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Record W4392096926 · doi:10.1038/s41398-024-02811-4

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

2024· article· en· W4392096926 on OpenAlexafffund
Anna Ou, Sara Brin 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 de Rosalmeida Dantas, Alexandre Dayer, Maria Del Zompo, Franziska Degenhardt, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Frederike T. Fellendorf, Ewa Ferensztajn‐Rochowiak, Andreas J. Forstner, Louise Frisén, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie Garnham, Fernando S. Goes, Maria Grigoroiu‐Serbânescu, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Stéphane 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 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, Tomáš 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 Rybakowski, Martin Schalling, Peter R. Schofield, Klaus Oliver Schubert, Thomas G. Schulze, Barbara Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Kazutaka Shimoda, Christian Simhandl, Claire Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopková, Sarah K. Tighe, Alfonso Tortorella, Gustavo Turecki, Eduard Vieta, Julia Volkert, Stephanie H. Witt, Naomi R. Wray, A. Jordan Wright, L. Trevor Young, Peter P. Zandi, John R. Kelsoe

Bibliographic record

VenueTranslational Psychiatry · 2024
Typearticle
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsUniversity of CalgaryMcGill UniversityDouglas Mental Health University InstituteMcGill University Health CentreUniversity of TorontoMontreal Neurological Institute and HospitalDalhousie University
FundersNational Cancer InstituteNational Institute of Mental HealthNational Health and Medical Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthRheinische Friedrich-Wilhelms-Universität BonnUnitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si InovariiMinistry of Education, IndiaVirginia Commonwealth UniversityVetenskapsrådetCentro de Investigación Biomédica en Red de Salud MentalNational Alliance for Research on Schizophrenia and DepressionKarolinska InstitutetMinisterstvo Zdravotnictví Ceské RepublikyBundesministerium für Bildung und ForschungUniversity of California, San DiegoU.S. Department of Veterans AffairsUniversity of New South WalesSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversity of OxfordBroad InstituteGenome CanadaAlfried Krupp von Bohlen und Halbach-StiftungNational Institute on Drug AbuseStanley Center for Psychiatric Research, Broad InstituteUniversity of PennsylvaniaUniversidad de AntioquiaDeutsche ForschungsgemeinschaftUniversity of LouisvilleJohns Hopkins UniversityBrain and Behavior Research FoundationRush UniversityWayne State UniversityNational Science Foundation
KeywordsPI3K/AKT/mTOR pathwayFocal adhesionProtein kinase BBipolar disorderLithium (medication)Genome-wide association studyPharmacogenomicsSignal transductionBioinformaticsNeuroscienceBiologyMedicineComputational biologyGeneticsSingle-nucleotide polymorphismPsychiatryGeneGenotype

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.051
Threshold uncertainty score0.603

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.298
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations22
Published2024
Admission routes2
Has abstractyes

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