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The Filter Cart provides a powerful way to query and access data for which you may be interested.  

A few points related to the filter cart are important to understand with the NDA Query/Filter implementation: 

First, the filter cart is populated asyncronously.  So, when you run a query, it may take a moment to populate but this will happen in the background so you can define other queries during this time.  

When you are adding your first filter, all data associated with your query will be added to the filter cart (whether it be a collection, a concept, a study, a data structure/elment or subjects). Not all data structures or collections will necessarily be displayed.  For example, if you select the NDA imaging structure image03, and further restrict that query to scan_type fMRI, only fMRI images will appear and only the image03 structure will be shown.  To see other data structures, select "Find All Subject Data" which will query all data for those subjects. When a secord or third filter is applied, an AND condition is used.  A subject must exist in all filters.  If the subject does not appear in any one filter, that subjects data will not be included in your filter cart. If that happens, clear your filter cart, and start over.  

It is best to package more data than you need and access those data using other tools, independent of the NDA (e.g. miNDAR snapshot), to limit the data selected.  If you have any questions on data access, are interested in using avaialble web services, or need help accessing data, please contact us for assistance.  

Frequently Asked Questions

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NDAR provides a single access to de-identified autism research data. For permission to download data, you will need an NDAR account with approved access to NDAR or a connected repository (AGRE, IAN, or the ATP). For NDAR access, you need to be a research investigator sponsored by an NIH recognized institution with federal wide assurance. See Request Access for more information.

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The filters you have selected from various query interfaces will be stored here, in the 'Filter Cart'. The database will be queried using filters added to your 'Filter Cart', when multiple filters are defined, each will be executed using 'AND' logic, so with each filter that is applied the result set gets smaller.

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Add New Study
Predictors of self-injurious behaviour exhibited by individuals with autism spectrum disorder #258
Richman DM; Barnard-Brak L, Bosch A, Thompson S, Grubb L, Abby L
Presence of an autism spectrum disorder is a risk factor for development of self-injurious behaviour (SIB) exhibited by individuals with developmental disorders. The most salient SIB risk factors historically studied within developmental disorders are level of intellectual disability, communication deficits and presence of specific genetic disorders. Recent SIB research has expanded the search for risk factors to include less commonly studied variables for people with developmental disorders:...
10.15154/1226464
Secondary Analysis
Finding
Statistical
Gastrointestinal Dysfunction in Autism: Parental Report, Clinical Evaluation, and Associated Factors #268
Levitt P; Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG
The objectives of this study were to characterize gastrointestinal dysfunction (GID) in autism spectrum disorder (ASD), to examine parental reports of GID relative to evaluations by pediatric gastroenterologists, and to explore factors associated with GID in ASD. One hundred twenty-one children were recruited into three groups: co-occurring ASD and GID, ASD without GID, and GID without ASD. A pediatric gastroenterologist evaluated both GID groups. Parents in all three groups completed...
10.15154/1163508
Primary Analysis
Finding
Statistical
Brain Hyperconnectivity in Children with Autism and its Links to Social Deficits #269
Menon, Vinod; Superkar, K; Uddin, LQ; Khouzam, A; Phillips, J; Gaillard, WD; Kenworthy, LE; Yerys, BE; Vaidya, CJ
Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at...
10.15154/1223791
Secondary Analysis
Finding
Neuro Signal Recordings
Epigenetics Marks as Peripheral Biomarkers of Autism #287
Warren S
We are studying a potential epigenetic component to the autism spectrum disorders (ASD) by interrogating DNA methylation (DNAm) using an established high-throughput assay that interrogates DNA methylation (DNAm) at 27578 highly informative CpG dinucleotides. To date, we have determined the DNA methylation (DNAm) profiles from whole blood-extracted DNA of over four hundred male sib-pairs discordant for ASD. A close statistical examination may ultimately identify ASD peripheral biomarkers and...
10.15154/1165651
Primary Analysis
Finding
Statistical
Autism Genome Project #288
Scherer S, Devlin B
The Autism Genome Project (AGP) Consortium represents more than 50 centers in North America and Europe. In an ongoing effort, the international AGP Consortium is collecting ASD families for ongoing genetic studies. The first phase of this initiative involved examining genetic linkage and chromosomal rearrangements in 1,168 families having at least two ASD individuals (PMID: 17322880). In this second phase of the project, we collected more families and genotyped them to examine for Copy Number...
10.15154/1165652
Primary Analysis
Finding
Genotyping/NGS
Somatic copy-number mosaicism in human skin revealed by induced pluripotent stem cell #289
Vaccarino FM; Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS, Tomasini L, Ferrandino AF, Rosenberg Belmaker LA, Szekely A, Wilson M, Kocabas A, Calixto NE, Grigorenko EL, Huttner A, Chawarska K, Weissman S, Urban AE, Gerstein M
Reprogramming human somatic cells into induced pluripotent stem cells (iPSC) has been suspected of causing de novo copy number variations (CNVs). To explore this issue, we performed a whole-genome and transcriptome analysis of 20 human iPSC lines derived from primary skin fibroblasts of 7 individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two CNVs not apparent in the fibroblasts from which the iPSC was derived. Using qPCR, PCR, and digital droplet PCR...
10.15154/1163509
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism #293
Walsh CA; Chahrour MH, Yu TW, Lim ET, Ataman B, Coulter ME, Hill RS, Stevens CR, Schubert CR; ARRA Autism Sequencing Collaboration, Greenberg ME, Gabriel SB
Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16...
10.15154/1163510
Primary Analysis
Finding
Genotyping/NGS
Study of potential epigenetic component to the autism spectrum disorders (ASD) by interrogating DNA methylation (DNAm) using an established high-throughput assay that interrogates DNA methylation (DNAm) at over 450,000 CpG dinucleotid #300
Warren S
We are studying a potential epigenetic component to the autism spectrum disorders (ASD) by interrogating DNA methylation (DNAm) using an established high-throughput assay that interrogates DNA methylation (DNAm) at over 450,000 highly informative CpG dinucleotides. To date, we have determined the DNA methylation (DNAm) profiles from whole blood-extracted DNA of over four hundred male sib-pairs discordant for ASD. A close statistical examination may ultimately identify ASD peripheral biomarkers...
10.15154/1163512
Primary Analysis
Finding
Statistical
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. #301
Eichler EE; Girirajan S, Dennis MY, Baker C, Malig M, Coe BP, Campbell CD, Mark K, Vu TH, Alkan C, Cheng Z, Biesecker LG, Bernier R
Rare copy-number variants (CNVs) have been implicated in autism and intellectual disability. These variants are large and affect many genes but lack clear specificity toward autism as opposed to developmental-delay phenotypes. We exploited the repeat architecture of the genome to target segmental duplication-mediated rearrangement hotspots (n = 120, median size 1.78 Mbp, range 240 kbp to 13 Mbp) and smaller hotspots flanked by repetitive sequence (n = 1,247, median size 79 kbp, range 3-96 kbp)...
10.15154/1163513
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Statistical
Convergent and Discriminant Validity and Reliability of the Pediatric Anxiety Rating Scale in Youth with Autism Spectrum Disorders #304
Storch EA; Wood JJ, Ehrenreich-May J, Jones AM, Park JM, Lewin AB, Murphy TK
The psychometric properties of the Pediatric Anxiety Rating Scale (PARS), a clinician-administered measure for assessing severity of anxiety symptoms, were examined in 72 children and adolescents diagnosed with an autism spectrum disorder (ASD). The internal consistency of the PARS was 0.59, suggesting that the items were related but not repetitive.The PARS was strongly correlated with clinician-ratings of overall anxiety severity and parent- report anxiety measures, supporting convergent...
10.15154/1226467
Primary Analysis
Finding
Statistical
The Study of Health Outcomes in Children with Autism and their Families #306
Anjali J; Burke JP, Yang W, Kelly JP, Kaiser M, Becker L, Lawer L, Newschaffer CJ
The purpose of this study was to validate autism spectrum disorder cases identified through claims-based case identification algorithms against a clinical review of medical charts. Charts were reviewed for 432 children who fell into one of the three following groups: (a) more than or equal to two claims with an autism spectrum disorder diagnosis code (n = 182), (b) one claim with an autism spectrum disorder diagnosis code (n = 190), and (c) those who had no claims for autism spectrum disorder...
10.15154/1163514
Primary Analysis
Finding
Statistical
Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing #307
Daly MJ; Sutcliffe J, Gibbs R, Buxbaum J, Schellenberg G
ARRA Autism Sequencing Collaboration The VCF files provided as Study Results for this study are what was provided at the time the study was created and consist of the Autism Only consent group. There is an additional General Research Use cohort, but those data are not provided here in this study. To obtain data from the General Research Use cohort please visit the dbGaP Study phs000298. It should be noted that the dbGaP study has been updated since the time this study was created, and the...
10.15154/1163515
Primary Analysis
Finding
Genotyping/NGS
Transmission disequilibrium of small CNVs in simplex autism. #312
Eichler EE; Krumm N, O'Roak BJ, Karakoc E, Mohajeri K, Nelson B, Vives L, Jacquemont S, Munson J, Bernier R
Cohorts: 411 ASD Quads from Simons Simplex Collection 177 Quads from Sanders et al. (PubMed ID: 22495306) 166 Quads from I. Iossifov et al. (PubMed ID: 22542183) 71 Quads from O'Roak et al. (PubMed ID: 22495309) Publication Abstract: We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference...
10.15154/1163542
Secondary Analysis
Finding
Genotyping/NGS
Statistical
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. #316
Eichler EE; O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, Levy R, Ko A, Lee C, Smith JD, Turner EH, Stanaway IB, Vernot B, Malig M, Baker C, Reilly B, Akey JM, Borenstein E, Rieder MJ, Nickerson DA, Bernier R, Shendure J
In addition to cohorts of Parents (N=418), Siblings (N=50), and Probands (N=209), the publication publication describes a subset of male (N=47) and female (N=26) autistic subjects, with significant impairment and intellectual disability, and with cognitive impairment, respectively. These subsets have been defined based on hi/low IQ value in Supplementary Table 1 from the publication. Publication Abstract: It is well established that autism spectrum disorders (ASD) have a strong genetic...
10.15154/1163543
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Patterns and rates of exonic de novo mutations in autism spectrum disorders. #317
Daly MJ; Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE, Sabo A, Lin CF, Stevens C, Wang LS, Makarov V, Polak P, Yoon S, Maguire J, Crawford EL, Campbell NG, Geller ET, Valladares O, Schafer C, Liu H, Zhao T, Cai G, Lihm J, Dannenfelser R, Jabado O, Peralta Z, et al.
Notes: Data submitted to NDAR did not include interview age. Publication Abstract: Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de...
10.15154/1163544
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
De Novo Gene Disruptions in Children on the Autistic Spectrum #318
Wigler M; Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR
Public Abstract: Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this...
10.15154/1163545
Primary Analysis
Finding
Genotyping/NGS
Comparative RNA editing in autistic and neurotypical cerebella. #319
Kunkel LM; Eran A, Li JB, Vatalaro K, McCarthy J, Rahimov F, Collins C, Markianos K, Margulies DM, Brown EN, Calvo SE, Kohane IS
Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene-environment interactions underlying complex behavior in health and disease. Synaptic...
10.15154/1163546
Primary Analysis
Finding
Genotyping/NGS
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders #320
Eichler EE; O'Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill G, Kumar A, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O'Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Shendure J
Abstract: Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or...
10.15154/1163547
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. #322
Sebat J; Michaelson JJ, Shi Y, Gujral M, Zheng H, Malhotra D, Jin X, Jian M, Liu G, Greer D, Bhandari A, Wu W, Corominas R, Peoples A, Koren A, Gore A, Kang S, Lin GN, Estabillo J, Gadomski T, Singh B, Zhang K, Akshoomoff N, Corsello C, McCarroll S, Iakoucheva LM, Li Y, Wang J
De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investigated global patterns of germline mutation by whole-genome sequencing of monozygotic twins concordant for ASD and their parents. Mutation rates varied widely throughout the genome (by 100-fold) and...
