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  • 1
    In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Wiley, Vol. 168, No. 5 ( 2015-07), p. 354-362
    Abstract: Transcription factor 4 ( TCF4 ) is one of the most robust of all reported schizophrenia risk loci and is supported by several genetic and functional lines of evidence. While numerous studies have implicated common genetic variation at TCF4 in schizophrenia risk, the role of rare, small‐sized variants at this locus‐such as single nucleotide variants and short indels which are below the resolution of chip‐based arrays requires further exploration. The aim of the present study was to investigate the association between rare TCF4 sequence variants and schizophrenia. Exon‐targeted resequencing was performed in 190 German schizophrenia patients. Six rare variants at the coding exons and flanking sequences of the TCF4 gene were identified, including two missense variants and one splice site variant. These six variants were then pooled with nine additional rare variants identified in 379 European participants of the 1000 Genomes Project, and all 15 variants were genotyped in an independent German sample (n = 1,808 patients; n = 2,261 controls). These data were then analyzed using six statistical methods developed for the association analysis of rare variants. No significant association ( P   〈  0.05) was found. However, the results from our association and power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations. © 2015 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 1552-4841 , 1552-485X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2143866-3
    SSG: 12
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  • 2
    In: European Eating Disorders Review, Wiley, Vol. 23, No. 6 ( 2015-11), p. 524-530
    Abstract: Anxiety disorders and anorexia nervosa are frequently acknowledged to be highly comorbid conditions, but still, little is known about the clinical and aetiological cohesion of specific anxiety diagnoses and anorexia nervosa. Using the comprehensive Danish population registers, we aimed to determine the risk of anorexia nervosa in patients with register‐detected severe anxiety disorders. We also explored whether parental psychopathology was associated with offspring's anorexia nervosa. Anxiety disorders increased the risk of subsequent anorexia nervosa, with the highest risk observed in obsessive–compulsive disorder. Especially, male anxiety patients were at an increased risk for anorexia nervosa. Furthermore, an increased risk was observed in offspring of fathers with panic disorder. A diagnosis of an anxiety disorder, specifically obsessive–compulsive disorder, constitutes a risk factor for subsequent diagnosis of anorexia nervosa. These observations support the notion that anxiety disorders and anorexia nervosa share etiological mechanisms and/or that anxiety represents one developmental pathway to anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
    Type of Medium: Online Resource
    ISSN: 1072-4133 , 1099-0968
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2135416-9
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  • 3
    In: European Journal of Immunology, Wiley, Vol. 38, No. 7 ( 2008-07), p. 2046-2047
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 1491907-2
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  • 4
    In: Movement Disorders, Wiley, Vol. 32, No. 4 ( 2017-04), p. 605-609
    Abstract: Background : Few studies have investigated mortality risk in individuals with tic disorders. Methods : We thus measured the risk of premature death in individuals with tic disorders and with Tourette syndrome in a prospective cohort study with 80 million person‐years of follow‐up. We estimated mortality rate ratios and adjusted for calendar year, age, sex, urbanicity, maternal and paternal age, and psychiatric disorders to compare individuals with and without tic disorders. Results : The risk of premature death was higher among individuals with tic disorders (mortality rate ratio, 2.02; 95% CI, 1.49‐2.66) and with Tourette syndrome (mortality rate ratio, 1.63; 95% CI, 1.11‐2.28) compared with controls. After the exclusion of individuals with comorbid attention‐deficit/hyperactivity disorder, obsessive‐compulsive disorder, and substance abuse, tic disorder remained associated with increased mortality risk (mortality rate ratio, 2.30; 95% CI, 1.57‐3.23), as did also Tourette Syndrome (mortality rate ratio, 1.81; 95% CI, 1.11–2.75). Conclusions : These results are of clinical significance for clinicians and advocacy organizations. Several factors may contribute to this increased risk of premature death, and more research mapping out these factors is needed. © 2017 International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2041249-6
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  • 5
    In: NMR in Biomedicine, Wiley, Vol. 27, No. 2 ( 2014-02), p. 228-234
    Abstract: Previously reported MRS findings in the aging brain include lower N‐acetylaspartate (NAA) and higher myo‐inositol (mI), total creatine (Cr) and choline‐containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A‐related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on ‘healthy aging’, we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted ‘U’‐shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age‐related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects. Copyright © 2013 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0952-3480 , 1099-1492
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2002003-X
    detail.hit.zdb_id: 1000976-0
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  • 6
    In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Wiley, Vol. 159B, No. 3 ( 2012-04), p. 263-273
    Abstract: The majority of genetic risk factors for major depressive disorder (MDD) still await identification. Since copy number variants (CNVs) have been implicated in various neuropsychiatric disorders, the question arises as to whether CNVs also play a role in MDD. We performed a genome‐wide CNV study using Illumina's SNP array data from 604 MDD patients and 1,643 controls. Putative CNVs were detected with the CNV algorithms QuantiSNP and PennCNV. CNVs with ≥30 consecutive SNPs and a log Bayes Factor/confidence value of ≥30 were statistically analyzed using PLINK. Further analyses and technical verification were only performed in the case of regions for which CNV calls from both programs showed nominal significance. Set‐based tests were used to test whether common variants in the CNV regions showed association in two GWAS datasets of MDD. CNVs from four chromosomal regions were associated with MDD. The following were more frequent in patients than controls: microdeletions in 7p21.3 ( P  = 0.033) and 18p11.32 ( P  = 0.030); microduplications in 15q26.3 ( P  = 0.033); and the combination of microdeletion/duplications in 16p11.2 ( P  ≤ 0.018). SNPs in CNV region 16p11.2 showed significant association in a set‐based test ( P  = 0.026). Microdeletions/duplications in 16p11.2 are the most promising CNVs, since these affect genes and CNVs in this region have been implicated in other neuropsychiatric disorders. The association finding for common SNPs provides further support for the hypothesis that this region is involved in the development of MDD. © 2012 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 1552-4841 , 1552-485X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2143866-3
