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Papers of the Week

  • 1) Int J Epidemiol. 2015 Apr 14. pii: dyv028. [Epub ahead of print]

    Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort.

    Feinberg JI(1), Bakulski KM(2), Jaffe AE(1), Tryggvadottir R(3), Brown SC(1),
    Goldman LR(1), Croen LA(3), Hertz-Picciotto I(3), Newschaffer CJ(1), Daniele
    Fallin M(1), Feinberg AP(1).
    
    Author information: 
    (1)Johns Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism 
    and Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine Johns
    Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and
    Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine. (2)Johns
    Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and
    Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine Johns
    Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and
    Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine Johns
    Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and
    Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine. (3)Johns
    Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and
    Developmental Disabilities, Johns Hopkins University, Center for Epigenetics,
    Johns Hopkins Bloomberg School of Public Health, Epidemiology, Lieber Institute
    for Brain Development, George Washington University, Milken Institute School of
    Public Health, Johns Hopkins Bloomberg School of Public Health, Kaiser
    Permanente, Division of Research, Autism Research Program, University of
    California Davis School of Medicine, Public Health Sciences, Drexel University,
    A.J. Drexel Autism Institute, Drexel University School of Public Health,
    Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, 
    Mental Health and Johns Hopkins University School of Medicine, Medicine.
    
    BACKGROUND: 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.
    OBJECTIVES: 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.
    METHODS: We examined genome-wide DNA methylation (DNAm) in paternal semen
    biosamples obtained from an autism spectrum disorder (ASD) enriched-risk
    pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI)
    cohort, to estimate associations between sperm DNAm and prospective ASD
    development, using a 12-month ASD symptoms assessment, the Autism Observation
    Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run 
    on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG 
    sites), including 30 samples also run on the Illumina Infinium
    HumanMethylation450 (450K) BeadChip platform (∼485 000 CpG sites). We also
    examined associated regions in an independent sample of post-mortem human brain
    ASD and control samples for which Illumina 450K DNA methylation data were
    available.
    RESULTS: Using region-based statistical approaches, we identified 193
    differentially methylated regions (DMRs) in paternal sperm with a family-wise
    empirical P-value [family-wise error rate (FWER)] <0.05 associated with
    performance on the Autism Observational Scale for Infants (AOSI) at 12 months of 
    age in offspring. The DMRs clustered near genes involved in developmental
    processes, including many genes in the SNORD family, within the Prader-Willi
    syndrome gene cluster. These results were consistent among the 75 probes on the
    Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75
    (24%) 450K array probes showed consistent differences in the cerebellums of
    autistic individuals compared with controls.
    CONCLUSIONS: These data suggest that epigenetic differences in paternal sperm may
    contribute to autism risk in offspring, and provide evidence that directionally
    consistent, potentially related epigenetic mechanisms may be operating in the
    cerebellum of individuals with autism.
    
    © The Author 2015; all rights reserved. Published by Oxford University Press on
    behalf of the International Epidemiological Association.
    
    PMID: 25878217  [PubMed - as supplied by publisher]
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  • 2) JAMA. 2015 Apr 21;313(15):1534-1540. doi: 10.1001/jama.2015.3077.

    Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism.

    Jain A(1), Marshall J(1), Buikema A(2), Bancroft T(2), Kelly JP(1), Newschaffer
    CJ(3).
    
    Author information: 
    (1)The Lewin Group, Falls Church, Virginia. (2)Optum, Eden Prairie, Minnesota.
    (3)A. J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania.
    
