Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.
Anna H OuSara B RosenthalMazda AdliKazufumi AkiyamaNirmala AkulaMartin AldaAzmeraw T AmareRaffaella ArdauBárbara AriasJean-Michel AubryLena BacklundMichael BauerBernhard T BauneFrank BellivierAntonio BenabarreSusanne BengesserAbesh Kumar BhattacharjeeJoanna M BiernackaPablo CervantesGuo-Bo ChenHsi-Chung ChenCaterina ChillottiSven CichonScott Richard ClarkFrancesc ColomDavid A CousinsCristiana CruceanuPiotr M CzerskiClarissa R DantasAlexandre DayerMaria Del ZompoFranziska DegenhardtJ Raymond DePauloBruno EtainPeter FalkaiFrederike Tabea FellendorfEwa Ferensztajn-RochowiakAndreas J ForstnerLouise FrisénMark A FryeJanice M FullertonSébastien GardJulie S GarnhamFernando S GoesMaria Grigoroiu-SerbanescuPaul GrofOliver GruberRyota HashimotoJoanna HauserUrs HeilbronnerStefan HermsPer HoffmannAndrea HofmannLiping HouStéphane JamainEsther JiménezJean-Pierre KahnLayla KassemTadafumi KatoSarah Kittel-SchneiderBarbara KönigPo-Hsiu KuoIchiro KusumiNina LacknerGonzalo LajeMikaél LandénCatharina LavebrattMarion LeboyerSusan G LeckbandCarlos A López JaramilloGlenda MacQueenMario MajMirko ManchiaCynthia Marie-ClaireLina MartinssonManuel MattheisenMichael J McCarthySusan L McElroyFrancis J McMahonPhilip B MitchellMarina MitjansFrancis M MondimorePalmiero MonteleoneCaroline M NievergeltMarkus Maria NöthenTomáš NovákUrban ÖsbyNorio OzakiSergi PapiolRoy H PerlisClaudia PisanuJames B PotashAndrea PfennigDaniela Reich-ErkelenzAndreas ReifEva Z ReininghausMarcella D C RietschelGuy A RouleauJanusz K RybakowskiMartin SchallingPeter R SchofieldKlaus Oliver SchubertThomas G SchulzeBarbara W SchweizerFlorian SeemüllerGiovanni SeverinoTatyana ShekhtmanPaul D ShillingKatzutaka ShimodaChristian SimhandlClaire M SlaneyAlessio SquassinaThomas StammPavla StopkovaSarah K TigheAlfonso TortorellaGustavo TureckiEduard VietaJulia VolkertStephanie-H WittNaomi R WrayAdam WrightL Trevor YoungPeter P ZandiJohn R KelsoePublished in: Translational psychiatry (2024)
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.
Keyphrases
- pi k akt
- bipolar disorder
- signaling pathway
- cell proliferation
- extracellular matrix
- cell cycle arrest
- end stage renal disease
- single cell
- emergency department
- genome wide association study
- cystic fibrosis
- chronic kidney disease
- electronic health record
- dna methylation
- pseudomonas aeruginosa
- patient reported outcomes
- brain injury
- biofilm formation
- rna seq
- network analysis