1. {{Autism}}. {Nurs Stand};2014 (Mar 12);28(28):19.
Essential facts Autism is a lifelong developmental disability that affects how individuals communicate with and relate to other people and the world around them. Autism is known as a spectrum condition because the symptoms vary from person to person and range from mild to severe. According to the National Autistic Society, autism affects around one in 100 people.
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2. Amoros E, Tzvetkovitch A. {{La médiation corporelle par l’eau auprès d’enfants autistes.}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):29-30.
Nursing practices with autistic children in child psychiatry can be approached through the experience of a body-centred therapy group. The support favours creativity, holding, vocal interaction, team work around the clinical aspect, multi-disciplinary perspectives and exchanges with the parents. An example of a workshop in a swimming pool in which holding is particularly important.
3. Andersen S, Laurberg P, Wu C, Olsen J. {{Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study}}. {BJOG};2014 (Mar 10)
OBJECTIVE: To examine the association between maternal hyper- and hypothyroidism and the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in the child. DESIGN: A population-based cohort study. SETTING: Singletons liveborn in Denmark between 1991 and 2004. POPULATION: A total of 857 014 singletons alive and living in Denmark at the age of 3 years. METHODS: Information on the diagnosis and/or treatment of maternal thyroid disease and the neurodevelopmental disorders ADHD and ASD in the child was obtained from Danish nationwide registers. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence interval (95% CI) for risk of ADHD and ASD in children born to mothers with thyroid dysfunction, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: ADHD and ASD in the child. RESULTS: Altogether, 30 295 singletons (3.5%) were born to mothers with thyroid dysfunction. Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05-1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14-1.59). No significant association was seen for maternal diagnosis and treatment prior to the birth of the child. CONCLUSIONS: Children born to mothers diagnosed and treated for the first time for thyroid dysfunction after their birth may have been exposed to abnormal levels of maternal thyroid hormone already present during the pregnancy, and this untreated condition could increase the risk of specific neurodevelopmental disorders in the child.
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4. Ashburner JK, Rodger SA, Ziviani JM, Hinder EA. {{Comment on: ‘An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial’ by Schaaf et al. (2013)}}. {J Autism Dev Disord};2014 (Mar 8)
The purpose of this letter to the editor is to comment on a recently published paper in the Journal of Autism and Developmental Disorders, ‘An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial’ by Schaaf et al. (2013). The authors are commended for undertaking a randomised clinical trial (RCT) examining the efficacy of occupational therapy using sensory integration (OT/SI). The study complies with many of the recommended standards of RCT’s including: (a) detailed eligibility criteria, (b) well-matched experimental and control groups, (c) use of gold-standard instruments to measure the symptoms of autism spectrum disorder, (d) the use of functionally relevant outcome measures, (e) fidelity checking, and (f) manualization of the intervention. Additional aspects of rigour that could be considered in subsequent research include: (a) independent blinded measure of observational outcomes, (b) treatment and control interventions of equivalent dose, (c) public access to the manualized treatment guidelines, and (d) the use of a comparison occupational therapy intervention to address the same goals as the OT/SI intervention.
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5. Becker JA, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL. {{Autistic-Like Syndrome in mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity}}. {Neuropsychopharmacology};2014 (Mar 12)
The etiology of Autism Spectrum Disorders (ASDs) remains largely unknown. Identifying vulnerability genes for autism represents a major challenge in the field, and allows the development of animal models for translational research. Mice lacking the mu opioid receptor gene (Oprm1-/-) were recently proposed as a monogenic mouse model of autism, based on severe deficits in social behavior and communication skills. We confirm this hypothesis by showing that adult Oprm1-/- animals recapitulate core and multiple comorbid behavioral symptoms of autism, and also display anatomical, neurochemical and genetic landmarks of the disease. Chronic facilitation of mGluR4 signaling, which we identified as a novel pharmacological target in ASDs in these mice, was more efficient in alleviating behavioral deficits than the reference molecule risperidone. Altogether, our data provide first evidence that disrupted mu opioid receptor signalling is sufficient to trigger a comprehensive autistic syndrome, maybe through blunted social reward processes, and this mouse model opens promising avenues for therapeutic innovation.Neuropsychopharmacology accepted article preview online, 12 March 2014; doi:10.1038/npp.2014.59.
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6. Camacho J, Jones K, Miller E, Ariza J, Noctor S, Van de Water J, Martinez-Cerdeno V. {{Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autism-like stereotypical behaviors in offspring mice}}. {Behav Brain Res};2014 (Mar 5)
Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypic behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.
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7. Cambier G, Machet L, Assouline B. {{Les troubles du spectre autistique}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):12-14.
Autism is an early onset neurodevelopmental syndrome, encompassing heterogeneous clinical situations and with disabling consequences for cognitive, social and emotional development. The condition is today considered to be a major public health issue.
8. Charvolin H. {{Regards sur l’autisme}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):15-17.
Over the last few years, the perception of autistic disorders, the theoretical references studied, diagnostic, assessment, care, educational and pedagogical practices have been transformed. Looking back at these developments helps to clarify current debates on autism and to resituate them in a historical perspective.
9. Coben R, Mohammad-Rezazadeh I, Cannon RL. {{Using quantitative and analytic EEG methods in the understanding of connectivity in autism spectrum disorders: a theory of mixed over- and under-connectivity}}. {Front Hum Neurosci};2014;8:45.
