-functioning ASC, aged 5-9, were compared to 58 TD children. On each site, groups were matched on age, sex, and IQ. Children were tested using four tasks, examining recognition of basic and complex emotions from voice recordings, videos of facial and bodily expressions, and emotional video scenarios including all modalities in context. RESULTS: Compared to their TD peers, children with ASC showed emotion recognition deficits in both basic and complex emotions on all three modalities and their integration in context. Complex emotions were harder to recognize, compared to basic emotions for the entire sample. Cross-cultural agreement was found for all major findings, with minor deviations on the face and body tasks. CONCLUSIONS: Our findings highlight the multimodal nature of ER deficits in ASC, which exist for basic as well as complex emotions and are relatively stable cross-culturally. Cross-cultural research has the potential to reveal both autism-specific universal deficits and the role that specific cultures play in the way empathy operates in different countries.
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2. Ghaffari MA, Mousavinejad E, Riahi F, Mousavinejad M, Afsharmanesh MR. {{Increased Serum Levels of Tumor Necrosis Factor-Alpha, Resistin, and Visfatin in the Children with Autism Spectrum Disorders: A Case-Control Study}}. {Neurol Res Int};2016;2016:9060751.
Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-alpha) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72 +/- 2.65 y; range; 4-12 y) and 30 healthy children (mean age: 8.4 +/- 2.66 y; range: 4-12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-alpha serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-alpha levels in children with ASD were significantly higher than that in the healthy patients (p < 0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-alpha in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-alpha, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD. Lien vers le texte intégral (Open Access ou abonnement)
3. Ji X, Kember RL, Brown CD, Bucan M. {{Increased burden of deleterious variants in essential genes in autism spectrum disorder}}. {Proc Natl Acad Sci U S A};2016 (Dec 27);113(52):15054-15059.
Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.
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4. Medhasi S, Pinthong D, Pasomsub E, Vanwong N, Ngamsamut N, Puangpetch A, Chamnanphon M, Hongkaew Y, Pratoomwun J, Limsila P, Sukasem C. {{Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients}}. {Front Pharmacol};2016;7:475.
The present study sought to investigate the genetic variants in drug metabolizing enzyme and transporter (DMET) genes associated with steady-state plasma concentrations of risperidone among Thai autism spectrum disorder (ASD) patients. ASD patients taking risperidone for at least 1 month were enrolled for this pharmacogenomic study. Genotyping profile was obtained using Affymetrix DMET Plus array interrogating 1931 variants in 231 genes. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry assay. The final analysis included 483 markers for 167 genes. Six variants, ABCB11 (c.3084A > G, c. *420A > G, c. *368G > A, and c. *236G > A) and ADH7 (c.690G > A and c.-5360G > A), were found to be associated with plasma concentrations of risperidone. 9-Hydroxyrisperidone and the total active-moiety levels were associated with six gene variants, SCLO1B1 (c.-11187G > A and c.521T > C), SLCO1B3 (c.334G > T, c.699A > G, and c.1557G > A), and SLC7A5 c. *438C > G. Polymorphisms in UGT2B4 c. *448A > G and CYP2D6 (c.1661G > C, c.4180G > C, and c.-2178G > A) showed considerable but not significant associations with metabolic ratio. This pharmacogenomic study identifies new genetic variants of DMET genes in monitoring risperidone therapy.
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5. Nath D. {{Complementary and Alternative Medicine in the School-Age Child With Autism}}. {J Pediatr Health Care};2016 (Dec 22)
This case study examines some common complementary and alternative treatments used in the management of behavioral and gastrointestinal symptoms associated with autism including food selectivity, abdominal pain, nausea, gastroesophageal reflux, constipation, and diarrhea. The current literature on the safety and efficacy of these treatments for pediatric patients is reviewed. This study examines therapies including gluten-free and casein-free diet, probiotics, vitamin B12, omega-3 fatty acid supplementation, chelation therapy, acupuncture, and chiropractic manipulations used in treating these core symptoms of autism.
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6. Schroeder DI, Schmidt RJ, Crary-Dooley FK, Walker CK, Ozonoff S, Tancredi DJ, Hertz-Picciotto I, LaSalle JM. {{Placental methylome analysis from a prospective autism study}}. {Mol Autism};2016;7:51.
BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. METHODS: In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. RESULTS: We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. CONCLUSIONS: These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families.
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7. Shi LJ, Liu WH, Shi HS, Yan C, Wang Y, Wang Y, Cheung EF, Chan RC. {{Co-occurrence of autistic and schizotypal traits and its association with emotional and psychosocial function in Chinese college students}}. {Psychiatry Res};2016 (Dec 20);248:64-70.
Empirical findings suggest an overlap between autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD). Co-occurring autistic and positive schizotypal traits may have a moderating effect on behaviour and cognition. This study attempted to examine the co-occurrence rate of autistic and schizotypal traits in otherwise healthy college students and to test the moderating effect of co-occurring autistic and schizotypal traits on executive function, emotion processing and social function. Eight hundred and sixty-four participants took part in the present study. The results showed that the co-occurrence rate of autistic and schizotypal trait was 3.4% at baseline and 2.4% at one-year follow-up. The interaction between autistic traits and schizotypal traits was associated with better executive functioning and social functioning but poorer emotional expression.
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8. Westmark CJ, Chuang SC, Hays SA, Filon MJ, Ray BC, Westmark PR, Gibson JR, Huber KM, Wong RK. {{APP Causes Hyperexcitability in Fragile X Mice}}. {Front Mol Neurosci};2016;9:147.
Amyloid-beta protein precursor (APP) and metabolite levels are altered in fragile X syndrome (FXS) patients and in the mouse model of the disorder, Fmr1KO mice. Normalization of APP levels in Fmr1KO mice (Fmr1KO /APPHET mice) rescues many disease phenotypes. Thus, APP is a potential biomarker as well as therapeutic target for FXS. Hyperexcitability is a key phenotype of FXS. Herein, we determine the effects of APP levels on hyperexcitability in Fmr1KO brain slices. Fmr1KO /APPHET slices exhibit complete rescue of UP states in a neocortical hyperexcitability model and reduced duration of ictal discharges in a CA3 hippocampal model. These data demonstrate that APP plays a pivotal role in maintaining an appropriate balance of excitation and inhibition (E/I) in neural circuits. A model is proposed whereby APP acts as a rheostat in a molecular circuit that modulates hyperexcitability through mGluR5 and FMRP. Both over- and under-expression of APP in the context of the Fmr1KO increases seizure propensity suggesting that an APP rheostat maintains appropriate E/I levels but is overloaded by mGluR5-mediated excitation in the absence of FMRP. These findings are discussed in relation to novel treatment approaches to restore APP homeostasis in FXS.
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9. Yip BH, Leonard H, Stock S, Stoltenberg C, Francis RW, Gissler M, Gross R, Schendel D, Sandin S. {{Caesarean section and risk of autism across gestational age: a multi-national cohort study of 5 million births}}. {Int J Epidemiol};2016 (Dec 25)
BACKGROUND: The positive association between caesarean section (CS) and autism spectrum disorder (ASD) may be attributed to preterm delivery. However, due to lack of statistical power, no previous study thoroughly examined this association across gestational age. Moreover, most studies did not differentiate between emergency and planned CS. METHODS: Using population-based registries of four Nordic countries and Western Australia, our study population included 4 987 390 singletons surviving their first year of life, which included 671 646 CS deliveries and 31 073 ASD children. We used logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (CI) for CS, adjusted for gestational age, site, maternal age and birth year. Stratified analyses were conducted by both gestational age subgroups and by week of gestation. We compared emergency versus planned CS to investigate their potential difference in the risk of ASD. RESULTS: Compared with vaginal delivery, the overall adjusted OR for ASD in CS delivery was 1.26 (95% CI 1.22-1.30). Stratified ORs were 1.25 (1.15-1.37), 1.16 (1.09-1.23), 1.34 (1.28-1.40) and 1.17 (1.04-1.30) for subgroups of gestational weeks 26-36, 37-38, 39-41 and 42-44, respectively. CS was significantly associated with risk of ASD for each week of gestation, from week 36 to 42, consistently across study sites (OR ranged 1.16-1.38). There was no statistically significant difference between emergency and planned CS in the risk of ASD. CONCLUSION: Across the five countries, emergency or planned CS is consistently associated with a modest increased risk of ASD from gestational weeks 36 to 42 when compared with vaginal delivery.
