1. Ailey SH, Brown PJ, Ridge CM. {{Improving hospital care of patients with intellectual and developmental disabilities}}. {Disabil Health J}. 2017.
People with intellectual disabilities and developmental disabilities (IDD) face poorer care and outcomes when hospitalized than patients without IDD. A panel discussion Hospital care for individuals with IDD: The Issues and Challenges was held at the Annual Conference of the American Academy of Developmental Medicine and Dentistry, held in Chicago July 8-10, 2016. Among the panelists were representatives from Rush University Medical Center in Chicago, IL and Saint Barnabas Medical Center in Livingston, NJ who discussed efforts to improve hospital care of patients with IDD at their institutions. Systemic changes are needed to improve care, however, programs that target improving care for patients with IDD are possible within current systems and with current staff who are empowered to make changes that improve the quality of care.
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2. Andrews DS, Avino TA, Gudbrandsen M, Daly E, Marquand A, Murphy CM, Lai MC, Lombardo MV, Ruigrok AN, Williams SC, Bullmore ET, The Mrc Aims C, Suckling J, Baron-Cohen S, Craig MC, Murphy DG, Ecker C. {{In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder}}. {Cereb Cortex}. 2017.
Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies. Lien vers le texte intégral (Open Access ou abonnement)
3. Bhattacharyya PJ. {{‘Crochetage’ sign on ECG in secundum ASD: clinical significance}}. {BMJ Case Rep}. 2016; 2016.
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4. Boucher O, Julvez J, Guxens M, Arranz E, Ibarluzea J, Sanchez de Miguel M, Fernandez-Somoano A, Tardon A, Rebagliato M, Garcia-Esteban R, O’Connor G, Ballester F, Sunyer J. {{Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain}}. {Pediatr Res}. 2017.
BACKGROUND: Several studies have related longer breastfeeding duration to better intellectual performance in children. By contrast, few studies have investigated the potential protective effects of breastfeeding against behavioral problems such as attention deficit hyperactivity disorder (ADHD) symptoms, and even fewer on autism spectrum disorders (ASD) traits. METHODS: We examined the association between breastfeeding duration and cognitive development, attention, ADHD symptoms, and autistic traits using data from the INMA Project, a Spanish multicenter birth-cohort study, and taking into account the intensity of breastfeeding. Duration of any, predominant, and exclusive breastfeeding was documented during infancy through maternal questionnaires. Children (N = 1,346; mean age = 4.9 y) were assessed using the McCarthy Scales of Children’s Abilities, Conners’ Kiddie Continuous Performance Test, criteria of the DSM-ADHD symptoms form list, and the Childhood Autism Spectrum Test. RESULTS: After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits. CONCLUSION: This study provides further evidence of a positive association of breastfeeding with cognitive function apart from socio-environmental factors, and also suggests a protective role against autistic traits. Results are in agreement with recommendations for prolonged breastfeeding duration to promote child development.Pediatric Research (2017); doi:10.1038/pr.2016.238.
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5. Brown LS. {{The Influence of Music on Facial Emotion Recognition in Children with Autism Spectrum Disorder and Neurotypical Children}}. {J Music Ther}. 2016.
BACKGROUND: Children with autism spectrum disorder (ASD) often struggle with social skills, including the ability to perceive emotions based on facial expressions. Research evidence suggests that many individuals with ASD can perceive emotion in music. Examining whether music can be used to enhance recognition of facial emotion by children with ASD would inform development of music therapy interventions. OBJECTIVE: The purpose of this study was to investigate the influence of music with a strong emotional valance (happy; sad) on children with ASD’s ability to label emotions depicted in facial photographs, and their response time. METHODS: Thirty neurotypical children and 20 children with high-functioning ASD rated expressions of happy, neutral, and sad in 30 photographs under two music listening conditions (sad music; happy music). During each music listening condition, participants rated the 30 images using a 7-point scale that ranged from very sad to very happy. Response time data were also collected across both conditions. RESULTS: A significant two-way interaction revealed that participants’ ratings of happy and neutral faces were unaffected by music conditions, but sad faces were perceived to be sadder with sad music than with happy music. Across both conditions, neurotypical children rated the happy faces as happier and the sad faces as sadder than did participants with ASD. Response times of the neurotypical children were consistently shorter than response times of the children with ASD; both groups took longer to rate sad faces than happy faces. Response times of neurotypical children were generally unaffected by the valence of the music condition; however, children with ASD took longer to respond when listening to sad music. CONCLUSIONS: Music appears to affect perceptions of emotion in children with ASD, and perceptions of sad facial expressions seem to be more affected by emotionally congruent background music than are perceptions of happy or neutral faces.