Neuroimaging technologies and research has shown that autism is largely a disorder of neuronal connectivity. While advanced work is being done with fMRI, MRI-DTI, SPECT and other forms of structural and functional connectivity analyses, the use of EEG for these purposes is of additional great utility. Cantor et al. (1986) were the first to examine the utility of pairwise coherence measures for depicting connectivity impairments in autism. Since that time research has shown a combination of mixed over and under-connectivity that is at the heart of the primary symptoms of this multifaceted disorder. Nevertheless, there is reason to believe that these simplistic pairwise measurements under represent the true and quite complicated picture of connectivity anomalies in these persons. We have presented three different forms of multivariate connectivity analysis with increasing levels of sophistication (including one based on principle components analysis, sLORETA source coherence, and Granger causality) to present a hypothesis that more advanced statistical approaches to EEG coherence analysis may provide more detailed and accurate information than pairwise measurements. A single case study is examined with findings from MR-DTI, pairwise and coherence and these three forms of multivariate coherence analysis. In this case pairwise coherences did not resemble structural connectivity, whereas multivariate measures did. The possible advantages and disadvantages of different techniques are discussed. Future work in this area will be important to determine the validity and utility of these techniques.
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10. Coron G. {{Autisme et protection de l’enfance}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):31-33.
The fostering of an autistic child deemed to be a child at risk leads one to question one’s professional practices. In a children’s home, an approach guided by psychoanalysis can recognise the benefits of behavioural or cognitive approaches. The aim of the professional’s particular educational position is therefore to construct a relationship with each child.
11. Curtin C, Jojic M, Bandini LG. {{Obesity in children with autism spectrum disorder}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):93-103.
Research suggests that the prevalence of obesity in children with autism spectrum disorder (ASD) is at least as high as that seen in typically developing children. Many of the risk factors for children with ASD are likely the same as for typically developing children, especially within the context of today’s obesogenic environment. The particular needs and challenges that this population faces, however, may render them more susceptible to the adverse effects of typical risk factors, and they may also be vulnerable to additional risk factors not shared by children in the general population, including psychopharmacological treatment, genetics, disordered sleep, atypical eating patterns, and challenges for engaging in sufficient physical activity. For individuals with ASD, obesity and its sequelae potentially represent a significant threat to independent living, self-care, quality of life, and overall health.
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12. Daniel S. {{Communiquer avec l’enfant autiste}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):24-25.
One of the basic aspects to be taken into account in the treatment of an autistic child is their impaired communication. Alternative or augmentative communication can take several forms: pictograms, gestural codes, writing. Speech therapists adapt their work to the child’s disorders.
13. De Felice C, Signorini C, Leoncini S, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J. {{[Oxidative stress and Rett syndrome.]}}. {Minerva Pediatr};2014 (Feb);66(1):41-62.
The oxidative stress (OS) hypothesis is able to explain several features of Rett syndrome (RTT), a pervasive development disorder almost exclusively affecting females mainly caused by a mutation in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. In particular, the generation of an OS imbalance is related to MeCP2 gene mutation type, as well as natural history, clinical heterogeneity of the disease, and is compatible with the potential reversibility of the disease observed in the RTT animal models. In addition, our findings indicate the importance of blood as a suitable biological fluid for detecting markers of central nervous system oxidative damage in RTT and underline the key role of interaction between organic chemists, OS biochemists, and clinicians in revealing potential new markers of the disease and identifying potential new targets and interventional strategies aimed at improving the quality of life of these patients, affected by a so far incurable disease. Further efforts in the near future are needed in order to dissect the « black box » of the molecular events likely linking the MeCP2 gene mutation to OS derangement and subsequent disease expression.
14. Gabriele S, Sacco R, Persico AM. {{Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis}}. {Eur Neuropsychopharmacol};2014 (Feb 19)
Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10-12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10-7]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.
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15. Gold WA, Williamson SL, Kaur S, Hargreaves IP, Land JM, Pelka GJ, Tam PP, Christodoulou J. {{Mitochondrial dysfunction in skeletal muscle of a mouse model of Rett Syndrome (RTT): Implications for the disease phenotype}}. {Mitochondrion};2014 (Mar 5)
Rett syndrome (RTT) is a severe neurodevelopmental disorder, predominantly caused by mutations in the X-linked Methyl-CpG-binding protein 2 (MECP2) gene. Patients present with numerous functional deficits including intellectual disability and abnormalities of movement. Clinical and biochemical features may overlap with those seen in patients with primary mitochondrial respiratory chain disorders. In the late stages of the disorder, patients suffer from motor deterioration and usually require assisted mobility. Using a mouse model of RTT (Mecp2tm1Tam), we studied mitochondrial function in the hind-limb skeletal muscle of these mice. We identified a reduction in cytochrome c oxidase subunit I (MTCO1) at both the transcript and protein level, in accordance with our previous findings in RTT patient brain studies. Mitochondrial respiratory chain (MRC) enzyme activity of complexes II+III (COII+III) and complex IV (COIV), and glutathione (GSH) levels were significantly reduced in symptomatic mice, but not in the pre-symptomatic mice. Our findings suggest that mitochondrial abnormalities in skeletal muscle may contribute to the progressive deterioration in mobility in RTT through the accumulation of free radicals, as evidenced by the decrease in reduced glutathione (GSH). We hypothesise that a diminution in GSH leads to an accumulation of free radicals and an increase in oxidative stress. This may impact on respiratory chain function and contribute in part to the progressive neurological and motor deterioration seen in the Mecp2-mutant mouse. Treatment strategies aimed at restoring cellular GSH levels may prove to be a novel target area to consider in future approaches to RTT therapies.
