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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Translational psychiatry

Authors: Anna H Ou, Sara B Rosenthal, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Martin Alda, Azmeraw T Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Michael Bauer, Bernhard T Baune, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Pablo Cervantes, Guo-Bo Chen, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, David A Cousins, Cristiana Cruceanu, Piotr M Czerski, Clarissa R Dantas, Alexandre Dayer, Maria Del Zompo, Franziska Degenhardt, J Raymond DePaulo, Bruno Étain, Peter Falkai, Frederike Tabea Fellendorf, Ewa Ferensztajn-Rochowiak, Andreas J Forstner, Louise Frisén, Mark A Frye, Janice M Fullerton, Sébastien Gard, Julie S Garnham, Fernando S Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, Sarah Kittel-Schneider, Barbara König, Po-Hsiu Kuo, Ichiro Kusumi, Nina Lackner, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Carlos A López Jaramillo, Glenda MacQueen, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Manuel Mattheisen, Michael J McCarthy, Susan L McElroy, Francis J McMahon, Philip B Mitchell, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Markus M Nöthen, Tomas Novák, Urban Ösby, Norio Ozaki, Sergi Papiol, Roy H Perlis, Claudia Pisanu, James B Potash, Andrea Pfennig, Daniela Reich-Erkelenz, Andreas Reif, Eva Z Reininghaus, Marcella Rietschel, Guy A Rouleau, Janusz K Rybakowski, Martin Schalling, Peter R Schofield, K Oliver Schubert, Thomas G Schulze, Barbara W Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Kazutaka Shimoda, Christian Simhandl, Claire M Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Sarah K Tighe, Alfonso Tortorella, Gustavo Turecki, Eduard Vieta, Julia Volkert, Stephanie Witt, Naomi R Wray, Adam Wright, L Trevor Young, Peter P Zandi, John R Kelsoe

Lithium 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.

© 2024. The Author(s).

PMID: 38395906

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