1. Bennett EA, Kolko RP, Chia L, Elliott JP, Kalarchian MA. {{Treatment of Obesity Among Youth With Intellectual and Developmental Disabilities}}. {West J Nurs Res};2017 (Mar 01):193945917697664.
Childhood obesity is a serious health issue, associated with medical comorbidity and psychosocial impairment that can persist into adulthood. In the United States, youth with intellectual and developmental disabilities are more likely to be obese than youth without disabilities. A large body of evidence supports the efficacy of family-based treatment of childhood obesity, including diet, physical activity, and behavior modification, but few interventions have been developed and evaluated specifically for this population. We highlight studies on treatment of obesity among youth with intellectual and developmental disabilities, including both residential/educational settings as well as outpatient/hospital settings. All interventions were delivered in-person, and further development of promising approaches and delivery via telenursing may increase access by youth and families. Nursing scientists can assume an important role in overcoming barriers to care for this vulnerable and underserved population.
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2. Boudjarane MA, Grandgeorge M, Marianowski R, Misery L, Lemonnier E. {{Perception of odors and tastes in autism spectrum disorders: A systematic review of assessments}}. {Autism Res};2017 (Mar 30)
Olfaction and gustation are major sensory functions implied in processing environmental stimuli. Some evidences suggest that loss of olfactory function is an early biomarker for neurodegenerative disorders and atypical processing of odor and taste stimuli is present in several neurodevelopmental disorders, notably in Autism Spectrum Disorders (ASD). In this paper, we conducted a systematic review investigating the assessments of olfaction and gustation with psychophysics methods in individuals with ASD. Pubmed, PMC and Sciencedirect were scrutinized for relevant literature published from 1970 to 2015. In this review, fourteen papers met our inclusion criteria. They were analyzed critically in order to evaluate the occurrence of olfactory and gustatory dysfunction in ASD, as well as to report the methods used to assess olfaction and gustation in such conditions. Regarding to these two senses, the overall number of studies is low. Most of studies show significant difference regarding to odor or taste identification but not for detection threshold. Overall, odor rating through pleasantness, intensity and familiarity do not differ significantly between control and individuals with ASD. The current evidences can suggest the presence of olfactory and gustatory dysfunction in ASD. Therefore, our analysis show a heterogeneity of findings. This is due to several methodological limitations such as the tools used or population studied. Understanding these disorders could help to shed light on other atypical behavior in this population such as feeding or social behavior. Autism Res 2017, 0: 000-000. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Bourghli A, Boissiere L, Larrieu D, Vital JM, Yilgor C, Pellise F, Alanay A, Acaroglu E, Perez-Grueso FJ, Kleinstuck F, Obeid I. {{Lack of improvement in health-related quality of life (HRQOL) scores 6 months after surgery for adult spinal deformity (ASD) predicts high revision rate in the second postoperative year}}. {Eur Spine J};2017 (Mar 30)
PURPOSE: ASD is assessed radiologically with the spinopelvic parameters and clinically with HRQOL scores. The revision rate after ASD surgery is high and usually occurs during the first or second postoperative year. The aim of this study is to find clinical or radiological factors that could predict revision surgery in the second postoperative year. MATERIALS AND METHODS: Inclusion criterion: ASD patients operated on by instrumented posterior fusion with more than 2 years follow-up were enrolled prospectively. Additional criterion was no revision surgery during the first postoperative year. From a multicenter database of 560 operated ASD patients, 164 patients met these criteria. The patients were divided into two groups depending on the need of revision surgery during the second postoperative year. Preoperative, 6-month, 1-year and 2-year data were collected and compared for both groups. RESULTS: A total of 22 patients needed revision surgery and 142 did not. All revisions were for mechanical complications (non-fusion and implant related). Preoperatively, there was a significant difference between the groups (no revision vs. revision) for age (48 vs. 60 years), ODI (37 vs. 53), and SVA (29 vs. 76 mm), respectively. At 6 months, a significant difference in sagittal alignment was found, though HRQOL scores were similar. At 1 year, the no revision group scores improved, whereas the revision group scores remained stable or worsened. At 2 years, the no revision group scores remained stable. Comparing 6- and 12-month data, patients with improved, stable and worsened HRQOL scores had 8, 15 and 28% revision rates, respectively. CONCLUSION: The revision rate at the second-year post-surgery (13.4%) remains high and demonstrated that a 2-year follow-up is mandatory. In addition to usual risk factors for mechanical complications in ASD surgery, stabilization or worsening of the HRQOL scores between the 6th and 12th month postop was highly predictive of revision rate. This observation is beneficial for ASD patient follow-up as clinical symptoms clearly precede mechanical failure.
