Pubmed du 08/09/17

vendredi 8 septembre 2017

1. Ackerman S, Schoenbrun S, Hudac C, Bernier R. Erratum to : Interactive Effects of Prenatal Antidepressant Exposure and Likely Gene Disrupting Mutations on the Severity of Autism Spectrum Disorder. J Autism Dev Disord ;2017 (Sep 08)

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2. Duan F, Watanabe K, Yoshimura Y, Kikuchi M, Minabe Y, Aihara K. Detection of atypical network development patterns in children with autism spectrum disorder using magnetoencephalography. PLoS One ;2017 ;12(9):e0184422.

Autism spectrum disorder (ASD) is a developmental disorder that involves developmental delays. It has been hypothesized that aberrant neural connectivity in ASD may cause atypical brain network development. Brain graphs not only describe the differences in brain networks between clinical and control groups, but also provide information about network development within each group. In the present study, graph indices of brain networks were estimated in children with ASD and in typically developing (TD) children using magnetoencephalography performed while the children viewed a cartoon video. We examined brain graphs from a developmental point of view, and compared the networks between children with ASD and TD children. Network development patterns (NDPs) were assessed by examining the association between the graph indices and the raw scores on the achievement scale or the age of the children. The ASD and TD groups exhibited different NDPs at both network and nodal levels. In the left frontal areas, the nodal degree and efficiency of the ASD group were negatively correlated with the achievement scores. Reduced network connections were observed in the temporal and posterior areas of TD children. These results suggested that the atypical network developmental trajectory in children with ASD is associated with the development score rather than age.

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3. Dudas RB, Lovejoy C, Cassidy S, Allison C, Smith P, Baron-Cohen S. The overlap between autistic spectrum conditions and borderline personality disorder. PLoS One ;2017 ;12(9):e0184447.

BACKGROUND : Both people with autism spectrum conditions (ASC) and borderline personality disorder (BPD) are significantly challenged in terms of understanding and responding to emotions and in interpersonal functioning. AIMS : To compare ASC, BPD, and comorbid patients in terms of autistic traits, empathy, and systemizing. METHODS : 624 ASC, 23 BPD, and 16 comorbid (ASC+BPD) patients, and 2,081 neurotypical controls (NC) filled in the Autism Spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient-Revised (SQ-R). RESULTS : On the AQ, the ASC group scored higher than the BPD group, who in turn scored higher than the comorbid group, who scored higher than controls. On the EQ, we found the comorbid and ASC groups scored lower than the BPD group, who were not different from controls. Finally, on the SQ-R, we found the ASC and BPD group both scored higher than controls. CONCLUSIONS : Similar to ASC, BPD patients have elevated autistic traits and a strong drive to systemize, suggesting an overlap between BPD and ASC.

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4. Fagan K, Crider A, Ahmed AO, Pillai A. Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents. Mol Neuropsychiatry ;2017 (Jul) ;3(1):19-27.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels in the middle frontal gyrus of ASD subjects compared to controls. Significant decreases in the mRNA levels of 2 key proinflammatory cytokines, IL-17 and IL-23 were observed in ASD subjects. Our study further demonstrated a strong association of complement genes with IL-17 and IL-23, suggesting a possible role of the complement system in immune dysregulation in ASD. We observed significant associations between complement components and abnormality of development scores in subjects with ASD. In rodents, C3 knockdown in the prefrontal cortex induced social interaction deficits and repetitive behavior in mice. Together, these studies suggest a potential role of C3 in the pathophysiology of ASD.

