1. Bartel T. {{Mystery solved: Our son’s autism and extreme self-injury is genetic and treatable}}. {Am J Med Genet A};2017 (Mar 21)
Our 17-year-old autistic son Jake is declining at the same rate his peers are developing. He has the pimples, the sudden height, and the hormones. But the right side of his body slumps like someone who has had a stroke. Once right handed, he now uses only his left hand. At 15, he knocked his eyes off their parallel tracks by slamming his temple into the corner of a wooden post. One eye looks straight ahead while the other looks up and to the side. Both optic nerves are damaged. All the damage is self-inflicted. He has been banging and punching his head since babyhood.
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2. Criado KK, Sharp WG, McCracken CE, De Vinck-Baroody O, Dong L, Aman MG, McDougle CJ, McCracken JT, Eugene Arnold L, Weitzman C, Leventhal JM, Vitiello B, Scahill L. {{Overweight and obese status in children with autism spectrum disorder and disruptive behavior}}. {Autism};2017 (Mar 01):1362361316683888.
Overweight and obesity are common in pediatric populations. Children with autism spectrum disorder and disruptive behavior may be at higher risk. This study examined whether children with autism spectrum disorder and disruptive behavior are more likely to be overweight or obese than matched controls. Baseline data from medication-free children with autism spectrum disorder who participated in trials conducted by the Research Units on Pediatric Psychopharmacology Autism Network (N = 276) were compared to 544 control children from the National Health and Nutrition Examination Survey database matched on age, sex, race, parent education, and era of data collection. The mean age of the children with autism spectrum disorder was 7.9 +/- 2.6 years; 84.4% were males. In the autism spectrum disorder group, the prevalence was 42.4% for overweight and 21.4% for obesity compared to 26.1% for overweight and 12.0% for obesity among controls (p < 0.001 for each contrast). Within the autism spectrum disorder sample, obesity was associated with minority status and lower daily living skills. These findings suggest that children with autism spectrum disorder and disruptive behavior are at increased risk for obesity and underscore the need for weight management interventions in this population. Lien vers le texte intégral (Open Access ou abonnement)
3. Du L, Zhao G, Duan Z, Li F. {{Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation}}. {Psychiatry Res};2017 (Mar 06);253:28-32.
The aim was to identify the effects of early vitamin D supplementation on autism-like behaviors (ASD) induced by valproic acid (VPA, an anti-convulsant and a mood stabilizer) in rats. 10 male Wistar rat pups with prenatal exposure to saline were in control group, and 20 Pups with prenatal exposure to VPA were divided into ASD-N (0.9% saline treated) and ASD-D group (vitamin D 80,000 IU/kg treated) on postnatal day 12. Self-grooming, olfactory habituation/dishabituation, and social interaction tests were conducted to assess social interaction, communication, and repetitive behaviors. Serum 25-hydroxyvitamin D (25(OH)D3) was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results showed that compared with the control group, the ASD-N group exhibited increased self-grooming, and decreased pinning and serum 25(OH)D3. Furthermore, the repetitive behavior of the ASD-N group exhibited a negative linear relationship with serum 25(OH)D3 on PND 42. In conclusion, early vitamin D supplementation in infant rat with ASD induced by VPA significantly improved development and behavior of rats related with ASD.
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4. El-Ansary A, Bjorklund G, Tinkov AA, Skalny AV, Al Dera H. {{Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children}}. {Metab Brain Dis};2017 (Mar 21)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.
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5. Fakhoury M. {{Imaging genetics in autism spectrum disorders: Linking genetics and brain imaging in the pursuit of the underlying neurobiological mechanisms}}. {Prog Neuropsychopharmacol Biol Psychiatry};2017 (Mar 16)
Autism spectrum disorders (ASD) include a wide range of heterogeneous neurodevelopmental conditions that affect an individual in several aspects of social communication and behavior. Recent advances in molecular genetic technologies have dramatically increased our understanding of ASD etiology through the identification of several autism risk genes, most of which serve important functions in synaptic plasticity and protein synthesis. However, despite significant progress in this field of research, the characterization of the neurobiological mechanisms by which common genetic risk variants might operate to give rise to ASD symptomatology has proven to be far more difficult than expected. The imaging genetics approach holds great promise for advancing our understanding of ASD etiology by bridging the gap between genetic variations and their resultant biological effects on the brain. This paper provides a conceptual overview of the contribution of genetics in ASD and discusses key findings from the emerging field of imaging genetics.