10.15154/1163548
Primary Analysis
Finding
Genotyping/NGS
Statistical
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations #323
Eichler EE; O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J
Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved...
10.15154/1163549
Primary Analysis
Finding
Genotyping/NGS
Detection of structural variants and indels within exome data. #324
Eichler EE; Karakoc E, Alkan C, O'Roak BJ, Dennis MY, Vives L, Mark K, Rieder MJ, Nickerson DA
We report an algorithm to detect structural variation and indels from 1 base pair (bp) to 1 Mbp within exome sequence data sets. Splitread uses one end-anchored placements to cluster the mappings of subsequences of unanchored ends to identify the size, content and location of variants with high specificity and sensitivity. The algorithm discovers indels, structural variants, de novo events and copy number-polymorphic processed pseudogenes missed by other methods.
10.15154/1163550
Primary Analysis
Finding
Genotyping/NGS
A genome-wide scan for common alleles affecting risk for autism. #325
Devlin B; Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, et al.
Publication authors did not provide a list of Subject IDs used in this publication, cohorts in this study consist of all subjects with SNP genotyping data deposited with NDAR under data-set 8133. Publication Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558...
10.15154/1163551
Primary Analysis
Finding
Genotyping/NGS
Functional impact of global rare copy number variation in autism spectrum disorders. #327
Devlin B; Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, et al.
Data submitter did not provide a listing of specific Subject IDs used in this publication. Cohorts consist of all subjects with CNV data deposited in NDAR from the Autism Genome Project. Data was not provided for non-parental controls. Publication Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary...
10.15154/1163552
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
A protein interaction network of alternatively-spliced isoforms from brain links genetic risk factors for autism #330
Iakoucheva LM; Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M
Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by...
10.15154/1163516
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Derivation of Quality Measures for Structural Images by Neuroimaging Pipelines #331
Kennedy D; Haselgrove C
Using the National Database for Autism Research cloud platform, MRI data were analyzed using neuroimaging pipelines that included packages available as part of the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) Computational Environment to derive standardized measures of MR image quality. Structural QA was performed according to Haselgrove, et al (http://journal.frontiersin.org/Journal/10.3389/fninf.2014.00052/abstract) to provide values for Signal to Noise (SNR) and...
10.15154/1149599
Secondary Analysis
Finding
Neuro Signal Recordings
Derivation of Brain Structure Volumes from MRI Neuroimages hosted by NDAR using NITRC-CE #332
Kennedy D; Haselgrove C
A draft publication is in progress. GitHub repository with code for working with NDAR Data is available here: https://github.com/chaselgrove/ndar **Note this study is ongoing; additional may be added.**
10.15154/1149600
Secondary Analysis
Finding
Neuro Signal Recordings
Derivation of Brain Structure Volumes from MRI Neuroimages hosted by NDAR using LONI Workflows #333
Van Horn JD; Liu, Zhizhong Petrosyan, Petros Torgerson, Carinna
LONI utilized de-identified data from NDAR's cloud and a LONI Pipeline (pipeline.loni.usc.edu) processing workflow to perform a secondary structural MRI examination. The workflow used in this study pulls data from and provided by NDAR to an instance on the LONI compute cluster, aligns data to a standard orientation using FSLreorient2stsd, and undergoes further image processing to eventually identify, extract, and analyze cortical and sub-cortical structures in different MRI brain volumes. Two...
10.15154/1169189
Secondary Analysis
Finding
Neuro Signal Recordings
Complete Realignment of Whole Exome Sequencing data from 2415 families in SSC Collection #334
Krumm, N; Eichler, E
Whole Exome Sequencing has been completed for ~ 2500 families from the Simons Simplex Collection. Sequencing was performed at three individual sequencing centers with original data submitted to NDAR Collections 1878, 1895, and 1936; subsets of these data have been analyzed by various methods and published. This study represents an effort to realign sequencing data from all three collection sin a uniform manner using the latest toolchains and algorithms available, which can be used as a resource...
10.15154/1169193
Secondary Analysis
Finding
Genotyping/NGS
De novo mutations revealed by whole exome sequencing are strongly associated with autism #336
State MW; Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, et al.
Multiple studies have confirmed the contribution of rare de novo copy number variations (CNVs) to the risk for Autism Spectrum Disorders (ASD). While de novo single nucleotide variants (SNVs) have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations has not been well characterized in matched unaffected controls, data that are vital to the interpretation of de novo coding mutations observed in...
10.15154/1163553
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. #340
Volk HE; Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, Campbell DB
Background: Independent studies report association of autism spectrum disorder with air pollution exposure and a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. Toxicologic data find altered brain Met expression in mice after prenatal exposure to a model air pollutant. Our objective was to investigate whether air pollution exposure and MET rs1858830 genotype interact to alter ASD risk. Methods: We studied 252 cases of autism spectrum disorder and...
10.15154/1163517
Primary Analysis
Finding
Genotyping/NGS
Statistical
Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. #341
Willsey AJ; Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, Reilly SK, Lin L, Fertuzinhos S, Miller JA, Murtha MT, Bichsel C, Niu W, Cotney J, Ercan-Sencicek AG, Gockley J, Gupta AR, Han W, He X, Hoffman EJ, Klei L, Lei J, Liu W, Liu L, Lu C, Xu X, et al.
NDAR Data for this study consist of Whole Exome sequencing for the additional 56 families from SSC collection. Other Whole Exome sequencing data and results used in this study were originally published elsewhere. NDAR Studies 340, 320, and 317 describe the data published in Iossifov et al., 2012; Neale et al., 2012; O'Roak et al., 2012b, respectively, as cited in this publication. The RNA-Seq data from this publication are available from NCBI at the given BioProject accession. Autism...
10.15154/1226480
Primary Analysis
Finding
Genotyping/NGS
Derivation of Brain Structure Volumes from MRI Neuroimages hosted by NDAR using C-PAC pipeline and ANTs #342
Craddock C; Clark D
An automated pipeline was developed to reference Neuroimages hosted by the National Database for Autism Research (NDAR) and derive volumes for distinct brain structures using Advanced Normalization Tools (ANTs) and the Configurable-Pipeline for the Analysis of Connectomes (C-PAC) platform. This pipeline utilized the ANTs cortical thickness methodology discuessed in "Large-Scale Evaluation of ANTs and Freesurfer Cortical Tchickness Measurements" [http://www.ncbi.nlm.nih.gov/pubmed/24879923] to...
10.15154/1165646
Secondary Analysis
Finding
Neuro Signal Recordings
Transcriptional consequences of 16p11.2 deletion and duplication in mouse cortex and multiplex autism families #343
Gusella JF; Blumenthal I, Ragavendran A, Erdin S, Klei L, Sugathan A, Guide JR, Manavalan P, Zhou JQ, Wheeler VC, Levin JZ, Ernst C, Roeder K, Devlin B, Talkowski ME
Publication Abstract: Reciprocal copy number variation (CNV) of a 593 kb region of 16p11.2 is a common genetic cause of autism spectrum disorder (ASD), yet it is not completely penetrant and can manifest in a wide array of phenotypes. To explore its molecular consequences, we performed RNA-sequencing of cerebral cortex from mouse models with CNV of the syntenic 7qF3 region, and lymphoblast lines from 34 members of seven multiplex ASD families harboring the 16p11.2 CNV. Expression of all...
10.15154/1163554
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Statistical
Genotypes of Swedish subjects used in "Most genetic risk for autism resides with common variation" study #346
Buxbaum JD; Gaugler T, Klei L , Sanders SJ, Bodea CA , Goldberg AP, Lee AB, Mahajan M, Manaa D, Pawitan Y, Reichert J, Ripke S, Sandin S, Sklar P, Svantesson O, Reichenberg A, Hultman CM, Devlin B, Roeder K
A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial...
10.15154/1165648
Primary Analysis
Finding
Genotyping/NGS
Statistical
Variant Recalling (GATK) from Whole Exome Sequencing data for 2415 families in SSC Collection #348
Krumm, N; Eichler, E
Whole Exome Sequencing has been completed for ~ 2500 families from the Simons Simplex Collection. Sequencing was performed at three individual sequencing centers with original data submitted to NDAR Collections 1878, 1895, and 1936; subsets of these data have been analyzed by various methods and published. This study represents an effort to call and annotate SNPs and Indels on data from all three collections in a uniform manner using the latest toolchains and algorithms available. Variant...
10.15154/1169195
Secondary Analysis
Finding
Genotyping/NGS
Variant Recalling (FreeBayes) from Whole Exome Sequencing data for 2415 families in SSC Collection #349
Krumm, N; Eichler, E
Whole Exome Sequencing has been completed for ~ 2500 families from the Simons Simplex Collection. Sequencing was performed at three individual sequencing centers with original data submitted to NDAR Collections 1878, 1895, and 1936; subsets of these data have been analyzed by various methods and published. This study represents an effort to call and annotate SNPs and Indels on data from all three collections in a uniform manner using the latest toolchains and algorithms available. Variant...
10.15154/1169197
Secondary Analysis
Finding
Genotyping/NGS
Derivation of Quality Measures for Time-Series Images by Neuroimaging Pipelines #350
Kennedy D; Haselgrove C
Using the National Database for Autism Research cloud platform, MRI data were analyzed using neuroimaging pipelines that included packages available as part of the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) Computational Environment to derive standardized measures of MR image quality. Time series QA was performed according to Friedman, et al. (http://www.ncbi.nlm.nih.gov/pubmed/16952468) providing values for Signal to Noise Ratio that can be compared to other subjects.
10.15154/1149598
Secondary Analysis
Finding
Neuro Signal Recordings
The contribution of de novo coding mutations to autism spectrum disorder #352
Wigler, M; Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E., Smith, J.D., Paeper, B., Nickerson, D.A., Dea, J., Dong, S., Gonzalez, L.E., Mandell, J.E., Mane, S.M., Murtha, M.T., Sullivan, C.A., Walker, M.F., Waqar, Z., Wei, L., Willsey, A.J., Yamrom, B., Lee, Y.H., Grabowska, E., Dalkic, E., Wang, Z., Marks, S., Andrews, P., Leotta, A., Kendall, J., Hakker, I., Rosenbaum, J., Ma, B., Rodgers, L., Troge, J., Narzisi, G., Yoon, S., Schatz, M.C., Ye, K., McCombie, W.R., Shendure, J., Eichler, E.E., State, M.W
Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute...
10.15154/1149697
Secondary Analysis
Finding
Genotyping/NGS
Excess of rare inherited truncating mutations in autism #353
Eichler E; Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K, Raja A, Coe BP, Stessman HA, He Z, Leal SM, Bernier R
In order to quantify the effect of private, inherited mutations on autism risk, we generated a callset of both inherited and de novo single nucleotide variants (SNVs) and copy number variants (CNVs) across 2,377 Simons Simplex Collection families. The publically deposited dataset includes 1,786 parents-child-unaffected sibling "quads" allowing us to compare burden of inherited and de novo mutations between affected and unaffected siblings in simplex autism families. We find that private,...
10.15154/1151812
Secondary Analysis
Finding
Genotyping/NGS
Cryptic and complex chromosomal aberrations in early onset neuropsychiatric disorders #357
Doyle AE; Brand H, Pillalamarri V, Collins R, Eggert S, O'Dushlaine C, Braaten EB, Stone M, Chambert K, Doty ND, Hanscom C, Ditmars H, Blais J, Mills R, Lee C, Gusella JF, McCarroll S, Smoller JW, Talkowski ME
Structural variation (SV) is a significant component of the genetic etiology of both neurodevelopmental and psychiatric disorders; however, routine guidelines for clinical genetic screening have been established only in the former category. Genome-wide chromosomal microarray (CMA) can detect genomic imbalances such as copy-number variants (CNVs), but balanced chromosomal abnormalities (BCAs) still require karyotyping for clinical detection. Moreover, submicroscopic BCAs and subarray threshold...
