1. Aramaki E, Shikata S, Miyabe M, Usuda Y, Asada K, Ayaya S, Kumagaya S. {{Understanding the Relationship between Social Cognition and Word Difficulty. A Language Based Analysis of Individuals with Autism Spectrum Disorder}}. {Methods Inf Med};2015 (Sep 22);54(5)
BACKGROUND: Few quantitative studies have been conducted on the relationship between society and its languages. Individuals with autistic spectrum disorder (ASD) are known to experience social hardships, and a wide range of clinical information about their quality of life has been provided through numerous narrative analyses. However, the narratives of ASD patients have thus far been examined mainly through qualitative approaches. OBJECTIVES: In this study, we analyzed adults with ASD to quantitatively examine the relationship between language abilities and ASD severity scores. METHODS: We generated phonetic transcriptions of speeches by 16 ASD adults at an ASD workshop, and divided the participants into 2 groups according to their Social Responsiveness ScaleTM, 2nd Edition (SRSTM-2) scores (where higher scores represent more severe ASD): Group A comprised high-scoring ASD adults (SRSTM-2 score: >/= 76) and Group B comprised low- and intermediate-scoring ASD adults (SRSTM-2 score: < 76). Using natural language processing (NLP)-based analytical methods, the narratives were converted into numerical data according to four language ability indicators, and the relationships between the language ability scores and ASD severity scores were compared. RESULTS AND DISCUSSION: Group A showed a marginally negative correlation with the level of Japanese word difficulty (p < .10), while the « social cognition » subscale of the SRSTM-2 score showed a significantly negative correlation (p < .05) with word difficulty. When comparing only male participants, Group A demonstrated a significantly lower correlation with word difficulty level than Group B (p < .10). CONCLUSION: Social communication was found to be strongly associated with the level of word difficulty in speech. The clinical applications of these findings may be available in the near future, and there is a need for further detailed study on language metrics designed for ASD adults.
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2. Bearss K, Taylor CA, Aman MG, Whittemore R, Lecavalier L, Miller J, Pritchett J, Green B, Scahill L. {{Using qualitative methods to guide scale development for anxiety in youth with autism spectrum disorder}}. {Autism};2015 (Sep 22)
Anxiety is common in youth with autism spectrum disorder. Despite this common co-occurrence, studies targeting anxiety in this population are hindered by the under-developed state of measures in youth with autism spectrum disorder. Content validity (the extent to which an instrument measures the domain of interest) and an instrument’s relevance to the patient population are key components of measurement development. This article describes the application of qualitative research methods in the initial development of a parent-rated instrument of anxiety symptoms in youth with autism spectrum disorder. Overall, 48 parents of 45 children (aged 3-17 years) with autism spectrum disorder and at least mild anxiety participated in one of six focus groups at two sites (three groups per site). Systematic coding of the focus group transcripts identified broad themes reflecting the situations and events that trigger anxiety in children with autism spectrum disorder, the behavioral manifestations of anxiety in children with autism spectrum disorder, the parent and the child’s own response to anxiety, and broad behavioral patterns that could be associated with anxiety. From the focus group data, investigators generated 52 candidate items for a parent-rating of anxiety in youth with autism spectrum disorder. This report provides a detailed description of these early steps in developing a patient-oriented outcome measure.
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3. Bilaver LA, Cushing LS, Cutler AT. {{Prevalence and Correlates of Educational Intervention Utilization Among Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Sep 21)
This study examined the prevalence and correlates of educational intervention utilization among U.S. preschool aged children with autism spectrum disorder (ASD) prior to recent policy changes. The analysis was based on a nationally representative longitudinal survey of children receiving special education services during the 2003-2004 school year. All children with parent or teacher identified ASD over a 3-year study period were analyzed. Outcomes included utilization of speech therapy, occupational therapy, behavior therapy, and mental health services by service sector. The analysis revealed low rates of behavioral therapy and mental health services. Parents reported that the overwhelming majority of services were received inside school only. This study identified gaps in the provision of services for young children with ASD.
