Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
John KelsoeAnna OuSara RosenthalMazda AdliKazufumi AkiyamaNirmala AkulaMartin AldaAzmeraw T AmareRaffaella ArdauBárbara AriasJean-Michel AubryLena BacklundClaudio BanzatoMichael BauerBernhard T BauneFrank BellivierAntonio BenabarreSusanne BengesserBhattacharjee AbeshJoanna M BiernackaElise BuiPablo CervantesGuo-Bo ChenHsi-Chung ChenCaterina ChillottiSven CichonScott R ClarkFrancesc ColomDavid CousinsCristiana CruceanuPiotr M CzerskiClarissa DantasAlexandre DayerFranziska DegenhardtJ Raymond DePauloBruno EtainPeter FalkaiFrederike FellendorfEwa Ferensztajn-RochowiakAndreas J ForstnerLouise FrisenMark A FryeJanice M FullertonSebastien GardJulie S GarnhamFernando GoesMaria Grigoroiu-SerbanescuPaul GrofOliver GruberRyota HashimotoJoanna HauserUrs HeilbronnerStefan HermsPer HoffmannAndrea HofmannLiping HouStéphane JamainEsther JiménezJean-Pierre KahnLayla KassemTadafumi KatoSarah Kittel-SchneiderBarbara KönigPo-Hsiu KuoIchiro KusumiNina DalknerGonzalo LajeMikaél LandénCatharina LavebrattMarion LeboyerSusan LeckbandCarlos López JaramilloGlenda MacQueenMario MajMirko ManchiaCynthia Marie-ClaireLina MartinssonManuel MattheisenMichael McCarthySusan McElroyFrancis J McMahonPhilip B MitchellMarina MitjansFrancis MondimorePalmiero MonteleoneCaroline M NievergeltMarkus Maria NöthenTomáš NovákUrban OsbyNorio OzakiSergi PapiolRoy PerlisAndrea PfennigJames PotashDaniela Reich-ErkelenzAndreas ReifEva Z ReininghausMarcella D C RietschelGuy A RouleauJanusz K RybakowskiMartin SchallingPeter R SchofieldKlaus Oliver SchubertThomas G SchulzeBarbara SchweizerFlorian SeemüllerGiovanni SeverinoTatyana ShekhtmanPaul D ShillingKatzutaka ShimodaChristian SimhandlClaire SlaneyAlessio SquassinaThomas StammPavla StopkovaSarah TigheAlfonso TortorellaGustavo TureckiEduard VietaJulia VolkertStephanie-H WittNaomi R WrayAdam WrightTrevor YoungPeter ZandiMaria Del ZompoPublished in: Research square (2023)
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 2,039 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.
Keyphrases
- pi k akt
- bipolar disorder
- signaling pathway
- cell cycle arrest
- cell proliferation
- extracellular matrix
- major depressive disorder
- end stage renal disease
- chronic kidney disease
- single cell
- cystic fibrosis
- newly diagnosed
- machine learning
- escherichia coli
- genome wide association study
- gene expression
- solid state
- patient reported outcomes
- blood brain barrier
- copy number
- patient reported
- network analysis
- replacement therapy