Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
Journal
Translational Psychiatry
Journal Volume
14
Journal Volume
14
Journal Issue
1
Journal Issue
1
Start Page
109
ISSN
2158-3188
Date Issued
2024-12
Author(s)
Ou, Anna H
Rosenthal, Sara B
Adli, Mazda
Akiyama, Kazufumi
Akula, Nirmala
Alda, Martin
Amare, Azmeraw T
Ardau, Raffaella
Arias, Bárbara
Aubry, Jean-Michel
Backlund, Lena
Bauer, Michael
Baune, Bernhard T
Bellivier, Frank
Benabarre, Antonio
Bengesser, Susanne
Bhattacharjee, Abesh Kumar
Biernacka, Joanna M
Cervantes, Pablo
Chen, Guo-Bo
Chillotti, Caterina
Cichon, Sven
Clark, Scott R
Colom, Francesc
Cousins, David A
Cruceanu, Cristiana
Czerski, Piotr M
Dantas, Clarissa R
Dayer, Alexandre
Del Zompo, Maria
Degenhardt, Franziska
DePaulo, J Raymond
Étain, Bruno
Falkai, Peter
Fellendorf, Frederike Tabea
Ferensztajn-Rochowiak, Ewa
Forstner, Andreas J
Frisén, Louise
Frye, Mark A
Fullerton, Janice M
Gard, Sébastien
Garnham, Julie S
Goes, Fernando S
Grigoroiu-Serbanescu, Maria
Grof, Paul
Gruber, Oliver
Hashimoto, Ryota
Hauser, Joanna
Heilbronner, Urs
Herms, Stefan
Hoffmann, Per
Hofmann, Andrea
Hou, Liping
Jamain, Stephane
Jiménez, Esther
Kahn, Jean-Pierre
Kassem, Layla
Kato, Tadafumi
Kittel-Schneider, Sarah
König, Barbara
Kusumi, Ichiro
Lackner, Nina
Laje, Gonzalo
Landén, Mikael
Lavebratt, Catharina
Leboyer, Marion
Leckband, Susan G
Jaramillo, Carlos A López
MacQueen, Glenda
Maj, Mario
Manchia, Mirko
Marie-Claire, Cynthia
Martinsson, Lina
Mattheisen, Manuel
McCarthy, Michael J
McElroy, Susan L
McMahon, Francis J
Mitchell, Philip B
Mitjans, Marina
Mondimore, Francis M
Monteleone, Palmiero
Nievergelt, Caroline M
Nöthen, Markus M
Novák, Tomas
Ösby, Urban
Ozaki, Norio
Papiol, Sergi
Perlis, Roy H
Pisanu, Claudia
Potash, James B
Pfennig, Andrea
Reich-Erkelenz, Daniela
Reif, Andreas
Reininghaus, Eva Z
Rietschel, Marcella
Rouleau, Guy A
Rybakowski, Janusz K
Schalling, Martin
Schofield, Peter R
Schubert, K Oliver
Schulze, Thomas G
Schweizer, Barbara W
Seemüller, Florian
Severino, Giovanni
Shekhtman, Tatyana
Shilling, Paul D
Shimoda, Kazutaka
Simhandl, Christian
Slaney, Claire M
Squassina, Alessio
Stamm, Thomas
Stopkova, Pavla
Tighe, Sarah K
Tortorella, Alfonso
Turecki, Gustavo
Vieta, Eduard
Volkert, Julia
Witt, Stephanie
Wray, Naomi R
Wright, Adam
Young, L Trevor
Zandi, Peter P
Kelsoe, John R
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.
Publisher
Springer Nature
Type
journal article