10.15154/1157584
Primary Analysis
Finding
Genotyping/NGS
Statistical
Psychometric Analysis of the Social Communication Questionnaire Using an Item-Response Theory Framework: Implications for the Use of the Lifetime and Current Forms #358
Richman DM; Wei T, Chestnut SR, Barnard-Brak L
The Social Communication Questionnaire (SCQ) was developed as a screener of Autism Spectrum Disorder (ASD). To date, the majority of the SCQ utility studies focused on its external validity (e.g., ROC curve analyses), but very few have addressed the internal validity issues. With samples consisting of 2,134 individuals available from the National Database for Autism Research (NDAR), the current study examined the factor structure, item-level characteristics, and measurement equivalence of the...
10.15154/1158938
Secondary Analysis
Finding
Statistical
Predicting Health Utilities for Children With Autism Spectrum Disorders #360
Tilford, MJ; Payakachat, N; Kuhlthau, KA; van Exel, NJ; Kovacs, E; Bellando, J; Pyne, JM; Brouwer, WBF
Comparative effectiveness of interventions for children with autism spectrum disorders (ASDs) that incorporates costs is lacking due to the scarcity of information on health utility scores or preference-weighted outcomes typically used for calculating quality-adjusted life years (QALYs). This study created algorithms for mapping clinical and behavioral measures for children with ASDs to health utility scores. The algorithms could be useful for estimating the value of different interventions and...
10.15154/1170418
Primary Analysis
Finding
Statistical
Copy Number Variants from SSC Collection ~ 2500 families by two Methods (XHMM and Conifer) #361
Krumm, N; Eichler, E
XHMM was run on a set of realigned BAM files from the SSC collection (see NDAR Study 334 for BAM files) using the attached scripts. These scripts calculate depth of coverage using GATK, pull the GATK output from an instance on NDAR's cloud, merge the output of GATK into a single matrix, process the read depth matrix (filter, center), normalize the matrix using principal component analysis (PCA), process the normalized read depth matrix (filter, z-score), run a hidden markov model (HMM) on...
10.15154/1169318
Secondary Analysis
Finding
Genotyping/NGS
fMRI for affective psychological studies #365
Lee, Ray
Taking advantage a newly developed dyadic fMRI system, this project studied two brains interactions via eye contact. This is the first direct observation of the dyadic affective states mediated by reciprocal visual stimulation. The dual system activation due to in vivo reciprocity, empathy system and metallization system, are clear evidences, while such systems often are not fully activated by pictorial stimuli. This method offers a direct and quantitative approach to estimate deficiency of...
10.15154/1170165
Primary Analysis
Finding
Neuro Signal Recordings
Recurrent de novo mutations implicate novel genes underlying simplex autism risk. #366
Eichler EE; O'Roak BJ, Stessman HA, Boyle EA, Witherspoon KT, Martin B, Lee C, Vives L, Baker C, Hiatt JB, Nickerson DA, Bernier R, Shendure J
Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally...
10.15154/1170505
Primary Analysis
Finding
Genotyping/NGS
Loss of delta-catenin function in severe autism #367
Chakravarti, Aravinda; Turner, TN; Sharma, K; Oh, EC; Liu, YP; Collins, RL; Sosa, MX; Auer, DR; Brand, H; Sanders, SJ; Moreno-De-Luca, D; Pihur, V; Plona, T; Pike, K; Soppet, DR; Smith, MW; Cheung, SW; Martin, CL; State, MW, Talkowski, ME; Cook, E; Huganir, R; Katsanis, N
Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from female-enriched multiplex families with severe disease, enhancing the detection of key autism genes in modest numbers of cases. Here we show the use of this...
10.15154/1171641
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Statistical
Decreased tryptophan metabolism in patients with Autism Spectrum Disorders #369
Charles Schwartz ; Boccuto, L; Chen, C; Pittman,A; Skinner, C; McCartney, H; Jones, K; Bochner, B; Stevenson, R.
Background: Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions. Methods: We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays. Results:...
10.15154/1178660
Primary Analysis
Finding
Microarray/Protein Analysis
No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins #370
State, Matthew; Murdoch, J; Gupta, A; Sanders, S; Walker, M; Keaney, J; Fernandez, T; Murtha, M; Anyanwu, S; Ober, G; Raubeson, M; DiLullo, N; Villa, N; Waqar, Z; Sullivan, C; Gonzalez, L; Willsey, J; Choe, S; Neale, B; Daly, M
Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point...
10.15154/1176904
Primary Analysis
Finding
Genotyping/NGS
Rare-Variant Extensions of the Transmission Disequilibrium Test: Application to Autism Exome Sequence Data #371
Leal, Suzanne; He, Z; O'Roak, B; Smith, J; Wang, G; Hooker, S; Santos-Cortez, R; Li, B; Kan, M; Krumm, N; Nickerson, D; Shendure, J; Eichler, E
Many population-based rare-variant (RV) association tests, which aggregate variants across a region, have been developed to analyze sequence data. A drawback of analyzing population-based data is that it is difficult to adequately control for population substructure and admixture, and spurious associations can occur. For RVs, this problem can be substantial, because the spectrum of rare variation can differ greatly between populations. A solution is to analyze parent-child trio data, by using...
10.15154/1177023
Primary Analysis
Finding
Genotyping/NGS
Statistical
RNA-Seq studies of gene expression in micro-dissected samples from the brains of individuals with autism and controls #372
Allman, John; Wold, Barbara
We seek to understand the cellular bases of autism by using a new technology, RNA-Seq, to determine differences in gene expression in autopsy brains of subjects with well described autism versus age and sex matched neurotypical individuals. We have investigated two specific cortical areas involved in self-awareness and social reciprocity which are abnormal in autism and have found increased expression in a network of genes related to inflammation in autism group A, whereas the remaining cases,...
10.15154/1195995
Primary Analysis
Finding
Genotyping/NGS
Development and validation of a brain maturation index using longitudinal neuroanatomical scans #374
Benson Mwangi PhD; Cao Bo, Hasan Khader, Selvaraj Sudhakar, Zeni Cristian, Zunta-Soares Giovan, Soares Jair.
Background Major psychiatric disorders are increasingly being conceptualized as ‘neurodevelopmental’, because they are associated with aberrant brain maturation. Several studies have hypothesized that a brain maturation index integrating patterns of neuroanatomical measurements may reliably identify individual subjects deviating from a normative neurodevelopmental trajectory. However, while recent studies have shown great promise in developing accurate brain maturation indices using...
10.15154/1195991
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
The Sensitivity and Specificity of the Social Communication Questionnaire for Autism Spectrum Disorder with Respect to Age #375
Barnard-Brak, Lucy; Brewer A; Chesnut S; Richman D; Shaeffer AM
Scientific Abstract The Social Communication Questionnaire (SCQ) assesses communication skills and social functioning in screening for symptoms of autism-spectrum disorder (ASD). The SCQ is recommended for individuals between 4 to 40 years with a cutoff score of 15 for referral. Mixed findings have been reported regarding the recommended cutoff score’s ability to accurately classify an individual as at-risk for ASD (sensitivity) versus an individual as not at-risk for ASD (specificity). Based...
10.15154/1195992
Secondary Analysis
Finding
Statistical
Revising the Social Communication Questionnaire scoring procedures for Autism Spectrum Disorder and potential Social Communication Disorder #376
Barnard-Brak, Lucy; Richman D; Chesnut S; Little TD
In analyzing data from the National Database for Autism Research, we examine revising the Social Communication Questionnaire (SCQ), a commonly used screening instrument for Autism Spectrum Disorder. A combination of Item Response Theory and Mokken scaling techniques were utilized to achieve this and abbreviated scoring of the SCQ is suggested. The psychometric sensitivity of this abbreviated SCQ was examined via bootstrapped Receiver Operator Characteristic (ROC) curve analyses. Additionally,...
10.15154/1195993
Secondary Analysis
Finding
Statistical
Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort #377
Feinberg, Andrew P.; Fallin, M. Daniele (Co-PIs); Feinberg, J; Bakulski, K; Jaffe, A; Tryggvadottir, R; Brown, S; Goldman, L; Croen, L; Hertz-Picciotto, I; Newschaffer, C
Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum...
10.15154/1195994
Primary Analysis
Finding
Microarray/Protein Analysis
Statistical
Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task. #378
Damarla SR; Keller T, Kana R, Cherkassky V, Williams D, Minshew N, Just M
Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance...
10.15154/1223858
Primary Analysis
Finding
Neuro Signal Recordings
Autonomy of lower-level perception from global processing in autism: evidence from brain activation and functional connectivity. #379
Liu Y; Cherkassky V, Minshew N, Just M
Previous behavioral studies have shown that individuals with autism are less hindered by interference from global processing during the performance of lower-level perceptual tasks, such as finding embedded figures. The primary goal of this study was to examine the brain manifestation of such atypicality in high-functioning autism using fMRI. Fifteen participants with high-functioning autism and fifteen age- and IQ-matched typical controls were asked to perform a lower-level perceptual...
10.15154/1223859
Primary Analysis
Finding
Neuro Signal Recordings
The neural basis of deictic shifting in linguistic perspective-taking in high-functioning autism #380
Mizuno A; Liu Y, Williams D, Keller T, Minshew N, Just M
Personal pronouns, such as 'I' and 'you', require a speaker/listener to continuously re-map their reciprocal relation to their referent, depending on who is saying the pronoun. This process, called 'deictic shifting', may underlie the incorrect production of these pronouns, or 'pronoun reversals', such as referring to oneself with the pronoun 'you', which has been reported in children with autism. The underlying neural basis of deictic shifting, however, is not understood, nor has the...
10.15154/1223860
Primary Analysis
Finding
Neuro Signal Recordings
Distinctive Neural Processes during Learning in Autism #381
Schipul SE; Williams D, Keller T, Minshew N, Just M
This functional magnetic resonance imaging study compared the neural activation patterns of 18 high-functioning individuals with autism and 18 IQ-matched neurotypical control participants as they learned to perform a social judgment task. Participants learned to identify liars among pairs of computer-animated avatars uttering the same sentence but with different facial and vocal expressions, namely those that have previously been associated with lying versus truth-telling. Despite showing a...
10.15154/1223861
Primary Analysis
Finding
Neuro Signal Recordings
Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders. #382
Yao, Gang; Daluwatte C; Miles JH; Sun J
Atypical pupillary light reflexes (PLR) has been observed in children with autism spectrum disorders (ASD), which suggests potential autonomic nervous system (ANS) dysfunction in ASD. ANS is also involved in modulating sensory processing and sensory dysfunction has been widely reported in children with ASD. However, the potential association between physiological measurements of PLR and behavioral observations (e.g. sensory behaviors) has not been examined extensively in literature. In this...
10.15154/1223865
Primary Analysis
Finding
Statistical
Atypical pupillary light reflex and heart rate variability in children with autism spectrum disorder #383
Yao, Gang; Daluwatte C, Miles JH, Christ SE, Beversdorf DQ, Takahashi N,
We investigated pupillary light reflex (PLR) in 152 children with ASD, 116 typically developing (TD) children, and 36 children with non-ASD neurodevelopmental disorders (NDDs). Heart rate variability (HRV) was measured simultaneously to study potential impairments in the autonomic nervous system (ANS) associated with ASD. The results showed that the ASD group had significantly longer PLR latency, reduced relative constriction amplitude, and shorter constriction/redilation time than those of the...
10.15154/1223868
Primary Analysis
Finding
Statistical
Identification of Infants at High-Risk for Autism Spectrum Disorder Using Multiparameter Multiscale White Matter Connectivity Networks #385
Shen, Dinggang; Jin, Yan; Wee, Chong-Yaw; Shi, Feng; Thung, Kim-Han; Ni, Dong; Yap, Pew-Thian
Autism spectrum disorder (ASD) is a wide range of disabilities that cause life-long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for...
