1. Boada L, Parellada M. {{Seeing the doctor without fear: www.doctortea.org for the desensitization from medical visits in Autism Spectrum Disorders}}. {Rev Psiquiatr Salud Ment};2016 (Dec 07)
INTRODUCTION: Doctor Tea is an online website designed to facilitate medical visits for those with autism spectrum disorder and other disabilities. People diagnosed with autism not only have greater medical needs than the general population, but also have particular characteristics that are often not accommodated by medical services. This lack of medical accommodation often creates a very complicated, and sometimes traumatic experience, when visiting medical facilities. Individuals with autism have great difficulty understanding social situations and contexts, such as medical tests or consultations, as well as difficulty in tolerating new situations and atypical sensory thresholds. Doctor Tea aims to reduce anxiety before medical consultations and procedures from a safe and well-known environment (school, home, etc.). MATERIAL AND METHOD: The website, www.doctortea.org, provides information and materials (videos, cartoon, 3D animations, pictogram sequences, etc.) about the most frequent medical procedures and practices for patients with autism. The website also offers information to the doctors and families of patients with autism about the most common medical problems associated with autism. RESULTS: A total of 17,199 different users visited the website during 2015, with a total of 23,348 online visitors from more than 70 different countries since the website’s release in November 2014. CONCLUSIONS: The familiarisation with the medical procedures and its environment appears to decrease the anxiety in patients with disabilities during medical visits, as well as optimising the effectiveness of their medical visits and tests.
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2. Greydanus DE, Gregoire-Bottex MM, Merrick J. {{Gastrointestinal dysfunction and autism: caution with misdiagnoses as many mysteries remain to be unraveled!}}. {Int J Adolesc Med Health};2016 (Dec 15)
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3. Guo X, Duan X, Long Z, Chen H, Wang Y, Zheng J, Zhang Y, Li R, Chen H. {{Decreased amygdala functional connectivity in adolescents with autism: A resting-state fMRI study}}. {Psychiatry Res};2016 (Oct 23);257:47-56.
The human brain undergoes dramatic changes in amygdala-related functional connectivity network during adolescence. Given that the amygdala is a vital component of the « social brain », the Amygdala Theory of Autism has been proposed to account for atypical patterns of socio-emotional behavior in autism. Most of the previous neuroimaging evidence has concentrated on local functional or structural abnormalities of the amygdala in relation to social deficits in autism, rather than on its integrated role as part of larger brain networks. To examine whether functional integration pattern of the amygdala is altered in autism, the current study examined sixty-five adolescent subjects (30 autism and 35 healthy controls, 12-18 years old) from two independent datasets (UCLA and Leuven) of the Autism Brain Imaging Data Exchange. Whole-brain resting-state functional connectivity maps seeded in the amygdala were calculated and compared between patient and control groups. Compared with healthy controls, adolescents with autism showed decreased functional connectivity between the amygdala and subcortical regions in both datasets, including the bilateral thalamus and right putamen. These findings support the Amygdala Theory of Autism, demonstrating altered functional connectivity pattern associated with the amygdala in autism, and provide new insights into the pathophysiology of autism.
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4. Larson FV, Wagner AP, Jones PB, Tantam D, Lai MC, Baron-Cohen S, Holland AJ. {{Psychosis in autism: comparison of the features of both conditions in a dually affected cohort}}. {Br J Psychiatry};2016 (Dec 15)
BACKGROUND: There is limited information on the presentation and characteristics of psychotic illness experienced by people with autism spectrum disorder (ASD). AIMS: To describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD-P) and compare this group with populations affected by either, alone. METHOD: We studied 116 individuals with ASD-P. We compared features of their ASD with people with ASD and no comorbid psychosis (ASD-NP), and clinical characteristics of psychosis in ASD-P with people with psychosis only. RESULTS: Individuals with ASD-P had more diagnoses of atypical psychosis and fewer of schizophrenia compared with individuals with psychosis only. People with ASD-P had fewer stereotyped interests/behaviours compared with those with ASD-NP. CONCLUSIONS: Our data show there may be a specific subtype of ASD linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance.