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6. Grossi E, Olivieri C, Buscema M. {{Diagnosis of autism through EEG processed by advanced computational algorithms: A pilot study}}. {Comput Methods Programs Biomed};2017 (Apr);142:73-79.
BACKGROUND: Multi-Scale Ranked Organizing Map coupled with Implicit Function as Squashing Time algorithm(MS-ROM/I-FAST) is a new, complex system based on Artificial Neural networks (ANNs) able to extract features of interest in computerized EEG through the analysis of few minutes of their EEG without any preliminary pre-processing. A proof of concept study previously published showed accuracy values ranging from 94%-98% in discerning subjects with Mild Cognitive Impairment and/or Alzheimer’s Disease from healthy elderly people. The presence of deviant patterns in simple resting state EEG recordings in autism, consistent with the atypical organization of the cerebral cortex present, prompted us in applying this potent analytical systems in search of a EEG signature of the disease. AIM OF THE STUDY: The aim of the study is to assess how effectively this methodology distinguishes subjects with autism from typically developing ones. METHODS: Fifteen definite ASD subjects (13 males; 2 females; age range 7-14; mean value = 10.4) and ten typically developing subjects (4 males; 6 females; age range 7-12; mean value 9.2) were included in the study. Patients received Autism diagnoses according to DSM-V criteria, subsequently confirmed by the ADOS scale. A segment of artefact-free EEG lasting 60 seconds was used to compute input values for subsequent analyses. MS-ROM/I-FAST coupled with a well-documented evolutionary system able to select predictive features (TWIST) created an invariant features vector input of EEG on which supervised machine learning systems acted as blind classifiers. RESULTS: The overall predictive capability of machine learning system in sorting out autistic cases from normal control amounted consistently to 100% with all kind of systems employed using training-testing protocol and to 84% – 92.8% using Leave One Out protocol. The similarities among the ANN weight matrixes measured with apposite algorithms were not affected by the age of the subjects. This suggests that the ANNs do not read age-related EEG patterns, but rather invariant features related to the brain’s underlying disconnection signature. CONCLUSION: This pilot study seems to open up new avenues for the development of non-invasive diagnostic testing for the early detection of ASD.
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7. Guan J, Li G. {{Injury Mortality in Individuals With Autism}}. {Am J Public Health};2017 (Mar 21):e1-e3.
OBJECTIVES: To examine epidemiological patterns of injury fatalities in individuals with a diagnosis of autism. METHODS: We identified individuals with a diagnosis of autism who died between 1999 and 2014 by screening causes of death in the multiple cause-of-death data files in the National Vital Statistics System based on the International Classification of Diseases, 10th Revision, code F84.0. We used the general US population as the reference to calculate proportionate mortality ratios (PMRs) and 95% confidence intervals (CIs). RESULTS: During the study period, 1367 deaths (1043 males and 324 females) in individuals with autism were recorded in the United States. The mean age at death for individuals with autism was 36.2 years (SD = 20.9 years), compared with 72.0 years (SD = 19.2 years) for the general population. Of the deaths in individuals with autism, 381 (27.9%) were attributed to injury (PMR = 2.93; 95% CI = 2.64, 3.24), with suffocation (n = 90; PMR = 31.93; 95% CI = 25.69, 39.24) being the leading cause of injury mortality, followed by asphyxiation (n = 78; PMR = 13.50; 95% CI = 10.68, 16.85) and drowning (n = 74; PMR = 39.89; 95% CI = 31.34, 50.06). CONCLUSIONS: Individuals with autism appear to be at substantially heightened risk for death from injury. (Am J Public Health. Published online ahead of print March 21, 2017: e1-e3. doi:10.2105/AJPH.2017.303696).
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8. Helverschou SB, Steindal K, Nottestad JA, Howlin P. {{Personal experiences of the Criminal Justice System by individuals with autism spectrum disorders}}. {Autism};2017 (Mar 01):1362361316685554.