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6. Cheng W, Rolls ET, Zhang J, Sheng W, Ma L, Wan L, Luo Q, Feng J. {{Functional connectivity decreases in autism in emotion, self, and face circuits identified by Knowledge-based Enrichment Analysis}}. {Neuroimage}. 2016.
A powerful new method is described called Knowledge based functional connectivity Enrichment Analysis (KEA) for interpreting resting state functional connectivity, using circuits that are functionally identified using search terms with the Neurosynth database. The method derives its power by focusing on neural circuits, sets of brain regions that share a common biological function, instead of trying to interpret single functional connectivity links. This provides a novel way of investigating how task- or function-related related networks have resting state functional connectivity differences in different psychiatric states, provides a new way to bridge the gap between task and resting-state functional networks, and potentially helps to identify brain networks that might be treated. The method was applied to interpreting functional connectivity differences in autism. Functional connectivity decreases at the network circuit level in 394 patients with autism compared with 473 controls were found in networks involving the orbitofrontal cortex, anterior cingulate cortex, middle temporal gyrus cortex, and the precuneus, in networks that are implicated in the sense of self, face processing, and theory of mind. The decreases were correlated with symptom severity.
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7. Cooper RA, Richter FR, Bays PM, Plaisted-Grant KC, Baron-Cohen S, Simons JS. {{Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism}}. {Cereb Cortex}. 2017.
Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.
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8. Fluegge K. {{Propionic acid metabolism, ASD, and vitamin B12: Is there a role for environmental nitrous oxide?}}. {Int J Dev Neurosci}. 2016; 57: 21-3.
Foley et al. (2014) published their findings in this journal on the role of prenatal exposure to propionic acid (PPA) and behavioral outcomes in treated rat pups. The authors show that PPA treated pups displayed subtle differences in behavior including nest seeking, novel object recognition, and locomotor activity. Others have previously proposed that PPA infusion in rat could represent a valid animal model of ASD since many of the diagnostic criteria for the disorder spectrum manifest under such conditions. A pathogenic makeover of gut microbiome to facilitate the growth of microbes capable of producing PPA, like Clostridia species, has been proposed as an infectious contributing etiology to the PPA model of ASD, however the reason for this pathogenic microbial overgrowth is not clear. This discussion highlights a previously identified novel environmental factor (i.e., nitrous oxide, N2O) in the etiopathogenesis of ASD and related neuropathology and posits that altered PPA metabolism in ASD may represent a key manifestation of this particular exposure. Trace environmental exposure to N2O may induce release of endogenous opioid peptides that have been shown to confer a virulence advantage to certain microbes, like Pseudomonas aeruginosa. Pathogenic overproduction of PPA in ASD may be a compensatory mechanism to curb this enhanced virulence potential. Therefore, future research on the PPA model of ASD should consider its role as a consequence of environmental exposure to N2O.
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9. Ghila A, Steciw S, Fallone B, Rathee S. {{SU-F-J-146: Experimental Validation of 6 MV Photon PDD in Parallel Magnetic Field Calculated by EGSnrc}}. {Med Phys}. 2016; 43(6): 3441.
