Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
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Published:2024-02-23
Issue:1
Volume:14
Page:
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ISSN:2158-3188
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Container-title:Translational Psychiatry
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language:en
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Short-container-title:Transl Psychiatry
Author:
Ou Anna H.ORCID, Rosenthal Sara B., Adli Mazda, Akiyama Kazufumi, Akula Nirmala, Alda MartinORCID, Amare Azmeraw T.ORCID, Ardau Raffaella, Arias BárbaraORCID, Aubry Jean-Michel, Backlund Lena, Bauer MichaelORCID, Baune Bernhard T.ORCID, Bellivier Frank, Benabarre Antonio, Bengesser Susanne, Bhattacharjee Abesh Kumar, Biernacka Joanna M.ORCID, Cervantes Pablo, Chen Guo-Bo, Chen Hsi-ChungORCID, Chillotti Caterina, Cichon Sven, Clark Scott R.ORCID, Colom Francesc, Cousins David A., Cruceanu CristianaORCID, Czerski Piotr M.ORCID, Dantas Clarissa R., Dayer Alexandre, Del Zompo MariaORCID, Degenhardt Franziska, DePaulo J. RaymondORCID, Étain BrunoORCID, Falkai Peter, Fellendorf Frederike Tabea, Ferensztajn-Rochowiak Ewa, Forstner Andreas J.ORCID, Frisén Louise, Frye Mark A.ORCID, Fullerton Janice M.ORCID, Gard Sébastien, Garnham Julie S.ORCID, Goes Fernando S., Grigoroiu-Serbanescu MariaORCID, Grof Paul, Gruber Oliver, Hashimoto RyotaORCID, Hauser JoannaORCID, Heilbronner UrsORCID, Herms Stefan, Hoffmann Per, Hofmann Andrea, Hou LipingORCID, Jamain StephaneORCID, Jiménez Esther, Kahn Jean-Pierre, Kassem Layla, Kato TadafumiORCID, Kittel-Schneider Sarah, König Barbara, Kuo Po-HsiuORCID, Kusumi IchiroORCID, Lackner Nina, Laje Gonzalo, Landén MikaelORCID, Lavebratt CatharinaORCID, Leboyer MarionORCID, Leckband Susan G., Jaramillo Carlos A. López, MacQueen Glenda, Maj Mario, Manchia MirkoORCID, Marie-Claire CynthiaORCID, Martinsson Lina, Mattheisen Manuel, McCarthy Michael J., McElroy Susan L., McMahon Francis J.ORCID, Mitchell Philip B.ORCID, Mitjans MarinaORCID, Mondimore Francis M., Monteleone Palmiero, Nievergelt Caroline M.ORCID, Nöthen Markus M.ORCID, Novák TomasORCID, Ösby Urban, Ozaki NorioORCID, Papiol SergiORCID, Perlis Roy H., Pisanu Claudia, Potash James B., Pfennig Andrea, Reich-Erkelenz Daniela, Reif AndreasORCID, Reininghaus Eva Z.ORCID, Rietschel MarcellaORCID, Rouleau Guy A.ORCID, Rybakowski Janusz K.ORCID, Schalling MartinORCID, Schofield Peter R.ORCID, Schubert K. OliverORCID, Schulze Thomas G.ORCID, Schweizer Barbara W., Seemüller Florian, Severino GiovanniORCID, Shekhtman Tatyana, Shilling Paul D.ORCID, Shimoda KazutakaORCID, Simhandl Christian, Slaney Claire M., Squassina AlessioORCID, Stamm Thomas, Stopkova Pavla, Tighe Sarah K., Tortorella Alfonso, Turecki GustavoORCID, Vieta EduardORCID, Volkert Julia, Witt StephanieORCID, Wray Naomi R.ORCID, Wright Adam, Young L. Trevor, Zandi Peter P., Kelsoe John R.
Abstract
AbstractLithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
Publisher
Springer Science and Business Media LLC
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