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Papers of the Week

  • 1) Autism. 2015 Feb 25. pii: 1362361314568900. [Epub ahead of print]

    Feasibility of an empirically based program for parents of preschoolers with autism spectrum disorder.

    Dababnah S(1), Parish SL(2).
    
    Author information: 
    (1)University of Maryland, USA sdababnah@ssw.umaryland.edu. (2)Brandeis
    University, USA.
    
    This article reports on the feasibility of implementing an existing empirically
    based program, The Incredible Years, tailored to parents of young children with
    autism spectrum disorder. Parents raising preschool-aged children (aged
    3-6 years) with autism spectrum disorder (N = 17) participated in a 15-week pilot
    trial of the intervention. Quantitative assessments of the program revealed
    fidelity was generally maintained, with the exception of program-specific videos.
    Qualitative data from individual post-intervention interviews reported parents
    benefited most from child emotion regulation strategies, play-based child
    behavior skills, parent stress management, social support, and visual resources. 
    More work is needed to further refine the program to address parent self-care,
    partner relationships, and the diverse behavioral and communication challenges of
    children across the autism spectrum. Furthermore, parent access and retention
    could potentially be increased by providing in-home childcare vouchers and a
    range of times and locations in which to offer the program. The findings suggest 
    The Incredible Years is a feasible intervention for parents seeking additional
    support for child- and family-related challenges and offers guidance to those
    communities currently using The Incredible Years or other related parenting
    programs with families of children with autism spectrum disorder.
    
    © The Author(s) 2015.
    
    PMID: 25717131  [PubMed - as supplied by publisher]
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  • 2) Autism. 2015 Feb 25. pii: 1362361314568899. [Epub ahead of print]

    Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder.

    Hiller RM(1), Young RL(2), Weber N(2).
    
    Author information: 
    (1)Flinders University, Australia University of Bath, UK R.Hiller@bath.ac.uk.
    (2)Flinders University, Australia.
    
    In the absence of intellectual impairment, girls are diagnosed with autism
    spectrum disorder significantly less and later than boys. This study explored
    potential reasons for why autism spectrum disorder may be more difficult to
    identify in girls, based on carer concerns during the pre-diagnosis period.
    Carers of 92 boys and 60 girls diagnosed with autism spectrum disorder from
    school age completed an online survey addressing concerns regarding the child's
    development during the pre-school years (pre-diagnosis). Significant sex
    differences were evident in key early concerns, as well as the strategies used to
    navigate pre-school social situations, and the types of restricted interests.
    Findings suggest, from carer perspective, that girls who went on to be diagnosed 
    with autism spectrum disorder presented differently when compared to boys,
    providing insight into why the diagnosis of autism spectrum disorder may be more 
    difficult to make with cognitively able girls.
    
    © The Author(s) 2015.
    
    PMID: 25717130  [PubMed - as supplied by publisher]
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  • 3) Autism Res. 2015 Feb 24. doi: 10.1002/aur.1474. [Epub ahead of print]

    Replication of Standardized ADOS Domain Scores in the Simons Simplex Collection.

    Bal VH(1), Lord C.
    
    Author information: 
    (1)Department of Psychology, University of Michigan, Ann Arbor, Michigan;
    Department of Psychiatry, University of California San Francisco, San Francisco, 
    California.
    
    Raw totals from diagnostic and screening measures for autism spectrum disorder
    (ASD) are frequently used as dimensional measures of autism symptom severity
    without appropriate correction for confounding factors, such as developmental
    level or non-ASD-specific behavior problems. Although these associated features
    are important to consider when diagnosing ASD and developing intervention plans, 
    both researchers and clinicians sometimes need metrics of ASD severity that are
    not influenced by these factors. The Autism Diagnostic Observation Schedule
    (ADOS) domain calibrated severity scores (CSS) were created to provide separate
    estimates of social affect (SA-CSS) and restricted, repetitive behaviors
    (RRB-CSS) that are relatively independent of child characteristics (Hus et al.,
    2014). Using a sample of 2,509 probands with ASD from the Simons Simplex
    Collection (SSC), this study provides the first replication of the ADOS domain
    CSS in an independent sample. Consistent with the original standardization study,
    when applied to existing SSC data, the ADOS domain CSS were less influenced by
    age and cognitive ability compared to raw domain totals. Domain CSS were also
    relatively independent of behavior problems. Use of the ADOS domain CSS to assess
    relationships between ASD symptoms and genetic risk factors will increase
    confidence that associations reflect domain-specific relationships. Scores also
    offer less developmentally-influenced estimates of ASD severity for future
    phenotypic explorations in the SSC. This independent replication provides support
    for the application of the ADOS domain CSS in other samples, though further
    replication in population-based samples will be an important next step. Autism
    Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals,
    Inc.
    
    © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    
    PMID: 25712123  [PubMed - as supplied by publisher]
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  • 4) J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):208-216.e1. doi: 10.1016/j.jaac.2014.12.005. Epub 2014 Dec 20.

    Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder.

    Soorya LV(1), Siper PM(2), Beck T(3), Soffes S(2), Halpern D(2), Gorenstein M(2),
    Kolevzon A(2), Buxbaum J(2), Wang AT(2).
    
    Author information: 
    (1)Rush University Medical Center, Chicago. Electronic address:
    latha_soorya@rush.edu. (2)Seaver Autism Center for Research and Treatment at the 
    Icahn School of Medicine at Mount Sinai, New York. (3)Rush University Medical
    Center, Chicago.
    
    OBJECTIVE: This study evaluated the efficacy of a targeted social skills training
    group in school-aged children with autism spectrum disorder (ASD). The
    intervention, Seaver-NETT (Nonverbal communication, Emotion recognition, and
    Theory of mind Training), is a 12-session cognitive-behavioral intervention (CBI)
    for verbal, school-aged children targeting ASD-specific social behavioral
    impairments.
    METHOD: Sixty-nine children with ASD, 8 to 11 years of age, with verbal IQs
    greater than 70, participated in a randomized comparative trial to examine the
    efficacy of NETT relative to a facilitated play group. Treatment outcomes
    included caregiver reports of social behavior and neuropsychological assessments 
    of social cognition conducted by blinded raters. Outcomes were collected at
    baseline, endpoint, and 3 months posttreatment.
    RESULTS: Significant improvements were found on social behavior outcomes such as 
    nonverbal communication, empathic responding, and social relations in the NETT
    condition relative to the active control at endpoint. Verbal IQ moderated the
    interaction effect on social behavior, with higher verbal IQ associated with
    improvements in the CBI condition. No significant improvements were found on
    social cognitive outcomes. No significant group differences were found at 3-month
    follow-up conducted with approximately half the sample (n = 34).
    CONCLUSION: These data indicate that targeted CBI social skills groups such as
    NETT improve social communication deficits in verbal, school-aged children with
    ASD. The moderating effects of high verbal IQ suggest a need to consider
    participant and treatment characteristics associated with outcomes in future
    studies. Clinical trial registration information-Neural and Behavioral Outcomes
    of Social Skills Groups in Children With Autism Spectrum Disorder;
    https://clinicaltrials.gov; NCT01190917.
    
    Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published
    by Elsevier Inc. All rights reserved.
    
    PMID: 25721186  [PubMed - in process]
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  • 5) Autism Res. 2015 Feb 26. doi: 10.1002/aur.1475. [Epub ahead of print]

    Meta-Analysis of Gene Expression in Autism Spectrum Disorder.

    Ch'ng C(1), Kwok W, Rogic S, Pavlidis P.
    
    Author information: 
    (1)Graduate Program in Bioinformatics, University of British Columbia, Vancouver,
    Canada, V6T 1Z4 (C.C.); Center for High Throughput Biology, University of British
    Columbia, Vancouver, Canada, V6T 1Z4 (C.C., W.K., S.R., P.P.).
    
    Autism spectrum disorders (ASD) are clinically heterogeneous and biologically
    complex. In general it remains unclear, what biological factors lead to changes
    in the brains of autistic individuals. A considerable number of transcriptome
    analyses have been performed in attempts to address this question, but their
    findings lack a clear consensus. As a result, each of these individual studies
    has not led to any significant advance in understanding the autistic phenotype as
    a whole. Here, we report a meta-analysis of more than 1000 microarrays across
    twelve independent studies on expression changes in ASD compared to unaffected
    individuals, in both blood and brain tissues. We identified a number of known and
    novel genes that are consistently differentially expressed across three studies
    of the brain (71 samples in total). A subset of the highly ranked genes is
    suggestive of effects on mitochondrial function. In blood, consistent changes
    were more difficult to identify, despite individual studies tending to exhibit
    larger effects than the brain studies. Our results are the strongest evidence to 
    date of a common transcriptome signature in the brains of individuals with ASD.
    Autism Res 2015. © 2015 International Society for Autism Research, Wiley
    Periodicals, Inc.
    
    © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    
    PMID: 25720351  [PubMed - as supplied by publisher]
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  • 6) Hum Brain Mapp. 2015 Feb 25. doi: 10.1002/hbm.22776. [Epub ahead of print]

    Multicenter mapping of structural network alterations in autism.

    Valk SL(1), Di Martino A, Milham MP, Bernhardt BC.
    