The processes of arrest, investigation, trial and imprisonment are often extremely difficult for individuals with autism spectrum disorders. In this study, nine offenders with autism spectrum disorders were interviewed about the circumstance surrounding the criminal acts, their views of the arrest, the police interrogation, the trial and the defence and their experiences of being in prison and/or life following the offence. The nine individuals described a range of different and often negative experiences with the Criminal Justice System. However, the majority of those given a custodial sentence coped well in prison, probably due to the high levels of structure and firm frameworks in that environment. Explanation factors associated with the offences indicated that autism spectrum disorder characteristics such as misunderstandings, obsessions and idiosyncratic beliefs and/or behaviours were frequently involved, but stress was the most common explanation provided by the participants. The findings suggest limited understanding of autism spectrum disorders within the Criminal Justice System which needs to be significantly improved in order to secure their legal protection.
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9. Hickey EJ, Dubois L, Hartley SL. {{Positive and negative social exchanges experienced by fathers and mothers of children with autism}}. {Autism};2017 (Mar 01):1362361316687117.
When faced with child-related challenges associated with autism spectrum disorder, positive and negative social exchanges may be critical to parents’ psychological well-being. This study examined the types and sources of positive and negative social exchanges reported by mothers and fathers of children with autism spectrum disorder and their association with parental depressive symptoms in 176 families of children (5-12 years; 85% male) with autism spectrum disorder. One-way repeated measure multivariate analyses of variance and multilevel modeling were used. Results indicated that informational was the most frequent type, and one’s spouse was the primary source, of both positive and negative social exchanges. Fathers reported fewer positive, and also fewer negative, social exchanges with family, friends, and health professionals than mothers. Positive and negative social exchanges with one’s spouse were most strongly associated with depressive symptoms. Findings have implications for interventions designed to foster optimal outcomes in families of children with autism spectrum disorder.
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10. Hudry K, Rumney L, Pitt N, Barbaro J, Vivanti G. {{Interaction Behaviors of Bilingual Parents With Their Young Children With Autism Spectrum Disorder}}. {J Clin Child Adolesc Psychol};2017 (Mar 21):1-8.
Given concerns that bilingual exposure might confuse children with disabilities-including autism spectrum disorder (ASD)-bilingual parents may restrict exposure to one language, often the community-dominant language. We investigated a potential consequence of this decision; the possibility that non-native language use might influence parental communicative behaviors during interaction with the child. We recruited 39 parent-child dyads, each with a young child with ASD (mostly boys) and parent/carer (mostly mothers). Parents were either monolingual speakers of community-dominant English (n = 20) or bilingual with English as the second language (n = 19). We confirmed our assumption that the latter group would have significantly poorer non-native English language via standardized assessment of expressive vocabulary, and ensured children were matched on age, ASD symptoms, and developmental level. We sampled parent-child interaction-including in each of bilinguals’ native and non-native languages-and coded parents’ amount and complexity of speech, communicative synchrony, and imitations and expansions of their child’s speech. Few differences presented across bilingual parents’ native versus non-native language samples, but this group showed reduced synchrony and use of expansions compared to monolinguals. Further, bilinguals’ English-language knowledge was associated with self-reported comfort using this language and with two coded interaction measures. These empirical data only partially support qualitative accounts that non-native language use may influence bilingual parents’ interaction behaviors with their young children. With growing rates of ASD diagnosis and increasing cultural/linguistic diversity around the world, further dedicated clinical and experimental attention to this issue is clearly warranted.
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11. Kanfiszer L, Davies F, Collins S. {{‘I was just so different’: The experiences of women diagnosed with an autism spectrum disorder in adulthood in relation to gender and social relationships}}. {Autism};2017 (Mar 01):1362361316687987.
Existing literature exploring autism spectrum disorders within female populations predominantly utilises quantitative methodology. A limited number of small-scale, qualitative studies have explored the experiences of adolescent girls with autism spectrum disorder, but adult women have remained largely unheard. This study aims to broaden the stories told within autobiographical literature and empower those within the wider community of women with autism spectrum disorder. In doing so, it seeks to extend existing conceptualisations of experience to include socially and culturally located factors. A qualitative methodology was adopted, utilising multi-stage narrative analysis. Seven semi-structured interviews with women who received a diagnosis in adulthood were conducted. Recruitment spanned community mental health services, an inpatient service and a community support group. From the women’s diverse experiences and stories emerged two broad categories related to gender identity and social relationships. The findings are discussed in relation to existing constructs of autism in women.