PURPOSE: Integrated linac-MR systems are uniquely suited for real time tumor tracking during radiation treatment. Understanding the magnetic field dose effects and incorporating them in treatment planning is paramount for linac-MR clinical implementation. We experimentally validated the EGSnrc dose calculations in the presence of a magnetic field parallel to the radiation beam travel. METHODS: Two cylindrical bore electromagnets produced a 0.21 T magnetic field parallel to the central axis of a 6 MV photon beam. A parallel plate ion chamber was used to measure the PDD in a polystyrene phantom, placed inside the bore in two setups: phantom top surface coinciding with the magnet bore center (183 cm SSD), and with the magnet bore’s top surface (170 cm SSD). We measured the field of the magnet at several points and included the exact dimensions of the coils to generate a 3D magnetic field map in a finite element model. BEAMnrc and DOSXYZnrc simulated the PDD experiments in parallel magnetic field (i.e. 3D magnetic field included) and with no magnetic field. RESULTS: With the phantom surface at the top of the electromagnet, the surface dose increased by 10% (compared to no-magnetic field), due to electrons being focused by the smaller fringe fields of the electromagnet. With the phantom surface at the bore center, the surface dose increased by 30% since extra 13 cm of air column was in relatively higher magnetic field (>0.13T) in the magnet bore. EGSnrc Monte Carlo code correctly calculated the radiation dose with and without the magnetic field, and all points passed the 2%, 2 mm Gamma criterion when the ion chamber’s entrance window and air cavity were included in the simulated phantom. CONCLUSION: A parallel magnetic field increases the surface and buildup dose during irradiation. The EGSnrc package can model these magnetic field dose effects accurately. Dr. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).
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10. Guo Y, Garfin DR, Ly A, Goldberg WA. {{Emotion Coregulation in Mother-Child Dyads: A Dynamic Systems Analysis of Children with and without Autism Spectrum Disorder}}. {J Abnorm Child Psychol}. 2017.
Few studies have investigated patterns of emotion coregulation in families of children with Autism Spectrum Disorder (ASD) or contrasted the ways in which their emotion coregulation patterns differ from families of typically developing (TD) children. To address this gap, we used a dynamic systems approach to compare flexible structure and emotional content of coregulation between mothers and children (3-7 years) with ASD (n = 47) and TD children (n = 26). Mother-child play interactions in the home were videotaped and emotion-engagement states were coded in micro-level 5-s intervals based on behavioral and affective expressions. Analyses indicated that mother-child dyads in the ASD group spent more time than dyads in the TD group in mismatched emotion-engagement states (e.g., child negative/mother positive), and children with ASD spent more time than TD children engaged exclusively with objects. Mother-child dyads in the TD group stayed longer in mutual positive engagement states. Compared to dyads in the TD group, mother-child dyads in the ASD group exhibited greater flexibility (i.e., a wider range of emotional-engagement states, more frequent changes in states, and less time in each state). These findings suggest that mothers and their children with ASD do not sustain dyadic positive engagement patterns in a low-stress environment. Findings confirmed the preference of children with ASD for objects over social partners, even when they are at home with their mothers, and elucidated a challenging mother-child interactional style. Results have implications for mother-child interventions aimed at regulating negative emotional states and sustaining positive ones in families raising children with ASD.
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11. Han YM, Chan AS. {{Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders}}. {Res Dev Disabil}. 2016; 61: 19-31.
The present study examined the executive function and cortical connectivity of children with autism spectrum disorders (ASD) and investigated whether the executive function deficits exhibited by these children were differentially affected and associated with the cortical connectivity. The present study compared high-functioning (HFA) and low-functioning (LFA) children with typically developing children (TDC) on their executive functions as measured by the Hong Kong List Learning Test, D2 Test of Concentration, Five Point Test, Children’s Color Trail Test, Tower of California Test, and Go/No-Go task and neural connectivity as measured by theta coherence in the distributed fronto-parietal network. Thirty-eight children with ASD (19 HFA and 19 LFA) and 28 TDC children, aged 8-17 years, participated voluntarily in the study. The results on executive function showed that the LFA group demonstrated the poorest performance as exhibited by their Executive Composite and individual executive function scores, while the TDC group exhibited the highest. These results have extended the findings of previous studies in demonstrating that HFA and LFA children have significant differences in their degree of executive function deficits. The results on neural connectivity also showed that children with ASD demonstrated a different pattern of electroencephalography (EEG) coherence from TDC children, as demonstrated by the significantly elevated theta coherence in the fronto-parietal network, and that the severity of executive dysfunction between high- and low-functioning children with ASD was found to be associated with the disordered neural connectivity in these children.