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16. Hanley GP, Jin CS, Vanselow NR, Hanratty LA. {{Producing meaningful improvements in problem behavior of children with autism via synthesized analyses and treatments}}. {J Appl Behav Anal};2014 (Feb 25)
Problem behaviors like self-injury, aggression, or disruption will likely require intervention at some point in the life of a person diagnosed with autism. Behavioral intervention has been proven to be effective for addressing these problems, especially when a functional assessment is conducted. Comprehensive treatment for problem behavior is, however, often fractured across studies, resulting in a dearth of studies that show socially validated improvements in these problem behaviors or illustrate the assessment and treatment process from start to finish. In this article, we describe an effective, comprehensive, and parent-validated functional assessment and treatment process for the severe problem behaviors of 3 children with autism. After an 8- to 14-week outpatient clinic consultation, no problem behavior was observed at the clinic and in the home. Furthermore, behavior that did not occur during baseline (e.g., functional communication, delay and denial tolerance, and compliance with instructions) occurred with regularity.
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17. Hazen EP, Stornelli JL, O’Rourke JA, Koesterer K, McDougle CJ. {{Sensory symptoms in autism spectrum disorders}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):112-124.
The aim of this review is to summarize the recent literature regarding abnormalities in sensory functioning in individuals with autism spectrum disorder (ASD), including evidence regarding the neurobiological basis of these symptoms, their clinical correlates, and their treatment. Abnormalities in responses to sensory stimuli are highly prevalent in individuals with ASD. The underlying neurobiology of these symptoms is unclear, but several theories have been proposed linking possible etiologies of sensory dysfunction with known abnormalities in brain structure and function that are associated with ASD. In addition to the distress that sensory symptoms can cause patients and caregivers, these phenomena have been correlated with several other problematic symptoms and behaviors associated with ASD, including restrictive and repetitive behavior, self-injurious behavior, anxiety, inattention, and gastrointestinal complaints. It is unclear whether these correlations are causative in nature or whether they are due to shared underlying pathophysiology. The best-known treatments for sensory symptoms in ASD involve a program of occupational therapy that is specifically tailored to the needs of the individual and that may include sensory integration therapy, a sensory diet, and environmental modifications. While some empirical evidence supports these treatments, more research is needed to evaluate their efficacy, and other means of alleviating these symptoms, including possible psychopharmacological interventions, need to be explored. Additional research into the sensory symptoms associated with ASD has the potential to shed more light on the nature and pathophysiology of these disorders and to open new avenues of effective treatments.
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18. Hom CL, Touchette P, Nguyen V, Fernandez G, Tournay A, Plon L, Himber P, Lott IT. {{The relationship between living arrangement and adherence to antiepileptic medications among individuals with developmental disabilities}}. {J Intellect Disabil Res};2014 (Mar 11)
BACKGROUND: Non-adherence to antiepileptic drugs (AEDs) is associated with considerable morbidity and mortality in the general population but little is known about adherence in individuals with intellectual disability (ID). METHOD: Using the records of a closed pharmacy billing system over a 30 month period, we examined the medication non-adherence rates for AEDs among 793 individuals with ID. We calculated the medication possession ratio (number of days each participant was in possession of an AED), and defined non-adherence as 25% or more of the exposure days without the possession of an AED. All participants studied had filled prescriptions for AEDs spanning at least 6 months. RESULTS: Controlling for age and gender, we found non-adherence rates varied by living arrangement. Compared with those living in group homes, individuals with ID living in family homes or in semi-independent settings were significantly less adherent to AEDs (P < 0.0003). CONCLUSION: Non-adherence to AEDs is a potential medical risk for individuals with ID that is significantly impacted by the type of community living arrangement.
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19. Hsiao EY. {{Gastrointestinal issues in autism spectrum disorder}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):104-111.
While autism spectrum disorder (ASD) is characterized by communication impairments, social abnormalities, and stereotypic behaviors, several medical comorbidities are observed in autistic individuals. Of these, gastrointestinal (GI) abnormalities are of particular interest given their reported prevalence and correlation with the severity of core autism-related behavioral abnormalities. This review discusses the GI pathologies seen in ASD individuals and the association of particular GI conditions with known genetic and environmental risk factors for autism. It further addresses how GI abnormalities can affect the neuropathological and behavioral features of ASD, as well as the development of autism-related endophenotypes such as immune dysregulation, hyperserotonemia, and metabolic dysfunction. Finally, it presents emerging evidence for a gut-brain connection in autism, wherein GI dysfunction may contribute to the pathogenesis or severity of ASD symptoms.
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20. Huss E, Sintzel F. {{Prise en charge de l’autisme, aspects ambulatoires et institutionnels}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):20-23.
The treatment of children suffering from autism must start early and be adapted to their development. After a multi-disciplinary assessment, it encompasses three areas: therapeutic, educational and pedagogical. Provided in an outpatient clinic or day hospital, it seeks to involve the different healthcare players and the families, to offer personalised support.