10.15154/1223873
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
Germline Mutations in Predisposition Genes in Pediatric Cancer #387
Jinghui Zhang; Michael F. Walsh, M.D.; Gang Wu, Ph.D.; Michael N. Edmonson, B.A.; Tanja A. Gruber, M.D.; Ph.D., John Easton; Ph.D., Dale Hedges; Ph.D., Xiaotu Ma; Ph.D., Xin Zhou; Ph.D., Donald A. Yergeau; Ph.D., Mark R. Wilkinson; B.S., Bhavin Vadodaria; B.A., Xiang Chen; Ph.D., Rose B. McGee; M.S., Stacy Hines-Dowell; D.N.P., Regina Nuccio; M.S., Emily Quinn; M.S., Sheila A. Shurtleff; Ph.D. Michael Rusch; B.A., Aman Patel; M.S., Jared B. Becksfort; M.S., Shuoguo Wang; Ph.D. Meaghann S. Weaver; M.D., Li Ding; Ph.D., Elaine R. Mardis; Ph.D., Richard K. Wilson; Ph.D., Amar Gajjar; M.D., David W. Ellison; M.D.; Ph.D., Alberto S. Pappo; M.D., Ching-Hon Pui; M.D., Kim E. Nichols, M.D.; and James R. Downing, M.D.
Background The prevalence and spectrum of predisposing mutations among children and adolescents with cancer are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families. Methods In 1120 patients younger than 20 years of age, we sequenced the whole genomes (in 595 patients), whole exomes (in 456), or both (in 69). We analyzed the DNA sequences of 565 genes, including 60 that have been...
10.15154/1334287
Secondary Analysis
Finding
Genotyping/NGS
Genome sequencing of autism families reveals disruption of putative noncoding regulatory DNA #388
Eichler, Evan; Turner, Tychele N.; Hormozdiari, Fereydoun; Duyzend, Michael H.; McClymont, Sarah A.; Hook, Paul W.; Iossifov, Ivan; Raja, Archana; Baker, Carl; Hoekzema, Kendra; Stessman, Holly A.; Zody, Michael C.; Nelson, Bradley J.; Huddleston, John; Sandstrom, Richard; Smith, Joshua D.; Hanna, David; Swanson, James M.; Faustman, Elaine M.; Bamshad, Michael J.; Stamatoyannopoulos, John; Nickerson, Deborah A.; McCallion, Andrew S.; Darnell, Robert
We performed whole-genome sequencing (WGS) of 160 genomes from 40 simplex autism families, the majority of which had no copy number variant (CNV) or candidate de novo gene-disruptive single nucleotide variant (SNV) by microarray or whole-exome sequencing (WES). SNV and CNV calling was achieved by a number of variant calling algorithms. This accession contains SNV (FreeBayes) and CNV (digital comparative genomic hybridization [dCGH], GenomeSTRiP, VariationHunter) calls from this study.
10.15154/1226523
Secondary Analysis
Finding
Genotyping/NGS
Maternal modifiers and parent-of-origin bias of the autism 16p11.2 CNV #389
Eichler EE; Duyzend MH, Nuttle X, Coe BP, Baker C, Nickerson DA, Bernier R
Recurrent deletions and duplications at chromosome 16p11.2 are a major genetic contributor to autism but also associate with a wider range of pediatric diagnoses. In order to investigate the potential genetic basis for phenotype variability, we assessed the parent-of-origin of the 16p11.2 copy number variant (CNV) and the presence of additional CNVs using commercial SNP microarrays in over 100 families where detailed phenotype data were available. Additional phenotypic and genotypic data is...
10.15154/1226522
Primary Analysis
Finding
Genotyping/NGS
Microarray/Protein Analysis
Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms #391
Walsh, CA; D’Gama, I; Pochareddy, S; Li, M; Jamuar, S; Reiff, RE; Lam, A; Sestan, N
Single nucleotide variants (SNVs), particularly loss-of-function mutations, are significant contributors to autism spectrum disorder (ASD) risk. Here we report the first systematic deep sequencing study of 55 postmortem ASD brains for SNVs in 78 known ASD candidate genes. Remarkably, even without parental samples, we find more ASD brains with mutations that are protein-altering (26/55 cases versus 12/50 controls, p = 0.015), deleterious (16/55 versus 5/50, p = 0.016), or loss-of-function (6/55...
10.15154/1227279
Primary Analysis
Finding
Genotyping/NGS
The topography of alpha-band activity tracks the content of spatial working memory #394
Awh, Edward & Vogel, Edward K.; Foster, J.J., Sutterer, D.S., Serences, J.T.
Working memory (WM) is a system for the online storage of information. An emerging view is that neuronal oscillations coordinate the cellular assemblies that code the content of WM. In line with this view, previous work has demonstrated that oscillatory activity in the alpha-band (8-12 Hz) plays a role in WM maintenance but the exact contributions of this activity have remained unclear. Here, we used an inverted spatial encoding model in combination with electroencephalography (EEG) to test...
10.15154/1334292
Primary Analysis
Finding
Neuro Signal Recordings
Trajectories of cortical thickness maturation in normal brain development #395
Ducharme, Simon; Albaugh M, Nguyen T, Hudziak J, Mateos-Pérez J, Labbe A, Evans A, Karama S
Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step, evaluated the impact of post-processing quality control (QC) procedures on identified...
10.15154/1240724
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain #396
Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Irfanoglu, M; Albert, Paul; Pierpaoli, Carlo; Brain Development Cooperative Group
Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent interindividual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different...
10.15154/1240725
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
A new template to study callosal growth shows specific growth in anterior and posterior regions of the corpus callosum in early childhood #397
Ansado, Jennyfer; Collins, Louis; Fonov, Vladimir; Garon, Mathieu; Alexandrov, Lubomir; Karama, Sherif; Evans, Alan; Beauchamp, Miriam; and Brain Development Cooperative Group
Most of the studies conducted on the development of the corpus callosum (CC) have been limited to a relatively simple assessment of callosal area, providing an estimation of the size of the CC in two dimensions rather than its actual measurement. The goal of this study was to revisit callosal development in childhood and adolescence by using a three-dimensional (3D) magnetic resonance imaging template of the CC that considers the horizontal width of the CC and compares this with the...
10.15154/1240718
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
Prediction of brain maturity based on cortical thickness at different spatial resolutions #398
Khundrakpam, Budhachandra; Tohka, Jussi; Evans, Alan; and the Brain Development Cooperative Group
Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders...
10.15154/1240720
Secondary Analysis
Finding
Neuro Signal Recordings
Statistical
The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI) #399
Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, Okan; Botteron, Kelly; McCracken, James; McKinstry, Robert; Rivkin, Michael; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo; the Brain Development Cooperative Group
The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians,which could serve...
10.15154/1240722
Secondary Analysis
Finding
Neuro Signal Recordings
Variants in adjacent oxytocin/vasopressin gene region and associations with ASD diagnosis and autism related endophenotypes #404
Cook, Edwin H.; Francis, Sunday M.; Kistner-Griffin, Emily; Yan, Zhongyu; Guter, Stephen; Jacob, Suma
Background: There has been increasing interest in oxytocin (peptide: OT, gene: OXT) as a treatment pathway for neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Neurodevelopmental disorders affect functional, social, and intellectual abilities. With advances in molecular biology, research has connected multiple gene regions to the clinical presentation of ASD. Studies have also shown that the neuropeptide hormones OT and arginine vasopressin (AVP) influence mammalian social...
10.15154/1303416
Primary Analysis
Finding
Genotyping/NGS
Statistical
The contribution of mosaic variants to autism spectrum disorder #405
Pevsner, Jonathan; Freed, Donald
De novo mutation is highly implicated in autism spectrum disorder (ASD). However, the contribution of post-zygotic mutation to ASD is poorly characterized. We performed both exome sequencing of paired samples and analysis of de novo variants from whole-exome sequencing of 2,388 families. While we find little evidence for tissue-specific mosaic mutation, multi-tissue post-zygotic mutation (i.e. mosaicism) is frequent, with detectable mosaic variation comprising 5.4% of all de novo mutations. We...
10.15154/1247692
Secondary Analysis
Finding
Genotyping/NGS
Statistical
De novo genic mutations among a Chinese autism spectrum disorder cohort #406
Eichler Evan; Tianyun W, Hui G, Bo X, Holly A.F. S, Huidan W, Bradley P. C, Tychele N. T, Yanling L, Wenjing Z, Kendra H, Laura V, Lu X, Meina T, Jianjun O, Biyuan C, Yidong S, Guanglei X, Min L, Janice L, Zev N. K, Yu P, Ting B, Honghui L, Xiaoyan K, Zhengmao H, Jingping Z, Xiaobing Z
Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations are important risk factors for autism spectrum disorders (ASD) but have been primarily investigated in cohorts of European ancestry. We sequenced 189 risk genes in 1,543 ASD probands (1,045 from trios) with Chinese ancestry. We report an 11-fold increase in the odds of DN LGD mutations compared to expectation under an exome-wide mutational rate model based on chimpanzee–human divergence. This enrichment for DN LGD mutations...
10.15154/1252218
Primary Analysis
Finding
Genotyping/NGS
Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder #407
Schultz, Stephen; Gould, G
Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restrictive behavior, interests, and activities. Our previous case-control study showed that use of acetaminophen at age 12-18 months is associated with increased likelihood for ASD (OR 8.37, 95% CI 2.08-33.7). In this study, we again show that acetaminophen use is associated with ASD (p = 0.013). Because these children are older than in our first study, the association is reversed; fewer children...
10.15154/1334293
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Statistical
Cross-trial prediction of treatment outcome in depression: a machine learning approach #408
Chekroud, Adam; Corlett, P; Krystal, J; Cannon, T; Trivedi, M; Johnson, M; Gueorguieva, R; Shehzad, Z; Zotti, R
Background: Antidepressant treatment efficacy is low, but might be improved by matching patients to interventions. At present, clinicians have no empirically validated mechanisms to assess whether a patient with depression will respond to a specific antidepressant. We aimed to develop an algorithm to assess whether patients will achieve symptomatic remission from a 12-week course of citalopram. Methods: We used patient-reported data from patients with depression (n=4041, with 1949 completers)...
10.15154/1334294
Secondary Analysis
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Statistical
Frequency and Complexity of De Novo Structural Mutation in Autism #410
Sebat, Jonathan; Corsello, Christina; Iakoucheva, Lilia; Courchesne, Eric
Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising...
10.15154/1324432
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Genotyping/NGS
Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci #411
Sanders, Stephan; He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, Murtha MT, Bal VH, Bishop SL, Dong S, Goldberg AP, Jinlu C, Keaney JF 3rd, Klei L, Mandell JD, Moreno-De-Luca D, Poultney CS, Robinson EB, Smith L, Solli-Nowlan T, Su MY, Teran NA, Walker MF, Werling DM, Beaudet AL, Cantor RM, Fombonne E, Geschwind DH, Grice DE, Lord C, Lowe JK, Mane SM, Martin DM, Morrow EM, Talkowski ME, Sutcliffe JS, Walsh CA, Yu TW: Autism Sequencing Consortium, Ledbetter DH, Martin CL, Cook EH, Buxbaum JD, Daly MJ, Devlin B, Roeder K, State MW
Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large...
10.15154/1334312
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Statistical
Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. #414
James Gusella; Tai DJ, Ragavendran A, Manavalan P, Stortchevoi A, Seabra CM, Erdin S, Collins RL, Blumenthal I, Chen X, Shen Y, Sahin M, Zhang C, Lee C, Gusella JF, Talkowski ME
Recurrent, reciprocal genomic disorders resulting from non-allelic homologous recombination (NAHR) between near-identical segmental duplications (SDs) are a major cause of human disease, often producing phenotypically distinct syndromes. The genomic architecture of flanking SDs presents a challenge for modeling these syndromes; however, the capability to efficiently generate reciprocal copy number variants (CNVs) that mimic NAHR would represent a valuable modeling tool. We describe here a...