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4. Kasari C, Dean M, Kretzmann M, Shih W, Orlich F, Whitney R, Landa R, Lord C, King B. {{Children with autism spectrum disorder and social skills groups at school: a randomized trial comparing intervention approach and peer composition}}. {J Child Psychol Psychiatry};2015 (Sep 22)
BACKGROUND: Peer relationships improve for children with autism spectrum disorder (ASD) in clinic-based social skills groups but rarely generalize to real world contexts. This study compares child outcomes of two social skills interventions conducted in schools with children in Kindergarten through fifth grade. METHOD: Children with ASD were randomized to one of two interventions that varied on group composition (mixed typical and ASD vs. all ASD or social difficulties) and intervention approach (didactic SKILLS based vs. activity-based ENGAGE groups). Interventions were implemented at school for 8 weeks (16 sessions) with an 8-week follow-up. Innovative measures of peer nomination and playground peer engagement, as well as teacher reports of child behavior problems and teacher-child relationship were analyzed for 137 children with ASD across four sites. RESULTS: On the primary outcome of social network connections from the peer nomination measure, there was no main effect of treatment, but there were moderator effects. Children with low teacher-child closeness or high conflict improved more in their social connections if they received the SKILLS intervention, whereas children with higher teacher-child closeness improved more if they received the ENGAGE intervention. Only two secondary outcome measures yielded significant effects of treatment. Children in the SKILLS groups increased peer engagement and decreased isolation during recess. Child behavior problems and teacher-child closeness moderated peer engagement such that children with higher behavior problems and lower closeness benefitted more from SKILLS groups. CONCLUSIONS: These findings suggest that social skills groups conducted at school can affect both peer engagement during recess as well as peer acceptability. Child characteristics and teacher-child relationship prior to intervention yield important information on who might benefit from a specific social skills intervention.
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5. Koehne S, Hatri A, Cacioppo JT, Dziobek I. {{Perceived interpersonal synchrony increases empathy: Insights from autism spectrum disorder}}. {Cognition};2015 (Sep 19);146:8-15.
This study investigated the effect of unilateral interpersonal synchrony on empathy in two simple leader-follower finger tapping communication tasks in individuals with and without autism spectrum disorder (ASD). In unilateral synchronization, one individual within a dyad (the follower) unilaterally adjusts his or her movements to entrain to the movements of the other (the leader). Perceived synchrony, i.e., being followed by a synchronous virtual partner when leading an interaction, increased subjective cognitive empathy (understanding other’s mental states) towards the virtual follower in participants without, but not those with ASD. In the ASD group, the degree of produced synchrony, i.e., entrainment to the virtual leader when following in an interaction, was associated with higher cognitive empathy performance as measured with external objective tasks. These results point to a mediating role for interpersonal synchronization in cognitive empathy, a mechanism that seems attenuated, yet not absent, in ASD.
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6. Krakowiak P, Goines PE, Tancredi DJ, Ashwood P, Hansen RL, Hertz-Picciotto I, Van de Water J. {{Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder}}. {Biol Psychiatry};2015 (Aug 14)
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. METHODS: We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. RESULTS: Interleukin (IL)-1beta and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1beta was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (beta = -3.63, SE = 1.33, p = .04). CONCLUSIONS: This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.
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7. Kuo PH, Chuang LC, Su MH, Chen CH, Wu JY, Yen CJ, Wu YY, Liu SK, Chou MC, Chou WJ, Chiu YN, Tsai WC, Gau SS. {{Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population}}. {PLoS One};2015;10(9):e0138695.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA) studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD-albeit with very little consensus across studies. METHODS: A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations. RESULTS: Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT) with significant empirical gene-based p-values in OR2M4 (p = 3.4*10-5) and MNT (p = 0.0008). Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993) and NAALADL2 (rs3914502 and rs2222447) genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02), and GLIPR1/KRR1 gene regions (p = 0.015). Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways. CONCLUSIONS: We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.
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8. Laghi F, Federico F, Lonigro A, Levanto S, Ferraro M, Baumgartner E, Baiocco R. {{Peer and Teacher-Selected Peer Buddies for Adolescents With Autism Spectrum Disorders: The Role of Social, Emotional, and Mentalizing Abilities}}. {J Psychol};2015 (Sep 23):1-22.
This study examined mentalizing abilities, social behavior, and social impact of adolescents who expressed the willingness to become peer buddies for adolescents with Autism Spectrum Disorders, and adolescents selected by their teachers and peers. Twenty-seven teachers and 395 adolescents from public high schools completed mentalizing abilities, social status, behavioral, and peer buddy nomination measures. Findings suggest that social status and preference play a significant role in the selection of peer buddies by both teachers and classmates. Furthermore, more advanced Theory of Mind (ToM) abilities and the engagement in prosocial behaviors differentiated peers selected as buddies from other classmates. When compared with nonparticipating students, adolescents who expressed willingness to participate were more often girls, and were more prosocial. Agreement between teacher and peer nominations of best peer was moderate.