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12. Kleinert JO. {{Pediatric Feeding Disorders and Severe Developmental Disabilities}}. {Semin Speech Lang};2017 (Apr);38(2):116-125.
Children with severe developmental disabilities face numerous challenges to function and participate in activities of daily life. One of the most significant challenges to accomplishing this goal is that of oral feeding disorders. Indeed, it is estimated that among children with developmental disabilities, up to 80 to 90% present with some level of feeding disorders. In addition, it has been shown that as the level of severity of intellectual disability increases, so does the severity of the oral feeding disorders. Due to the broad range of etiologies that result in developmental disabilities, types of feeding disorders in the population vary greatly. This article is designed to provide information regarding assessment and intervention approaches currently used in this area and to provide an overview of the evidence available to support these approaches. Suggestions for much needed future clinically relevant and immediately transferable research are included.
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13. Lombardo MV, Moon HM, Su J, Palmer TD, Courchesne E, Pramparo T. {{Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder}}. {Mol Psychiatry};2017 (Mar 21)
Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in the ASD cortex later in life and which are canonically known for roles in affecting prenatally late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD cortical transcriptome throughout life and has downstream impact on cell cycle processes. The cap-dependent translation initiation gene, EIF4E, is one of the most MIA-dysregulated of all ASD-associated genes and targeted network analyses demonstrate prominent MIA-induced transcriptional dysregulation of mTOR and EIF4E-dependent signaling. This dysregulation of translation initiation via alteration of the Tsc2-mTor-Eif4e axis was further validated across MIA rodent models. MIA may confer increased risk for ASD by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD.Molecular Psychiatry advance online publication, 21 March 2017; doi:10.1038/mp.2017.15.
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14. Sadeghi M, Khosrowabadi R, Bakouie F, Mahdavi H, Eslahchi C, Pouretemad H. {{Screening of autism based on task-free fMRI using graph theoretical approach}}. {Psychiatry Res};2017 (Mar 09);263:48-56.
Studies on autism spectrum disorder (ASD) have indicated several dysfunctions in the structure, and functional organization of the brain. However, findings have not been established as a general diagnostic tool yet. In this regard, current study proposed an automatic screening method for recognition of ASDs from healthy controls (HCs) based on their brain functional abnormalities. In this paradigm, brain functional networks of 60 adolescent and young adult males (29 ASDs and 31 HCs) were estimated from subjects’ task-free fMRI data. Then, autism screening was developed based on characteristics of the functional networks using the following steps: A) local and global parameters of the brain functional network were calculated using graph theory. B) network parameters of the ASDs were statistically compared to the HCs. C) significantly altered parameters were used as input features of the screening system. D) performance of the system was verified using various classification techniques. The support vector machine showed superiority to others with an accuracy of 92%. Subsequently, reliability of the results was examined using an independent dataset including 20 ASDs and 20 HCs. Our findings suggest that local parameters of the brain functional network, despite the individual variability, can potentially be used for autism screening.
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15. Shapiro JR, Boskey AL, Doty SB, Lukashova L, Blue ME. {{Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome}}. {Bone};2017 (Mar 18);99:1-7.
Rett syndrome (RTT) is a neurodevelopmental disorder predominately affecting young females, caused by deficiency of the global transcriptional protein methyl CpG binding protein 2 (MeCP2). Osteoblasts express MeCP2 and girls with RTT experience early onset osteoporosis, decreased bone mass and an increased fracture risk. There is no defined treatment for osteoporosis associated with RTT. The present study evaluated the effects of zoledronic acid (ZA), a third generation nitrogen-containing bisphosphonate with primarily anti-osteoclastic activity, in a mouse model of MeCP2 deficiency. Mice received weekly injections of 20mug/kg ZA for six weeks. Due to the shortened lifespan of hemizygous male (Mecp2-null) mice, treatment began at 3weeks of age for this group and corresponding wildtype (WT) male mice. Treatment for heterozygous (HET) and WT female mice began at 8weeks of age. Micro-computed tomography (micro-CT) and dynamic analyses of bone turnover were performed. ZA treatment led to significant increases in bone volume fraction, number, connectivity density and apparent density of trabecular bone in all genotypes of mice. In contrast, cortical bone generally was unaffected by ZA injections. Parameters of bone turnover, including mineral apposition rate, labeled bone surface and bone formation rate decreased after treatment with ZA. Mecp2-null mice had reduced labeled bone surface and bone formation rate compared to WT male mice. The results indicate that ZA treatment significantly improved trabecular bone mass in a murine model of RTT with little effect on cortical bone.