10.15154/1334313
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Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism. #416
Cook, Edwin H.; Chen, Rui; Davis, Lea K.; Guter, Stephen; Wie, Qiang; Jacob, Suma; Potter, Melissa H.; Cox, Nancy J.; Sutcliffe, James S.; Li, Bingshan
Background: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers is an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic...
10.15154/1271285
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Genotyping/NGS
The clinical relevance of self-reported premenstrual worsening of depressive symptoms in the management of depressed outpatients: a STAR*D report. #417
A. John Rush; Haley CL, Sung SC, Rush AJ, Trivedi MH, Wisniewski SR, Luther JF, Kornstein SG
OBJECTIVE: To determine the incidence, clinical and demographic correlates, and relationship to treatment outcome of self-reported premenstrual exacerbation of depressive symptoms in premenopausal women with major depressive disorder who are receiving antidepressant medication. METHOD: This post-hoc analysis used clinical trial data from treatment-seeking, premenopausal, adult female outpatients with major depression who were not using hormonal contraceptives. For this report, citalopram was...
10.15154/1334299
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Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis. #418
Cai, James J; Guan, Jinting; Yang, Ence; Yang, Jizhou; Zeng, Yong; Ji, Guoli
Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an...
10.15154/1334300
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Statistical
Preliminary findings suggest the number and volume of supragranular and infragranular pyramidal neurons are similar in the anterior superior temporal area of control subjects and subjects with autism. #420
Veronica Martinez Cerdeno; Kim E, Camacho J, Combs Z, Ariza J, Lechpammer M, Noctor SC, Martínez-Cerdeño V
We investigated the cytoarchitecture of the anterior superior temporal area (TA2) of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched typically developing subjects between the ages of 13 and 56 years. The superior temporal gyrus is involved in auditory processing and social cognition and its pathology has been correlated with autism. We quantified the number and soma volume of pyramidal neurons in the supragranular layers and pyramidal neurons in the infragranular...
10.15154/1334291
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The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Medial Prefrontal Cortex in Autism. #421
Veronica Martinez Cerdeno; Hashemi E, Ariza J, Rogers H, Noctor SC, Martínez-Cerdeño V
UNASSIGNED: The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We...
10.15154/1336398
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Targeted sequencing identifies 91 neurodevelopmental disorder risk genes with autism and developmental disability biases #425
Eichler, Evan; Stessman, H; Xiong, B; Coe, B; Wang, T; Hoekzema, K; Fenckova, M; Kvarnung, M; Gerdts, J; Trinh, S; Cosemans, N; Vives, L; Lin, J; Turner, T; Santen, G; Gecz, J; Shaw, M; Anderlid, B; Nordgren, A; Lindstrand, A; Schwartz, C; Kooy, F; Vandeweyer, G; Helsmoortel, C; Romano, C; Alberti, A; Vinci, M; Avola, E; Giusto, S; Courchesne, E; Pramparo, T; Pierce, K; Nalabolu, S; Amaral, D; Scheffer, I; Delatycki, M; Lockhart, P; Hormozdiari, F; Harich, B; Castells-Hobau, A; Xia, K; Peeters, H; Nordenskjold, M; Schenck, A; Bernier, R
Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 patients and >2,867 controls. We report 91 genes with an excess of de novo mutations or private disruptive mutations in 5.7% of patients, including 38 novel NDD genes. Drosophila functional assays of a subset bolster their involvement in NDDs. We identify 25 genes that show a bias for autism versus intellectual...
10.15154/1340671
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Genotyping/NGS
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ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR #427
Cook, Edwin; Francis, Sunday M.; Kim, Soo-Jeong; Kistner-Griffin, Emily; Guter, Stephen; Jacob, Suma
Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as, ASD-related phenotypes. Researchers have also found the manipulation of these systems affect social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased....
10.15154/1345185
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Genotyping/NGS
Cognitive remediation for individuals with psychosis: Efficacy and mechanisms of treatment effects #428
Joanna M Fiszdon, Ph.D.; Kee-Hong Choi, Ph.D.; Morris D Bell, Ph.D.; Jimmy Choi, Psy.D.; Steven M Silverstein, Ph.D.
The popularity of cognitive remediation (CR) interventions for individuals with psychosis is in part based on the well-established link between cognition and functioning and the assumption that by targeting cognition, function can improve. While numerous trials have reported CR's efficacy, it is still not considered an evidencebased treatment. Importantly, little is known about the mechanisms through which it may affect functioning. Method: In this study, we evaluated CR's proximal and...
10.5072/1338195
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Statistical
The evolution and population diversity of human-specific segmental duplications #431
Eichler, EE; Dennis, MY; Dougherty, ML; Harshman, L; Nelson, BJ; Penn, O; Cantsilieris, S; Huddleston, J; Antonacci, F; Penewit, F; Denman, L; Raja, A; Baker, C; Mark, K; Malig, M; Janke, N; Espinoza, C; Stessman, HAF; Nuttle, X; Hoekzema, K; Lindsay-Graves, TA; Wilson, RK
Segmental duplications contribute to human evolution, adaptation and genomic instability but are often poorly characterized. We investigate the evolution, genetic variation and coding potential of human-specific segmental duplications (HSDs). We identify 218 HSDs based on analysis of 322 deeply sequenced archaic and contemporary hominid genomes. We sequence 550 human and nonhuman primate genomic clones to reconstruct the evolution of the largest, most complex regions with protein-coding...
10.15154/1338620
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Genotyping/NGS
Defining the spectrum of large inversions, complex structural variation, and chromothripsis in the morbid genome #433
Talkowski, Michael; Collins, Ryan; Brand, Harrison; Redin, Claire; Hanscom, Carrie; Antolik, Caroline; Stone, Matthew; Glessner, Joseph; Mason, Tamara; Pregno, Giulia; Dorrani, Naghmeh; Mandrile, Giorgia; Giachino, Daniel; Perrin, Danielle; Walsh, Cole; Cipicchio, Michelle; Costello, Maura; Stortchevoi, Alexei; An, Joon-Yong; Currall, Benjamin; Seabra, Catarina; Ragavendran, Ashok; Margolin, Lauren; Martinez-Agosto, Julian; Lucente, Diane; Levy, Brynn; Sanders, Stephan; Wapner, Ronald; Quintero-Rivera, Fabiola; Kloosterman, Wigard; Talkowski, Michael.
Background: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. Results: We sequenced 689 subjects with autism spectrum disorder and other developmental abnormalities to construct a genome-wide map of large SV. Using long-insert jumping libraries at 105X mean physical coverage and linked-read whole-genome sequencing from 10X Genomics, we...
10.15154/1336394
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Genotyping/NGS
Statistical
Paternally inherited noncoding structural variants contribute to autism #434
Sebat, Jonathan; Brandler, W; Gujral, M; Antaki, D; Iakoucheva, L; Corsello, C; Hervas, A; Mutori, A
The genetic architecture of autism spectrum disorder (ASD) is known to consist of contributions from gene-disrupting de novo mutations and common variants of modest effect. We hypothesize that the unexplained heritability of ASD also includes rare inherited variants with intermediate effects. We investigated the genome-wide distribution and functional impact of structural variants (SVs) through whole genome analysis (>30X coverage) of 3,169 subjects from 829 families affected by ASD. Genes that...
10.15154/1340302
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Genotyping/NGS
Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder. #435
Corbett, Blythe; Key, A.P.; Qualls, L.; Fecteau, S.; Newsom, C.; & Yoder, P.
The efficacy of a peer-mediated, theatre-based intervention on social competence in participants with autism spectrum disorder (ASD) was tested. Thirty 8-to-14 year-olds with ASD were randomly assigned to the treatment (n = 17) or a wait-list control (n = 13) group. Immediately after treatment, group effects were seen on social ability, (d = .77), communication symptoms (d = -.86), group play with toys in the company of peers (d = .77), immediate memory of faces as measured by...
10.15154/1343428
Secondary Analysis
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Statistical
Identifying Clinical Net Benefit of Psychotropic Medication Use with Latent Variable Techniques: Evidence from Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) #437
Bareis, Natalie; Lu, Juan; Kirkwood, Cynthia; Kornstein, Susan; Wu, Elwin; Mezuk, Briana
Background: Poor medication adherence is common among individuals with Bipolar Disorder (BD). Understanding the sources of heterogeneity in clinical net benefit (CNB) and how it is related to psychotropic medications can provide new insight into ways to improve adherence. Methods: Data come from the baseline assessments of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB, and validity of this construct was assessed...
10.15154/1338252
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Statistical
Lack of early improvement with antipsychotics is a marker for subsequent non-response in behavioral and psychological symptoms of dementia: Analysis of CATIE-AD data #439
Uchida, Hiroyuki; Yoshida, K; Roberts, R; Suzuki, T; Lebowitz, B; Reeves, S; Howard, R; Abe, T; Mimura, M
Objective: Prediction of response/non-response to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. We aimed to examine whether presence/absence of early improvement of BPSD with antipsychotics is associated with subsequent response/non-response. Design: Post-hoc analysis of the Clinical Antipsychotic Trials in Intervention Effectiveness with Alzheimer’s Disease (CATIE-AD)...
10.15154/1345184
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Statistical
One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin #440
Flora M. Vaccarino; Alexej Abyzov, Livia Tomasini, Bo Zhou, Nikolaos Vasmatzis, Gianfilippo Coppola, Mariangela Amenduni, Reenal Pattni, Michael Wilson, Mark Gerstein, Sherman Weissman, Alexander E. Urban
Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single cell whole genome amplification. We estimate that on average a fibroblast cell in children...
10.15154/1342749
Secondary Analysis
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Genotyping/NGS
How anxious do you think I am? Relationship between state and trait anxiety in children with and without ASD during social tasks #445
Grossman, Ruth; Mertens, J.; Zane, E.R.; Neumeyer, K.; Grossman, R.B.
Individuals with autism spectrum disorder (ASD) often exhibit increased anxiety, even in non-stressful situations. We investigate general anxiousness (anxiety trait) and responses to stressful situations (anxiety state) in 22 adolescents with ASD and 32 typically developing controls. We measured trait anxiety with standardized self- and parent-reported questionnaires. We used a Biopac system to capture state anxiety via skin conductance responses, mean heart rate and heart rate variability...
10.15154/1345819
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Statistical
Training Parents of Youth with Autism Spectrum Disorder to Advocate for Adult Disability Services: Results from a Pilot Randomized Controlled Trial. #446
Julie L. Taylor; Taylor JL, Hodapp RM, Burke MM, Waitz-Kudla SN, Rabideau C
This study presents findings from a pilot randomized controlled trial, testing a 12-week intervention to train parents of youth with autism spectrum disorder (ASD) to advocate for adult disability services-the Volunteer Advocacy Program-Transition (VAP-T). Participants included 41 parents of youth with ASD within 2 years of high school exit, randomly assigned to a treatment (N = 20) or wait-list control (N = 21) group. Outcomes, collected before and after the intervention, included parental...
10.15154/1346187
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Statistical
Upper limb motor coordination based early diagnosis in high risk subjects for Autism #451
Wedyan, Mohammad; Al-Jumaily,Adel
Autism is a lifelong condition present from early childhood. Medical specialists' diagnosis autism based on observation is of great difficulty in communicating, difficulties for forming relationships with other people, and delayed speech. The scientists tried to discover other early signs to reach the early detection of Autism Spectrum Disorders (ASD). Early diagnosing is very important to initiate and improve treatment results. One of these signs is based on examination of upper limb motor...
10.15154/1351615
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Neuro Signal Recordings
Statistical
Violation Differentiation #454
Norman, Ken; Kim, Ghootae; Turk-Browne, Nick
When an item is predicted in a particular context but the prediction is violated, memory for that item is weakened (Kim et al., 2014). Here, we explore what happens when such previously mispredicted items are later reencountered. According to prior neural network simulations, this sequence of events-misprediction and subsequent restudy-should lead to differentiation of the item's neural representation from the previous context (on which the misprediction was based). Specifically, misprediction...