    SSG: 12
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  • 7
    In: Journal of Ultrasound in Medicine, Wiley, Vol. 35, No. 9 ( 2016-09), p. 1957-1965
    Abstract: Accreditation of cerebrovascular ultrasound laboratories by the Intersocietal Accreditation Commission (IAC) and equivalent organizations is supported by the Joint Commission certification of stroke centers. Limited information exists on the accreditation status and geographic distribution of cerebrovascular testing facilities in the United States. Our study objectives were to identify the proportion of IAC‐accredited outpatient cerebrovascular testing facilities used by Medicare beneficiaries, describe their geographic distribution, and identify variations in cerebrovascular testing procedure types and volumes by accreditation status. Methods As part of the VALUE (Vascular Accreditation, Location, and Utilization Evaluation) Study, we examined the proportion of IAC‐accredited facilities that conducted cerebrovascular testing in a 5% Centers for Medicare and Medicaid Services random Outpatient Limited Data Set in 2011 and investigated their geographic distribution using geocoding. Results Among 7327 outpatient facilities billing Medicare for cerebrovascular testing, only 22% (1640) were IAC accredited. The proportion of IAC‐accredited cerebrovascular testing facilities varied by region (χ 2 [3] = 177.1; P 〈 .0001), with 29%, 15%, 13%, and 10% located in the Northeast, South, Midwest, and West, respectively. However, of the total number of cerebrovascular outpatient procedures conducted in 2011 (38,555), 40% (15,410) were conducted in IAC‐accredited facilities. Most cerebrovascular testing procedures were carotid duplex, with 40% of them conducted in IAC‐accredited facilities. Conclusions The proportion of facilities conducting outpatient cerebrovascular testing accredited by the IAC is low and varies by region. The growing number of certified stroke centers should be accompanied by more accredited outpatient vascular testing facilities, which could potentially improve the quality of stroke care.
    Type of Medium: Online Resource
    ISSN: 0278-4297 , 1550-9613
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2067124-6
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  • 8
    In: Limnology and Oceanography: Methods, Wiley, Vol. 15, No. 7 ( 2017-07), p. 663-677
    Abstract: We established a new indoor mesocosm facility, 12 fully controlled “Planktotrons”, designed to conduct marine and freshwater experiments for biodiversity and food web approaches using natural or artificial, benthic or planktonic communities. The Planktotrons are a unique and custom‐tailored facility allowing long‐term experiments. Wall growth can be inhibited by a rotating gate paddle with silicone lips. Additionally, temperature and light intensity are individually controllable for each Planktotron and the large volume (600 L) enables high‐frequency or volume‐intense measurements. In a pilot freshwater experiment various trophic levels of a pelagic food web were maintained for up to 90 d. First, an artificially assembled phytoplankton community of 11 species was inoculated in all Planktotrons. After 22 d, two ciliates were added to all, and three Daphnia species were added to six Planktotrons. After 72 d, dissolved organic matter (DOM, an alkaline soil extract) was added as an external disturbance to six of the 12 Planktotrons, involving three Planktotrons stocked with Daphnia and three without, respectively. We demonstrate the suitability of the Planktotrons for food web and biodiversity research. Variation among replicated Planktotrons ( n  = 3 minimum) did not differ from other laboratory systems and field experiments. We investigated population dynamics and interactions among the different trophic levels, and found them affected by the sequence of ciliate and Daphnia addition and the disturbance caused by addition of DOM.
    Type of Medium: Online Resource
    ISSN: 1541-5856 , 1541-5856
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2161715-6
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  • 9
    In: European Journal of Neuroscience, Wiley, Vol. 38, No. 6 ( 2013-09), p. 2941-2945
    Abstract: Recently, genome‐wide association between schizophrenia and an intronic variant in AMBRA 1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level‐dependent ( BOLD ) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity‐related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis ( n  = 848) and a functional magnetic resonance imaging ( fMRI ) task ( n  = 512). Various aspects of impulsivity were assessed using the T emperament and C haracter I nventory‐ R evised, the S ubstance U se R isk P rofile S cale, the C ambridge C ognition N europsychological T est A utomated B attery, and the S top S ignal T ask ( SST ) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito‐frontal target region during the SST , which declined to trend status after F amily W ise E rror correction. Our findings support the hypothesis that the schizophrenia‐related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.
    Type of Medium: Online Resource
    ISSN: 0953-816X , 1460-9568
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2005178-5
    SSG: 12
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  • 10
    In: Autism Research, Wiley, Vol. 13, No. 1 ( 2020-01), p. 134-144
    Abstract: Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub‐phenotypes, we conducted a whole‐population cohort study in Denmark. We followed births 1991–2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD‐8 and ICD‐10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism − no ADHD, 2,205 autism + ID, and 11,342 autism − no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub‐phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13–1.22] ) but attenuated in the maternal cluster (0.98 [0.88–1.09]) and sibling (0.86 [0.64–1.15] ) models. Similarly, risks of autism sub‐phenotypes with maternal smoking were attenuated in the family‐based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub‐phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134–144 . © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Smoking during pregnancy has many harmful impacts, which may include harming the baby's developing brain. However, in a study of thousands of families in Denmark, it does not appear that smoking in pregnancy leads to autism or autism in combination with intellectual problems or attention deficits, once you account for the way smoking patterns and developmental disabilities run in families.
    Type of Medium: Online Resource
    ISSN: 1939-3792 , 1939-3806
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2418112-2
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