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5. Haakonsen Smith C, Turbitt E, Muschelli J, Leonard L, Lewis KL, Freedman B, Muratori M, Biesecker BB. Feasibility of Coping Effectiveness Training for Caregivers of Children with Autism Spectrum Disorder : a Genetic Counseling Intervention. J Genet Couns ;2017 (Sep 06)

Caregivers of children with autism spectrum disorder (ASD) may find it difficult to feel a sense of control and to cope with the overall physical and emotional demands of caring for their child. While caregivers are able to successfully cope with a high level of stress, there are limits to their resources and abilities to cope over time. Genetic counselors working with affected families may be able to help parents more effectively manage stress related to the disorder. Few short-term interventions have been reported in genetic counseling yet implementation of evidence-based examples may be achievable. This study aimed to assess the feasibility of a coping effectiveness training (CET) intervention designed to enhance coping self-efficacy (CSE) among caregivers of children with ASD, with the eventual goal of translating this intervention into genetic counseling practice. A randomized treatment-control design was used to investigate the feasibility of an intervention using CET among caregivers of children with ASD. The primary outcome was the feasibility of the intervention ; the secondary outcome was improvements in CSE in the intervention group as compared to the control group. Caregivers were recruited and randomized into the treatment (n=15) or control (n=13) groups. Of these, 22 completed the study (retention : 78.6%). The intervention was highly feasible ; most caregivers found the CET helpful, practical, useful, and relatively easy to attend. The treatment group demonstrated significantly increased CSE from pre-intervention to post-intervention (p=0.02). Between group differences were not significant when comparing the pre-post changes. We provide preliminary evidence that CET may be beneficial to caregivers of children with ASD. The results of this feasibility study support development of a phase II study of this intervention in a larger cohort, aimed to be implemented into a genetic counseling setting.

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6. Holyfield C, Drager KDR, Kremkow JMD, Light J. Systematic review of AAC intervention research for adolescents and adults with autism spectrum disorder. Augment Altern Commun ;2017 (Sep 08):1-12.

Much of augmentative and alternative communication (AAC) research for individuals with autism spectrum disorder has focused on young children. Given that the lives, communication, strengths, and needs of adolescents and adults with autism spectrum disorder are quite different from those of young children, the purpose of the current study was to consolidate current AAC intervention research findings specific to these individuals. A systematic review was conducted to identify and evaluate relevant research. Results indicate that AAC intervention benefits adolescents and adults with autism spectrum disorder. However, more research is urgently needed. Future research focused on supporting communicative functions other than requesting (e.g., social closeness, information transfer) while participating in contexts important to the lives of adolescents and adults may be particularly valuable.

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7. Huang AX, Hughes TL, Sutton LR, Lawrence M, Chen X, Ji Z, Zeleke W. Understanding the Self in Individuals with Autism Spectrum Disorders (ASD) : A Review of Literature. Front Psychol ;2017 ;8:1422.

When the system of self is explored in individuals with Autism Spectrum Disorders (ASDs), it is important to measure it via both their own perceptions of the self and their understanding of others’ perceptions on themselves at a multidimensional level. This paper reviews existing research in this area using a three-dimension approach. Researchers have found that impairments in the self-system are usually correlated with these individuals’ social and cognitive functioning levels : high functioning individuals with ASD who have higher IQ are found to have better awareness of their limitations in social and communication domains than those with lower IQ. Many researchers believe that there are impairments in the psychological (but not physical) self in individuals with ASD, such as theory of mind deficits due to social and communicative impairments. On the other hand, some researchers argue that individuals with ASD have selective rather than global impairments in the self. In other words, the impairment usually lies in a specific aspect of functioning in individuals with ASD. Insights from the review of existing literature on this topic may be able to shed some lights on the development of effective intervention programs to improve social communication deficits in this population.

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8. Jo CW, Park CH, Lee JH, Kim JH. Managing the behavior of a patient with autism by sedation via submucosal route during dental treatment. J Dent Anesth Pain Med ;2017 (Jun) ;17(2):157-161.

In sedation via the submucosal route, the drug is administered through the maxillary buccal submucosa. It is time saving, effective, and safe. Patients with autism, a mental disorder, often find it hard to make relationships with other people. These patients display a strong resistance to dental treatment and sedation. This study reports a successful case of behavioral management during dental treatment, using sedation via the submucosal route. The patient was strongly resistant to sedation via the oral, intramuscular, and intravenous routes. The drug used was 9 mg (0.1 mg/kg) of midazolam. Through this case report, we reaffirm the significance of sedation via the submucosal route, and expect that it will be used more frequently for patients with autism, who display behaviors that are difficult to manage, patients with other disabilities, and children.