10.15154/1356633
Primary Analysis
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Neuro Signal Recordings
Statistical
Inflexible neurobiological signatures precede atypical development in infants at high risk for autism #455
Denisova, Kristina; Zhao, Guihu
Variability in neurobiological signatures is ubiquitous in early life but the link to adverse developmental milestones in humans is unknown. We examined how levels of signal and noise in movement signatures during the 1st year of life constrain early development in 71 healthy typically developing infants, either at High or Low familial Risk (HR or LR, respectively) for developing Autism Spectrum Disorders (ASD). Delays in early learning developmental trajectories in HR infants (validated in an...
10.15154/1372051
Secondary Analysis
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Neuro Signal Recordings
Statistical
Risk of weight gain for specific antipsychotic drugs: A Bayesian network meta-analysis of individual participant level clinical trial data #463
Normand, Sharon-Lise; Spertus, Jacob; Horvitz-Lennon, Marcela; Abing, Haley; Normand, Sharon-Lise
People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard ‘as-randomized’ analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of...
10.15154/1373363
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Finding
Genotyping/NGS
Stimulation of the Posterior Cortical-Hippocampal Network Enhances Precision of Memory Recollection. #465
Joel Voss; Nilakantan AS, Bridge DJ, Gagnon EP, VanHaerents SA, Voss JL
Episodic memory is thought to critically depend on interaction of the hippocampus with distributed brain regions [1-3]. Specific contributions of distinct networks have been hypothesized, with the hippocampal posterior-medial (HPM) network implicated in the recollection of highly precise contextual and spatial information [3-6]. Current evidence for HPM specialization is mostly indirect, derived from correlative measures such as neural activity recordings. Here we tested the causal role of the...
10.15154/1367896
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Neuro Signal Recordings
Statistical
Early brain development in infants at high risk for autism spectrum disorder #468
Hazlett, Heather; Hazlett, Heather; Gu, Hongbin; Munsell, Brent C.; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J.; Elison, Jed T.; Swanson, Meghan R.; Zhu, Hongtu; Botteron, Kelly N.; Collins, D. Louis; Constantino, John N.; Dager, Stephen R.; Estes, M.; Evans, Alan C.; Fonov, Vladimir S.; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C.; Pandey, Juhi; Paterson, Sarah; Pruett Jr., John R.; Schultz, Robert T.; Shaw, Dennis W.; Zwaigenbaum, Lonnie
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development1, 2. Studies of infants at high familial risk of autism can provide insight into the...
10.15154/1375033
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Neuro Signal Recordings
Statistical
Combining Gaze and Demographic Feature Descriptors for Autism Classification #472
Canavan, Shaun; Chen, Melanie; Chen, Song; Valdez, Robert; Yaeger, Miles; Lin, Huiyi; Yin, Lijun
People with autism suffer from social challenges and communication difficulties, which may prevent them from leading a fruitful and enjoyable life. It is imperative to diagnose and start treatments for autism as early as possible and, in order to do so, accurate methods of identifying the disorder are vital. We propose a novel method for classifying autism through the use of eye gaze and demographic feature descriptors that include a subject’s age and gender. We construct feature descriptors...
10.15154/1376893
Secondary Analysis
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Statistical
PING Genomics Derived Data #477
Jernigan, Terry; Dale, Anders; Jernigan, Terry; Dale, Anders
The PING Data Resource is the product of a multi-site project involving developmental researchers across the United States including UC San Diego the University of Hawaii UC Los Angeles Childrens Hospital of Los Angeles of the University of Southern California UC Davis Kennedy Krieger Institute of Johns Hopkins University Sackler Institute of Cornell University University of Massachusetts Massachusetts General Hospital at Harvard University and Yale University. The Data Resource includes...
10.15154/1376898
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Genotyping/NGS
How We Transmit Memories to Other Brains: Constructing Shared Neural Representations Via Communication. #483
Hasson, Uri; Zadbood, Asieh; Chen, Janice; Leong, Yuan C.; Norman, Kenneth A.
Humans are able to mentally construct an episode when listening to another person's recollection, even though they themselves did not experience the events. However, it is unknown how strongly the neural patterns elicited by mental construction resemble those found in the brain of the individual who experienced the original events. Using fMRI and a verbal communication task, we traced how neural patterns associated with viewing specific scenes in a movie are encoded, recalled, and then...
10.15154/1399251
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Neuro Signal Recordings
Alpha-Band Oscillations Enable Spatially and Temporally Resolved Tracking of Covert Spatial Attention. #485
Edward Awh; Foster JJ, Sutterer DW, Serences JT, Vogel EK, Awh E
Covert spatial attention is essential for humans' ability to direct limited processing resources to the relevant aspects of visual scenes. A growing body of evidence suggests that rhythmic neural activity in the alpha frequency band (8-12 Hz) tracks the spatial locus of covert attention, which suggests that alpha activity is integral to spatial attention. However, extant work has not provided a compelling test of another key prediction: that alpha activity tracks the temporal dynamics of covert...
10.15154/1362041
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Neuro Signal Recordings
Amplification of local changes along the timescale processing hierarchy. #487
Uri Hasson; Yeshurun Y, Nguyen M, Hasson U
Small changes in word choice can lead to dramatically different interpretations of narratives. How does the brain accumulate and integrate such local changes to construct unique neural representations for different stories? In this study, we created two distinct narratives by changing only a few words in each sentence (e.g., "he" to "she" or "sobbing" to "laughing") while preserving the grammatical structure across stories. We then measured changes in neural responses between the two stories....
10.15154/1400378
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Neuro Signal Recordings
Treating a broader range of depressed adolescents with combined therapy #494
Foster, Simon; Mohler-Kuo, Meichun
Background: Traditional statistical analyses of clinical trials encompass the central tendency of outcomes and, hence, are restricted to a treatment's average effectiveness. Our aim was to get a more complete picture of the effectiveness of standard treatment options for adolescent depression, by analyzing treatment effects across low, middle, and high levels of response. Methods: Secondary data analysis was performed of the Treatment for Adolescents with Depression Study (TADS,...
10.15154/1468925
Secondary Analysis
Finding
Statistical
Mitochondrial DNA mutations in Autism Spectrum Disorder #495
Gu, Zhenglong; Wang, Yiqin
Mitochondrial dysfunction is frequently observed in Autism Spectrum Disorders (ASD). Thus, variations in the mitochondrial DNA (mtDNA) sequences may contribute to increased ASD risks. In the current study, we evaluated mtDNA variations, including homoplasmy and heteroplasmy, in 903 ASD individuals along with their mothers and non-ASD siblings by using off-target reads from whole-exome sequencing data sets of Simons Foundation Autism Research Initiative (SFARI) Simons Collection available on...
10.15154/1407407
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Genotyping/NGS
Different mutational rates and mechanisms in human cells at pre-gastrulation and neurogenesis #496
Vaccarino Flora; Abyzov, Alexej; Bae, Taejeong; Tomasini, Livia; Mariani, Jessica; Zhou, Bo; Roychowdhury, Tanmoy; Franjic, Daniel; Pletikos, Mihovil; Pattni, Reenal; Chen, Bo-Juen; Venturini, Elisa; Riley-Gillis, Bridget; Sestan, Nenad; Urban, Alexander
Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks post-conception) using clonal cell populations. We detected 200-400 single nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were shared with the spleen, revealing a pre-gastrulation...
10.15154/1410419
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Genotyping/NGS
Adolescent Brain Cognitive Development Study (ABCD) - Annual Release 1.0 #500
Jernigan, Terry L; Casey, Bettybj; Clark, Duncan; Colrain, Ian; Dale, Anders; Ernst, Thomas; Gonzalez, Raul; Heitzeg, Mary; Lisdahl, Krista; Luciana, Monica; Nagel, Bonnie; Sowell, Elizabeth; Squeglia, Lindsay; Tapert, Susan; Yurgeluntodd, Deborah;
The ABCD Curated Annual Release 1.0 includes high quality baseline data from the first ~4,500 research participants, including minimally processed brain image volumes and tabulated structural MRI, diffusion MRI, resting-state fMRI and task fMRI results, as well as all non-imaging assessment data from the physical & mental health, neurocognition, substance use, biospecimens and culture & environment domains. All personally identifiable information is removed from the data to ensure participant...
10.15154/1412097
Primary Analysis
Release-Archived
Neuro Signal Recordings
Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in Visual Working Memory. #508
Edward Awh; Foster JJ, Bsales EM, Jaffe RJ, Awh E
An emerging view suggests that spatial position is an integral component of working memory (WM), such that non-spatial features are bound to locations regardless of whether space is relevant [1, 2]. For instance, past work has shown that stimulus position is spontaneously remembered when non-spatial features are stored. Item recognition is enhanced when memoranda appear at the same location where they were encoded [3-5], and accessing non-spatial information elicits shifts of spatial attention...
Primary Analysis
Finding
Neuro Signal Recordings
Changes in ventromedial prefrontal and insular cortex support the development of metamemory from childhood into adolescence. #510
Simona Ghetti; Fandakova Y, Selmeczy D, Leckey S, Grimm KJ, Wendelken C, Bunge SA, Ghetti S
Metamemory monitoring, or the ability to introspect on the accuracy of one's memories, improves considerably during childhood, but the underlying neural changes and implications for intellectual development are largely unknown. The present study examined whether cortical changes in key brain areas hypothesized to support metacognition contribute to the development of metamemory monitoring from late childhood into early adolescence. Metamemory monitoring was assessed among 7- to 12-y-old...
10.15154/1418277
Primary Analysis
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Neuro Signal Recordings
Statistical
Unravelling the Collective Diagnostic Power Behind the Features in the Autism Diagnostic Observation Schedule #513
Kusalik, Anthony; Bhullar, H; MacKay, K; Ovens K
Background: Autism is a group of heterogeneous disorders defined by deficits in social interaction and communication. Typically, diagnosis depends on the results of a behavioural examination called the Autism Diagnostic Observation Schedule (ADOS). Unfortunately, administration of the ADOS exam is time-consuming and requires a significant amount of expert intervention, leading to delays in diagnosis and access to early intervention programs. The diagnostic power of each feature in the ADOS exam...
10.15154/1421921
Secondary Analysis
Finding
Statistical
Measuring the individual benefit of a medical or behavioral treatment using generalized linear mixed-effects models #514
Francisco J. Diaz; Francisco J. Diaz
A statistical measure of the individual benefit of medical or behavioral treatment and of the severity of a chronic illness is proposed, which are used to develop a graphical method that can be used by statisticians and clinicians in the data analysis of clinical trials from the perspective of personalized medicine. The method focuses on assessing and comparing individual effects of treatments rather than average effects and can be used with continuous and discrete responses under generalized...
10.15154/1422371
Secondary Analysis
Clinical Trial
Statistical
Bayesian Meta-Analysis of Multiple Continuous Treatments: An Application to Antipsychotic Drugs #517
Normand, Sharon-Lise; Horvitz-Lennon, Marcela; Spertus, J.V.; Horvitz-Lennon, M.; Normand, S-L. T.
Modeling dose-response relationships of drugs is essential to understanding their eect on patient outcomes under realistic circumstances. While intention-to-treat analyses of clinical trials provide the eect of assignment to a particular drug and dose, they do not capture observed exposure after factoring in non-adherence and dropout. We develop Bayesian methods to exibly model dose-response relationships of binary outcomes with continuous treatment, allowing for treatment eect...
10.15154/1422780
Secondary Analysis
Finding
Genotyping/NGS
Data-Driven Generation of Synthetic Behavioral Feature Vectors Modeling Children with Autism Spectrum Disorders #518
Baraka, Kim; Baraka, Kim; Melo, Francisco S.; Veloso, Manuela
Behavioral data on children with Autism Spectrum Disorders (ASD) are available thanks to standardized diagnostic tools, such as the Autism Diagnostic Observation Schedule (ADOS). This data can be of great use to enhance the learning and reasoning of agents interacting with children with ASD. However, the amount of such available data is limited and may not prove useful by itself to inform the algorithms of complex agents. To address this data scarcity problem, we present a method for generating...
