1. Bello-Mojeed MA, Bakare MO. {{Improving Treatment of Children with Autism Spectrum Disorder in Low- and Middle-Income Countries: The Role of Non-specialist Care Providers}}. {PLoS medicine}. 2013 Dec;10(12):e1001573.
Mashudat Bello-Mojeed and Muideen O. Bakare discuss the unmet challenges in care of children with autism spectrum disorders in low- and middle-income countries. Please see later in the article for the Editors’ Summary.
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2. Bowers JM, Konopka G. {{ASD-relevant Animal Models of the Foxp Family of Transcription Factors}}. {Autism-open access}. 2012 Dec 5;Suppl 1(10).
Autism is a neurodevelopmental disorder with a multifaceted association between genes and the environment. Currently, in the majority of patients, the etiology of autism is not known and coupled with increasing prevalence rates, along with the high degree of heritability of autism, the development of animal models is crucial for studying and developing therapies for autism. A key characteristic of autism is marked abnormalities in the acquisition and use of language. Thus, to understand and ultimately treat autism is an especially difficult task because no animal produces language, as it is defined in humans. In this review, we will discuss the FOXP family of genes, which are a group of transcription factors that have been linked to both autism, as well as language in humans. Due to the association of language/communication and the Foxp family of transcription factors, animal models with targeted disruptions of Foxp functioning are powerful tools for understanding the developmental signaling pathways that may be vulnerable in autism.
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3. Geier DA, Hooker BS, Kern JK, King PG, Sykes LK, Geier MR. {{A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States}}. {Translational neurodegeneration}. 2013;2(1):25.
BACKGROUND: Autism spectrum disorder (ASD) is defined by standardized criteria of qualitative impairments in social interaction, qualitative impairments in communication, and restricted and stereotyped patterns of behavior, interests, and activities. A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills, which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth. To date, the etiology of ASD remains under debate, however, many studies suggest toxicity, especially from mercury (Hg), in individuals diagnosed with an ASD. The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal (49.55% Hg by weight) in childhood vaccines by conducting a two-phased (hypothesis generating/hypothesis testing) study with documented exposure to varying levels of Thimerosal from vaccinations. METHODS: A hypothesis generating cohort study was undertaken to evaluate the relationship between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in comparison to a Thimerosal-free DTaP vaccine administered, from 1998 through 2000, for the risk of ASD as reported in the Vaccine Adverse Event Reporting System (VAERS) database (phase I). A hypothesis testing case-control study was undertaken to evaluate the relationship between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines administered at specific intervals in the first six months of life among cases diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine Safety Datalink (VSD) database (phase II). RESULTS: In phase I, it was observed that there was a significantly increased risk ratio for the incidence of ASD reported following the Thimerosal-containing DTaP vaccine in comparison to the Thimerosal-free DTaP vaccine. In phase II, it was observed that cases diagnosed with an ASD were significantly more likely than controls to receive increased organic-Hg from Thimerosal-containing hepatitis B vaccine administered within the first, second, and sixth month of life. CONCLUSIONS: Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence supporting an association between increasing organic-Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ASD diagnosis.
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4. Haessler F, Gaese F, Colla M, Huss M, Kretschmar C, Brinkman M, Schieb H, Peters H, Elstner S, Pittrow D. {{EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization, treatment pathways, and patient-related outcomes of Fragile X Syndrome}}. {BMC psychiatry}. 2013;13(1):339.
BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on the X chromosome, is the most common inherited form of intellectual disability and autism spectrum disorders. Comprehensive data are lacking, however, on the characteristics and management patients with FXS in Germany. METHODS/DESIGN: EXPLAIN is a prospective, observational, longitudinal registry with a non-probability sampling approach. It collects data on patient characteristics, therapeutic interventions, psychosocial parameters (including those of family members and caregivers), quality of life of caregiver and patient, caregiver burden, and health economic parameters, such as hospitalisation time. It is designed to include data from 300 patients in ambulatory care from about 50 centres that employ psychiatrists, paediatricians, neurologists, and other relevant specialists, in Germany. The study was initiated in March, 2013. Patients will be followed for at least two years. DISCUSSION: The registry is expected to provide much-needed data on the characteristics and management of patients with FXS in Germany. It will also allow comparisons with other countries, and will enable gap analyses based on current guidelines for management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov identifier is NCT01711606.
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5. Kamien B, Harraway J, Lundie B, Smallhorne L, Gibbs V, Heath A, Fullerton JM. {{Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in a patient with behavioral disturbance, autism spectrum disorder, and epilepsy}}. {American journal of medical genetics Part A}. 2013 Dec 19.