    Importance: Despite research showing no link between the measles-mumps-rubella
    (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine
    causes autism persist, leading to lower vaccination levels. Parents who already
    have a child with ASD may be especially wary of vaccinations.
    Objective: To report ASD occurrence by MMR vaccine status in a large sample of US
    children who have older siblings with and without ASD.
    Design, Setting, and Participants: A retrospective cohort study using an
    administrative claims database associated with a large commercial health plan.
    Participants included children continuously enrolled in the health plan from
    birth to at least 5 years of age during 2001-2012 who also had an older sibling
    continuously enrolled for at least 6 months between 1997 and 2012.
    Exposures: MMR vaccine receipt (0, 1, 2 doses) between birth and 5 years of age.
    Main Outcomes and Measures: ASD status defined as 2 claims with a diagnosis code 
    in any position for autistic disorder or other specified pervasive developmental 
    disorder (PDD) including Asperger syndrome, or unspecified PDD (International
    Classification of Diseases, Ninth Revision, Clinical Modification 299.0x, 299.8x,
    299.9x).
    Results: Of 95 727 children with older siblings, 994 (1.04%) were diagnosed with 
    ASD and 1929 (2.01%) had an older sibling with ASD. Of those with older siblings 
    with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings
    (P < .001). MMR vaccination rates (≥1 dose) were 84% (n = 78 564) at age 2 years 
    and 92% (n = 86 063) at age 5 years for children with unaffected older siblings, 
    vs 73% (n = 1409) at age 2 years and 86% (n = 1660) at age 5 years for children
    with affected siblings. MMR vaccine receipt was not associated with an increased 
    risk of ASD at any age. For children with older siblings with ASD, at age 2, the 
    adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was
    0.76 (95% CI, 0.49-1.18; P = .22), and at age 5, the RR of ASD for 2 doses
    compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052). For children
    whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1
    dose was 0.91 (95% CI, 0.67-1.20; P = .50) and at age 5, the RR of ASD for 2
    doses was 1.12 (95% CI, 0.78-1.59; P = .55).
    Conclusions and Relevance: In this large sample of privately insured children
    with older siblings, receipt of the MMR vaccine was not associated with increased
    risk of ASD, regardless of whether older siblings had ASD. These findings
    indicate no harmful association between MMR vaccine receipt and ASD even among
    children already at higher risk for ASD.
    
    PMID: 25898051  [PubMed - as supplied by publisher]
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  • 3) JAMA. 2015 Apr 21;313(15):1524-1533. doi: 10.1001/jama.2015.3150.

    Effect of Parent Training vs Parent Education on Behavioral Problems in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

    Bearss K(1), Johnson C(2), Smith T(3), Lecavalier L(4), Swiezy N(5), Aman M(4),
    McAdam DB(3), Butter E(6), Stillitano C(7), Minshawi N(5), Sukhodolsky DG(8),
    Mruzek DW(3), Turner K(9), Neal T(5), Hallett V(10), Mulick JA(6), Green B(1),
    Handen B(11), Deng Y(12), Dziura J(13), Scahill L(1).
    
    Author information: 
    (1)Department of Pediatrics, Marcus Autism Center, Children's Healthcare of
    Atlanta and Emory University, Atlanta, Georgia. (2)Department of Pediatrics,
    University of Pittsburgh, Pittsburgh, Pennsylvania13Dr Johnson is now with the
    Department of Clinical and Health Psychology, University of Florida, Gainesville.
    (3)Department of Pediatrics, University of Rochester, Rochester, New York.
    (4)Departments of Psychology and Psychiatry, Nisonger Center, UCEDD, Ohio State
    University, Columbus. (5)Department of Psychiatry, Indiana University,
    Indianapolis. (6)Department of Pediatrics, Ohio State University and Nationwide
    Children's Hospital, Columbus. (7)Department of Pediatrics, University of
    Pittsburgh, Pittsburgh, Pennsylvania. (8)Child Study Center, Yale University, New
    Haven, Connecticut. (9)Division of Education Leadership and Innovation, Mary Lou 
    Fulton Teachers College, Arizona State University, Tempe. (10)Institute of
    Psychiatry, Psychology, and Neuroscience, King's College London, Department of
    Psychology, London, United Kingdom. (11)Department of Psychiatry, University of
    Pittsburgh, Pittsburgh, Pennsylvania. (12)School of Public Health, Yale
    University, New Haven, Connecticut. (13)Department of Emergency Medicine, Yale
    University, New Haven, Connecticut.
    