10.15154/1423206
Secondary Analysis
Finding
Statistical
The Importance of Knowing When You Don't Remember: Neural Signaling of Retrieval Failure Predicts Memory Improvement Over Time. #520
Simona Ghetti; Fandakova Y, Bunge SA, Wendelken C, Desautels P, Hunter L, Lee JK, Ghetti S
Just as the ability to remember prior events is critical for guiding our decision-making, so too is the ability to recognize the limitations of our memory. Indeed, we hypothesize that neural signaling of retrieval failure promotes more accurate memory judgments over time. To test this hypothesis, we collected longitudinal functional magnetic resonance imaging data from 8 to 9 years olds, 10 to 12 years olds, and adults, with two time points spaced approximately 1.4 years apart (198 scan...
10.15154/1423469
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
Age- and performance-related differences in hippocampal contributions to episodic retrieval. #521
Simona Ghetti; Sastre M, Wendelken C, Lee JK, Bunge SA, Ghetti S
The goal of the present study was to investigate whether hippocampal contribution to episodic memory retrieval varies as a function of age (8-9 versus 10-11 versus adults), performance levels (high versus low) and hippocampal sub-region (head, body, tail). We examined fMRI data collected during episodic retrieval from a large sample (N=126). Participants judged whether a stimulus had been encoded previously, and, if so, which of three scenes it had been paired with (i.e., source judgment). For...
10.15154/1423471
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
A Time and Place for Everything: Developmental Differences in the Building Blocks of Episodic Memory. #522
Simona Ghetti; Lee JK, Wendelken C, Bunge SA, Ghetti S
This research investigated whether episodic memory development can be explained by improvements in relational binding processes, involved in forming novel associations between events and the context in which they occurred. Memory for item-space, item-time, and item-item relations was assessed in an ethnically diverse sample of 151 children aged 7-11 years and 28 young adults. Item-space memory reached adult performance by 9½ years, whereas item-time and item-item memory improved into adulthood....
10.15154/1423633
Primary Analysis
Finding
Statistical
White Matter Tracts Connected to the Medial Temporal Lobe Support the Development of Mnemonic Control. #523
Simona Ghetti; Wendelken C, Lee JK, Pospisil J, Sastre M, Ross JM, Bunge SA, Ghetti S
One of the most important factors driving the development of memory during childhood is mnemonic control, or the capacity to initiate and maintain the processes that guide encoding and retrieval operations. The ability to selectively attend to and encode relevant stimuli is a particularly useful form of mnemonic control, and is one that undergoes marked improvement over childhood. We hypothesized that structural integrity of white matter tracts, in particular those connecting medial temporal...
10.15154/1423632
Primary Analysis
Finding
Neuro Signal Recordings
T1 white/gray contrast as a predictor of chronological age, and an index of cognitive performance #524
Evans, Alan C.; Lewis, John D.; Tohka, Jussi
Knowing the maturational schedule of typical brain development is critical to our ability to identify deviations from it; such deviations have been related to cognitive performance and even developmental disorders. Chronological age can be predicted from brain images with considerable accuracy, but with limited spatial specificity, particularly in the case of the cerebral cortex. Methods using multi-modal data have shown the greatest accuracy, but have made limited use of cortical measures....
10.15154/1425407
Primary Analysis
Finding
Statistical
Brief Report: Social Functioning Predicts Externalizing Problem Behaviors in Autism Spectrum Disorder. #527
Natalie Russo; Shea N, Payne E, Russo N
Individuals with ASD often display externalizing behaviors, which have been associated with lower quality of life in adulthood. Social difficulties have been hypothesized to underlie externalizing problems among individuals with ASD (Klin and Volkmar in Asperger Syndrome, 340-366, 2000), but this has never been tested empirically. We examined whether socialization abilities predicted externalizing problems assessed by parent report in a group of 29 individuals with ASD (age range 7-16 years)...
10.15154/1430695
Primary Analysis
Finding
Statistical
Osteoarthritis Initiative (OAI) 18-Month Follow-Up Visit (V02) #538
Multiple
This NDA Study contains all images collected as part of the OAI 18-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1464949
Primary Analysis
Release
Neuro Signal Recordings
Neural overlap in item representations across episodes impairs context memory #539
Turk-Browne, Nick B.; Kim, Ghootae; Norman, Ken A.
We frequently encounter the same item in different contexts, and when that happens, memories of earlier encounters can get reactivated in the brain. Here we examined how these existing memories are changed as a result of such reactivation. We hypothesized that when an item’s initial and subsequent neural representations overlap, this allows the initial item to become associated with novel contextual information, interfering with later retrieval of the initial context. That is, we predicted a...
10.5072/1357077
Primary Analysis
Finding
Neuro Signal Recordings
Direct Brain Recordings Reveal Prefrontal Cortex Dynamics of Memory Development #542
Ofen, Noa; Johnson E L; Tang L; Yin Q; Asano E; Ofen N
Prevailing theories link prefrontal cortex (PFC) maturation to the development of declarative memory. However, the precise spatiotemporal correlates of memory formation in the developing brain are not known. We provide rare intracranial evidence that the spatiotemporal propagation of frontal activity supports memory formation in children. Seventeen subjects (6.2-19.4 years) studied visual scenes in preparation for a recognition memory test while undergoing direct cortical monitoring. Earlier...
10.15154/1481790
Primary Analysis
Finding
Neuro Signal Recordings
NIMH, NHGRI data-sharing project #547
Philip Shaw; John A. Lee, Adam Thomas, Gustavo Sudre, Nino Migineishvilli, Dylan Nielson, Peter A. Bandatettini
An MRI dataset of 441 inidividuals from 321 nuclear families, containing a T1w anatomical scan for each subject. At the time of the scan are individuals did not have any psychiatric disorders, as assessed by clinician-administrated interviews. High resolution (1.07 x 1.07 x 1.2mm) T1 weighted volumetric structural imaging data were collected on a 3-T GE Signa scanner with an eight-channel head coil. Magnetization prepared rapid gradient echo (MPRAGE) sequences were obtained with ASSET...
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) Pre-Screening Visit (P001) #549
Multiple
This NDA Study contains all images collected as part of the OAI Pre-Screening visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1357865
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) Baseline Visit (V00) #550
Multiple
This NDA Study contains all images collected as part of the OAI Baseline visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1357866
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 12-Month Follow-up Visit (V01) #551
Multiple
This NDA Study contains all images collected as part of the 12-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1357867
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 30-Month Follow-up Visit (V04) #554
Multiple
This NDA Study contains all images collected as part of the OAI 30-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358134
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 36-Month Follow-up Visit (V05) #555
Multiple
This NDA Study contains all images collected as part of the OAI 36-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358135
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 48-Month Follow-up Visit (V06) #556
Multiple
This NDA Study contains all images collected as part of the OAI 48-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358136
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 72-Month Follow-up Visit (V08) #557
Multiple
This NDA Study contains all images collected as part of the OAI 72-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358137
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 96-Month Follow-up Visit (V10) #558
Multiple
This NDA Study contains all images collected as part of the OAI 96-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358138
Primary Analysis
Release
Neuro Signal Recordings
Osteoarthritis Initiative (OAI) 24-Month Follow-Up Visit (V03) #560
Multiple
This NDA Study contains all images collected as part of the OAI 24-Month Follow-up visit. The Osteoarthritis Initiative (OAI) is a multi-center, ten-year observational study of men and women, sponsored by the NIH. The goals of the OAI are to provide resources to enable a better understanding of prevention and treatment of knee osteoarthritis, one of the most common causes of disability in adults.
10.15154/1358174
Primary Analysis
Release
Neuro Signal Recordings
Social Responsiveness Scale (SRS) in Relation to Longitudinal Cortical Thickness Changes in Autism Spectrum Disorder. #563
Janet Lainhart; Prigge MBD; Bigler ED; Travers BG; Froehlich A; Abildskov T; Anderson JS; Alexander AL; Lange N; Lainhart JE; Zielinski BA
The relationship between brain development and clinical heterogeneity in autism (ASD) is unknown. This study examines the Social Responsiveness Scale (SRS) in relation to the longitudinal development of cortical thickness. Participants (N = 91 ASD, N = 56 TDC; 3-39 years at first scan) were scanned up to three times over a 7-year period. Mixed-effects models examined cortical thickness in relation to SRS score. ASD participants with higher SRS scores showed regionally increased age-related...
10.5072/1358260
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
Impact of tobacco, alcohol and cannabis use on treatment outcomes among patients experiencing first episode psychosis: Data from the national RAISE-ETP study #564
Oluwoye, Oladunni; Monroe-DeVita, Maria; Burduli, Ekaterina; Chwastiak, Lydia; McPherson, Sterling; McClellan, Jon M; McDonell, Michael G
The primary aim of this study was to examine the effect of recent tobacco, alcohol and cannabis use on treatment outcomes among participants experiencing first episode psychosis (FEP). Secondary data analyses were conducted on 404 participants enrolled in the Recovery After an Initial Schizophrenia Episode—Early Treatment Program (RAISE-ETP) study. RAISEETP investigated the effectiveness of a coordinated specialty care (CSC) intervention for FEP in community mental health agencies in the...
10.15154/1358262
Secondary Analysis
Finding
Statistical
Suicidal Ideation in First-Episode Psychosis (FEP): Examination of Symptoms of Depression and Psychosis Among Individuals in an Early Phase of Treatment #569
Bornheimer, Lindsay, A.
First-episode psychosis (FEP) is a particularly high-risk period for suicide, in which risk elevates by 60% within a first year of treatment as compared to later stages of illness. To date, much of the literature has focused on individuals with a longer duration of psychosis; thus, there is an urgency for research to examine suicide risk among individuals in FEP in the beginning stage of treatment. This study aimed to identify the relationships between demographic characteristics,...
10.15154/1459208
Secondary Analysis
Analysis
Statistical
Adolescent Brain Cognitive Development Study (ABCD) - Annual Release 1.1 #576
Terry Jernigan; Jernigan, Terry L; Casey, Bettybj; Clark, Duncan; Colrain, Ian; Dale, Anders; Ernst, Thomas; Gonzalez, Raul; Heitzeg, Mary; Lisdahl, Krista; Luciana, Monica; Nagel, Bonnie; Sowell, Elizabeth; Squeglia, Lindsay; Tapert, Susan; Yurgeluntodd, Deborah;
The ABCD Curated Annual Release 1.1 includes high quality baseline data from the first ~4,500 research participants, including minimally processed brain image volumes and tabulated structural MRI, diffusion MRI, resting-state fMRI and task fMRI results, as well as all non-imaging assessment data from the genetics, physical & mental health, neurocognition, substance use, biospecimens and culture & environment domains. All personally identifiable information is removed from the data to ensure...
10.15154/1460410
Primary Analysis
Release
Genotyping/NGS
Neuro Signal Recordings
Measuring theory of mind in schizophrenia research: Cross-cultural validation. #583
Michal Assaf; Lee HS; Corbera S; Poltorak A; Park K; Assaf M; Bell MD; Wexler BE; Cho YI; Jung S; Brocke S; Choi KH
Theory of mind (ToM) is the ability to understand mental states of others and it is crucial for building sensitivity to other persons or events. Measuring ToM is important for understanding and rehabilitating social cognitive impairments in persons with schizophrenia. The Social Attribution Task-Multiple Choice (SAT-MC) has been successfully employed to measure ToM between individuals with schizophrenia (SZ) and healthy controls (HC) in North America. Given that the SAT-MC uses geometric...
10.15154/1461178
Secondary Analysis
Analysis
Statistical
Human hippocampal replay during rest prioritizes weakly-learned information and predicts memory performance #585
Norman, K.A.; Schapiro, A.C.; McDevitt, E.A.; Rogers, T.T.; Mednick, S.C.
There is now extensive evidence that the hippocampus replays experiences during quiet rest periods, and that this replay benefits subsequent memory. A critical open question is how memories are prioritized for replay during these offline periods. We addressed this question in an experiment in which participants learned the features of 15 objects and then underwent fMRI scanning to track item-level replay in the hippocampus using pattern analysis during a rest period. Objects that were...