We present a patient with a behavioral disorder, epilepsy, and autism spectrum disorder who has a 520 kb chromosomal deletion at 15q26.1 encompassing three genes: ST8SIA2, C15orf32, and FAM174B. Alpha-2,8-Sialyltransferase 2 (ST8SIA2) is expressed in the developing brain and appears to play an important role in neuronal migration, axon guidance and synaptic plasticity. It has recently been implicated in a genome wide association study as a potential factor underlying autism, and has also been implicated in the pathogenesis of bipolar disorder and schizophrenia. This case provides supportive evidence that ST8SIA2 haploinsufficiency may play a role in neurobehavioral phenotypes. (c) 2013 Wiley Periodicals, Inc.
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6. Park Y, Won S, Nam M, Chung JH, Kwack K. {{Interaction Between MAOA and FOXP2 in Association With Autism and Verbal Communication in a Korean Population}}. {Journal of child neurology}. 2013 Dec 18.
Expression levels of monoamine oxidase A (MAOA), the enzyme that related to monoamine neurotransmitters metabolism such as serotonin, are related to schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a transcription factor, is associated with abnormal language development and is expressed in several areas of the central nervous system in response to serotonin. For this reason, we undertook interaction analysis between MAOA and FOXP2 in autism spectrum disorder, including testing the verbal communication score of the childhood autism rating scale. In interaction analysis, the FOXP2-TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323-rs1801291-rs3027407) haplotype were significantly associated with autism spectrum disorder in males. However, when the interaction term was omitted, neither MAOA nor FOXP2 was associated with autism spectrum disorder or verbal communication. These results indicate that language and speech ability is affected by an interaction between FOXP2 and MAOA, but not by either gene separately.
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7. Pilnick A, James D. {{« I’m thrilled that you see that »: Guiding parents to see success in interactions with children with deafness and autistic spectrum disorder}}. {Social science & medicine (1982)}. 2013 Dec;99:89-101.
Children with deafness who are also on the autistic spectrum are a group with complex support needs. Carers worry about their ability to communicate with them, and are often uncertain about what constitutes ‘good’ communication in this context. This paper analyses the use of a therapeutic intervention, Video Interaction Guidance (VIG), which originates in developmental psychology and focuses on the relational foundations of communication. We draw on a single case using an ethnomethodological/conversation analytic framework, and in particular Goodwin’s (1994) work on ‘professional vision’, to show how the ability to see ‘success’ is a socially situated activity. Since what counts as success in this setting is often far removed from everyday ideas of good communication, how guiders facilitate particular ‘ways of seeing’ are critical for both the support of carers and the impact of the intervention. We argue that this work has implications in three areas: for the practice of VIG itself; for the role of qualitative, interactional research addressing the way in which interaction-based interventions are protocolised, enacted and assessed; and for the way in which expertise is conceptualised in professional/client interactions in health and social care.
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8. Reichow B, Servili C, Yasamy MT, Barbui C, Saxena S. {{Non-specialist psychosocial interventions for children and adolescents with intellectual disability or lower-functioning autism spectrum disorders: a systematic review}}. {PLoS medicine}. 2013 Dec;10(12):e1001572.
BACKGROUND: The development of effective treatments for use by non-specialists is listed among the top research priorities for improving the lives of people with mental illness worldwide. The purpose of this review is to appraise which interventions for children with intellectual disabilities or lower-functioning autism spectrum disorders delivered by non-specialist care providers in community settings produce benefits when compared to either a no-treatment control group or treatment-as-usual comparator. METHODS AND FINDINGS: We systematically searched electronic databases through 24 June 2013 to locate prospective controlled studies of psychosocial interventions delivered by non-specialist providers to children with intellectual disabilities or lower-functioning autism spectrum disorders. We screened 234 full papers, of which 34 articles describing 29 studies involving 1,305 participants were included. A majority of the studies included children exclusively with a diagnosis of lower-functioning autism spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were randomized controlled trials and just under half of all effect sizes (29 of 59, 49%) were greater than 0.50, of which 18 (62%) were statistically significant. For behavior analytic interventions, the best outcomes were shown for development and daily skills; cognitive rehabilitation, training, and support interventions were found to be most effective for improving developmental outcomes, and parent training interventions to be most effective for improving developmental, behavioral, and family outcomes. We also conducted additional subgroup analyses using harvest plots. Limitations include the studies’ potential for performance bias and that few were conducted in lower- and middle-income countries. CONCLUSIONS: The findings of this review support the delivery of psychosocial interventions by non-specialist providers to children who have intellectual disabilities or lower-functioning autism spectrum disorders. Given the scarcity of specialists in many low-resource settings, including many lower- and middle-income countries, these findings may provide guidance for scale-up efforts for improving outcomes for children with developmental disorders or lower-functioning autism spectrum disorders. PROTOCOL REGISTRATION: PROSPERO CRD42012002641 Please see later in the article for the Editors’ Summary.