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21. Jaramillo TC, Liu S, Pettersen A, Birnbaum SG, Powell CM. {{Autism-Related Neuroligin-3 Mutation Alters Social Behavior and Spatial Learning}}. {Autism Res};2014 (Mar 11)
Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Sudhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Sudhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin-3 R451C point mutant knock-in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism-relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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22. Koehler AD, Fagnano M, Montes G, Halterman JS. {{Elevated Burden for Caregivers of Children with Persistent Asthma and a Developmental Disability}}. {Matern Child Health J};2014 (Mar 12)
To evaluate how having a child with both persistent asthma and a developmental disability (DD) affects caregiver burden and quality of life (QOL). 3-10 year old children with persistent asthma in urban Rochester, NY. Cross-sectional baseline survey (2006-2009). Parent report of autism spectrum disorder or other behavioral disorder requiring medication. Caregiver burden and QOL as measured by scores on previously validated depression, parenting confidence, and asthma-related QOL scales as well as an assessment of competing demands on the caregiver. Bivariate and multivariate regression analyses controlling for caregiver age, education, marital status, race, ethnicity, and child asthma symptom severity. We enrolled 530 children as part of a larger study (response rate: 74; 63 % Black, 73 % Medicaid). Of this sample, 70 children (13 %) were defined as having a DD. There were no differences in asthma symptom severity between children with and without a DD diagnosis. However, even after adjusting for potential confounders, caregivers of children with a DD reported worse scores on the depression (p = .003), parenting confidence (p < .001), and competing demands (p = .013) scales and worse asthma-related QOL (p = .035) compared to caregivers of typically developing children with asthma. Despite having similar asthma symptom severity, caregivers of children with both persistent asthma and a DD diagnosis report more burden and lower QOL compared to that of caregivers of typically developing children and persistent asthma. Further attention to this subgroup is needed to promote optimal support for caregivers.
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23. Labruyere N, Sonie S. {{Autisme et neuropsychologie}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):18-19.
In neuropsychology, the deficiencies associated with autism are generally classed into three areas: social cognition, executive functioning and central coherence. Autistic people however have singular capacities, notably with regard to their perceptual processing focused on details.
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24. Li X, Sjostedt C, Sundquist K, Zoller B, Sundquist J. {{Neighborhood deprivation and childhood autism: A nationwide study from Sweden}}. {J Psychiatr Res};2014 (Feb 26)
OBJECTIVE: To examine whether there is an association between neighborhood deprivation and childhood autism, after accounting for family- and individual-level sociodemographic characteristics. METHODS: An open cohort of all children aged 2-11 years was followed between January 1, 2000 and December 31, 2010. Childhood residential locations were geocoded and classified according to neighborhood deprivation (an index of low education, low income, unemployment, and receipt of welfare assistance). Data were analyzed by multilevel logistic regression, with family- and individual-level characteristics at the first level and level of neighborhood deprivation at the second level. RESULTS: During the study period, among a total of 643,456 children, 1699 (0.3%) were diagnosed with childhood autism. Age-standardized cumulative incidence, defined as first registration for childhood autism during the study period, increased with increasing level of neighborhood deprivation. In the study population, 2.2 per 1000 and 3.6 per 1000 children in the least and most deprived neighborhoods, respectively, were diagnosed with childhood autism. Incidence of childhood autism increased with increasing neighborhood-level deprivation across all family and individual-level sociodemographic categories. The odds ratio (OR) for childhood autism for those living in high-deprivation neighborhoods versus those living in low-deprivation neighborhoods was 1.59 (95% confidence interval = 1.35-1.88). High neighborhood deprivation remained significantly associated with odds of childhood autism after adjustment for family- and individual-level sociodemographic characteristics (OR = 1.28, 95% confidence interval = 1.07-1.53, P = 0.007). CONCLUSIONS: This study is the largest so far on potential neighborhood influences on childhood autism. Our results show that neighborhood deprivation is associated with childhood autism, independently of family- and individual-level sociodemographic characteristics.
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25. Limeres-Posse J, Castano-Novoa P, Abeleira-Pazos M, Ramos-Barbosa I. {{Behavioural aspects of patients with Autism Spectrum Disorders (ASD) that affect their dental management}}. {Med Oral Patol Oral Cir Bucal};2014 (Mar 8)
Dental treatment in patients with Autism Spectrum Disorders (ASD) can be complicated due to the presence of behavioral alterations. In this group, there are no specific behavioral profiles that allow dentist to anticipate the attitude that a patient will show during a visit. Thus, behavioral attitudes have been described that vary from total permissiveness and collaboration during even bloody procedures, to the absolute impossibility in conducting a simple oral examination. There is no effective behavioral management technique for all ASD patients. Prior information, such as the type of ASD or the presence of certain concurrent pathologies can help predict the patient’s likely behavior. Therefore, gathering all the information in a preliminary interview with the parents/guardians of the patient is recommended. Knowing these factors will allow individualized behavioral management strategies to be designed and facilitates the planning of dental treatment.
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26. Liyanage VR, Rastegar M. {{Rett Syndrome and MeCP2}}. {Neuromolecular Med};2014 (Mar 11)
Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.
