1. Heifert TA, Susi A, Hisle-Gorman E, Erdie-Lalena CR, Gorman G, Min SB, Nylund CM. {{Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis}}. {J Pediatr Gastroenterol Nutr};2016 (Jun 8)
OBJECTIVE: Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASD) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE. METHODS: A retrospective matched case-cohort study was performed using the Military Health System database from Oct 2008 to Sept 2013. We performed a 1:5 case:control match by age, gender, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined utilizing diagnostic and procedure codes. RESULTS: There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared to controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared to other atopic conditions, among both children with ASD (7.17, 95% CI 4.87-10.5) and controls (11.5, 95% CI 7.57-17.5). Compared to controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39-1.88). CONCLUSIONS: Children with ASD are more likely to be diagnosed with EoE compared to controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.
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2. Libero LE, Nordahl CW, Li DD, Ferrer E, Rogers SJ, Amaral DG. {{Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder}}. {Autism Res};2016 (Jun 8)
A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age-matched, typically developing controls. We determined whether 3-year-old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3-5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Mashayekhi F, Mizban N, Bidabadi E, Salehi Z. {{The association of SHANK3 gene polymorphism and autism}}. {Minerva Pediatr};2016 (Jun 8)
BACKGROUND: Autism spectrum disorder (ASD) and Autism are both general terms for a group of complex disorders of brain development. These disorders are characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Many genes have been shown to be involved in Autism. SHANK3 (SH3 and multiple ankyrin repeat domain 3) is a member of the highly conserved Shank/ProSAP family of synaptic scaffolding proteins. SHANK3 is suggested as a strong candidate gene for the pathogenesis of Autism and its loss results in disruption of synaptic function. The rs9616915 SNP, which directly affects SHANK3 gene function of splicing regulation and protein structure damage, is a non- synonymous SNP (T>C) that found in exon 6, leads to substitution of Isoleucine to Threonine. The present study was aimed to evaluate whether rs9616915 polymorphism of SHANK3 are related with the susceptibility to Autism. METHODS: Samples were obtained from 90 patients diagnosed with Autism and 100 controls subjects and genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The results of this study showed that there is a significant association in genotype distribution between cases and controls (P= 0.0001). RESULTS: Our findings revealed that individuals with TC genotypes were associated with increased risk of Autism disorder (OR=4.35, 95% CI=2.15 – 8.80, P=0.0001) but no significant differences were found in allele distributions (P= 0.1). CONCLUSIONS: In conclusion, our results indicated that the SHANK3 rs9616915 polymorphism is associated with increased risk of Autism. Larger studies with more patients and controls are needed to confirm the results.
4. Muller E, Cannon LR, Kornblum C, Clark J, Powers M. {{Description and Preliminary Evaluation of a Curriculum for Teaching Conversational Skills to Children With High-Functioning Autism and Other Social Cognition Challenges}}. {Lang Speech Hear Serv Sch};2016 (Jun 8):1-18.
Purpose: The purpose of this clinical focus article is to provide (a) a detailed description of a school-based intervention designed to teach children with high-functioning autism spectrum disorders (HF-ASDs) and other social cognition challenges both the how and the why of conversation and (b) a preliminary evaluation of program outcomes. Method: This pilot study involved (a) qualitative and quantitative analysis of video footage of participants’ conversational skills at baseline, during intervention, and postintervention; (b) interviews with participants’ speech-language pathologist (third author) about individual participant progress; and (c) interviews with instructors responsible for implementing the curriculum regarding overall program effectiveness. Participants were four elementary-aged children with HF-ASDs and other social cognition challenges with deficits in expressive language and auditory processing and comprehension. Results: Analyses of video-recorded footage indicated increases for all four participants in terms of peer-directed interactions, questions asked, use of wh-words to introduce new topics and/or extend conversation on existing topics, and attempts at conversational repair. Three participants also demonstrated increased use of attention-gaining behaviors. Qualitative analysis of transcripts, as well as in-depth interviews with the participants’ speech-language pathologist and other program instructors, supported these findings. Conclusions: Preliminary findings from this pilot study suggest that providing comprehensive instruction in many of the basic components required for successful conversation, including explanations for why these components are necessary, may be a promising means of teaching children with HF-ASDs and other social cognition challenges to engage in successful peer-to-peer conversation.
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5. Schuetze M, Park MT, Cho IY, MacMaster FP, Chakravarty MM, Bray SL. {{Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder}}. {Neuropsychopharmacology};2016 (Jun 8)
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7-35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.Neuropsychopharmacology advance online publication, 8 June 2016; doi:10.1038/npp.2016.64.
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6. Yang WY, He F, Strack RL, Oh SY, Frazer M, Jaffrey SR, Todd PK, Disney MD. {{Small Molecule Recognition and Tools to Study Modulation of r(CGG)exp in Fragile X-Associated Tremor Ataxia Syndrome}}. {ACS Chem Biol};2016 (Jun 8)
RNA transcripts containing expanded nucleotide repeats cause many incurable diseases via various mechanisms. One such disorder, Fragile X-associated tremor ataxia syndrome (FXTAS), is caused by a non-coding r(CGG) repeat expansion (r(CGG)exp) that: (i) sequesters proteins involved in RNA metabolism in nuclear foci, causing deregulation of alternative pre-mRNA splicing; and (ii) undergoes repeat associated non-ATG translation (RANT), which produces toxic homopolymeric proteins without using a start codon. Here we describe the design of two small molecules that inhibit both modes of toxicity and the implementation of various tools to study perturbation of these cellular events. Competitive Chemical Cross Linking and Isolation by Pull Down (C-Chem-CLIP) established that compounds bind r(CGG)exp in cells and also defined small molecule occupancy of RNA targets in cells, the first approach to do so. Using an RNA GFP mimic, r(CGG)exp-Spinach2, we observe that our optimal designed compound binds r(CGG)exp and affects RNA localization by disrupting pre-formed RNA foci. These events correlate with improvement of pre-mRNA splicing defects caused by RNA gain-of-function. In addition, the compounds reduced the formation of toxic homopolymeric proteins formed via RANT. Polysome profiling studies showed that small molecules decreased loading of polysomes onto r(CGG)exp, explaining decreased translation.