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12. Incekas Gassaloglu S, Baykara B, Avcil S, Demiral Y. {{[Validity and Reliability Analysis of Turkish Version of Childhood Autism Rating Scale]}}. {Turk Psikiyatri Derg}. 2016; 27(4): 266-74.
OBJECTIVE: The purpose of this study is to expand validity and reliability analysis of Turkish Version of Childhood Autism Rating Scale (CARS), whose internal consistency,content validity and discriminant validity for a limited size of sample group were examined by Sucuoglu et al. METHOD: 96 children and adolescents aged between 4-18, (48 diagnosed with pervasive developmental disorder (PDD) and 48 diagnosed with mental disability (MD) and developmental delay based on DSM-IV-TR criteria,) were included in the study. Regarding reliability analysis of Turkish Version of the scale; Cronbach’s alpha values as internal consistency indicator, inter-rater reliability, and test-retest reliability were calculated. Principal components analysis and Varimax rotation were used in order to determine factors. The scale was compared with Autism Behavior Checklist and Clinical Global Impression-Severity of Illness. The most appropriate cut-off point was determined for CARS by conducting ROC analysis. RESULTS: As a result of principal components analysis and Varimax rotation, one component factor was obtained. Correlations between CARS and the other scales were statistically significant. The Cronbach’s alpha value of total score of the scale was determined as 0,95. Test-retest reliability (r=0,98, p<0,01), and inter-rater reliability (r=0,98, p<0,01) were determined for total score of the scale. The cut-off point of the scale was 29,5. CONCLUSION: All of these results support that the scale adapted into Turkish is a valid and reliable assessment instrument. Lien vers Pubmed
13. Lin C, Chao T, Nien H, Tu P, Yueh C, Wu C. {{SU-F-T-69: Correction Model of NIPAM Gel and Presage for Electron and Proton PDD Measurement}}. {Med Phys}. 2016; 43(6): 3477.
PURPOSE: The current standard equipment for proton PDD measurement is multilayer-parallel-ion-chamber. Disadvantage of multilayer-parallel-ion-chamber is expensive and complexity manipulation. NIPAM-gel and Presage are options for PDD measurement. Due to different stopping power, the result of NIPAM-gel and Presage need to be corrected. This study aims to create a correction model for NIPAM-gel and Presage PDD measurement. METHODS: Standard water based PDD profiles of electron 6MeV, 12MeV, and proton 90MeV were acquired. Electron PDD profile after 1cm thickness of NIPAM-gel added on the top of water was measured. Electron PDD profile with extra 1cm thickness of solid water, PTW RW3, was measured. The distance shift among standard PDD, NIPAM-gel PDD, and solid water PDD at R50% was compared and water equivalent thickness correction factor (WET) was calculated. Similar process was repeated. WETs for electron with Presage, proton with NIPAM-gel, and proton with Presage were calculated. PDD profiles of electron and proton with NIPAM-gel and Presage columns were corrected with each WET. The corrected profiles were compared with standard profiles. RESULTS: WET for electron 12MeV with NIPAM-gel was 1.135, and 1.034 for electron 12Mev with Presage. After correction, PDD profile matched to the standard profile at the fall-off range well. The difference at R50% was 0.26mm shallower and 0.39mm deeper. The same WET was used to correct electron 6MeV profile. Energy independence of electron WET was observed. The difference at R50% was 0.17mm deeper for NIPAM-gel and 0.54mm deeper for Presage. WET for proton 90MeV with NIPAM-gel was 1.056. The difference at R50% was 0.37 deeper. Quenching effect at Bragg peak was revealed. The underestimated dose percentage at Bragg peak was 27%. CONCLUSION: This correction model can be used to modify PDD profile with depth error within 1mm. With this correction model, NIPAM-gel and Presage can be practical at PDD profile measurement.
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14. Lin IF, Shirama A, Kato N, Kashino M. {{The singular nature of auditory and visual scene analysis in autism}}. {Philos Trans R Soc Lond B Biol Sci}. 2017; 372(1714).