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27. Lokody I. {{Epigenetics: Mechanisms underlying fragile X syndrome}}. {Nat Rev Genet};2014 (Mar 11)
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28. Mazefsky CA, Borue X, Day TN, Minshew NJ. {{Emotion Regulation Patterns in Adolescents With High-Functioning Autism Spectrum Disorder: Comparison to Typically Developing Adolescents and Association With Psychiatric Symptoms}}. {Autism Res};2014 (Mar 7)
Autism spectrum disorder (ASD) is often associated with poor emotional control and psychopathology, such as anxiety and depression; however, little is known about the underlying mechanisms. Emotion regulation (ER) is a potential contributing factor, but there has been limited research on ER and its role in comorbid psychopathology in ASD. In this study, we compared self-reported ER with self- and parent reports of psychopathology in 25 high-functioning adolescents with ASD and 23 age- and Intelligence Quotient (IQ)-matched typically developing controls. Contrary to expectations, both groups reported similar levels of adaptive, voluntary forms of ER (problem solving, acceptance, etc.). However, the ASD group reported significantly greater use of involuntary forms of ER that are typically maladaptive, including remaining focused on the stressor (e.g. rumination and emotional arousal) and shutting down (e.g. emotional numbing and being unable to think or act). Associations between ER and psychopathology were generally more robust using self-report rather than parent report. For both groups, greater endorsement of involuntary ER strategies was associated with higher ratings of psychopathology, whereas voluntary ER strategies focused on changing or adapting to the situation were significantly associated with lower levels of psychopathology. The magnitude and direction of association between ER types and psychopathology were similar for measures of depression and anxiety. These findings can help guide the development of psychosocial treatments targeting dysfunctional ER in adolescents with ASD. Interventions focused on ER as a transdiagnostic process may be a more robust method to improve emotional control and decrease emotional distress in ASD than disorder-specific interventions. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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29. Ohba C, Nabatame S, Iijima Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Tanaka F, Ozono K, Saitsu H, Matsumoto N. {{De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain}}. {J Hum Genet};2014 (Mar 13)
Rett syndrome (RTT) is a neurodevelopmental disorder mostly caused by MECP2 mutations. We identified a de novo WDR45 mutation, which caused a subtype of neurodegeneration with brain iron accumulation, in a patient showing clinically typical RTT. The mutation (c.830+1G>A) led to aberrant splicing in lymphoblastoid cells. Sequential brain magnetic resonance imaging demonstrated that iron deposition in the globus pallidus and the substantia nigra was observed as early as at 11 years of age. Because the patient showed four of the main RTT diagnostic criteria, WDR45 should be investigated in patients with RTT without MECP2 mutations.Journal of Human Genetics advance online publication, 13 March 2014; doi:10.1038/jhg.2014.18.
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30. Paul JD. {{The Vacuum of the Mind: A Self-Report on the Phenomenology of Autistic, Obsessive-Compulsive, and Depressive Comorbidity}}. {Schizophr Bull};2014 (Mar 13)
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31. Perron L. {{L’art-therapie pour accompagner la personne autiste}}. {Soins Pediatr Pueric};2014 (Jan-Feb)(276):36-38.
Art therapy, the result of a psychodynamic approach with mediation, can help autistic children and adults to express themselves and communicate. A one-to-one session gives rise to a therapeutic encounter which uses both analytical and educationaI approaches.
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32. Pinder-Amaker S. {{Identifying the unmet needs of college students on the autism spectrum}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):125-137.
The number of students entering college with high-functioning autism spectrum disorders (ASDs) is expected to surge in coming years. The diagnostic features and psychiatric risks of ASD, coupled with the transitions and stresses that define college life, present extraordinary challenges for these students, their parents, and institutions of higher education. This article applies a bioecological framework for conceptualizing the systemic strengths and barriers at the secondary and postsecondary levels of education in supporting students with ASD. This theoretical orientation is used to illustrate the importance of offering services and programs in a more coordinated and fluid manner within and between systems to support students more effectively. Evidence-based programs, practices, and interventions associated with successful academic and mental health outcomes for youth and young adults with ASD, as well as for college students with mental health and other challenges, are reviewed for their applicability to the target population. It is proposed that more fluid transitions and improved mental health and academic outcomes for college students with ASD can be achieved by integrating elements from secondary and postsecondary educational systems and also from existing, effective approaches with youth and young adults. Building upon the disjointed, but promising, evidence from youth, young adult, and college mental health literatures, recommendations for developing more effective transition plans for students with ASD are proposed.
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33. Politte LC, Henry CA, McDougle CJ. {{Psychopharmacological interventions in autism spectrum disorder}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):76-92.
Learning Objectives: After participating in this educational activity, the physician should be better able to1. Prescribe the appropriate psychotropic medication to treat symptoms of ASD.2. Identify the side effects of the psychotropic medications used to treat ASD.Autism spectrum disorders (ASDs) are characterized by core deficits in social communication and language, and restrictive and repetitive behaviors that cause significant functional impairment and distress for affected individuals and their caregivers. The increasing prevalence of ASD, most recently estimated as 1 in 88 children, presents an ever-increasing burden on families, schools, medical systems, and society at large. Individuals with ASD commonly present for treatment of associated emotional and behavioral disturbances that include anxiety, symptoms of ADHD, compulsions and other repetitive behaviors, mood lability, irritability, aggression, and sleep disturbance. Psychotropic medications are widely utilized in alleviating these symptoms, though rigorous clinical trials in ASD are lacking for most areas of impairment. Strong evidence from randomized, placebo-controlled trials supports the use of atypical antipsychotics, particularly risperidone and aripiprazole, for managing severe irritability and aggression in ASD. Serotonin reuptake inhibitors are commonly used to treat anxiety and compulsions, though reports of efficacy in the literature are mixed, and behavioral side effects in children are common. Minimal evidence supports the utility of anticonvulsants and traditional mood stabilizers in managing mood lability and aggression. Stimulant and nonstimulant ADHD medications can be effective for reducing hyperactivity, inattention, and impulsivity, though to a lesser degree than in ADHD populations without ASD and with greater risk of adverse effects. Psychopharmacological interventions in development for core symptoms of autism include those that target the glutamatergic and GABAergic neurotransmitter systems and the neuropeptide oxytocin. Further research is needed to establish evidence-based interventions in ASD populations.