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9. Keim SA, Sheppard KW. Long-standing Challenges to Exposure Measurement and Outcome Definitions : the Case of Alcohol and Autism Spectrum Disorder. Paediatr Perinat Epidemiol ;2017 (Sep 07)

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10. Kennedy T, Broadie K. Fragile X Mental Retardation Protein Restricts Small Dye Iontophoresis Entry into Central Neurons. J Neurosci ;2017 (Sep 08)

Fragile X Mental Retardation Protein (FMRP) loss causes Fragile X syndrome (FXS), a major disorder characterized by autism, intellectual disability, hyperactivity and seizures. FMRP is both an RNA- and channel-binding regulator, with critical roles in neural circuit formation and function. However, it remains unclear how these FMRP activities relate to each other and how dysfunction in their absence underlies FXS neurological symptoms. In testing circuit level defects in the Drosophila FXS model, we discovered a completely unexpected and highly robust neuronal dye iontophoresis phenotype in the well-mapped Giant Fiber (GF) circuit. Controlled dye injection into the GF Interneuron (GFI) results in a dramatic increase in dye uptake in neurons lacking FMRP. Transgenic wildtype FMRP reintroduction rescues the mutant defect, demonstrating a specific FMRP requirement. This phenotype affects only small dyes, but is independent of dye charge polarity. Surprisingly, the elevated dye iontophoresis persists in shaking B mutants that eliminate gap junctions and dye coupling among GF circuit neurons. We therefore used a wide range of manipulations to investigate the dye uptake defect, including timed injection series, pharmacology and ion replacement, and optogenetic activity studies. The results show FMRP strongly limits the rate of dye entry via a cytosolic mechanism. This study reveals an unexpected new phenotype in a physical property of central neurons lacking FMRP that could underlie aspects of FXS disruption of neural function.SIGNIFICANCE STATEMENTFXS is a leading heritable cause of intellectual disability and autism spectrum disorders. Although researchers established the causal link with FMRP loss over 25 years ago, studies continue to reveal diverse FMRP functions. The Drosophila FXS model is key to discovering new FMRP roles, owing to its genetic malleability and individually-identified neuron maps. Taking advantage of a well-characterized Drosophila neural circuit, we discovered that neurons lacking FMRP take up dramatically more current-injected small dye. After examining many neuronal properties, we determined that this dye defect is cytoplasmic and occurs due to a highly elevated dye iontophoresis rate. We also report several new factors affecting neuron dye uptake. Understanding how FMRP regulates iontophoresis should reveal new molecular factors underpinning FXS dysfunction.

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11. Lassalle A, Asberg Johnels J, Zurcher NR, Hippolyte L, Billstedt E, Ward N, Lemonnier E, Gillberg C, Hadjikhani N. Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes. Hum Brain Mapp ;2017 (Sep 07)

Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutral faces and faces expressing anger, happiness, and fear at low and high intensity, with a fixation cross between the eyes. Group differences in whole brain activity were examined for expressive faces at high and low intensity versus neutral faces. Group differences in neural activity were also investigated in regions of interest within the social brain, including the amygdala and the ventromedial prefrontal cortex (vmPFC). In response to low intensity fearful faces, ASD participants showed increased activation in the social brain regions, and decreased functional coupling between the amygdala and the vmPFC. This oversensitivity to low intensity fear coupled with a lack of emotional regulation capacity could indicate an excitatory/inhibitory imbalance in their socio-affective processing system. This may result in social disengagement and avoidance of eye-contact to handle feelings of strong emotional reaction. Our results also demonstrate the importance of careful control of gaze when investigating emotional processing in ASD. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

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12. Li YJ, Ou JJ, Li YM, Xiang DX. Dietary Supplement for Core Symptoms of Autism Spectrum Disorder : Where Are We Now and Where Should We Go ?. Front Psychiatry ;2017 ;8:155.

