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

Ou AH, Rosenthal SB, Adli M, Akiyama K, Akula N, Alda M, Amare AT, Ardau R, Arias B, Aubry JM, Backlund L, Bauer M, Baune BT, Bellivier F, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Cervantes P, Chen GB, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cousins DA, Cruceanu C, Czerski PM, Dantas CR, Dayer A, Del Zompo M, Degenhardt F, DePaulo JR, Étain B, Falkai P, Fellendorf FT, Ferensztajn-Rochowiak E, Forstner AJ, Frisén L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Gruber O, Hashimoto R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hofmann A, Hou L, Jamain S, Jiménez E, Kahn JP, Kassem L, Kato T, Kittel-Schneider S, König B, Kuo PH, Kusumi I, Lackner N, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Jaramillo CA, MacQueen G, Maj M, Manchia M, Marie-Claire C, Martinsson L, Mattheisen M, McCarthy MJ, McElroy SL, McMahon FJ, Mitchell PB, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Novák T, Ösby U, Ozaki N, Papiol S, Perlis RH, Pisanu C, Potash JB, Pfennig A, Reich-Erkelenz D, Reif A, Reininghaus EZ, Rietschel M, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schubert KO, Schulze TG, Schweizer BW, Seemüller F, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Tighe SK, Tortorella A, Turecki G, Vieta E, Volkert J, Witt S, Wray NR, Wright A, Young LT, Zandi PP, Kelsoe JR (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 14

Article Number: 109

Journal Issue: 1

DOI: 10.1038/s41398-024-02811-4

Abstract

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.

Involved external institutions

University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) Dokkyo Medical University Japan (JP) National Institute of Mental Health Information Resource Center United States (USA) (US) University of Queensland Australia (AU) Dalhousie University Canada (CA) University of Adelaide Australia (AU) Università degli Studi di Cagliari Italy (IT) Mayo Clinic United States (USA) (US) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Université Paris Cité France (FR) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Medizinische Universität Graz Austria (AT) Newcastle University United Kingdom (GB) Institut Mondor de Recherche Biomédicale France (FR) Douglas Mental Health University Institute Canada (CA) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Universidade Estadual de Campinas (UNICAMP) / University of Campinas Brazil (BR) Université de Lorraine France (FR) Johns Hopkins University (JHU) United States (USA) (US) RIKEN Center for Brain Science (CBS) Japan (JP) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) National Taiwan University (NTU) Taiwan (TW) Neuroscience Research Australia NeuRA Australia (AU) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Centre Hospitalier Charles Perrens (CHCP) France (FR) Hospital Albert Chenevier Ap-Hp / Hôpital Albert Chenevier AP-HP Paris France (FR) "Prof. Dr. Alexandru Obregia" Clinical Hospital of Psychiatry / Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia Romania (RO) VA San Diego Healthcare System United States (USA) (US) Universidad de Antioquía (UDEA) Colombia (CO) Mood Disorders Ottawa Canada (CA) Universitätsklinikum Göttingen Germany (DE) University of Calgary Canada (CA) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Karolinska Institute Sweden (SE) Aarhus University Denmark (DK) Städtisches Klinikum Neunkirchen Germany (DE) University of Cincinnati United States (USA) (US) National Institute of Mental Health (NIMH) / Národní ústav duševního zdraví (NUDZ) Czech Republic (CZ) University of New South Wales (UNSW) Australia (AU) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Università degli Studi di Salerno Italy (IT) Nagoya University / 名古屋大学 Japan (JP) Ludwig-Maximilians-Universität (LMU) Germany (DE) Massachusetts General Hospital United States (USA) (US) University of Iowa United States (USA) (US) Montreal Neurological Institute and Hospital (MNI, The Neuro) Canada (CA) University of Toronto Canada (CA)

How to cite

APA:

Ou, A.H., Rosenthal, S.B., Adli, M., Akiyama, K., Akula, N., Alda, M.,... Kelsoe, J.R. (2024). Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study. Translational Psychiatry, 14(1). https://doi.org/10.1038/s41398-024-02811-4

MLA:

Ou, Anna H., et al. "Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study." Translational Psychiatry 14.1 (2024).

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