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Association of poly...
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Amare, Azmeraw T
(author)
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- Article/chapterEnglish2023
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LIBRIS-ID:oai:gup.ub.gu.se/332981
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https://gup.ub.gu.se/publication/332981URI
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https://doi.org/10.1038/s41380-023-02149-1DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:153440760URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Thalamuthu, Anbupalam
(author)
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Schubert, Klaus Oliver
(author)
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Fullerton, Janice M
(author)
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Ahmed, Muktar
(author)
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Hartmann, Simon
(author)
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Papiol, Sergi
(author)
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Heilbronner, Urs
(author)
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Degenhardt, Franziska
(author)
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Tekola-Ayele, Fasil
(author)
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Hou, Liping
(author)
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Hsu, Yi-Hsiang
(author)
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Shekhtman, Tatyana
(author)
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Adli, Mazda
(author)
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Akula, Nirmala
(author)
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Akiyama, Kazufumi
(author)
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Ardau, Raffaella
(author)
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Arias, Bárbara
(author)
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Aubry, Jean-Michel
(author)
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Hasler, Roland
(author)
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Richard-Lepouriel, Hélène
(author)
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Perroud, Nader
(author)
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Backlund, LenaKarolinska Institutet
(author)
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Bhattacharjee, Abesh Kumar
(author)
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Bellivier, Frank
(author)
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Benabarre, Antonio
(author)
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Bengesser, Susanne
(author)
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Biernacka, Joanna M
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Birner, Armin
(author)
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Marie-Claire, Cynthia
(author)
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Cervantes, Pablo
(author)
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Chen, Hsi-Chung
(author)
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Chillotti, CaterinaKarolinska Institutet
(author)
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Cichon, Sven
(author)
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Cruceanu, Cristiana
(author)
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Czerski, Piotr M
(author)
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Dalkner, Nina
(author)
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Del Zompo, Maria
(author)
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DePaulo, J Raymond
(author)
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Étain, Bruno
(author)
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Jamain, Stephane
(author)
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Falkai, Peter
(author)
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Forstner, Andreas J
(author)
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Frisen, LouiseKarolinska Institutet
(author)
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Frye, Mark A
(author)
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Gard, Sébastien
(author)
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Garnham, Julie S
(author)
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Goes, Fernando S
(author)
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Grigoroiu-Serbanescu, Maria
(author)
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Fallgatter, Andreas J
(author)
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Stegmaier, Sophia
(author)
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Ethofer, Thomas
(author)
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Biere, Silvia
(author)
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Petrova, Kristiyana
(author)
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Schuster, Ceylan
(author)
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Adorjan, Kristina
(author)
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Budde, Monika
(author)
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Heilbronner, Maria
(author)
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Kalman, Janos L
(author)
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Kohshour, Mojtaba Oraki
(author)
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Reich-Erkelenz, Daniela
(author)
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Schaupp, Sabrina K
(author)
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Schulte, Eva C
(author)
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Senner, Fanny
(author)
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Vogl, Thomas
(author)
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Anghelescu, Ion-George
(author)
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Arolt, Volker
(author)
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Dannlowski, Udo
(author)
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Dietrich, Detlef
(author)
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Figge, Christian
(author)
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Jäger, Markus
(author)
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Lang, Fabian U
(author)
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Juckel, Georg
(author)
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Konrad, Carsten
(author)
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Reimer, Jens
(author)
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Schmauß, Max
(author)
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Schmitt, Andrea
(author)
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Spitzer, Carsten
(author)
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von Hagen, Martin
(author)
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Wiltfang, Jens
(author)
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Zimmermann, Jörg
(author)
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Andlauer, Till F M
(author)
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Fischer, Andre
(author)
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Bermpohl, Felix
(author)
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Ritter, Philipp
(author)
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Matura, Silke
(author)
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Gryaznova, Anna
(author)
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Falkenberg, Irina
(author)
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Yildiz, Cüneyt
(author)
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Kircher, Tilo
(author)
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Schmidt, Julia
(author)
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Koch, Marius
(author)
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Gade, Kathrin
(author)
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Trost, Sarah
(author)
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Haussleiter, Ida S
(author)
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Lambert, Martin
(author)
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Rohenkohl, Anja C
(author)
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Kraft, Vivien
(author)
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Grof, Paul
(author)
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Hashimoto, Ryota
(author)
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Hauser, Joanna
(author)
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Herms, Stefan
(author)
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Hoffmann, Per
(author)
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Jiménez, Esther
(author)
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Kahn, Jean-Pierre
(author)
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Kassem, Layla
(author)
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Kuo, Po-Hsiu
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Kato, Tadafumi
(author)
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Kelsoe, John
(author)