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4. Chahboun S, Vulchanov V, Saldana D, Eshuis H, Vulchanova M. {{Can you tell it by the prime? A study of metaphorical priming in high-functioning autism in comparison with matched controls}}. {Int J Lang Commun Disord};2017 (Mar 30)
BACKGROUND: Problems with pragmatic aspects of language are well attested in individuals on the autism spectrum. It remains unclear, however, whether figurative language skills improve with language status and whether problems in figurative language are no longer present in highly verbal individuals with autism. AIMS: To investigate whether highly verbal individuals with autism perform similarly as age-, intelligence- and verbal comprehension-matched controls on the processing of one of the most common types of figurative language, metaphors. The goal was to establish whether the participants with autism are primed similarly to controls by figurative expressions (metaphors) presented in different conditions. METHODS & PROCEDURES: The experiment was designed as a cross-modal lexical-decision task where metaphors served as primes for target words related to their figurative or literal meaning. OUTCOMES & RESULTS: Our findings show that both ASD and control participants made very few errors in the experimental task. However, the participants with ASD presented with problems in performance on the task, reflected in significantly slower reaction times compared with the typically developing peer groups. The similar response speed observed between the younger typical control children and the adult ASD participants suggests that the mechanisms underlying metaphor processing (e.g., selection of metaphorical versus literal interpretation) are still developing in high-functioning autism, very much like in typical children. CONCLUSIONS & IMPLICATIONS: These results may suggest that metaphor processing requires more than adequate language competences. The findings are also suggestive of a delay in developing sensitivity to figurative language, rather than sheer inability. This suggests that a timely training programme can be implemented to improve figurative language abilities in ASD.
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5. Coretti L, Cristiano C, Florio E, Scala G, Lama A, Keller S, Cuomo M, Russo R, Pero R, Paciello O, Mattace Raso G, Meli R, Cocozza S, Calignano A, Chiariotti L, Lembo F. {{Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder}}. {Sci Rep};2017 (Mar 28);7:45356.
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.
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6. Dotson WH, Rasmussen EE, Shafer A, Colwell M, Densley RL, Brewer AT, Alonzo MC, Martinez LA. {{Evaluating the Ability of the PBS Children’s Show Daniel Tiger’s Neighborhood to Teach Skills to Two Young Children with Autism Spectrum Disorder}}. {Behav Anal Pract};2017 (Mar);10(1):67-71.
Daniel Tiger’s Neighborhood is a children’s television show incorporating many elements of video modeling, an intervention that can teach skills to children with autism spectrum disorders (ASD). This study evaluated the impact of watching Daniel Tiger’s Neighborhood episodes on the accurate performance of trying new foods and stopping play politely with two five-year-old children with ASD. Both children showed improved performance of skills only following exposure to episodes of Daniel Tiger’s Neighborhood, suggesting that watching episodes can help children with ASD learn specific skills.
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7. Espluga-Frigola N, Cardoner N, Pamias-Massana M, Palao-Vidal DJ. {{Comorbidity of autism spectrum disorder and bipolar disorder}}. {Actas Esp Psiquiatr};2017 (Mar);45(2):79-88.
8. Grow LL, Van Der Hijde R. {{A Comparison of Procedures for Teaching Receptive Labeling of Sight Words to a Child with Autism Spectrum Disorder}}. {Behav Anal Pract};2017 (Mar);10(1):62-66.