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34. Rzhetsky A, Bagley SC, Wang K, Lyttle CS, Cook EH, Jr., Altman RB, Gibbons RD. {{Environmental and state-level regulatory factors affect the incidence of autism and intellectual disability}}. {PLoS Comput Biol};2014 (Mar);10(3):e1003518.
Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins. Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males (an increase in ASD incidence by 283% for every percent increase in incidence of malformations, 95% CI: [91%, 576%], p<6×10-5). Such congenital malformations were barely significant for ID (94% increase, 95% CI: [1%, 250%], p = 0.0384). Other congenital malformations in males (excluding those affecting the reproductive system) appeared to significantly affect both phenotypes: 31.8% ASD rate increase (CI: [12%, 52%], p<6×10-5), and 43% ID rate increase (CI: [23%, 67%], p<6×10-5). Furthermore, the state-mandated rigor of diagnosis of ASD by a pediatrician or clinician for consideration in the special education system was predictive of a considerable decrease in ASD and ID incidence rates (98.6%, CI: [28%, 99.99%], p = 0.02475 and 99% CI: [68%, 99.99%], p = 0.00637 respectively). Thus, the observed spatial variability of both ID and ASD rates is associated with environmental and state-level regulatory factors; the magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives. The estimated county-level random effects exhibited marked spatial clustering, strongly indicating existence of as yet unidentified localized factors driving apparent disease incidence. Finally, we found that the rates of ASD and ID at the county level were weakly but significantly correlated (Pearson product-moment correlation 0.0589, p = 0.00101), while for females the correlation was much stronger (0.197, p<2.26×10-16).
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35. Schuwerk T, Vuori M, Sodian B. {{Implicit and explicit Theory of Mind reasoning in autism spectrum disorders: The impact of experience}}. {Autism};2014 (Mar 13)
This study aimed to investigate the relationship between explicit and implicit forms of Theory of Mind reasoning and to test the influence of experience on implicit Theory of Mind reasoning in individuals with autism spectrum disorders and in neurotypical adults. Results from two standard explicit Theory of Mind tasks are mixed: Individuals with autism spectrum disorders did not differ from neurotypical adults in their performance in the Strange Stories Test, but scored significantly lower on the Reading the Mind in the Eyes Test. Furthermore, in an implicit false-belief task, individuals with autism spectrum disorders differed from neurotypical adults in false belief-congruent anticipatory looking. However, this group difference disappeared by (1) providing participants with the outcome of a false belief-based action and (2) subsequently repeating this test trial. Although the tendency to fixate the false belief-congruent location significantly increased from the first to the second test trial in individuals with autism spectrum disorders, it differed in neither test trial from chance. These findings support the notion of an implicit Theory of Mind deficit in autism spectrum disorders, but give rise to the idea that anticipatory looking behaviors in autism spectrum disorders may be affected by experience. Additionally, the pattern of results from implicit and explicit Theory of Mind measures supports the theory of two independent Theory of Mind reasoning systems.
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36. Silva IM, Rosenfeld J, Antoniuk SA, Raskin S, Sotomaior VS. {{A 1.5Mb terminal deletion of 12p associated with autism spectrum disorder}}. {Gene};2014 (Mar 5)
We report a patient with a terminal 12p deletion associated with autism spectrum disorder (ASD). This 12p13.33 deletion is 1.5Mb in size and encompasses 13 genes (B4GALNT3, CCDC77, ERC1, FBXL14, IQSEC3, KDM5A, LINC00942, LOC574538, NINJ2, RAD52, SLC6A12, SLC6A13 and WNK1). All previous cases reported with partial monosomy of 12p13.33 are associated with neurodevelopmental delay, and we suggest that ERC1, which encodes a regulator of neurotransmitter release, is the best gene candidate contributing to this phenotype as well as to the ASD of our patient.
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37. Sims TB, Neufeld J, Johnstone T, Chakrabarti B. {{Autistic traits modulate frontostriatal connectivity during processing of rewarding faces}}. {Soc Cogn Affect Neurosci};2014 (Mar 13)
Deficits in facial mimicry have been widely reported in autism. Some studies have suggested that these deficits are restricted to spontaneous mimicry and do not extend to volitional mimicry. We bridge these apparently inconsistent observations by testing the impact of reward value on neural indices of mimicry and how autistic traits modulate this impact. Neutral faces were conditioned with high and low reward. Subsequently, functional connectivity between the ventral striatum (VS) and inferior frontal gyrus (IFG) was measured while neurotypical adults (n = 30) watched happy expressions made by these conditioned faces. We found greater VS-IFG connectivity in response to high reward vs low reward happy faces. This difference was negatively proportional to autistic traits, suggesting that reduced spontaneous mimicry of social stimuli seen in autism, may be related to a failure in the modulation of the mirror system by the reward system rather than a circumscribed deficit in the mirror system.