Autism spectrum disorders (ASDs) are a class of severe and chronic conditions and core symptoms are deficits in social interaction, language communication impairments, and repetitive/stereotyped behavior. Given the limitations of available treatments and substantially increased prevalence of the disease, additional interventions are needed. Since the use of dietary supplements for ASD is of high prevalence, up-to-date information about those supplements are required for both parents and clinicians. Relevant articles were identified through a systematic search of PubMed, EMBASE, Cochrane library, and PsychINFO databases (through May 2017). Current best evidences of 22 randomized controlled trials on 8 different dietary supplements for core symptoms of ASD were reviewed. For each supplement, this report focuses on the definition and potential therapeutic mechanisms, the latest advances, and discussion of study limitations and future directions. Most studies were small and short term, and there is little evidence to support effectiveness of dietary supplements for children with ASD.

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13. Rosbergen GJ, Jansen MP, Rosbergen-De Vries AR, Roke Y, Otten R. [Sleep-wake patterns in adults with autism spectrum disorders in a clinical setting : a pilot study]. Tijdschr Psychiatr ;2017 ;59(9):520-527.

BACKGROUND : The negative consequences of sleep-wake disorders in the general population and in children with an autism spectrum disorder (ASD) are well-established. However, little is known about sleep-wake disorders in adults with ASD.
AIM : To study and measure sleep-wake disorders and sleep-wake patterns in adults in a clinical facility who have been diagnosed primarily as having ASD without any comorbid intellectual disability.
METHOD : We assessed the sleep patterns of 19 patients in a residential facility. We asked patients to provide their sleep history, answer questionnaires and keep a sleep diary (subjective measurement). We also asked patients to collect actigraphy data (objective measurement) for seven days and to provide information about comorbid symptoms of anxiety and depression and use of medication.
RESULTS : Nine patients (47%) had undiagnosed comorbid sleep-wake disorders. Patients in our study overrated their sleep efficiency (diary) compared to objective data (actigraphy). However, patients’ subjective sleep quality did match patients’ sleep efficiency. Only two out of 14 patients with symptoms of anxiety and/or depression were diagnosed with a comorbid depressive disorder, 15 patients were treated with medication.
CONCLUSION : Sleep-wake disorders and comorbid symptoms of anxiety and depression might be more prevalent in adults with ASD in a residential facility than reported so far. This possibility needs to be considered more carefully during the diagnostic process and during treatment.

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14. Singer AB, Aylsworth AS, Cordero C, Croen LA, DiGuiseppi C, Fallin MD, Herring AH, Hooper SR, Pretzel RE, Schieve LA, Windham GC, Daniels JL. Prenatal Alcohol Exposure in Relation to Autism Spectrum Disorder : Findings from the Study to Explore Early Development (SEED). Paediatr Perinat Epidemiol ;2017 (Sep 07)

BACKGROUND : Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). METHODS : We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report. RESULTS : Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk. CONCLUSIONS : These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.

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15. Wiggins LD, Tian LH, Levy SE, Rice C, Lee LC, Schieve L, Pandey J, Daniels J, Blaskey L, Hepburn S, Landa R, Edmondson-Pretzel R, Thompson W. Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development. J Autism Dev Disord ;2017 (Sep 06)

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis : mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed.

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16. Zamberletti E, Gabaglio M, Parolaro D. The Endocannabinoid System and Autism Spectrum Disorders : Insights from Animal Models. Int J Mol Sci ;2017 (Sep 07) ;18(9)

Autism spectrum disorder (ASD) defines a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction with restricted or repetitive motor movements, frequently associated with general cognitive deficits. Although it is among the most severe chronic childhood disorders in terms of prevalence, morbidity, and impact to the society, no effective treatment for ASD is yet available, possibly because its neurobiological basis is not clearly understood hence specific drugs have not yet been developed. The endocannabinoid (EC) system represents a major neuromodulatory system involved in the regulation of emotional responses, behavioral reactivity to context, and social interaction. Furthermore, the EC system is also affected in conditions often present in subsets of patients diagnosed with ASD, such as seizures, anxiety, intellectual disabilities, and sleep pattern disturbances. Despite the indirect evidence suggestive of an involvement of the EC system in ASD, only a few studies have specifically addressed the role of the EC system in the context of ASD. This review describes the available data on the investigation of the presence of alterations of the EC system as well as the effects of its pharmacological manipulations in animal models of ASD-like behaviors.

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