We compared the effectiveness and efficiency of a modified simple-conditional method and the conditional-only method for teaching receptive labeling of sight words. Jon, a 6-year-old boy diagnosed with autism spectrum disorder, participated. Across three comparative evaluations, the conditional-only method resulted in fewer sessions to mastery than a modified simple-conditional method. Textual responses emerged after Jon mastered the sight words as receptive labels. Practitioners should avoid teaching component simple discriminations as a strategy for facilitating conditional discrimination training in clinical practice.
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9. Guest PC, Martins-de-Souza D. {{What Have Proteomic Studies Taught Us About Novel Drug Targets in Autism?}}. {Adv Exp Med Biol};2017;974:49-67.
Autism spectrum disorders (ASDs) are a heterogeneous group of conditions with complex behavioural phenotypes. Although ASDs show a high rate of heritability, genetic research alone has not provided a complete understanding of the underlying causes. Recent developments using imaging techniques and proteomic-based molecular profiling approaches have now begun to generate new insights into the underlying pathways affected in both the brain and the periphery in individuals with these conditions. Of potential high importance is the constant finding of gender-specific biomarker profiles in ASD patients. This suggests that there are either distinct adaptive mechanisms or different aetiological causes in male and female ASD patients. This chapter addresses the findings using these approaches with a view to identification of novel drug targets or new treatment strategies based on personalized medicine objectives. Eventually, this will lead to a better disease understanding of ASD at the physiological and molecular levels, which may facilitate novel drug discovery efforts in this challenging area of medicine.
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10. Guilhardi P, Smith J, Rivera C, Ross RK. {{Learner Preference Between Massed- and Alternating-Trial Sequencing when Teaching Stimulus Relations to Children with Autism}}. {Behav Anal Pract};2017 (Mar);10(1):77-82.
Two children with autism were assessed for preference between intersession distribution of mastered and unknown instructional trials on a computerized matching-to-sample task consisting of 12 total learning opportunities. Choice responses yielded presentation of either massed-trial sequencing (six unknown/six mastered stimuli relations or vice-versa) or alternating-trial sequencing delivery (alternation of unknown and mastered stimuli relations) followed by reinforcement for correct responses. An extinction condition served as an experimental control. Both children demonstrated a preference for the alternating-trial sequencing condition, and implications for instructional programming and possible effects to delays to higher rates of reinforcement are discussed.
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11. Killian JT, Lane JB, Lee HS, Skinner SA, Kaufmann WE, Glaze DG, Neul JL, Percy AK. {{Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors}}. {Pediatr Neurol};2017 (Feb 07)
BACKGROUND: Scoliosis is prominent in Rett syndrome (RTT). Following the prior report from the US Natural History Study, the onset and progression of severe scoliosis (>/=40 degrees Cobb angle) and surgery were examined regarding functional capabilities and specific genotypes, addressing the hypothesis that abnormal muscle tone, poor oral feeding, puberty, and delays or absence of sitting balance and ambulation may be responsible for greater risk in RTT. METHODS: The multicenter RTT Natural History Study gathered longitudinal data for classic RTT, including mutation type, scoliosis, muscle tone, sitting, ambulation, hand function, and feeding. Cox regression models were used to examine the association between scoliosis and functional characteristics. All analyses utilized SAS 9.4; two-sided P values of <0.05 were considered significant. RESULTS: A total of 913 females with classic RTT were included. Scoliosis frequency and severity increased with age. Severe scoliosis was found in 251 participants (27%), 113 of whom developed severe scoliosis during the follow-up assessments; 168 (18%) had surgical correction. Severe MECP2 mutations (R106W, R168X, R255X, R270X, and large deletions) showed a higher proportion of scoliosis. Individuals developing severe scoliosis or requiring surgery were less likely to sit, ambulate, or use their hands and were more likely to have begun puberty. Significant differences were absent for epilepsy rates, sleep problems, or constipation. DISCUSSION: Scoliosis requires vigilance regarding the risk factors noted, particularly specific mutations and the role of puberty and motor abilities. Bracing is recommended for moderate curves and surgery for severe curves in accordance with published guidelines for scoliosis management. Lien vers le texte intégral (Open Access ou abonnement)
12. Kourtian S, Soueid J, Makhoul NJ, Guisso DR, Chahrour M, Boustany RN. {{Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population}}. {Sci Rep};2017 (Mar 30);7:45336.
Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: gamma2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.
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13. Kruusvee V, Lyst MJ, Taylor C, Tarnauskaite Z, Bird AP, Cook AG. {{Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders}}. {Proc Natl Acad Sci U S A};2017 (Mar 27)
Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the « NCoR/SMRT interaction domain » (NID) of MeCP2 directly contacts transducin-beta like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT. We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and confirm by in vitro and ex vivo assays that mutation of interacting residues of TBLR1 and TBL1 disrupts binding to MeCP2. Strikingly, the four MeCP2-NID residues mutated in RTT are those residues that make the most extensive contacts with TBLR1. Moreover, missense mutations in the gene for TBLR1 that are associated with intellectual disability also prevent MeCP2 binding. Our study therefore reveals the molecular basis of an interaction that is crucial for optimal brain function.
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14. Kumar A, Jaryal A, Gulati S, Chakrabarty B, Singh A, Deepak KK, Pandey RM, Gupta N, Sapra S, Kabra M, Khajuria R. {{Cardiovascular Autonomic Dysfunction in Children and Adolescents With Rett Syndrome}}. {Pediatr Neurol};2017 (Jan 17)
BACKGROUND: Autonomic dysfunction is common in children with Rett syndrome. They usually manifest with agitation, persistent screaming, constipation, gastroesophageal reflux, aerophagia, hyperventilation, and breath-holding episodes. Cardiovascular autonomic dysfunction may result in fatal a arrhythmia. Many of these events are mistaken for seizures and treated with antiepileptics. METHODS: The present study was conducted in a tertiary care teaching hospital in north India for more than a six month period. MeCP2 mutation positive, 24 cases with Rett syndrome and 24 age-matched healthy girls were evaluated for cardiovascular autonomic dysfunction (heart rate variability, head-up tilt test, and cold pressor test). RESULTS: The mean age was 9.06 years (+/-3.4) and 9.75 years (+/-3.13) for patients and control subjects, respectively. The heart rate variability contributed independently by parasympathetic and sympathetic nervous system was significantly reduced in cases compared with control subjects (P = 0.033 and P = 0.001, respectively). There was significant sympathovagal imbalance with sympathetic overactivity in cases compared with control subjects (P = 0.001). The mean longest QTc interval was significantly prolonged in cases compared with control subjects (P = 0.001). Cold pressor test and head-up tilt test could be done in 16 Rett syndrome patients (because of poor cooperation) and in all 24 control subjects. The change in blood pressure during cold pressor test and head-up tilt test was not significantly different in cases and control subjects. CONCLUSIONS: Children with Rett syndrome exhibited significant cardiovascular autonomic dysfunction in the form of sympathetic overactivity, parasympathetic underactivity, and sympathovagal imbalance. These findings have potentially important therapeutic- and outcome-related implications.
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15. Miller KL. {{The Use of Evaluation in Treatment Programs for Children with Autism}}. {Behav Anal Pract};2017 (Mar);10(1):35-44.
Program evaluation is the use of planned activities to monitor process, outcomes, and impact of a health program or intervention. The application of program evaluation to behavioral analytic treatment programs for children with autism is a useful and necessary activity to inform practitioners and other stakeholders of the efficacy of these programs and to promote adherence to best-practice treatments. A brief survey of behavioral providers in California and Texas and search of the behavioral literature suggest that the practice of program evaluation is underutilized among providers of behavioral services. Current organizational practices primarily involve reporting on individualized consumer goals. The purpose of this paper is to provide an introduction to evaluation processes and procedures to promote the implementation of some or all of these components. Areas discussed include defining the population served and program stakeholders, describing the program and intervention, selecting evaluation goals and objectives, ethical considerations, and reporting.