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38. Skirrow P, Jackson P, Perry E, Hare DJ. {{I Collect Therefore I am-Autonoetic Consciousness and Hoarding in Asperger Syndrome}}. {Clin Psychol Psychother};2014 (Feb 25)
A growing number of studies have highlighted impairments in the ability of individuals with autism spectrum disorders to recall specific, personally experienced material. These difficulties have been related to underlying problems with autonoetic consciousness, namely the subjective awareness of one’s own existence in subjective time. The current paper describes the manifestation of these difficulties in three individuals diagnosed with Asperger syndrome. For the people described, lifelong collecting and hoarding behaviours appeared to serve the function of constituting and maintaining aspects of their sense of self, particularly the sense of continuity and agency over time. On the basis of this clinical information and previous research into self-related processes in people with autism spectrum disorders, an initial model of collecting and hoarding behaviours amongst individuals with Asperger syndrome was formulated. The implications of this formulation for both clinical practice and future research are discussed. Copyright (c) 2014 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: People with Asperger syndrome can have problems in developing a functional sense of self. Collecting and hoarding behaviour by people with Asperger syndrome may reflect such underlying difficulties in their sense of self rather than being symptoms of comorbid mental illness. Interventions need to take account of the function of such behaviours rather than solely regarding them as discrete pathological signs.
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39. Strang JF, Kenworthy L, Dominska A, Sokoloff J, Kenealy LE, Berl M, Walsh K, Menvielle E, Slesaransky-Poe G, Kim KE, Luong-Tran C, Meagher H, Wallace GL. {{Increased Gender Variance in Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder}}. {Arch Sex Behav};2014 (Mar 12)
Evidence suggests over-representation of autism spectrum disorders (ASDs) and behavioral difficulties among people referred for gender issues, but rates of the wish to be the other gender (gender variance) among different neurodevelopmental disorders are unknown. This chart review study explored rates of gender variance as reported by parents on the Child Behavior Checklist (CBCL) in children with different neurodevelopmental disorders: ASD (N = 147, 24 females and 123 males), attention deficit hyperactivity disorder (ADHD; N = 126, 38 females and 88 males), or a medical neurodevelopmental disorder (N = 116, 57 females and 59 males), were compared with two non-referred groups [control sample (N = 165, 61 females and 104 males) and non-referred participants in the CBCL standardization sample (N = 1,605, 754 females and 851 males)]. Significantly greater proportions of participants with ASD (5.4 %) or ADHD (4.8 %) had parent reported gender variance than in the combined medical group (1.7 %) or non-referred comparison groups (0-0.7 %). As compared to non-referred comparisons, participants with ASD were 7.59 times more likely to express gender variance; participants with ADHD were 6.64 times more likely to express gender variance. The medical neurodevelopmental disorder group did not differ from non-referred samples in likelihood to express gender variance. Gender variance was related to elevated emotional symptoms in ADHD, but not in ASD. After accounting for sex ratio differences between the neurodevelopmental disorder and non-referred comparison groups, gender variance occurred equally in females and males.
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40. Takahashi H, Nakahachi T, Komatsu S, Ogino K, Iida Y, Kamio Y. {{Hyperreactivity to weak acoustic stimuli and prolonged acoustic startle latency in children with autism spectrum disorders}}. {Mol Autism};2014 (Mar 12);5(1):23.
BACKGROUND: People with autism spectrum disorders (ASD) are known to have enhanced auditory perception, however, acoustic startle response to weak stimuli has not been well documented in this population. The objectives of this study are to evaluate the basic profile of acoustic startle response, including peak startle latency and startle magnitude to weaker stimuli, in children with ASD and typical development (TD), and to evaluate their relationship to ASD characteristics. METHODS: We investigated acoustic startle response with weak and strong acoustic stimuli in 12 children with ASD and 28 children with TD, analyzing the relationship between startle measures and quantitative autistic traits assessed with the Social Responsiveness Scale (SRS). The electromyographic activity of the left orbicularis oculi muscle to acoustic stimuli of 65 to 115 dB sound pressure level (SPL), in increments of 5 dB, was measured to evaluate acoustic startle response. The average eyeblink magnitude for each acoustic stimuli intensity and the average peak startle latency of acoustic startle response were evaluated. RESULTS: The magnitude of the acoustic startle response to weak stimuli (85 dB or smaller) was greater in children with ASD. The peak startle latency was also prolonged in individuals with ASD. The average magnitude of the acoustic startle response for stimulus intensities greater than 85 dB was not significantly larger in the ASD group compared with the controls. Both greater startle magnitude in response to weak stimuli (particularly at 85 dB) and prolonged peak startle latency were significantly associated with total scores, as well as several subscales of the SRS in the whole sample. We also found a significant relationship between scores on the social cognition subscale of the SRS and the average magnitude of the acoustic startle response for stimulus intensities of 80 and 85 dB in the TD group. CONCLUSIONS: Children with ASD exhibited larger startle magnitude to weak stimuli and prolonged peak startle latency. These startle indices were related to several characteristics of ASD. A comprehensive investigation of acoustic startle response, including the magnitude of startle responses to weak stimuli and peak startle latency, might further our understanding of the neurophysiological impairments underlying ASD.
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41. Talkowski ME, Minikel EV, Gusella JF. {{Autism spectrum disorder genetics: diverse genes with diverse clinical outcomes}}. {Harv Rev Psychiatry};2014 (Mar-Apr);22(2):65-75.
