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| Verfasst von: | Nunes, Abraham [VerfasserIn]  |
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| | Stone, William [VerfasserIn] |
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| | Ardau, Raffaella [VerfasserIn] |
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| | Berghöfer, Anne [VerfasserIn] |
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| | Bocchetta, Alberto [VerfasserIn] |
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| | Chillotti, Caterina [VerfasserIn] |
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| | Deiana, Valeria [VerfasserIn] |
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| | Degenhardt, Franziska [VerfasserIn] |
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| | Forstner, Andreas J. [VerfasserIn] |
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| | Garnham, Julie S. [VerfasserIn] |
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| | Grof, Eva [VerfasserIn] |
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| | Hajek, Tomas [VerfasserIn] |
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| | Manchia, Mirko [VerfasserIn] |
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| | Mattheisen, Manuel [VerfasserIn] |
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| | McMahon, Francis [VerfasserIn] |
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| | Müller-Oerlinghausen, Bruno [VerfasserIn] |
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| | Nöthen, Markus Maria [VerfasserIn] |
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| | Pinna, Marco [VerfasserIn] |
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| | Pisanu, Claudia [VerfasserIn] |
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| | O’Donovan, Claire [VerfasserIn] |
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| | Rietschel, Marcella [VerfasserIn] |
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| | Rouleau, Guy [VerfasserIn] |
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| | Schulze, Thomas [VerfasserIn] |
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| | Severino, Giovanni [VerfasserIn] |
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| | Slaney, Claire M. [VerfasserIn] |
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| | Squassina, Alessio [VerfasserIn] |
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| | Suwalska, Aleksandra [VerfasserIn] |
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| | Turecki, Gustavo [VerfasserIn] |
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| | Uher, Rudolf [VerfasserIn] |
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| | Zvolsky, Petr [VerfasserIn] |
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| | Cervantes, Pablo [VerfasserIn] |
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| | del Zompo, Maria [VerfasserIn] |
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| | Grof, Paul [VerfasserIn] |
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| | Rybakowski, Janusz [VerfasserIn] |
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| | Tondo, Leonardo [VerfasserIn] |
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| | Trappenberg, Thomas [VerfasserIn] |
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| | Alda, Martin [VerfasserIn] |
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| Titel: | Exemplar scoring identifies genetically separable phenotypes of lithium responsive bipolar disorder |
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| Verf.angabe: | Abraham Nunes, William Stone, Raffaella Ardau, Anne Berghöfer, Alberto Bocchetta, Caterina Chillotti, Valeria Deiana, Franziska Degenhardt, Andreas J. Forstner, Julie S. Garnham, Eva Grof, Tomas Hajek, Mirko Manchia, Manuel Mattheisen, Francis McMahon, Bruno Müller-Oerlinghausen, Markus M. Nöthen, Marco Pinna, Claudia Pisanu, Claire O’Donovan, Marcella D.C. Rietschel, Guy Rouleau, Thomas Schulze, Giovanni Severino, Claire M. Slaney, Alessio Squassina, Aleksandra Suwalska, Gustavo Turecki, Rudolf Uher, Petr Zvolsky, Pablo Cervantes, Maria del Zompo, Paul Grof, Janusz Rybakowski, Leonardo Tondo, Thomas Trappenberg and Martin Alda |
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| E-Jahr: | 2021 |
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| Jahr: | 11 January 2021 |
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| Umfang: | 13 S. |
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| Fussnoten: | Gesehen am 06.05.2021 |
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| Titel Quelle: | Enthalten in: Translational Psychiatry |
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| Ort Quelle: | London : Nature Publishing Group, 2011 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 11(2021), Artikel-ID 36, Seite 1-13 |
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| ISSN Quelle: | 2158-3188 |
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| Abstract: | Predicting lithium response (LiR) in bipolar disorder (BD) may inform treatment planning, but phenotypic heterogeneity complicates discovery of genomic markers. We hypothesized that patients with “exemplary phenotypes”—those whose clinical features are reliably associated with LiR and non-response (LiNR)—are more genetically separable than those with less exemplary phenotypes. Using clinical data collected from people with BD (n = 1266 across 7 centers; 34.7% responders), we computed a “clinical exemplar score,” which measures the degree to which a subject’s clinical phenotype is reliably predictive of LiR/LiNR. For patients whose genotypes were available (n = 321), we evaluated whether a subgroup of responders/non-responders with the top 25% of clinical exemplar scores (the “best clinical exemplars”) were more accurately classified based on genetic data, compared to a subgroup with the lowest 25% of clinical exemplar scores (the “poor clinical exemplars”). On average, the best clinical exemplars of LiR had a later illness onset, completely episodic clinical course, absence of rapid cycling and psychosis, and few psychiatric comorbidities. The best clinical exemplars of LiR and LiNR were genetically separable with an area under the receiver operating characteristic curve of 0.88 (IQR [0.83, 0.98]), compared to 0.66 [0.61, 0.80] (p = 0.0032) among poor clinical exemplars. Variants in the Alzheimer’s amyloid-secretase pathway, along with G-protein-coupled receptor, muscarinic acetylcholine, and histamine H1R signaling pathways were informative predictors. This study must be replicated on larger samples and extended to predict response to other mood stabilizers. |
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| DOI: | doi:10.1038/s41398-020-01148-y |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1038/s41398-020-01148-y |
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| | Volltext: https://www.nature.com/articles/s41398-020-01148-y |
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| | DOI: https://doi.org/10.1038/s41398-020-01148-y |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1757256954 |
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| Verknüpfungen: | → Zeitschrift |
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Exemplar scoring identifies genetically separable phenotypes of lithium responsive bipolar disorder / Nunes, Abraham [VerfasserIn]; 11 January 2021 (Online-Ressource)