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9. Louwerse A, Eussen ML, Van der Ende J, de Nijs PF, Van Gool AR, Dekker LP, Verheij C, Verheij F, Verhulst FC, Greaves-Lord K. {{ASD Symptom Severity in Adolescence of Individuals Diagnosed with PDD-NOS in Childhood: Stability and the Relation with Psychiatric Comorbidity and Societal Participation}}. {J Autism Dev Disord};2015 (Sep 22)
The current 7-year follow-up study investigated: (1) the stability of ASD severity, and (2) associations of ASD severity in adolescence with (a) childhood and concurrent psychiatric comorbidity, and (b) concurrent societal functioning. The Autism Diagnostic Observation Schedule (ADOS) and the Diagnostic Interview Schedule for Children were administered in childhood (ages 6-12) and in adolescence (ages 12-20) to 72 individuals with a pervasive developmental disorder-not otherwise specified (PDD-NOS). ADOS calibrated severity scores showed a large stability (r = .51). Psychiatric comorbidity in childhood and adolescence were not associated with ASD severity in adolescence. Mental health care use (87 %) and special education needs were high (71 %). Reevaluation of ASD severity and psychiatric comorbidity later in life seem useful when PDD-NOS is diagnosed in childhood.
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10. Masi A, Lampit A, Glozier N, Hickie IB, Guastella AJ. {{Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis}}. {Transl Psychiatry};2015;5:e640.
Large placebo responses in many clinical trials limit our capacity to identify effective therapeutics. Although it is often assumed that core behaviors in children with autism spectrum disorders (ASDs) rarely remit spontaneously, there has been limited investigation of the size of the placebo response in relevant clinical trials. These trials also rely on caregiver and clinical observer reports as outcome measures. The objectives of this meta-analysis are to identify the pooled placebo response and the predictors of placebo response in pharmacological and dietary supplement treatment trials for participants with a diagnosis of ASD. Randomized controlled trials (RCTs) in pediatric ASD, conducted between 1980 and August 2014, were identified through a search of Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and clinicaltrials.gov. RCTs of at least 14 days duration, comparing the treatment response for an oral active agent and placebo using at least one of the common outcome measures, were included. Analysis of 25 data sets (1315 participants) revealed a moderate effect size for overall placebo response (Hedges’ g=0.45, 95% confidence interval (0.34-0.56), P<0.001). Five factors were associated with an increase in response to placebo, namely: an increased response to the active intervention; outcome ratings by clinicians (as compared with caregivers); trials of pharmacological and adjunctive interventions; and trials located in Iran. There is a clear need for the identification of objective measures of change in clinical trials for ASD, such as evaluation of biological activity or markers, and for consideration of how best to deal with placebo response effects in trial design and analyses.
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11. Mazefsky CA. {{Emotion Regulation and Emotional Distress in Autism Spectrum Disorder: Foundations and Considerations for Future Research}}. {J Autism Dev Disord};2015 (Sep 21)
Autism spectrum disorder (ASD) is often associated with emotional distress and psychiatric comorbidities. Atypical emotion regulation (ER) may underlie these accompanying features. This special issue of the Journal of Autism and Developmental Disorders presents a series of mechanistic and applied papers on ER and emotional experiences in ASD. Important concepts for future research are discussed, including how to conceptualize emotion dysregulation in ASD, the importance of capturing variability in emotion dysregulation in ASD studies, and the promise of intervention approaches that target ER impairments. This special issue highlights the growing emphasis on ER and emotional distress in ASD, and aims to encourage continued research in this area given the potential for this line of inquiry to lead to improved outcomes.
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12. McCormick C, Hepburn S, Young GS, Rogers SJ. {{Sensory symptoms in children with autism spectrum disorder, other developmental disorders and typical development: A longitudinal study}}. {Autism};2015 (Sep 22)
Sensory symptoms are prevalent in autism spectrum disorder but little is known about the early developmental patterns of these symptoms. This study examined the development of sensory symptoms and the relationship between sensory symptoms and adaptive functioning during early childhood. Three groups of children were followed across three time points from 2 to 8 years of age: autism spectrum disorder, developmental delay, and typical development. At each time point, parents filled out questionnaires regarding their child’s sensory symptoms and adaptive functioning. At the initial time point, parents of children with autism spectrum disorder reported more sensory symptoms in their children than parents in the typical development group. Parents in the autism spectrum disorder group reported more sensory symptoms than parents in the developmental delay group within smell, taste, and auditory domains. While the typical development group decreased in reported sensory symptoms across the study period, the clinical groups demonstrated no significant change across assessment points. Sensory symptoms for all groups were not independently predictive of adaptive functioning when verbal mental age was also included in the model. The young age range at the initial assessment and pattern of results suggest that sensory symptoms are present early in the etiology of autism spectrum disorder and other developmental disorders and remain stable over time.