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5. Liu T, Chen Y, Chen D, Li C, Qiu Y, Wang J. {{Altered electroencephalogram complexity in autistic children shown by the multiscale entropy approach}}. {Neuroreport};2016 (Dec 15)
Autism spectrum disorder (ASD) is a severe neurodevelopment disorder. This study tests the hypothesis that children with ASD show atypical intrinsic complexity of brain activity. Electroencephalogram data were collected from boys with ASD and matching normal typically developing children while performing an observation and an imitation task. The multiscale entropy was estimated within the 0.5-30 Hz frequency band over 30 time scales using a coarse-grained procedure. A decreased electroencephalogram complexity was observed in the ASD children both during the observation and during the imitation tasks. On comparing the two tasks, significant differences were observed between groups in the right hemisphere, and also the central cortex for the observation task. Multiscale entropy could provide further evidence of the relationship between ASD and cerebral dysfunction.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
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6. Loth E, Murphy DG, Spooren W. {{Defining Precision Medicine Approaches to Autism Spectrum Disorders: Concepts and Challenges}}. {Front Psychiatry};2016;7:188.
The tremendous clinical and etiological variability between individuals with autism spectrum disorder (ASD) has made precision medicine the most promising treatment approach. It aims to combine new pathophysiologically based treatments with objective tests (stratification biomarkers) to predict which treatment may be beneficial for a particular person. Here we discuss significant advances and current challenges for this approach: rare monogenic forms of ASD have provided a major breakthrough for the identification of treatment targets by providing a means to trace causal links from a gene to specific molecular alterations and biological pathways. To estimate whether treatment targets thus identified may be useful for larger patient groups we need a better understanding of whether different etiologies (i.e., genetic and environmental risk factors acting at different critical time points) lead to convergent or divergent molecular mechanisms, and how they map onto differences in circuit-level brain and cognitive development, and behavioral symptom profiles. Several recently failed clinical trials with syndromic forms of ASD provide valuable insights into conceptual and methodological issues linked to limitations in the translatability from animal models to humans, placebo effects, and a need for mechanistically plausible, objective outcome measures. To identify stratification biomarkers that enrich participant selection in clinical trials, large-scale multi-modal longitudinal observational studies are underway. Addressing these different factors in the next generation of research studies requires a translatable developmental perspective and multidisciplinary, collaborative efforts, with a commitment to sharing protocols and data, to increase transparency and reproducibility.
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7. Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, Hartl C, Leppa V, Ubieta LT, Huang J, Lowe JK, Blencowe BJ, Horvath S, Geschwind DH. {{Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism}}. {Nature};2016 (Dec 15);540(7633):423-427.
Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood. Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge, we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder.
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8. Quesnel-Vallieres M, Dargaei Z, Irimia M, Gonatopoulos-Pournatzis T, Ip JY, Wu M, Sterne-Weiler T, Nakagawa S, Woodin MA, Blencowe BJ, Cordes SP. {{Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders}}. {Mol Cell};2016 (Dec 15);64(6):1023-1034.
A key challenge in understanding and ultimately treating autism is to identify common molecular mechanisms underlying this genetically heterogeneous disorder. Transcriptomic profiling of autistic brains has revealed correlated misregulation of the neuronal splicing regulator nSR100/SRRM4 and its target microexon splicing program in more than one-third of analyzed individuals. To investigate whether nSR100 misregulation is causally linked to autism, we generated mutant mice with reduced levels of this protein and its target splicing program. Remarkably, these mice display multiple autistic-like features, including altered social behaviors, synaptic density, and signaling. Moreover, increased neuronal activity, which is often associated with autism, results in a rapid decrease in nSR100 and splicing of microexons that significantly overlap those misregulated in autistic brains. Collectively, our results provide evidence that misregulation of an nSR100-dependent splicing network controlled by changes in neuronal activity is causally linked to a substantial fraction of autism cases.
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9. Sajid U, Argiropoulos B, Wei XC, Parboosingh JS, Lamont RE, Khan A, Greenway SC. {{Two De Novo Mutations in an Autistic Child Who Had Previously Undergone Transplantation for Dilated Cardiomyopathy: The Importance of Keeping an Open Mind}}. {Can J Cardiol};2016 (Sep 26)
We report the finding of 2 de novo mutations in an 8-year-old boy with developmental delay and autism who underwent heart transplantation at 1 year of age for idiopathic dilated cardiomyopathy. We identified a de novo microdeletion at chromosome 2p16.3 involving the neurexin-1 (NRXN1) gene and a de novo pathologic variant (Pro838Leu) in the myosin heavy chain 7 (MYH7) gene. This case emphasizes the importance of comprehensive genetic evaluation in patients with cardiomyopathy, particularly if they have extracardiac abnormalities, and the necessity of interpreting variants with attention to the phenotype. A complete genetic diagnosis may require multiple testing modalities.