    Importance: Disruptive behavior is common in children with autism spectrum
    disorder. Behavioral interventions are used to treat disruptive behavior but have
    not been evaluated in large-scale randomized trials.
    Objective: To evaluate the efficacy of parent training for children with autism
    spectrum disorder and disruptive behavior.
    Design, Setting, and Participants: This 24-week randomized trial compared parent 
    training (n = 89) to parent education (n = 91) at 6 centers (Emory University,
    Indiana University, Ohio State University, University of Pittsburgh, University
    of Rochester, Yale University). We screened 267 children; 180 children (aged 3-7 
    years) with autism spectrum disorder and disruptive behaviors were randomly
    assigned (86% white, 88% male) between September 2010 and February 2014.
    Interventions: Parent training (11 core, 2 optional sessions; 2 telephone
    boosters; 2 home visits) provided specific strategies to manage disruptive
    behavior. Parent education (12 core sessions, 1 home visit) provided information 
    about autism but no behavior management strategies.
    Main Outcomes and Measures: Parents rated disruptive behavior and noncompliance
    on co-primary outcomes: the Aberrant Behavior Checklist-Irritability subscale
    (range, 0-45) and the Home Situations Questionnaire-Autism Spectrum Disorder
    (range, 0-9). On both measures, higher scores indicate greater severity and a 25%
    reduction indicates clinical improvement. A clinician blind to treatment
    assignment rated the Improvement scale of the Clinical Global Impression (range, 
    1-7), a secondary outcome, with a positive response less than 3.
    Results: At week 24, the Aberrant Behavior Checklist-Irritability subscale
    declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for
    parent education (23.9 to 16.3) (treatment effect, -3.9; 95% CI, -6.2 to -1.7;
    P < .001, standardized effect size = 0.62). The Home Situations
    Questionnaire-Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared
    with 34.2% in parent education (3.8 to 2.5) (treatment effect, -0.7; 95% CI, -1.1
    to -0.3; P < .001, standardized effect size = 0.45). Neither measure met the
    prespecified minimal clinically important difference. The proportions with a
    positive response on the Clinical Global Impression-Improvement scale were 68.5% 
    for parent training vs 39.6% for parent education (P < .001).
    Conclusions and Relevance: For children with autism spectrum disorder, a 24-week 
    parent training program was superior to parent education for reducing disruptive 
    behavior on parent-reported outcomes, although the clinical significance of the
    improvement is unclear. The rate of positive response judged by a blinded
    clinician was greater for parent training vs parent education.
    Trial Registration: clinicaltrials.gov Identifier: NCT01233414.
    
    PMID: 25898050  [PubMed - as supplied by publisher]
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  • 4) Neuropsychiatr Dis Treat. 2015 Apr 7;11:999-1005. doi: 10.2147/NDT.S78707. eCollection 2015.

    "Recovery" from the diagnosis of autism - and then?

    Olsson MB(1), Westerlund J(2), Lundström S(3), Giacobini M(4), Fernell E(5),
    Gillberg C(3).
    
    Author information: 
    (1)Gillberg Neuropsychiatry Centre, Institution of Neuroscience and Physiology,
    Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ; PRIMA Child and 
    Adult Psychiatry, Stockholm, Sweden. (2)Gillberg Neuropsychiatry Centre,
    Institution of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg
    University, Gothenburg, Sweden ; Department of Psychology, Stockholm University, 
    Stockholm, Sweden. (3)Gillberg Neuropsychiatry Centre, Institution of
    Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University,
    Gothenburg, Sweden. (4)PRIMA Child and Adult Psychiatry, Stockholm, Sweden ;
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm,
    Sweden. (5)Gillberg Neuropsychiatry Centre, Institution of Neuroscience and
    Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ;
    Research and Development Centre, Skaraborg's Hospital, Skövde, Sweden.
    
    BACKGROUND: The aim of this study was to follow up the 17 children, from a total 
    group of 208 children with autism spectrum disorder (ASD), who "recovered from
    autism". They had been clinically diagnosed with ASD at or under the age of 4
    years. For 2 years thereafter they received intervention based on applied
    behavior analysis. These 17 children were all of average or borderline
    intellectual functioning. On the 2-year follow-up assessment, they no longer met 
    criteria for ASD.
    METHODS: At about 10 years of age they were targeted for a new follow-up. Parents
    were given a semistructured interview regarding the child's daily functioning,
    school situation, and need of support, and were interviewed using the Vineland
    Adaptive Behavior Scales (VABS) and the Autism - Tics,
    Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC)
    telephone interview.
    RESULTS: The vast majority of the children had moderate-to-severe problems with
    attention/activity regulation, speech and language, behavior, and/or social
    interaction. A majority of the children had declined in their VABS scores. Most
    of the 14 children whose parents were A-TAC-interviewed had problems within many 
    behavioral A-TAC domains, and four (29%) had symptom levels corresponding to a
    clinical diagnosis of ASD, AD/HD, or both. Another seven children (50%) had
    pronounced subthreshold indicators of ASD, AD/HD, or both.
    CONCLUSION: Children diagnosed at 2-4 years of age as suffering from ASD and who,
    after appropriate intervention for 2 years, no longer met diagnostic criteria for
    the disorder, clearly needed to be followed up longer. About 3-4 years later,
    they still had major problems diagnosable under the umbrella term of ESSENCE
    (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations).
    They continued to be in need of support, educationally, from a neurodevelopmental
    and a medical point of view. According to parent interview data, a substantial
    minority of these children again met diagnostic criteria for ASD.
    