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16. Siemann JK, Muller CL, Forsberg CG, Blakely RD, Veenstra-VanderWeele J, Wallace MT. {{An autism-associated serotonin transporter variant disrupts multisensory processing}}. {Transl Psychiatry};2017 (Mar 21);7(3):e1067.
Altered sensory processing is observed in many children with autism spectrum disorder (ASD), with growing evidence that these impairments extend to the integration of information across the different senses (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD. A gain-of-function coding variant in the serotonin transporter (SERT) associates with sensory aversion in humans, and when expressed in mice produces traits associated with ASD, including disruptions in social and communicative function and repetitive behaviors. The current study set out to test whether these mice also exhibit changes in multisensory function when compared with wild-type (WT) animals on the same genetic background. Mice were trained to respond to auditory and visual stimuli independently before being tested under visual, auditory and paired audiovisual (multisensory) conditions. WT mice exhibited significant gains in response accuracy under audiovisual conditions. In contrast, although the SERT mutant animals learned the auditory and visual tasks comparably to WT littermates, they failed to show behavioral gains under multisensory conditions. We believe these results provide the first behavioral evidence of multisensory deficits in a genetic mouse model related to ASD and implicate the serotonin system in multisensory processing and in the multisensory changes seen in ASD.
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17. Smith A. {{Autistic phenomena in The Adventures of Pinocchio}}. {J Anal Psychol};2017 (Apr);62(2):263-283.
This paper seeks to demonstrate that the protagonist of Carlo Collodi’s The Adventures of Pinocchio illustrates numerous autistic phenomena such as communication difficulties, sensory and perceptual distortions and mindblindness. While Pinocchio is viewed as a literary construct with contraindications of autism, it will be argued that his autistic traits are sufficient to suggest the possibility that Collodi had a partial intuition of the syndrome 60 years before it was identified by Leo Kanner. Approaching Collodi’s text in this manner is taken as an opportunity to survey and reflect upon the psychoanalytic literature on autism and to position it in relation to contemporary theories from cognitive neuroscience.
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18. Song J, Mailick MR, Greenberg JS. {{The Impact of the Great Recession on Midlife and Older parents of Individuals With a Mental Health Problem or a Developmental Disability}}. {Gerontologist};2017 (Mar 13)
Background and Objectives : Parents of sons and daughters with disabilities have ongoing financial burdens and vulnerability due to the demands of caregiving responsibilities and their related direct and indirect costs. This study aims to investigate whether midlife and older parents of individuals with a mental health problem or a developmental disability were particularly vulnerable to the impact of the recession. Research Design and Methods : The data were drawn from Midlife in the United States (MIDUS), a longitudinal survey of a national probability sample in the United States, Waves II (2004-2006) and III (2013-2014; 84 parents of individuals with a mental health problem, 98 parents of individuals with a developmental disability, and 2,029 parents of individuals without any conditions as a comparison group). Results : The findings suggest that the midlife and older parents whose son or daughter had a mental health problem experienced more recession impacts than comparison parents, even after controlling prerecession financial status and sociodemographic characteristics. Discussion and Implications : The results indicate the need for policies that provide effective financial support and reduce restrictions on health service access in order to relieve the financial burden experienced by midlife and older parents of individuals with a mental health problem.
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19. Stoppel LJ, Auerbach BD, Senter RK, Preza AR, Lefkowitz RJ, Bear MF. {{beta-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X}}. {Cell Rep};2017 (Mar 21);18(12):2807-2814.
Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu5), yet how mGlu5 couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that beta-arrestin2 mediates mGlu5-stimulated protein synthesis in the hippocampus and show that genetic reduction of beta-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1-/y mouse model of FX. Importantly, reducing beta-arrestin2 does not induce psychotomimetic activity associated with full mGlu5 inhibitors and does not affect Gq signaling. Thus, in addition to identifying a key requirement for mGlu5-stimulated protein synthesis, these data suggest that beta-arrestin2-biased negative modulators of mGlu5 offer significant advantages over first-generation inhibitors for the treatment of FX and related disorders.
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20. The Lancet N. {{Investing in autism: better evidence for better care}}. {Lancet Neurol};2017 (Apr);16(4):251.
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21. Velez-Coto M, Rodriguez-Fortiz MJ, Rodriguez-Almendros ML, Cabrera-Cuevas M, Rodriguez-Dominguez C, Ruiz-Lopez T, Burgos-Pulido A, Garrido-Jimenez I, Martos-Perez J. {{SIGUEME: Technology-based intervention for low-functioning autism to train skills to work with visual signifiers and concepts}}. {Res Dev Disabil};2017 (Mar 16);64:25-36.
BACKGROUND: People with low-functioning ASD and other disabilities often find it difficult to understand the symbols traditionally used in educational materials during the learning process. Technology-based interventions are becoming increasingly common, helping children with cognitive disabilities to perform academic tasks and improve their abilities and knowledge. Such children often find it difficult to perform certain tasks contained in educational materials since they lack necessary skills such as abstract reasoning. In order to help these children, the authors designed and created SIGUEME to train attention and the perceptual and visual cognitive skills required to work with and understand graphic materials and objects. METHODS: A pre-test/post-test design was implemented to test SIGUEME. Seventy-four children with low-functioning ASD (age=13.47, SD=8.74) were trained with SIGUEME over twenty-five sessions and compared with twenty-eight children (age=12.61, SD=2.85) who had not received any intervention. RESULTS: There was a statistically significant improvement in the experimental group in Attention (W=-5.497, p<0.001). There was also a significant change in Association and Categorization (W=2.721, p=0.007) and Interaction (W=-3.287, p=0.001). CONCLUSIONS: SIGUEME is an effective tool for improving attention, categorization and interaction in low-functioning children with ASD. It is also a useful and powerful instrument for teachers, parents and educators by increasing the child's motivation and autonomy. Lien vers le texte intégral (Open Access ou abonnement)
22. Wang P, Mokhtari R, Pedrosa E, Kirschenbaum M, Bayrak C, Zheng D, Lachman HM. {{CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells}}. {Mol Autism};2017;8:11.
BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing. A significant number of ASD and SZ candidate genes were among those that were differentially expressed in a comparison of heterozygous KO lines (CHD8+/-) vs isogenic controls (CHD8+/-), including the SZ and bipolar disorder (BD) candidate gene TCF4, which was markedly upregulated in CHD8+/- neuronal cells. METHODS: In the current study, RNA-seq was carried out on CHD8+/- and isogenic control (CHD8+/+) cerebral organoids, which are 3-dimensional structures derived from iPS cells that model the developing human telencephalon. RESULTS: TCF4 expression was, again, significantly upregulated. Pathway analysis carried out on differentially expressed genes (DEGs) revealed an enrichment of genes involved in neurogenesis, neuronal differentiation, forebrain development, Wnt/beta-catenin signaling, and axonal guidance, similar to our previous study on NPCs and monolayer neurons. There was also significant overlap in our CHD8+/- DEGs with those found in a transcriptome analysis carried out by another group using cerebral organoids derived from a family with idiopathic ASD. Remarkably, the top DEG in our respective studies was the non-coding RNA DLX6-AS1, which was markedly upregulated in both studies; DLX6-AS1 regulates the expression of members of the DLX (distal-less homeobox) gene family. DLX1 was also upregulated in both studies. DLX genes code for transcription factors that play a key role in GABAergic interneuron differentiation. Significant overlap was also found in a transcriptome study carried out by another group using iPS cell-derived neurons from patients with BD, a condition characterized by dysregulated WNT/beta-catenin signaling in a subgroup of affected individuals. CONCLUSIONS: Overall, the findings show that distinct ASD, SZ, and BD candidate genes converge on common molecular targets-an important consideration for developing novel therapeutics in genetically heterogeneous complex traits.