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10. Shire SY, Chang YC, Shih W, Bracaglia S, Kodjoe M, Kasari C. {{Hybrid implementation model of community-partnered early intervention for toddlers with autism: a randomized trial}}. {J Child Psychol Psychiatry};2016 (Dec 14)
BACKGROUND: Interventions found to be effective in research settings are often not as effective when implemented in community settings. Considering children with autism, studies have rarely examined the efficacy of laboratory-tested interventions on child outcomes in community settings using randomized controlled designs. METHODS: One hundred and thirteen children with autism enrolled in public early intervention classrooms in low resource neighborhoods were randomized to Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) intervention or treatment as usual waitlist for 10 weeks with 1-month follow-up. RESULTS: Teaching assistants delivered JASPER at adequate fidelity. Children randomized to JASPER demonstrated significant gains over treatment as usual in core developmental outcomes of joint engagement, joint attention, and play skills that were maintained at follow-up. CONCLUSIONS: Supervised teaching assistants delivered JASPER intervention with a range of toddlers with autism leading to significant gains in developmental outcomes.
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11. Soderberg B, Vaskelyte L, Gafoor S, Hofmann I, Mellmann A, Bernhard J, Sievert H. {{TCT-826 Prospective single center First In Human (FIH) clinical trial to evaluate the safety and effectiveness of a septal occluder with bioresorbable framework in patients with clinically significant atrial septum defect (ASD) or patent foramen ovale (PFO)}}. {J Am Coll Cardiol};2016 (Nov 01);68(18s):B334.
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12. Tchaconas A, Adesman A. {{Diagnostic Evaluation of Children with Autism Spectrum Disorders: Clinician Compliance with Published Guidelines}}. {J Dev Behav Pediatr};2016 (Dec 15)
OBJECTIVE: To assess to what extent child neurologists (CNs) and developmental-behavioral pediatricians (DBPs) order diagnostic tests that are not recommended/indicated and/or fail to order tests that are recommended/indicated when evaluating children with an autism spectrum disorder (ASD). METHOD: CNs and DBPs in the United States were asked which laboratory tests they would « routinely order » for a preschool child with ASD and IQ = 58 (ASD + Intellectual Disability (ID)), and a preschool child with ASD and IQ = 85 (ASD-ID). Chi-square tests were performed to identify differences (CNs vs DBPs) in laboratory testing. RESULTS: The sample consisted of 267 respondents (127 CN’s; 140 DBPs). When evaluating ASD + ID or ASD – ID, inappropriate tests (>/=1) were ordered by 76.8% and 76.4% of MDs, respectively. There was no significant difference between specialties in compliance with evaluation guidelines for ASD + ID (CN = 20.5% vs DBP = 16.4%; chi = 0.73). No significant differences were noted (DBP vs CN) regarding the percent ordering inappropriate tests for either clinical case or within each specialty when comparing testing for ASD + ID versus ASD – ID. Relative to DBPs, CNs were more likely to order EEGs and MRIs when evaluating children with ASD + ID or ASD – ID. 10% and 40% of respondents did not order any recommended genetic tests when evaluating ASD + ID and ASD – ID, respectively. CONCLUSION: When evaluating children with ASD, many CNs and DBPs fail to order tests that should be routinely performed and often order tests that are not routinely indicated yet are neither benign nor inexpensive. Recommended molecular genetic tests are often not ordered. Clinical guidelines must be updated and better promulgated.
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13. Vakorin VA, Doesburg SM, Leung RC, Vogan VM, Anagnostou E, Taylor MJ. {{Developmental changes in neuromagnetic rhythms and network synchrony in autism}}. {Ann Neurol};2016 (Dec 15)
OBJECTIVE: There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear if and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder. METHODS: To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography (MEG) from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity). RESULTS: While no overall group differences were observed, significant alterations in linear and non-linear age-related changes in resting oscillatory power and network synchrony were found. These differences were frequency- and region-specific and implicated brain systems thought to play a prominent role in ASD, such as the frontal cortex and cerebellum. We also found correlations between the Autism Diagnostic Observation Schedule (ADOS) scores and the degree to which connectivity in cerebellar networks is ‘idiosyncratic’ in an individual with autism. INTERPRETATION: We provide the first evidence that it is the curvatures of maturational changes in neurophysiological oscillations and synchrony, rather than disturbances in a particular direction, which characterizes the brain function in individuals with ASD. Moreover, the patterns of idiosyncratic distortions of network synchrony relative to the group curve are associated with behavioral symptoms of ASD. This article is protected by copyright. All rights reserved.