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13. Mosca-Boidron AL, Gueneau L, Huguet G, Goldenberg A, Henry C, Gigot N, Pallesi-Pocachard E, Falace A, Duplomb L, Thevenon J, Duffourd Y, St-Onge J, Chambon P, Riviere JB, Thauvin-Robinet C, Callier P, Marle N, Payet M, Ragon C, Goubran Botros H, Buratti J, Calderari S, Dumas G, Delorme R, Lagarde N, Pinoit JM, Rosier A, Masurel-Paulet A, Cardoso C, Mugneret F, Saugier-Veber P, Campion D, Faivre L, Bourgeron T. {{A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability}}. {Eur J Hum Genet};2015 (Sep 23)
Semaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We then used Sanger sequencing to search for deleterious variants affecting SEMA5A in 142 patients with ASD. We also identified two independent heterozygous variants located in a conserved functional domain of the protein. Both variants were maternally inherited and predicted as deleterious. Our genetic screens identified the first case of a de novo SEMA5A microdeletion in a patient with ASD and ID. Although our study alone cannot formally associate SEMA5A with susceptibility to ASD, it provides additional evidence that Semaphorin dysfunction could lead to ASD and ID. Further studies on Semaphorins are warranted to better understand the role of this family of genes in susceptibility to neurodevelopmental disorders.European Journal of Human Genetics advance online publication, 23 September 2015; doi:10.1038/ejhg.2015.211.
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14. Navot N, Jorgenson AG, Vander Stoep A, Toth K, Webb SJ. {{Family planning and family vision in mothers after diagnosis of a child with autism spectrum disorder}}. {Autism};2015 (Sep 22)
The diagnosis of a child with autism has short- and long-term impacts on family functioning. With early diagnosis, the diagnostic process is likely to co-occur with family planning decisions, yet little is known about how parents navigate this process. This study explores family planning decision making process among mothers of young children with autism spectrum disorder in the United States, by understanding the transformation in family vision before and after the diagnosis. A total of 22 mothers of first born children, diagnosed with autism between 2 and 4 years of age, were interviewed about family vision prior to and after their child’s diagnosis. Grounded Theory method was used for data analysis. Findings indicated that coherence of early family vision, maternal cognitive flexibility, and maternal responses to diagnosis were highly influential in future family planning decisions. The decision to have additional children reflected a high level of adaptability built upon a solid internalized family model and a flexible approach to life. Decision to stop childrearing reflected a relatively less coherent family model and more rigid cognitive style followed by ongoing hardship managing life after the diagnosis. This report may be useful for health-care providers in enhancing therapeutic alliance and guiding family planning counseling.
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15. Percinel I, Yazici KU. {{The Use of Aripiprazole in Young Children with Autism Spectrum Disorders: The Treatment and 16 Week Follow-Up of a 23-Month-old Male Patient}}. {J Child Adolesc Psychopharmacol};2015 (Sep 23)
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16. Schmunk G, Boubion BJ, Smith IF, Parker I, Gargus JJ. {{Shared functional defect in IPR-mediated calcium signaling in diverse monogenic autism syndromes}}. {Transl Psychiatry};2015;5:e643.
Autism spectrum disorder (ASD) affects 2% of children, and is characterized by impaired social and communication skills together with repetitive, stereotypic behavior. The pathophysiology of ASD is complex due to genetic and environmental heterogeneity, complicating the development of therapies and making diagnosis challenging. Growing genetic evidence supports a role of disrupted Ca2+ signaling in ASD. Here, we report that patient-derived fibroblasts from three monogenic models of ASD-fragile X and tuberous sclerosis TSC1 and TSC2 syndromes-display depressed Ca2+ release through inositol trisphosphate receptors (IP3Rs). This was apparent in Ca2+ signals evoked by G protein-coupled receptors and by photoreleased IP3 at the levels of both global and local elementary Ca2+ events, suggesting fundamental defects in IP3R channel activity in ASD. Given the ubiquitous involvement of IP3R-mediated Ca2+ signaling in neuronal excitability, synaptic plasticity, gene expression and neurodevelopment, we propose dysregulated IP3R signaling as a nexus where genes altered in ASD converge to exert their deleterious effect. These findings highlight potential pharmaceutical targets, and identify Ca2+ screening in skin fibroblasts as a promising technique for early detection of individuals susceptible to ASD.