10.15154/1463093
Primary Analysis
Finding
Neuro Signal Recordings
Evolutionary and Genetic Analysis of Synonymous Nucleotide Substitutions in Subjects with Autism Spectrum Disorders #586
Schaffer, Alejandro A.; Rogozin, Igor B; Schaffer, Alejandro A.
The director of the project, Dr. Igor Rogozin, analyzed a modest collection of synonymous nucleotide substitutions from two small databases of mutations observed in autistic subjects [1]. Dr. Rogozin and his colleagues found that there was a statistically significant tendency for these synonymous nucleotide substitutions to replace a reference codon supportive of faster protein translation with a non-reference codon that is known to be associated with slower translation [1]. In the proposed...
10.15154/1462716
Secondary Analysis
Analysis
Genotyping/NGS
Whole-brain, time-locked activation with simple tasks revealed using massive averaging and model-free analysis #588
Peter A Bandettini; Javier Gonzalez-Castillo Ziad S. Saad, Daniel A. Handwerker, Souheil J. Inati, Noah Brenowitz
The brain is the body's largest energy consumer, even in the absence of demanding tasks. Electrophysiologists report on-going neuronal firing during stimulation or task in regions beyond those of primary relationship to the perturbation. Although the biological origin of consciousness remains elusive, it is argued that it emerges from complex, continuous whole-brain neuronal collaboration. Despite converging evidence suggesting the whole brain is continuously working and adapting to anticipate...
10.15154/1464517
Primary Analysis
Release
Neuro Signal Recordings
Task Dependence, Tissue Specificity, and Spatial Distribution of Widespread Activations in Large Single-Subject Functional MRI Datasets at 7T #589
Peter A. Bandettini; Javier Gonzalez-Castillo, Colin W. Hoy, Daniel A. Handwerker, Vinai Roopchansingh, Souheil J. Inati, Ziad S. Saad, Robert W. Cox
It was recently shown that when large amounts of task-based blood oxygen level–dependent (BOLD) data are combined to increase contrast- and temporal signal-to-noise ratios, the majority of the brain shows significant hemodynamic responses time-locked with the experimental paradigm. Here, we investigate the biological significance of such widespread activations. First, the relationship between activation extent and task demands was investigated by varying cognitive load across participants....
10.15154/1464520
Primary Analysis
Release
Neuro Signal Recordings
Markers of Autism Spectrum Disorders in At-Risk Toddlers: A Pilot Study #590
Thurm, AE; Thurm, AE
This is the release of MRI data from a study is to learn more about risk factors for autism by studying the behavior and brain functioning of toddlers with early communication delays and typically developing toddlers. Children 12 or 18 months of age with language delays (i.e., no words at 18 months, limited vocalizations at 12 months) and typically developing toddlers may be eligible to participate. This study was conducted at the NIH Clinical Center in Bethesda, Maryland. There was be an...
10.15154/1464602
Primary Analysis
Release
Neuro Signal Recordings
Reductions in Retrieval Competition Predict the Benefit of Repeated Testing #604
Norman, Ken; Rafidi, N.S.; Hulbert, J.C.; Brooks, P.P.
Repeated testing leads to improved long-term memory retention compared to repeated study, but the mechanism underlying this improvement remains controversial. In this work, we test the hypothesis that retrieval practice benefits subsequent recall by reducing competition from related memories. This hypothesis implies that the degree of reduction in competition between retrieval practice attempts should predict subsequent memory for practiced items. To test this prediction, we collected...
10.15154/1466212
Primary Analysis
Finding
Neuro Signal Recordings
Associative prediction of visual shape in the hippocampus. #606
Kenneth Norman; Kok P; Turk-Browne NB
The way we perceive the world is to a great extent determined by our prior knowledge. Despite this intimate link between perception and memory, these two aspects of cognition have mostly been studied in isolation. Here we investigate their interaction by asking how memory systems that encode and retrieve associations can inform perception. We find that upon hearing a familiar auditory cue, the hippocampus represents visual information that had previously co-occurred with the cue, even when this...
10.15154/1469793
Primary Analysis
Finding
Neuro Signal Recordings
Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences #608
Francisco J. Diaz
The estimation of carry-over effects is a difficult problem in the design and analysis of clinical trials of treatment sequences including cross-over trials. Except for simple designs, carry-over effects are usually unidentifiable and therefore nonestimable. Solutions such as imposing parameter constraints are often unjustified and produce differing carry-over estimates depending on the constraint imposed. Generalized inverses or treatment-balancing often allow estimating main treatment...
10.15154/1503327
Secondary Analysis
Clinical Trial
Statistical
Representation of real-world event schemas during narrative perception #609
Norman, K.A.; Baldassano, C; Hasson, U
Understanding movies and stories requires maintaining a high-level situation model that abstracts away from perceptual details to describe the location, characters, actions, and causal relationships of the currently unfolding event. These models are built not only from information present in the current narrative, but also from prior knowledge about schematic event scripts, which describe typical event sequences encountered throughout a lifetime. We analyzed fMRI data from 44 human...
10.15154/1471546
Primary Analysis
Finding
Neuro Signal Recordings
People represent their own mental states more distinctly than others’ #610
Diana I. Tamir; Mark A. Thornton, Miriam E. Weaverdyck, Judith N. Mildner, Diana I. Tamir
One can never know the internal workings of another person – one can only infer others’ mental states based on external cues. In contrast, each person has direct access to the contents of their own mind. Here we test the hypothesis that this privileged access shapes the way people represent internal mental experiences, such that they represent their own mental states more distinctly than the states of others. Across four studies, participants considered their own and others’ mental states;...
10.15154/1473907
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
The social brain automatically predicts others’ future mental states #611
Diana I. Tamir; Mark A. Thornton, Miriam E. Weaverdyck, Diana I. Tamir
Social life requires people to predict the future: people must anticipate others’ thoughts, feelings,and actions in order to interact with them successfully. The theory of predictive coding suggests that the social brain may meet this need by automatically predicting others’ social futures. If so, when representing others’ current mental state, the brain should already start representing their future states. To test this hypothesis, we used functional neuroimaging to measure participants’...
10.15154/1473919
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
Learning Naturalistic Temporal Structure in the Posterior Medial Network. #616
Uri Hasson; Aly M; Chen J; Turk-Browne NB; Hasson U
The posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on preexisting event schemas, but temporal structure can also arise de novo from learning. Here, we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the...
10.15154/1476770
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
Assessment of the Prodromal Questionnaire-Brief Child Version for Measurement of Self-Reported Psychoticlike Experiences in Childhood #620
Karcher, Nicole; Karcher NR; Barch DM; Avenevoli S; Savill M; Huber RS; Simon TJ; Leckliter IN; Sher KJ; Loewy RL
IMPORTANCE: Childhood psychoticlike experiences (PLEs) are associated with greater odds of a diagnosis of a psychotic disorder during adulthood. However, no known, well-validated self-report tools have been designed to measure childhood PLEs. OBJECTIVE: To examine the construct validity and psychometric properties of a measure of PLEs, the Prodromal Questionnaire-Brief Child Version (PQ-BC). DESIGN, SETTING, AND PARTICIPANTS: This validation study used data from the first wave of the...
10.15154/1503203
Secondary Analysis
Finding
Statistical
Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance. #621
Edward Awh; Adam KCS; Robison MK; Vogel EK
Neural measures of working memory storage, such as the contralateral delay activity (CDA), are powerful tools in working memory research. CDA amplitude is sensitive to working memory load, reaches an asymptote at known behavioral limits, and predicts individual differences in capacity. An open question, however, is whether neural measures of load also track trial-by-trial fluctuations in performance. Here, we used a whole-report working memory task to test the relationship between CDA amplitude...
10.15154/1479110
Primary Analysis
Finding
Neuro Signal Recordings
Statistical
ABCD Neurocognitive Prediction Challenge 2019: Training Set #635
Kilian Pohl and Wes Thompson; Ehsan Adeli, Stanford University; Bennett A. Landman, Vanderbilt University; Marius G. Linguraru, Children’s National Health System; Susan F. Tapert, University of California – San Diego
Training data set for the ABCD Neurocognitive Prediction Challenge 2019 containing skull stripped and segmented T1-weighted MRIs, volumetric brain measures, and residual fluid intelligence scores of 3739 participants of the ABCD study. https://sibis.sri.com/abcd-np-challenge provides a detailed description about the processing. When using the data in publications, the Data Supplement of "Pfefferbaum et al., Altered Brain Developmental Trajectories in Adolescents After Initiating Drinking....
10.15154/1503213
Secondary Analysis
Analysis
Neuro Signal Recordings
Statistical
Neurons with complex karyotypes are rare in aged human neocortex #636
McConnell, Michael; Chronister WD; Burbulis IE; Wierman MB; Wolpert MJ; Haakenson MF; Smith ACB; Kleinman JE; Hyde TM; Weinberger DR; Bekiranov S; McConnell MJ
Megabase-scale somatic copy number variants (CNVs) lead to complex karyotypes that alter allelic diversity in a subset of human neocortical neurons. Reported frequencies of neurons with complex karyotypes range from ~5% of neurons in some individuals to greater than 30% in other individuals. Genome-wide and familial studies implicitly assume a constant brain genome when assessing the genetic risk architecture of neurological disease, thus it is critical to determine whether divergent levels...
10.15154/1503237
Primary Analysis
Analysis
Genotyping/NGS
ABCD Neurocognitive Prediction Challenge 2019: Validation set #642
Kilian Pohl and Wes Thompson; Ehsan Adeli, Stanford University; Bennett A. Landman, Vanderbilt University; Marius G. Linguraru, Children’s National Health System; Susan F. Tapert, University of California – San Diego
Validation data set for the ABCD Neurocognitive Prediction Challenge 2019 containing skull stripped and segmented T1-weighted MRIs, volumetric brain measures, and residual fluid intelligence scores of 415 participants of the ABCD study. https://sibis.sri.com/abcd-np-challenge provides a detailed description about the processing. When using the data in publications, the Data Supplement of "Pfefferbaum et al., Altered Brain Developmental Trajectories in Adolescents After Initiating Drinking....
10.15154/1503306
Secondary Analysis
Analysis
Neuro Signal Recordings
Statistical
ABCD Neurocognitive Prediction Challenge 2019: Test Set #643
Kilian Pohl and Wes Thompson; Ehsan Adeli, Stanford University; Bennett A. Landman, Vanderbilt University; Marius G. Linguraru, Children’s National Health System; Susan F. Tapert, University of California – San Diego
The test data set for the ABCD Neurocognitive Prediction Challenge 2019 contains skull stripped and segmented T1-weighted MRIs, and volumetric brain measures of 3648 participants of the ABCD study. https://sibis.sri.com/abcd-np-challenge provides a detailed description about the processing. When using the data in publications, the Data Supplement of "Pfefferbaum et al., Altered Brain Developmental Trajectories in Adolescents After Initiating Drinking. Am J Psychiatry, 175(4), pp. 370-380,...
10.15154/1503307
Secondary Analysis
Analysis
Neuro Signal Recordings
Statistical
Racial-Ethnic Disparities in First-Episode Psychosis Treatment Outcomes From the RAISE-ETP Study. #645
Oluwoye, Oladunni; Stiles B, Monroe-DeVita M, Chwastiak L, McClellan JM, Dyck D, Cabassa LJ, McDonell MG
Abstract OBJECTIVE: This study examined racial and ethnic differences in treatment outcomes among participants in a randomized controlled trial of an intervention for first-episode psychosis called NAVIGATE. METHODS: Secondary data analyses were conducted for participants randomly assigned to usual community care (N=181) and NAVIGATE (N=223). Generalized estimating equations assessed whether race and ethnicity were associated with psychiatric symptoms and service use (medication management,...
10.15154/1503347
Secondary Analysis
Finding
Statistical
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