Individuals with autism spectrum disorder often have difficulty acquiring relevant auditory and visual information in daily environments, despite not being diagnosed as hearing impaired or having low vision. Resent psychophysical and neurophysiological studies have shown that autistic individuals have highly specific individual differences at various levels of information processing, including feature extraction, automatic grouping and top-down modulation in auditory and visual scene analysis. Comparison of the characteristics of scene analysis between auditory and visual modalities reveals some essential commonalities, which could provide clues about the underlying neural mechanisms. Further progress in this line of research may suggest effective methods for diagnosing and supporting autistic individuals.This article is part of the themed issue ‘Auditory and visual scene analysis’.
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15. Logan K, Iacono T, Trembath D. {{A systematic review of research into aided AAC to increase social-communication functions in children with autism spectrum disorder}}. {Augment Altern Commun}. 2016: 1-14.
Augmentative and alternative communication (AAC) interventions have been shown to be effective in supporting children with autism spectrum disorder (ASD) to communicate, particularly to request preferred items and activities. The aim of this systematic review was to examine the effectiveness of AAC interventions in supporting children to produce a broader range of communicative functions and determine the extent to which these interventions have been evaluated beyond immediate effectiveness to address maintenance, generalization, and social validity. A systematic search and application of inclusion criteria yielded 30 interventions that focused on communication functions beyond object requests. In many of the studies, flaws detracted from the certainty of evidence, and maintenance, generalization, and/or social validity were not addressed. Further research is needed to evaluate the extent to which AAC interventions can support children with ASD to communicate using a variety of communication functions, as well as to demonstrate sustained, transferable, and meaningful change.
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16. Rossi M, Chatron N, Labalme A, Ville D, Carneiro M, Edery P, des Portes V, Lemke JR, Sanlaville D, Lesca G. {{Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy}}. {Eur J Hum Genet}. 2017.
We report on two consanguineous sibs affected with severe intellectual disability and autistic features due to a homozygous missense variant of GRIN1. Massive parallel sequencing was performed using a gene panel including 450 genes related to intellectual disability and autism spectrum disorders. We found a homozygous missense variation of GRIN1 (c.679G>C; p.(Asp227His)) in the two affected sibs, which was inherited from both unaffected heterozygous parents. Heterozygous variants of GRIN1, encoding the GluN1 subunit of the NMDA receptor, have been reported in patients with neurodevelopmental disorders including epileptic encephalopathy, severe intellectual disability, and movement disorders. The p.(Asp227His) variant is located in the same aminoterminal protein domain as the recently published p.(Arg217Trp), which was found at the homozygous state in two patients with a similar phenotype of severe intellectual disability and autistic features but without epilepsy. In silico predictions were consistent with a deleterious effect. The present findings further expand the clinical spectrum of GRIN1 variants and support the existence of hypomorphic variants causing severe neurodevelopmental impairment with autosomal recessive inheritance.European Journal of Human Genetics advance online publication, 4 January 2017; doi:10.1038/ejhg.2016.163.
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17. Salehi M, Kamali E, Karahmadi M, Mousavi SM. {{RORA and Autism in The Isfahan Population: Is There An Epigenetic Relationship}}. {Cell J}. 2017; 18(4): 540-6.
OBJECTIVE: Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORalpha) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan. MATERIALS AND METHODS: The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions -200 to -64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results. RESULTS: This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORalpha transcripts in the blood lymphocytes between autistic and healthy children. CONCLUSION: The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated.
18. Schmitz Olin S, McFadden BA, Golem DL, Pellegrino JK, Walker AJ, Sanders DJ, Arent SM. {{The Effects of Exercise Dose on Stereotypical Behavior in Children with Autism}}. {Med Sci Sports Exerc}. 2017.