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17. Sullivan JM, Badimon A, Schaefer U, Ayata P, Gray J, Chung CW, von Schimmelmann M, Zhang F, Garton N, Smithers N, Lewis H, Tarakhovsky A, Prinjha RK, Schaefer A. {{Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice}}. {J Exp Med};2015 (Sep 21)
Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain-containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858-affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.
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18. Tang L, Bie B. {{The stigma of autism in China: an analysis of newspaper portrayals of autism between 2003 and 2012}}. {Health Commun};2015 (Sep 23):1-8.
Autism is a highly stigmatized developmental disability in many societies, and the media are major contributors to such stigma. Presented here is the first systematic analysis of Chinese newspapers’ coverage of autism for stigma-causing content. More specifically, this analysis examines the age of autistic people reported, the image of autistic people, and the use of stigma cues (in terms of peril, mark, and shame) and challenge cues (in terms of personification, hope, and fight) in five leading newspapers in China between 2003 and 2012. It finds that while the reportage of autism increases over time, which might contribute to the public’s heightened awareness of the condition, such reportage is often biased. The most common stereotypes about autism in Chinese newspapers are autistic people as children, as patients, or as savants. The most often-used challenge cues are personification and hope, but their uses significantly decrease in percentage from 2003 to 2012. The most often used stigma cues are peril and mark. The use of the shame cue is relatively less frequent, but it increases significantly over the 10-year period. Theoretically, this article provides an application of stigma communication theory in a non-Western context. Practically, it not only contributes to the current knowledge about media representation of autism in China, but also suggests that it is important for media agencies and health care professionals to promote media guidelines and train health journalists for reporting disability issues in a nonstigmatizing way.
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19. Telias M, Mayshar Y, Amit A, Ben-Yosef D. {{Molecular mechanisms regulating impaired neurogenesis of fragile X syndrome human embryonic stem cells}}. {Stem Cells Dev};2015 (Sep 22)
Fragile X Syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1gene and its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually down-regulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally-regulated FMR1 inactivation when subjected to in-vitro neural differentiation. In this study, we used this in-vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the ‘GSK3beta theory of FXS’ for the first time in a human-based model. We found no evidence for a pathological increase in GSK3beta levels upon cellular loss of FMRP, in contrast to what was found in the brain of FMR1 knock-out mice. Our study adds novel data on potential downstream targets of FMRP, and highlights the importance of the FX-hESCs in-vitro neural differentiation system.
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20. Yamasue H. {{Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders}}. {Psychiatry Clin Neurosci};2015 (Sep 22)
Oxytocin is a potential therapeutic for the core symptoms of autism spectrum disorder (ASD), which is currently untreatable with pharmacotherapy. Previous clinical trials of a single dose of oxytocin have consistently reported significantly positive effects on various experimental measures associated with the core symptoms of ASD. These studies used various experimental measures as surrogate endpoints of the trials. However, to date, randomized clinical trials of continual administration of oxytocin have failed to reveal significant positive effects on clinically meaningful endpoints, such as how those with ASD interact during interpersonal interactions.. This article reviews both the negative and positive effects of oxytocin on the core symptoms of ASD and their surrogate markers. Some unresolved and critical issues on the development of oxytocin as a new therapeutic have been extracted: optimization of dose, duration of oxytocin treatment, and the development of objective and reliable measurements of clinically meaningful endpoints for the core symptoms of ASD. Furthermore, optimization to intranasal delivery system and careful consideration of how individuals respond differently to treatments should be addressed in future studies.
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21. Yen P. {{ASD and VSD Flow Dynamics and Anesthetic Management}}. {Anesth Prog};2015 (Fall);62(3):125-130.
Atrial septal defects and ventricular septal defects are often encountered in patients presenting for treatment under anesthesia. The flow mechanisms for both defects are predominantly left to right shunting prior to long-term maladaptive changes that may occur. Close examination of the shunt dynamics demonstrates a minor right to left shunt that occurs as well. The article discusses these dynamics and the impact on an anesthetic plan.
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22. Yin A, Qiu Y, Beijia, Song T, Yu Y, Alberts I, Zhong M. {{Retraction notice to « The developmental pattern of the RAS/RAF/Erk1/2 pathway in the BTBR autism mouse model » [Int. J. Dev. Neurosci. 39 (2014) 2-8]}}. {Int J Dev Neurosci};2015 (Aug);44:102.