    Author information: 
    (1)Department of Social Neuroscience, Max-Planck Institute for Human Cognitive
    and Brain Sciences, Leipzig, Germany.
    
    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions
    primarily characterized by abnormalities in social cognition. Abundant previous
    functional MRI studies have shown atypical activity in networks encompassing
    medial prefrontal cortex (mPFC) and medial parietal regions corresponding to
    posterior cingulate cortex and precuneus (PCC/PCU). Conversely, studies assessing
    structural brain anomalies in ASD have been rather inconsistent. The current work
    evaluated whether structural changes in ASD can be reliability detected in a
    large multicenter dataset. Our comprehensive structural MRI framework encompassed
    cortical thickness mapping and structural covariance analysis based on three
    independent samples comprising individuals with ASD and controls (n = 220),
    selected from the Autism Brain Imaging Data Exchange open-access database.
    Surface-based analysis revealed increased cortical thickness in ASD relative to
    controls in mPFC and lateral prefrontal cortex. Clusters encompassing mPFC were
    embedded in altered inter-regional covariance networks, showing decreased
    covariance in ASD relative to controls primarily to PCC/PCU and inferior parietal
    regions. Cortical thickness increases and covariance reductions in ASD were
    consistent, yet of variable effect size, across the different sites evaluated and
    measurable both in children and adults. Our multisite study shows regional and
    network-level structural alterations in mPFC in ASD that, possibly, relate to
    atypical socio-cognitive functions in this condition. Hum Brain Mapp, 2015. ©
    2015 Wiley Periodicals, Inc.
    
    © 2015 Wiley Periodicals, Inc.
    
    PMID: 25727858  [PubMed - as supplied by publisher]
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  • 7) Am J Psychiatry. 2015 Mar 1;172(3):266-75. doi: 10.1176/appi.ajp.2014.14050576. Epub 2014 Nov 7.

    Social responsiveness, an autism endophenotype: genomewide significant linkage to two regions on chromosome 8.

    Lowe JK(1), Werling DM, Constantino JN, Cantor RM, Geschwind DH.
    
    Author information: 
    (1)From the Neurogenetics Program and Department of Neurology, David Geffen
    School of Medicine, University of California, Los Angeles; the Center for Autism 
    Research and Treatment, Semel Institute, David Geffen School of Medicine,
    University of California, Los Angeles; the Center for Neurobehavioral Genetics,
    Semel Institute, David Geffen School of Medicine, University of California, Los
    Angeles; the Interdepartmental Ph.D. Program in Neuroscience, Brain Research
    Institute, University of California, Los Angeles; the Departments of Psychiatry
    and Pediatrics, Washington University School of Medicine, St. Louis; and the
    Department of Human Genetics, University of California, Los Angeles.
    
    OBJECTIVE: Autism spectrum disorder is characterized by deficits in social
    function and the presence of repetitive and restrictive behaviors. Following a
    previous test of principle, the authors adopted a quantitative approach to
    discovering genes contributing to the broader autism phenotype by using social
    responsiveness as an endophenotype for autism spectrum disorder.
    METHOD: Linkage analyses using scores from the Social Responsiveness Scale were
    performed in 590 families from the Autism Genetic Resource Exchange, a largely
    multiplex autism spectrum disorder cohort. Regional and genomewide association
    analyses were performed to search for common variants contributing to social
    responsiveness.
    RESULTS: Social Responsiveness Scale scores were unimodally distributed in male
    offspring from multiplex autism families, in contrast with a bimodal distribution
    observed in female offspring. In correlated analyses differing by Social
    Responsiveness Scale respondent, genomewide significant linkage for social
    responsiveness was identified at chr8p21.3 (multipoint LOD=4.11; teacher/parent
    scores) and chr8q24.22 (multipoint LOD=4.54; parent-only scores), respectively.
    Genomewide or linkage-directed association analyses did not detect common
    variants contributing to social responsiveness.
    CONCLUSIONS: The sex-differential distributions of Social Responsiveness Scale
    scores in multiplex autism families likely reflect mechanisms contributing to the
    sex ratio for autism observed in the general population and form a quantitative
    signature of reduced penetrance of inherited liability to autism spectrum
    disorder among females. The identification of two strong loci for social
    responsiveness validates the endophenotype approach for the identification of
    genetic variants contributing to complex traits such as autism spectrum disorder.
    While causal mutations have yet to be identified, these findings are consistent
    with segregation of rare genetic variants influencing social responsiveness and
    underscore the increasingly recognized role of rare inherited variants in the
    genetic architecture of autism spectrum disorder.
    
    PMID: 25727539  [PubMed - in process]
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