1. {{Antispsychotics: ‘last option’ for people with autism}}. {Nurs Stand};2014 (Jan 29);28(22):10.
People with autism should be prescribed antipsychotics only if the severity of their challenging behaviour cannot be tackled using any other intervention, according to new quality standards.
Lien vers le texte intégral (Open Access ou abonnement)
2. Bayat M. {{The stories of ‘snake children’: killing and abuse of children with developmental disabilities in West Africa}}. {J Intellect Disabil Res};2014 (Jan 27)
BACKGROUND: Killing and abuse of children with disabilities are covert phenomena, occurring in some developing regions, such as in some African countries. Similar to the practice of ritual killing of spirit children in Ghana, the phenomenon of the snake child in Cote d’Ivoire (known as Ivory Coast), is the ritual abandonment or killing of children with intellectual disability (ID). METHOD: This study is a qualitative ethnographic investigation into understanding this phenomenon. Three major questions were of interest: (1) Who are the snake children? (2) How are these children viewed and treated? (3) What are ways of changing negative attitudes towards children with developmental disabilities? RESULTS: The practices of killing, abandonment and abuse of children with disabilities take place in Cote d’Ivoire today, although the extent is not known. CONCLUSION: Killing and abuse of children with ID are explained within the context of indigenous African religions, animism and folk culture. The concept of disability ‘otherness’ and inferiority is also explored as a framework for reflection and ethical debate.
Lien vers le texte intégral (Open Access ou abonnement)
3. Heavner K, Newschaffer C, Hertz-Picciotto I, Bennett D, Burstyn I. {{Quantifying the potential impact of measurement error in an investigation of autism spectrum disorder (ASD)}}. {J Epidemiol Community Health};2014 (Jan 27)
The Early Autism Risk Longitudinal Investigation (EARLI), an ongoing study of a risk-enriched pregnancy cohort, examines genetic and environmental risk factors for autism spectrum disorders (ASDs). We simulated the potential effects of both measurement error (ME) in exposures and misclassification of ASD-related phenotype (assessed as Autism Observation Scale for Infants (AOSI) scores) on measures of association generated under this study design. We investigated the impact on the power to detect true associations with exposure and the false positive rate (FPR) for a non-causal correlate of exposure (X2, r=0.7) for continuous AOSI score (linear model) versus dichotomised AOSI (logistic regression) when the sample size (n), degree of ME in exposure, and strength of the expected (true) OR (eOR)) between exposure and AOSI varied. Exposure was a continuous variable in all linear models and dichotomised at one SD above the mean in logistic models. Simulations reveal complex patterns and suggest that: (1) There was attenuation of associations that increased with eOR and ME; (2) The FPR was considerable under many scenarios; and (3) The FPR has a complex dependence on the eOR, ME and model choice, but was greater for logistic models. The findings will stimulate work examining cost-effective strategies to reduce the impact of ME in realistic sample sizes and affirm the importance for EARLI of investment in biological samples that help precisely quantify a wide range of environmental exposures.
Lien vers le texte intégral (Open Access ou abonnement)
4. Jeste SS, Geschwind DH. {{Disentangling the heterogeneity of autism spectrum disorder through genetic findings}}. {Nat Rev Neurol};2014 (Jan 28)
Autism spectrum disorder (ASD) represents a heterogeneous group of disorders, which presents a substantial challenge to diagnosis and treatment. Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. We argue that only through such advances will we begin to define endophenotypes that can benefit from targeted, hypothesis-driven treatments. We review the latest technologies used to identify and characterize the genetics underlying ASD and then consider three themes-single-gene disorders, the gender bias in ASD, and the genetics of neurological comorbidities-that highlight ways in which we can use genetics to define the many phenotypes within the autism spectrum. We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment.
Lien vers le texte intégral (Open Access ou abonnement)
5. Matsunami N, Hensel CH, Baird L, Stevens J, Otterud B, Leppert T, Varvil T, Hadley D, Glessner JT, Pellegrino R, Kim C, Thomas K, Wang F, Otieno FG, Ho K, Christensen GB, Li D, Prekeris R, Lambert CG, Hakonarson H, Leppert MF. {{Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population}}. {Mol Autism};2014 (Jan 27);5(1):5.
BACKGROUND: Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. METHODS: We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. RESULTS: We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. CONCLUSIONS: Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants.
Lien vers le texte intégral (Open Access ou abonnement)
6. Steeb H, Ramsey JM, Guest PC, Stocki P, Cooper JD, Rahmoune H, Ingudomnukul E, Auyeung B, Ruta L, Baron-Cohen S, Bahn S. {{Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome}}. {Mol Autism};2014;5(1):4.
BACKGROUND: The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. METHODS: Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. RESULTS: Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. CONCLUSION: Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.