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Kittel-Schneider, Sarah
(author)
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Ferensztajn-Rochowiak, Ewa
(author)
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König, Barbara
(author)
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Kusumi, Ichiro
(author)
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Laje, Gonzalo
(author)
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Landén, Mikael,1966Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt
(author)
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Lavebratt, Catharina
(author)
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Leboyer, Marion
(author)
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Leckband, Susan G
(author)
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Tortorella, Alfonso
(author)
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Manchia, MirkoKarolinska Institutet
(author)
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Martinsson, LinaKarolinska Institutet
(author)
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McCarthy, Michael J
(author)
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McElroy, Susan
(author)
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Colom, Francesc
(author)
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Millischer, VincentKarolinska Institutet
(author)
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Mitjans, Marina
(author)
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Mondimore, Francis M
(author)
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Monteleone, Palmiero
(author)
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Nievergelt, Caroline M
(author)
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Nöthen, Markus M
(author)
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Novák, Tomas
(author)
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O'Donovan, Claire
(author)
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Ozaki, Norio
(author)
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Pfennig, Andrea
(author)
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Pisanu, Claudia
(author)
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Potash, James B
(author)
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Reif, Andreas
(author)
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Reininghaus, Eva
(author)
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Rouleau, Guy A
(author)
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Rybakowski, Janusz K
(author)
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Schalling, Martin
(author)
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Schofield, Peter R
(author)
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Schweizer, Barbara W
(author)
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Severino, Giovanni
(author)
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Shilling, Paul D
(author)
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Shimoda, Katzutaka
(author)
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Simhandl, Christian
(author)
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Slaney, Claire M
(author)
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Squassina, Alessio
(author)
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Stamm, Thomas
(author)
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Stopkova, Pavla
(author)
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Maj, Mario
(author)
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Turecki, Gustavo
(author)
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Vieta, Eduard
(author)
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Veeh, Julia
(author)
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Witt, Stephanie H
(author)
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Wright, Adam
(author)
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Zandi, Peter P
(author)
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Mitchell, Philip B
(author)
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Bauer, Michael
(author)
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Alda, Martin
(author)
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Rietschel, Marcella
(author)
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McMahon, Francis J
(author)
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Schulze, Thomas G
(author)
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Clark, Scott R
(author)
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Baune, Bernhard T
(author)
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Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Molecular psychiatry28, s. 5251-52611476-5578
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Amare, Azmeraw T
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Thalamuthu, Anbu ...
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Schubert, Klaus ...
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Fullerton, Janic ...
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Ahmed, Muktar
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Dietrich, Detlef
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Jäger, Markus
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Lang, Fabian U
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Juckel, Georg
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Konrad, Carsten
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Reimer, Jens
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Schmauß, Max
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Schmitt, Andrea
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Spitzer, Carsten
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von Hagen, Marti ...
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Wiltfang, Jens
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Zimmermann, Jörg
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Andlauer, Till F ...
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Fischer, Andre
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Bermpohl, Felix
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Ritter, Philipp
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Matura, Silke
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Falkenberg, Irin ...
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Yildiz, Cüneyt
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Kircher, Tilo
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Schmidt, Julia
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Koch, Marius
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Gade, Kathrin
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Trost, Sarah
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Haussleiter, Ida ...
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Lambert, Martin
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Rohenkohl, Anja ...
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Kraft, Vivien
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Grof, Paul
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Hashimoto, Ryota
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Hauser, Joanna
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Herms, Stefan
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Hoffmann, Per
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Jiménez, Esther
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Kahn, Jean-Pierr ...
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Kassem, Layla
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Kuo, Po-Hsiu
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Kato, Tadafumi
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König, Barbara
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Kusumi, Ichiro
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Rouleau, Guy A
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Rybakowski, Janu ...
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Squassina, Aless ...
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Stamm, Thomas
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Stopkova, Pavla
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Maj, Mario
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Turecki, Gustavo
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Vieta, Eduard
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Veeh, Julia
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Witt, Stephanie ...
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Wright, Adam
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Zandi, Peter P
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Mitchell, Philip ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Psychiatry
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- MEDICAL AND HEALTH SCIENCES
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Molecular psychi ...
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University of Gothenburg
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Karolinska Institutet