    PMID: 25897237  [PubMed]
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  • 5) Lancet Neurol. 2015 Apr 16. pii: S1474-4422(15)00044-7. doi: 10.1016/S1474-4422(15)00044-7. [Epub ahead of print]

    Gene hunting in autism spectrum disorder: on the path to precision medicine.

    Geschwind DH(1), State MW(2).
    
    Author information: 
    (1)Neurogenetics Program, Department of Neurology, and Center for Autism Research
    and Treatment, Semel Institute, David Geffen School of Medicine, University of
    California, Los Angeles, CA, USA. Electronic address: dhg@ucla.edu. (2)Department
    of Psychiatry, Langley Porter Psychiatric Institute, University of California,
    San Francisco, CA, USA.
    
    Autism spectrum disorder is typical of the majority of neuropsychiatric syndromes
    in that it is defined by signs and symptoms, rather than by aetiology. Not
    surprisingly, the causes of this complex human condition are manifold and include
    a substantial genetic component. Recent developments in gene-hunting technologies
    and methods, and the resulting plethora of genetic findings, promise to open new 
    avenues to understanding of disease pathophysiology and to contribute to improved
    clinical management. Despite remarkable genetic heterogeneity, evidence is
    emerging for converging pathophysiology in autism spectrum disorder, but how this
    notion of convergent pathways will translate into therapeutics remains to be
    established. Leveraging genetic findings through advances in model systems and
    integrative genomic approaches could lead to the development of new classes of
    therapies and a personalised approach to treatment.
    
    Copyright © 2015 Elsevier Ltd. All rights reserved.
    
    PMID: 25891009  [PubMed - as supplied by publisher]
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  • 6) Lancet Neurol. 2015 Apr 16. pii: S1474-4422(15)00050-2. doi: 10.1016/S1474-4422(15)00050-2. [Epub ahead of print]

    Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan.

    Ecker C(1), Bookheimer SY(2), Murphy DG(3).
    
    Author information: 
    (1)Sackler Institute for Translational Neurodevelopment, Department of Forensic
    and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and
    Neuroscience, King's College London, London, UK. Electronic address:
    christine.ecker@kcl.ac.uk. (2)Center for Cognitive Neurosciences, University of
    California, Los Angeles, CA, USA. (3)Sackler Institute for Translational
    Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences,
    Institute of Psychiatry, Psychology and Neuroscience, King's College London,
    London, UK.
    
    Over the past decade, in-vivo MRI studies have provided many invaluable insights 
    into the neural substrates underlying autism spectrum disorder (ASD), which is
    now known to be associated with neurodevelopmental variations in brain anatomy,
    functioning, and connectivity. These systems-level features of ASD pathology seem
    to develop differentially across the human lifespan so that the cortical
    abnormalities that occur in children with ASD differ from those noted at other
    stages of life. Thus, investigation of the brain in ASD poses particular
    methodological challenges, which must be addressed to enable the comparison of
    results across studies. Novel analytical approaches are also being developed to
    facilitate the translation of findings from the research to the clinical setting.
    In the future, the insights provided by human neuroimaging studies could
    contribute to biomarker development for ASD and other neurodevelopmental
    disorders, and to new approaches to diagnosis and treatment.
    
    Copyright © 2015 Elsevier Ltd. All rights reserved.
    
    PMID: 25891007  [PubMed - as supplied by publisher]
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  • 7) J Am Acad Child Adolesc Psychiatry. 2015 May;54(5):369-376.e3. doi: 10.1016/j.jaac.2015.02.005. Epub 2015 Feb 17.

