JavaScript NENÍ povolen !

Prosím povolte JavaScript.

* Zobrazit nápovědu

Reset

Autor: Davidson, Michael

16 záznamů v Medvik Filtry

Článek online

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Trubetskoy, Vassily
Autor Trubetskoy, Vassily Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany
Pardiñas, Antonio F
Autor Pardiñas, Antonio F MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
Qi, Ting
Autor Qi, Ting Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia School of Life Sciences, Westlake University, Hangzhou, China
Panagiotaropoulou, Georgia
Autor Panagiotaropoulou, Georgia Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany
Awasthi, Swapnil
Autor Awasthi, Swapnil Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany
Bigdeli, Tim B
Autor Bigdeli, Tim B Department of Psychiatry and the Behavioral Sciences, SUNY Downstate Medical Center, New York, NY, USA Institute for Genomic Health, SUNY Downstate Medical Center, New York, NY, USA Department of Psychiatry, Veterans Affairs New York Harbor Healthcare System, New York, NY, USA
Bryois, Julien
Autor Bryois, Julien Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Chen, Chia-Yen
Autor Chen, Chia-Yen Biogen, Cambridge, MA, USA Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
Dennison, Charlotte A
Autor Dennison, Charlotte A MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
Hall, Lynsey S
Autor Hall, Lynsey S MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK

Nature. 2022 ; 604 (7906) : 502-508. [pub] 20220408

ISSN 1476-4687
Medvik
Zdroj

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

MeSH
alely MeSH
celogenomová asociační studie * MeSH
genetická predispozice k nemoci genetika MeSH
genomika MeSH
jednonukleotidový polymorfismus genetika MeSH
lidé MeSH
schizofrenie * genetika MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH

Článek online

Do Patterns of Instability or Severity of Psychopathology During Screening Predict Relapse in Schizophrenic Outpatient Subjects with Moderate to Severe Negative Symptoms Assigned to Placebo?

Innovations in clinical neuroscience. 2020 ; 17 (1-3) : 27-29. [pub] 2020Jan01

Innov Clin Neurosci
ISSN 2158-8333
Medvik
Zdroj

Background: Patients with schizophrenia who, prior to inclusion in placebo-controlled trials, experience the most severe and/or unstable symptoms might be more likely to manifest symptomatic worsening upon antipsychotic discontinuation. Methods: This retrospective analysis included all randomized patients assigned to placebo (n=83) in a 12-week, double-blind, placebo-controlled outpatient trial of MIN-101 (roluperidone) for the treatment of negative symptoms in schizophrenia. The following risk factors were defined for exacerbation: instability between screening and baseline defined operationally as patients with the highest 10 percent of absolute change from the screening visit to baseline in the Positive and Negative Syndrome Scale (PANSS) total or one of the five PANSS Marder factors; screening or baseline severity in PANSS total or one of the five PANSS Marder factors; and gender and age. We used two operational criteria of relapse and the odds ratios of meeting the relapse criteria were calculated for each risk factor. Results: The odds of meeting one of the operational thresholds for relapse after antipsychotic discontinuation were not statistically significantly increased in the subjects who were unstable on the PANSS total or on one of the five PANSS Marder factors before antipsychotic discontinuation. Further, the severity of PANSS total and Marder factor scores at screening and baseline were not statistically significantly associated with odds of relapse. Neither age nor gender had any effect on relapse rates. Conclusion: Mild to moderate symptomatic variations in the severity of symptoms during screening and more severe symptomology at baseline as measured by the PANSS were not predictive of increased risk of subsequent relapse in schizophrenic patients.