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16. Mitra M. {{Postpartum Health of Women with Intellectual and Developmental Disabilities: A Call to Action}}. {J Womens Health (Larchmt)};2017 (Mar 29)
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17. Nadig A, Mulligan A. {{Intact non-word repetition and similar error patterns in language-matched children with autism spectrum disorders: A pilot study}}. {J Commun Disord};2017 (Mar 18);66:13-21.
PURPOSE: We investigated whether enhanced auditory short-term memory may contribute to the learning of novel word forms in children with Autism Spectrum Disorder. We also evaluated whether delayed but qualitatively normal, versus atypical, cognitive processes underlie non-word repetition in this population via a detailed error analysis. METHOD: English-speaking children with Autism Spectrum Disorder (who had significant language delay) and typically-developing children matched pairwise on language ability were compared on the Syllable Repetition Task (Shriberg et al., 2009). RESULTS: All children exhibited better performance on stimuli of shorter vs. longer syllable length. In addition there was a significant interaction whereby children with Autism Spectrum Disorder performed better than typically-developing children at the longest syllable length. Repetition accuracy was significantly correlated with language level in both groups. In contrast, the relationship between Repetition accuracy and age was only marginally significant in the Autism Spectrum Disorder group and did not reach significance in the typically-developing group. This underscores the importance of language level to non-word repetition performance, and supports the practice of matching on language rather than age alone. An error analysis (Shriberg et al., 2012) showed many similarities between groups in terms of number of consonants deleted, encoding accuracy, and transcoding accuracy components of the task. However the Autism Spectrum Disorder group tended to display better auditory short-term memory with a medium effect size, though this did not reach significance given the small sample size. CONCLUSION: These findings extend evidence of delayed but qualitatively normal non-word repetition previously described in preadolescents with Autism Spectrum Disorder (Williams et al., 2013) to younger kindergarten-age children with Autism Spectrum Disorder and language delay, indicating that non-word repetition is not an area of specific difficulty for this population. With respect to enhanced auditory short-term memory, we found preliminary evidence of better memory for longer nonwords in children with Autism Spectrum Disorder compared to younger typically developing children who were matched on language.
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18. Page SV, Griffith K, Penrod B. {{Reduction of Rapid Eating in an Adolescent Female with Autism}}. {Behav Anal Pract};2017 (Mar);10(1):87-91.
Rapid eating, a potentially dangerous and socially inappropriate behavior, has received relatively little attention in the literature. This study sought to extend the research in this area by further evaluating the effectiveness of a vibrating pager combined with a rule for increasing inter-response time between bites in one adolescent female diagnosed with autism. Results indicated that inter-response time increased from baseline only after a vocal prompt to « wait » was introduced across clinic and home settings. Implications for promoting autonomy in individuals with developmental disabilities are discussed.This antecedent-based intervention can easily be generalized to caregiversThe unobtrusive nature of the intervention allows for implementation in inclusive settingsThere are implications for promoting social skills in naturalistic environmentsThe intervention can promote independence through teaching self-management.
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19. Pardo M, Cheng Y, Velmeshev D, Magistri M, Eldar-Finkelman H, Martinez A, Faghihi MA, Jope RS, Beurel E. {{Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice}}. {JCI Insight};2017 (Mar 23);2(6):e91782.
Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3beta (GSK3beta), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1-/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.