    Depressive and Anxiety Symptom Trajectories From School Age Through Young Adulthood in Samples With Autism Spectrum Disorder and Developmental Delay.

    Gotham K(1), Brunwasser SM(2), Lord C(3).
    
    Author information: 
    (1)Vanderbilt University School of Medicine, Nashville. Electronic address:
    katherine.gotham@vanderbilt.edu. (2)Vanderbilt University Kennedy Center,
    Nashville. (3)Center for Autism and the Developing Brain, Weill-Cornell Medical
    College, New York.
    
    OBJECTIVE: The objectives of this study were to model growth in anxiety and
    depressive symptoms from late school age through young adulthood in individuals
    with autism spectrum disorder (ASD) and controls with developmental delay (DD),
    and to assess relationships among internalizing growth patterns, participant
    characteristics, baseline predictors, and distal outcomes.
    METHOD: Data were collected between ages 6 and 24 years in 165 participants (n = 
    109 with ASD; n = 56 with nonspectrum DD), most of whom received diagnostic
    evaluations in both childhood and early adulthood. Questionnaires were collected 
    approximately every 3 to 6 months between ages 9 and 24 years. Parent-rated Child
    Behavior Checklist (CBCL), Adult Behavior Checklist (ABCL), and Developmental
    Behaviour Checklist anxiety- and depression-related subscale distributions were
    modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ
    (VIQ), gender, and significant 2- and 3-way interactions.
    RESULTS: Anxiety was positively associated with VIQ, and controlling for VIQ,
    both anxiety and depressive symptoms were greater in ASD than nonspectrum
    participants. Female gender predicted greater increases over time in anxiety and 
    depressive symptoms for both diagnostic groups. Lower maternal education was
    associated with increasing internalizing symptoms in a subset of less verbal
    individuals with ASD. In exploratory post hoc analyses, internalizing symptoms
    were associated with poorer emotional regulation in school age, and with lower
    life satisfaction and greater social difficulties in early adulthood.
    CONCLUSION: Findings support previous claims that individuals with ASD are at
    particular risk for affect- and anxiety-specific problems. Although symptom
    levels in females increase at a faster rate throughout adolescence, males with
    ASD appear to have elevated levels of depressive symptoms in school age that are 
    maintained into young adulthood.
    
    Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published
    by Elsevier Inc. All rights reserved.
    
    PMID: 25901773  [PubMed - as supplied by publisher]
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  • 8) Am J Med Genet A. 2015 Apr 21. doi: 10.1002/ajmg.a.37071. [Epub ahead of print]

    Children with 7q11.23 duplication syndrome: Psychological characteristics.

    Mervis CB(1), Klein-Tasman BP, Huffman MJ, Velleman SL, Pitts CH, Henderson DR,
    Woodruff-Borden J, Morris CA, Osborne LR.
    
    Author information: 
    (1)Department of Psychological and Brain Sciences, University of Louisville,
    Louisville, Kentucky.
    
    To begin to delineate the psychological characteristics associated with classic
    7q11.23 duplication syndrome (duplication of the classic Williams syndrome
    region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged
    4-17 years. Sixteen toddlers aged 18-45 months with classic Dup7 and 12 adults
    identified by cascade testing also were assessed. For the child group, median
    General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II 
    was 85.0 (low average), with a range from severe disability to high average
    ability. Median reading and mathematics achievement standard scores were at the
    low average to average level, with a range from severe impairment to high average
    or superior ability. Adaptive behavior was considerably more limited; median
    Scales of Independent Behavior-Revised Broad Independence standard score was 62.0
    (mild impairment), with a range from severe adaptive impairment to average
    adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed
    with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety
    Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with 
    Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant
    Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the
    children screened positive for a possible Autism Spectrum Disorder and 82.3% were
    diagnosed with Speech Sound Disorder. We compare these findings to previously
    reported results for children with Williams syndrome and argue that
    genotype/phenotype studies involving the Williams syndrome region offer important
    opportunities to understand the contribution of genes in this region to common
    disorders affecting the general population. © 2015 Wiley Periodicals, Inc.
    
    © 2015 Wiley Periodicals, Inc.
    