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9. Ronconi L, Facoetti A, Bulf H, Franchin L, Bettoni R, Valenza E. {{Paternal Autistic Traits are Predictive of Infants Visual Attention}}. {J Autism Dev Disord}. 2013 Dec 20.
Since subthreshold autistic social impairments aggregate in family members, and since attentional dysfunctions appear to be one of the earliest cognitive markers of children with autism, we investigated in the general population the relationship between infants’ attentional functioning and the autistic traits measured in their parents. Orienting and alerting attention systems were measured in 8-month-old infants using a spatial cueing paradigm. Results showed that only paternal autistic traits were linked to their children’s: (1) attentional disengagement; (2) rapid attentional orienting and (3) alerting. Our findings suggest that an early dysfunction of orienting and alerting systems might alter the developmental trajectory of future ability in social cognition and communication.
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10. Samson AC, Phillips JM, Parker KJ, Shah S, Gross JJ, Hardan AY. {{Emotion Dysregulation and the Core Features of Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2013 Dec 21.
The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child Behavior Checklist. Compared to typically developing controls, children and adolescents with ASD showed more emotion dysregulation and had significantly greater symptom severity on all scales. Within ASD participants, emotion dysregulation was related to all core features of the disorder, but the strongest association was with repetitive behaviors. These findings may facilitate the development of more effective therapeutic strategies targeting emotion dysregulation in order to optimize long-term outcomes for individuals with ASD.
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11. Sgado P, Provenzano G, Dassi E, Adami V, Zunino G, Genovesi S, Casarosa S, Bozzi Y. {{Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders}}. {Molecular autism}. 2013 Dec 19;4(1):51.
BACKGROUND: Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. METHODS: Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. RESULTS: Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. CONCLUSIONS: Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD.
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12. Shah P, Gaule A, Bird G, Cook R. {{Robust orienting to protofacial stimuli in autism}}. {Current biology : CB}. 2013 Dec 16;23(24):R1087-8.
Newborn infants exhibit a remarkable tendency to orient to faces. This behavior is thought to be mediated by a subcortical mechanism tuned to the protoface stimulus: a face-like configuration comprising three dark areas on a lighter background. When this unique stimulus translates across their visual field, neurotypical infants will change their gaze or head direction to track the protoface [1-3]. Orienting to this low spatial frequency pattern is thought to encourage infants to attend to faces, despite their poor visual acuity [2,3]. By biasing the input into the newborn’s visual system, this primitive instinct may serve to ‘canalize’ the development of more sophisticated face representation. Leading accounts attribute deficits of face perception associated with Autism Spectrum Disorders (ASD) [4] to abnormalities within this orienting mechanism. If infants who are later diagnosed with ASD exhibit reduced protoface orienting, this may compromise the emergence of perceptual expertise for faces [5]. Here we report a novel effect that confirms that the protoface stimulus captures adults’ attention via an involuntary, exogenous process (Experiment 1). Contrary to leading developmental accounts of face perception deficits in ASD, we go on to show that this orienting response is intact in autistic individuals (Experiment 2).
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13. Yamamoto T, Togawa M, Shimada S, Sangu N, Shimojima K, Okamoto N. {{Narrowing of the responsible region for severe developmental delay and autistic behaviors in WAGR syndrome down to 1.6 Mb including PAX6, WT1, and PRRG4}}. {American journal of medical genetics Part A}. 2013 Dec 19.
Interstitial deletions of the 11p13 region are known to cause WAGR (Wilms tumor, aniridia, genitourinary malformation, and « mental retardation ») syndrome, a contiguous gene deletion syndrome due to haploinsufficiencies of the genes in this region, including WT1 and PAX6. Developmental delay and autistic features are major complications of this syndrome. Previously, some genes located in this region have been suggested as responsible for autistic features. In this study, we identified two patients who showed the chromosomal deletions involving 11p13. Patient 1, having an 8.6 Mb deletion of chr11p14.1p12:29,676,434-38,237,948, exhibited a phenotype typical of WAGR syndrome and had severe developmental delay and autistic behaviors. On the other hand, Patient 2 had a larger aberration region in 11p14.1-p12 which was split into two regions, that is, a 2.2-Mb region of chr11p14.1: 29,195,161-31,349,732 and a 10.5-Mb region of chr11p13p12: 32,990,627-43,492,580. As a consequence, 1.6 Mb region of the WAGR syndrome critical region was intact between the two deletions. This patient showed no symptom of WAGR syndrome and no autistic behaviors. Therefore, the region responsible for severe developmental delay and autistic features on WAGR syndrome can be narrowed down to the region remaining intact in Patient 2. Thus, the unique genotype identified in this study suggested that haploinsufficiencies of PAX6 or PRRG4 included in this region are candidate genes for severe developmental delay and autistic features characteristic of WAGR syndrome. (c) 2013 Wiley Periodicals, Inc.