The last several years have seen unprecedented advances in deciphering the genetic etiology of autism spectrum disorders (ASDs). Heritability studies have repeatedly affirmed a contribution of genetic factors to the overall disease risk. Technical breakthroughs have enabled the search for these genetic factors via genome-wide surveys of a spectrum of potential sequence variations, from common single-nucleotide polymorphisms to essentially private chromosomal abnormalities. Studies of copy-number variation have identified significant roles for both recurrent and nonrecurrent large dosage imbalances, although they have rarely revealed the individual genes responsible. More recently, discoveries of rare point mutations and characterization of balanced chromosomal abnormalities have pinpointed individual ASD genes of relatively strong effect, including both loci with strong a priori biological relevance and those that would have otherwise been unsuspected as high-priority biological targets. Evidence has also emerged for association with many common variants, each adding a small individual contribution to ASD risk. These findings collectively provide compelling empirical data that the genetic basis of ASD is highly heterogeneous, with hundreds of genes capable of conferring varying degrees of risk, depending on their nature and the predisposing genetic alteration. Moreover, many genes that have been implicated in ASD also appear to be risk factors for related neurodevelopmental disorders, as well as for a spectrum of psychiatric phenotypes. While some ASD genes have evident functional significance, like synaptic proteins such as the SHANKs, neuroligins, and neurexins, as well as fragile x mental retardation-associated proteins, ASD genes have also been discovered that do not present a clear mechanism of specific neurodevelopmental dysfunction, such as regulators of chromatin modification and global gene expression. In its sum, the progress from genetic studies to date has been remarkable and increasingly rapid, but the interactive impact of strong-effect genetic lesions coupled with weak-effect common polymorphisms has not yet led to a unified understanding of ASD pathogenesis or explained its highly variable clinical expression. With an increasingly firm genetic foundation, the coming years will hopefully see equally rapid advances in elucidating the functional consequences of ASD genes and their interactions with environmental/experiential factors, supporting the development of rational interventions.
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42. Visootsak J, Hipp H, Clark H, Berry-Kravis E, Anderson T, Laney D. {{Climbing the Branches of a Family Tree: Diagnosis of Fragile X Syndrome}}. {J Pediatr};2014 (Mar 6)
OBJECTIVE: To determine the average number of family members diagnosed with a Fragile X Mental Retardation-1 (FMR1) mutation after a proband receives the initial diagnosis of fragile X syndrome (FXS). STUDY DESIGN: We reviewed pedigrees of families who had been evaluated at the Fragile X Syndrome Center at Emory University in Atlanta, Georgia. Through these pedigrees, we determined the number of additional family members diagnosed as FMR1 premutation carriers or with full mutation FXS after the initial diagnosis in each proband. RESULTS: The fragile X pedigree review identified 176 probands, including 108 males (61%) and 68 females (39%). A total of 785 family members were diagnosed with expanded fragile X alleles, including 278 males (35%) and 507 females (65%). These family members included 227 individuals with full mutation FXS (219 males and 8 females) and 558 premutation carriers (59 males and 499 females). After the initial diagnosis of a proband with FXS, on average at least 5 additional family members were diagnosed with an FMR1 mutation. CONCLUSION: Our findings confirm that obtaining a detailed family history after diagnosis of a proband with FXS is likely to identify multiple family members with FMR1 mutations. It is important that the pediatrician or other health care provider making a diagnosis of FXS recognize the value of a detailed family history for timely diagnosis and treatment of additional individuals who may be FMR1 premutation carriers or have full mutation FXS.
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43. Wegiel J, Flory M, Kuchna I, Nowicki K, Ma SY, Imaki H, Cohen IL, London E, Brown WT, Wisniewski T. {{Brain-region-specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism}}. {Acta Neuropathol Commun};2014 (Mar 10);2(1):28.
Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.
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44. Weyn-Vanhentenryck SM, Mele A, Yan Q, Sun S, Farny N, Zhang Z, Xue C, Herre M, Silver PA, Zhang MQ, Krainer AR, Darnell RB, Zhang C. {{HITS-CLIP and Integrative Modeling Define the Rbfox Splicing-Regulatory Network Linked to Brain Development and Autism}}. {Cell Rep};2014 (Mar 4)
The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of the quantifiable targets show dynamic changes during brain development. Of particular interest are 111 events from 48 candidate autism-susceptibility genes, including syndromic autism genes Shank3, Cacna1c, and Tsc2. Alteration of Rbfox targets in some autistic brains is correlated with downregulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing-regulatory network.
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45. Wolfe B, Song J, Greenberg JS, Mailick MR. {{Ripple effects of developmental disabilities and mental illness on nondisabled adult siblings}}. {Soc Sci Med};2014 (Jan 25);108C:1-9.
Developmental disabilities and severe mental illness are costly to the affected individual and frequently to their family as well. Little studied are their nondisabled siblings. Here we examine major life course outcomes (education, employment, and marriage) of these siblings in adulthood using data from the Wisconsin Longitudinal Study. Our sample comprises 113 individuals with developmental disabilities and 337 of their nondisabled siblings; 97 individuals with mental illness and 235 of their nondisabled siblings; and 17,126 unaffected comparison group members. We find that siblings of individuals with mental illness have less education and less employment than the unaffected comparison group, whereas those who have a sibling with developmental disabilities had normative patterns of education and employment, but less marriage and more divorce. Robustness tests incorporating genetic data do not change the conclusions based on the nongenetic analyses.