    PMID: 25900101  [PubMed - as supplied by publisher]
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  • 9) J Autism Dev Disord. 2015 Apr 23. [Epub ahead of print]

    Autism Symptomatology in Boys with Fragile X Syndrome: A Cross Sectional Developmental Trajectories Comparison with Nonsyndromic Autism Spectrum Disorder.

    Thurman AJ(1), McDuffie A, Kover ST, Hagerman RJ, Abbeduto L.
    
    Author information: 
    (1)MIND Institute, University of California Davis, 2825 50th Street, Room 2101,
    Sacramento, CA, 95817, USA, ajthurman@ucdavis.edu.
    
    Although males with fragile X syndrome (FXS) are frequently described as
    demonstrating autism symptomatology, there is much debate regarding whether the
    behavioral symptoms representing the core domains of autism are the result of the
    same or different underlying neurological/psychological mechanisms. The present
    study used a cross-sectional developmental trajectories approach to compare the
    profiles of autism symptomatology relative to chronological age (CA), nonverbal
    IQ, and expressive vocabulary ability between individuals with FXS and
    individuals with nonsyndromic ASD. Results suggest that the onset of autism
    symptoms and their developmental trajectories in males with FXS differ in
    important ways as a function of CA, nonverbal cognitive ability, and expressive
    vocabulary relative to males with nonsyndromic ASD. Theoretical and clinical
    implications are discussed.
    
    PMID: 25904201  [PubMed - as supplied by publisher]
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  • 10) J Autism Dev Disord. 2015 Apr 25. [Epub ahead of print]

    Dismantling the Active Ingredients of an Intervention for Children with Autism.

    Pellecchia M(1), Connell JE, Beidas RS, Xie M, Marcus SC, Mandell DS.
    
    Author information: 
    (1)Perelman School of Medicine, University of Pennsylvania, 3535 Market St, 3rd
    Floor, Philadelphia, PA, 19104, USA, pmelanie@upenn.edu.
    
    This study evaluated the association of fidelity to each of the components of the
    Strategies for Teaching based on Autism Research (STAR) program, a comprehensive 
    treatment package for children with autism that includes discrete trial training,
    pivotal response training, and teaching in functional routines, on outcomes for
    191 students ages 5-8 years in a large public school district. Fidelity to all
    components was relatively low, despite considerable training and support,
    suggesting the need to develop new implementation strategies. Fidelity to pivotal
    response training, but not discrete trial training or functional routines, was
    positively associated with gains in cognitive ability despite low levels of
    fidelity, and may be an effective intervention choice in under-resourced
    settings.
    
    PMID: 25911305  [PubMed - as supplied by publisher]
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  • 11) Autism. 2015 Apr 24. pii: 1362361315577518. [Epub ahead of print]

    Child characteristics associated with outcome for children with autism in a school-based behavioral intervention.

    Pellecchia M(1), Connell JE(2), Kerns CM(2), Xie M(3), Marcus SC(3), Mandell
    DS(3).
    
    Author information: 
    (1)University of Pennsylvania, USA pmelanie@upenn.edu. (2)Drexel University, USA.
    (3)University of Pennsylvania, USA.
    
    This study examined the extent to which clinical and demographic characteristics 
    predicted outcome for children with autism spectrum disorder. Participants
    included 152 students with autism spectrum disorder in 53
    kindergarten-through-second-grade autism support classrooms in a large urban
    public school district. Associations between child characteristics (including
    age, language ability, autism severity, social skills, adaptive behavior,
    co-occurring psychological symptoms, and restrictive and repetitive behavior) and
    outcome, as measured by changes in cognitive ability following one academic year 
    of an intervention standardized across the sample were evaluated using linear
    regression with random effects for classroom. While several scales and subscales 
    had statistically significant bivariate associations with outcome, in adjusted
    analysis, only age and the presence of symptoms associated with social anxiety,
    such as social avoidance and social fearfulness, as measured through the Child
    Symptom Inventory-4, were associated with differences in outcome. The findings
    regarding the role of social anxiety are new and have important implications for 
    treatment. Disentangling the construct of social anxiety to differentiate between
    social fearfulness and social motivation has important implications for shifting 
    the focus of early treatment for children with autism spectrum disorder.
    
    © The Author(s) 2015.
    