INTRODUCTION: Autism Spectrum Disorder (ASD) is a prevalent neurological disorder in children characterized by restrictive, repetitive patterns of behavior that place an added burden on everyday functions. Aerobic exercise has the propensity to reduce stereotypic behaviors in children with ASD. This study sought to quantify the acute effect of exercise and assess the influence of duration and intensity on frequency of stereotypic behaviors in children with ASD. METHODS: Participants in this study (N=7, Mage=13.0 +/- 1.4 yrs, Mheight=1.64 +/- 0.01m, Mweight=60.1 +/- 13.7kg) underwent five separate days of treatments including a control (C), low intensity 10 min (10L), high intensity 10 min (10H), low intensity 20 min (20L), and high intensity 20 min (20H) conditions in which intensity was quantified using HR as well as RPE. Prior to and for 60 min following exercise, frequency of stereotypic behaviors was recorded. RESULTS: Results indicated a reduction in behaviors in response to exercise compared to the C trial throughout all conditions except 20H. Interestingly, the most exhaustive exercise session led to increased stereotypic behaviors at all post time periods compared to the other exercise trials (p<.10). The 10L condition showed the greatest reduction at 60 min post compared to the 20H or the control trials' response (p<.05). Examining the behavioral responses to exercise using effect sizes indicated the 10L condition showed the greatest reduction in frequency throughout all 4 time points (ESrange= -.87 to -1.03) compared to baseline. CONCLUSION: While it appears high-intensity aerobic exercise may exacerbate stereotypic behaviors in children with ASD, low-to-moderate intensity exercise produces significant and large reductions in these behaviors. This provides an easily administered and cost-effective way to positively impact these individuals. Lien vers le texte intégral (Open Access ou abonnement)
19. Sellier C, Buijsen RA, He F, Natla S, Jung L, Tropel P, Gaucherot A, Jacobs H, Meziane H, Vincent A, Champy MF, Sorg T, Pavlovic G, Wattenhofer-Donze M, Birling MC, Oulad-Abdelghani M, Eberling P, Ruffenach F, Joint M, Anheim M, Martinez-Cerdeno V, Tassone F, Willemsen R, Hukema RK, Viville S, Martinat C, Todd PK, Charlet-Berguerand N. {{Translation of Expanded CGG Repeats into FMRpolyG Is Pathogenic and May Contribute to Fragile X Tremor Ataxia Syndrome}}. {Neuron}. 2017.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limited expansion of CGG repeats in the 5′ UTR of FMR1. Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific proteins, and translation of CGG repeats into a polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing CGG repeat RNA with or without FMRpolyG. Expression of FMRpolyG is pathogenic, while the sole expression of CGG RNA is not. FMRpolyG interacts with the nuclear lamina protein LAP2beta and disorganizes the nuclear lamina architecture in neurons differentiated from FXTAS iPS cells. Finally, expression of LAP2beta rescues neuronal death induced by FMRpolyG. Overall, these results suggest that translation of expanded CGG repeats into FMRpolyG alters nuclear lamina architecture and drives pathogenesis in FXTAS.
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20. St Pourcain B, Robinson EB, Anttila V, Sullivan BB, Maller J, Golding J, Skuse D, Ring S, Evans DM, Zammit S, Fisher SE, Neale BM, Anney RJ, Ripke S, Hollegaard MV, Werge T, Ronald A, Grove J, Hougaard DM, Borglum AD, Mortensen PB, Daly MJ, Davey Smith G. {{ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties}}. {Mol Psychiatry}. 2017.
Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.Molecular Psychiatry advance online publication, 3 January 2017; doi:10.1038/mp.2016.198.
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21. Vargason T, Howsmon DP, Melnyk S, James SJ, Hahn J. {{Mathematical modeling of the methionine cycle and transsulfuration pathway in individuals with autism spectrum disorder}}. {J Theor Biol}. 2016; 416: 28-37.
Previous research has shown a connection between metabolic abnormalities in the methionine cycle and transsulfuration pathway and autism spectrum disorder. Using clinical data from a case-control study investigating measurements of transmethylation and transsulfuration metabolites, a steady-state model of these metabolites in liver cells was developed and participant-specific parameters were identified. Comparison of mean parameter values and parameter distributions between neurotypical study participants and those on the autism spectrum revealed significant differences for four model parameters. Sensitivity analysis identified the parameter describing the rate of glutamylcysteine synthesis, the rate-limiting step in glutathione production, to be particularly important in determining steady-state metabolite concentrations. These results may provide insight into key reactions to target for potential intervention strategies relating to autism spectrum disorder.