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20. Rapanelli M, Frick LR, Xu M, Groman SM, Jindachomthong K, Tamamaki N, Tanahira C, Taylor JR, Pittenger C. {{Targeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice}}. {Biol Psychiatry};2017 (Feb 10)
BACKGROUND: Interneuronal pathology is implicated in many neuropsychiatric disorders, including autism spectrum disorder (ASD) and Tourette syndrome (TS). Interneurons of the striatum, including the parvalbumin-expressing fast-spiking interneurons (FSIs) and the large cholinergic interneurons (CINs), are affected in patients with TS and in preclinical models of both ASD and TS. METHODS: To test the causal importance of these neuronal abnormalities, we recapitulated them in vivo in developmentally normal mice using a combination transgenic-viral strategy for targeted toxin-mediated ablation. RESULTS: We found that conjoint ~50% depletion of FSIs and CINs in the dorsal striatum of male mice produces spontaneous stereotypy and marked deficits in social interaction. Strikingly, these behavioral effects are not seen in female mice; because ASD and TS have a marked male predominance, this observation reinforces the potential relevance of the finding to human disease. Neither of these effects is seen when only one or the other interneuronal population is depleted; ablation of both is required. Depletion of FSIs, but not of CINs, also produces anxiety-like behavior, as has been described previously. Behavioral pathology in male mice after conjoint FSI and CIN depletion is accompanied by increases in activity-dependent signaling in the dorsal striatum; these alterations were not observed after disruption of only one interneuron type or in doubly depleted female mice. CONCLUSIONS: These data indicate that disruption of CIN and FSI interneurons in the dorsal striatum is sufficient to produce network and behavioral changes of potential relevance to ASD, in a sexually dimorphic manner.
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21. Shulyakova N, Andreazza AC, Mills LR, Eubanks JH. {{Mitochondrial Dysfunction in the Pathogenesis of Rett Syndrome: Implications for Mitochondria-Targeted Therapies}}. {Front Cell Neurosci};2017;11:58.
First described over 50 years ago, Rett syndrome (RTT) is a neurodevelopmental disorder caused primarily by mutations of the X-linked MECP2 gene. RTT affects predominantly females, and has a prevalence of roughly 1 in every 10,000 female births. Prior to the discovery that mutations of MECP2 are the leading cause of RTT, there were suggestions that RTT could be a mitochondrial disease. In fact, several reports documented altered mitochondrial structure, and deficiencies in mitochondrial enzyme activity in different cells or tissues derived from RTT patients. With the identification of MECP2 as the causal gene, interest largely shifted toward defining the normal function of MeCP2 in the brain, and how its absence affects the neurodevelopment and neurophysiology. Recently, though, interest in studying mitochondrial function in RTT has been reignited, at least in part due to observations suggesting systemic oxidative stress does play a contributing role in RTT pathogenesis. Here we review data relating to mitochondrial alterations at the structural and functional levels in RTT patients and model systems, and present a hypothesis for how the absence of MeCP2 could lead to altered mitochondrial function and elevated levels of cellular oxidative stress. Finally, we discuss the prospects for treating RTT using interventions that target specific aspects of mitochondrial dysfunction and/or oxidative stress.
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22. Stevenson JL, Hart KR. {{Psychometric Properties of the Autism-Spectrum Quotient for Assessing Low and High Levels of Autistic Traits in College Students}}. {J Autism Dev Disord};2017 (Mar 27)
The current study systematically investigated the effects of scoring and categorization methods on the psychometric properties of the Autism-Spectrum Quotient. Four hundred and three college students completed the Autism-Spectrum Quotient at least once. Total scores on the Autism-Spectrum Quotient had acceptable internal consistency and test-retest reliability using a binary or Likert scoring method, but the results were more varied for the subscales. Overall, Likert scoring yielded higher internal consistency and test-retest reliability than binary scoring. However, agreement in categorization of low and high autistic traits was poor over time (except for a median split on Likert scores). The results support using Likert scoring and administering the Autism-Spectrum Quotient at the same time as the task of interest with neurotypical participants.
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23. Touzet S, Occelli P, Schroder C, Manificat S, Gicquel L, Stanciu R, Schaer M, Oreve MJ, Speranza M, Denis A, Zelmar A, Falissard B, Georgieff N, Bahrami S, Geoffray MM. {{Impact of the Early Start Denver Model on the cognitive level of children with autism spectrum disorder: study protocol for a randomised controlled trial using a two-stage Zelen design}}. {BMJ Open};2017 (Mar 27);7(3):e014730.