    PMID: 25911092  [PubMed - as supplied by publisher]
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  • 12) Autism. 2015 Apr 24. pii: 1362361315577517. [Epub ahead of print]

    The health status of adults on the autism spectrum.

    Croen LA(1), Zerbo O(2), Qian Y(2), Massolo ML(2), Rich S(3), Sidney S(2), Kripke
    C(4).
    
    Author information: 
    (1)Kaiser Permanente Northern California-Oakland, USA Lisa.A.Croen@kp.org.
    (2)Kaiser Permanente Northern California-Oakland, USA. (3)Kaiser Permanente
    Northern California-Santa Rosa, USA. (4)University of California, San Francisco, 
    USA.
    
    Compared to the general pediatric population, children with autism have higher
    rates of co-occurring medical and psychiatric illnesses, yet very little is known
    about the general health status of adults with autism. The objective of this
    study was to describe the frequency of psychiatric and medical conditions among a
    large, diverse, insured population of adults with autism in the United States.
    Participants were adult members of Kaiser Permanente Northern California enrolled
    from 2008 to 2012. Autism spectrum disorder cases (N = 1507) were adults with
    autism spectrum disorder diagnoses (International Classification of
    Diseases-9-Clinical Modification codes 299.0, 299.8, 299.9) recorded in medical
    records on at least two separate occasions. Controls (N = 15,070) were adults
    without any autism spectrum disorder diagnoses sampled at a 10:1 ratio and
    frequency matched to cases on sex and age. Adults with autism had significantly
    increased rates of all major psychiatric disorders including depression, anxiety,
    bipolar disorder, obsessive-compulsive disorder, schizophrenia, and suicide
    attempts. Nearly all medical conditions were significantly more common in adults 
    with autism, including immune conditions, gastrointestinal and sleep disorders,
    seizure, obesity, dyslipidemia, hypertension, and diabetes. Rarer conditions,
    such as stroke and Parkinson's disease, were also significantly more common among
    adults with autism. Future research is needed to understand the social,
    healthcare access, and biological factors underlying these observations.
    
    © The Author(s) 2015.
    
    PMID: 25911091  [PubMed - as supplied by publisher]
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  • 13) Immunity. 2015 Apr 21;42(4):600-2. doi: 10.1016/j.immuni.2015.04.002.

    Brains, Blood, and Guts: MeCP2 Regulates Microglia, Monocytes, and Peripheral Macrophages.

    Schafer DP(1), Stevens B(2).
    
    Author information: 
    (1)Department of Neurobiology, University of Massachusetts Medical School,
    Worcester, MA 01605, USA. Electronic address: dorothy.schafer@umassmed.edu.
    (2)Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's
    Hospital, Harvard Medical School, Boston, MA 02115.
    
    Mutations in methyl-CpG-binding protein 2 (MECP2) underlie most cases of Rett
    Syndrome, a neurodevelopmental disorder with neurological and somatic
    impairments. In this issue of Immunity, Cronk et al. (2015) find that macrophages
    in MeCP2-deficient mice are abnormal in number, as well as in glucocorticoid,
    hypoxia, and inflammatory responses.
    
    Copyright © 2015 Elsevier Inc. All rights reserved.
    
    PMID: 25902477  [PubMed - in process]
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  • 14) Neuron. 2015 Apr 22;86(2):353-5. doi: 10.1016/j.neuron.2015.03.059.

    Gene length matters in neurons.

    Zylka MJ(1), Simon JM(2), Philpot BD(2).
    
    Author information: 
    (1)Department of Cell Biology and Physiology, UNC Neuroscience Center, The
    Carolina Institute for Developmental Disabilities, The University of North
    Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA. Electronic address:
    zylka@med.unc.edu. (2)Department of Cell Biology and Physiology, UNC Neuroscience
    Center, The Carolina Institute for Developmental Disabilities, The University of 
    North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA.
    
    A recent study by Gabel et al. (2015) found that Mecp2, the gene mutated in Rett 
    syndrome, represses long (> 100 kb) genes associated with neuronal physiology and
    connectivity by binding to methylated CA sites in DNA. This study adds to a
    growing body of literature implicating gene length and transcriptional mechanisms
    in neurodevelopmental and neurodegenerative disorders.
    
    Copyright © 2015 Elsevier Inc. All rights reserved.
    
    PMID: 25905808  [PubMed - in process]
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