INTRODUCTION: Early intervention for autism spectrum disorder (ASD) in the European French-speaking countries is heterogeneous and poorly evaluated to date. Early intervention units applying the Early Start Denver Model (ESDM) for toddlers and young children with ASD have been created in France and Belgium to improve this situation. It is essential to evaluate this intervention for the political decision-making process regarding ASD interventions in European French-speaking countries. We will evaluate the effectiveness of 12 hours per week ESDM intervention on the cognitive level of children with ASD, over a 2-year period. METHODS AND ANALYSIS: The study will be a multicentre, randomised controlled trial, using a two-stage Zelen design. Children aged 15-36 months, diagnosed with ASD and with a developmental quotient (DQ) of 30 or above on the Mullen Scale of Early Learning (MSEL) will be included. We will use a stratified minimisation randomisation at a ratio 1:2 in favour of the control group. The sample size required is 180 children (120 in the control and 60 in the intervention group). The experimental group will receive 12 hours per week ESDM by trained therapists 10 hours per week in the centre and 2 hours in the toddlers’ natural environment (alternatively by the therapist and the parent). The control group will receive care available in the community. The primary outcome will be the change in cognitive level measured with the DQ of the MSEL scored at 2 years. Secondary outcomes will include change in autism symptoms, behavioural adaptation, communicative and productive language level, sensory profile and parents’ quality of life. The primary analysis will use the intention-to-treat principle. An economic evaluation will be performed. DISSEMINATION: Findings from the study will be disseminated through peer reviewed publications and meetings. TRIAL REGISTRATION NUMBER: NCT02608333 (clinicaltrials.gov); Pre-results.
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24. Van der Hallen R, Vanmarcke S, Noens I, Wagemans J. {{Hierarchical Letters in ASD: High Stimulus Variability Under Different Attentional Modes}}. {J Autism Dev Disord};2017 (Mar 27)
Studies using hierarchical patterns to test global precedence and local-global interference in individuals with ASD have produced mixed results. The current study focused on stimulus variability and locational uncertainty, while using different attentional modes. Two groups of 44 children with and without ASD completed a divided attention task as well as a global and local selective attention task. The results revealed global-to-local and local-to-global interference in ASD, to the same extent as in the TD group. Both groups struggled with the same type of stimuli (i.e., ignoring the global level information) and performed similar in all three tasks. Future studies on (visual) information processing in ASD should pursue the impact of stimulus noise and trial-by-trial uncertainty further.
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25. Vivanti G, Fanning PA, Hocking DR, Sievers S, Dissanayake C. {{Social Attention, Joint Attention and Sustained Attention in Autism Spectrum Disorder and Williams Syndrome: Convergences and Divergences}}. {J Autism Dev Disord};2017 (Mar 27)
There is limited knowledge on shared and syndrome-specific attentional profiles in autism spectrum disorder (ASD) and Williams syndrome (WS). Using eye-tracking, we examined attentional profiles of 35 preschoolers with ASD, 22 preschoolers with WS and 20 typically developing children across social and non-social dimensions of attention. Children with ASD and those with WS presented with overlapping deficits in spontaneous visual engagement with the target of others’ attention and in sustained attention. Children with ASD showed syndrome-specific abnormalities in monitoring and following a person’s referential gaze, as well as a lack of preferential attention to social stimuli. Children with ASD and WS present with shared as well as syndrome-specific abnormalities across social and non-social dimensions of attention.
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26. Zhou H, Wu W, Zhang Y, He H, Yuan Z, Zhu Z, Zhao Z. {{Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2stop mice}}. {Behav Brain Res};2017 (Mar 30);322(Pt A):51-59.
RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2stop mice to determine the cholinergic MeCP2 effects on rescuing the RTT-like phenotypes. We found cholinergic MeCP2 preservation could reverse some aspects of the RTT-like phenotypes in mice including hypolocomotion and increased anxiety level, and delay the onset of underweight, instead of improving the hypersocial abnormality and the poor general conditions such as short lifespan, low brain weight, and increasing severity score. Our findings suggest that selective activation of cholinergic MeCP2 is sufficient to reverse the locomotor impairment and increased anxiety-like behaviors at least in early symptomatic stage, supporting future development of RTT therapies associated with cholinergic system.
