Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jul:96:17-27.
doi: 10.1016/j.euroneuro.2025.05.004. Epub 2025 May 22.

Predicted plasma proteomics from genetic scores and treatment outcomes in major depression: a meta-analysis

Vincenzo Oliva  1 , Chiara Possidente  2 , Giuseppe Fanelli  3 , Katharina Domschke  4 , Alessandra Minelli  5 , Massimo Gennarelli  5 , Paolo Martini  6 , Marco Bortolomasi  7 , Alessio Squassina  8 , Claudia Pisanu  8 , Siegfried Kasper  9 , Joseph Zohar  10 , Daniel Souery  11 , Stuart Montgomery  12 , Diego Albani  13 , Gianluigi Forloni  13 , Panagiotis Ferentinos  14 , Dan Rujescu  15 , Julien Mendlewicz  16 , Bernhard T Baune  17 ; European College of Neuropsychopharmacology (ECNP) Pharmacogenomics & Transcriptomics Network; Eduard Vieta  18 , Alessandro Serretti  19 , Chiara Fabbri  20
Affiliations
Free article
Meta-Analysis

Predicted plasma proteomics from genetic scores and treatment outcomes in major depression: a meta-analysis

Vincenzo Oliva et al. Eur Neuropsychopharmacol. 2025 Jul.
Free article

Abstract

Proteomics has been scarcely explored for predicting treatment outcomes in major depressive disorder (MDD), due to methodological challenges and costs. Predicting protein levels from genetic scores provides opportunities for exploratory studies and the selection of targeted panels. In this study, we examined the association between genetically predicted plasma proteins and treatment outcomes - including non-response, non-remission, and treatment-resistant depression (TRD) - in 3559 patients with MDD from four clinical samples. Protein levels were predicted from individual-level genotypes using genetic scores from the publicly available OmicsPred database, which estimated genetic scores based on genome-wide genotypes and proteomic measurements from the Olink and SomaScan platforms. Associations between predicted protein levels and treatment outcomes were assessed using logistic regression models, adjusted for potential confounders including population stratification. Results were meta-analysed using a random-effects model. The Bonferroni correction was applied. We analysed 257 proteins for Olink and 1502 for SomaScan; 111 proteins overlapped between the two platforms. Despite no association was significant after multiple-testing correction, many top results were consistent across phenotypes, in particular seven proteins were nominally associated with all the analysed outcomes (CHL1, DUSP13, EVA1C, FCRL2, KITLG, SMAP1, and TIM3/HAVCR2). Additionally, three proteins (CXCL6, IL5RA, and RARRES2) showed consistent nominal associations across both the Olink and SomaScan platforms. The convergence of results across phenotypes is in line with the hypothesis of the involvement of immune-inflammatory mechanisms and neuroplasticity in treatment response. These results can provide hints for guiding the selection of protein panels in future proteomic studies.

Keywords: Genomics; Inflammation; Major depression; Precision medicine; Proteomics; Treatment-resistant depression (TRD).

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Vincenzo Oliva, Chiara Possidente, Giuseppe Fanelli, Alessandra Minelli, Massimo Gennarelli, Paolo Martini, Marco Bortolomasi, Alessio Squassina, Claudia Pisanu, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Alessandro Serretti, and Chiara Fabbri declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Giuseppe Fanelli is Managing Editor for International Clinical Psychopharmacology (Wolters Kluwer Health, Inc.) and Associate Editor for Frontiers in Psychiatry (Frontiers) and was not involved in the editorial review or the decision to publish this article. Katharina Domschke is an Editorial Board Member for Lundbeck Neurotorium and was not involved in the editorial review or the decision to publish this article. Eduard Vieta is the Editor-in-Chief for European Neuropsychopharmacology and was not involved in the editorial review or the decision to publish this article. Alessandro Serretti is an Editor in Chief Editor for International Clinical Psychopharmacology and was not involved in the editorial review or the decision to publish this article. Chiara Fabbri is an Editorial Board member for International Journal of Psychiatry in Clinical Practice, International Clinical Psychopharmacology and Neuropsychopharmacology Reports, and was not involved in the editorial review or the decision to publish this article. Alessio Squassina is an Associate Editor for Frontiers in Pharmacology (section of Pharmacogenetics), Associate Editor for BMC Psychiatry, member of the editorial board of The Pharmacogenomics Journal, Pharmacogenomics, Human Genomics, Frontiers in Psychiatry, and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katharina Domschke has been a member of the Steering Committee Neurosciences, Janssen Pharmaceuticals, and has received speaker’s honoraria from Janssen Pharmaceuticals. Inc. In the past 3 years Siegfried Kasper served as a consultant or on advisory boards for Angelini, Biogen, Boehringer, Esai, Janssen, IQVIA, Mylan, Recordati, Rovi, and Schwabe; and he has served on speakers bureaus for Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Recordati, Schwabe, Servier, Sothema, and Sun Pharma. Joseph Zohar has received grant/research support from Lundbeck, Servier, and Pfizer; he has served as a consultant on the advisory boards for Servier, Pfizer, Solvay, and Actelion; and he has served on speakers’ bureaus for Lundbeck, GSK, Jazz, and Solvay. Daniel Souery has received grant/research support from GlaxoSmithKline and Lundbeck, and he has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, and Lundbeck. Stuart Montgomery has been a consultant or served on advisory boards for Lundbeck. Bernhard T Baune: Advisory Board - Lundbeck, Janssen-Cilag; Consultant - National Health and Medical Research Council, Australia; Grant/Research Support - AstraZeneca, Fay Fuller Foundation, James & Diana Ramsay Foundation, National Health and Medical Research Council, Australia, German Research Council (DFG), Sanofi, Lundbeck; Honoraria - AstraZeneca, Bristol-Myers Squibb, Lundbeck, Pfizer, Servier Laboratories, Wyeth Pharmaceuticals, Takeda, Janssen, LivaNova PLC. Eduard Vieta has received grants and served as a paid consultant, advisor, or CME speaker for AB-Biotics, Abbott, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Cambridge University Press, Casen-Recordati, Celon, Compass, Dainippon Sumitomo, Elsevier, Ethypharm, Ferrer, Galenica, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Neuraxpharm, Newron, Novartis, Oxford University Press, Orion, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, out of the submitted work.

Publication types

MeSH terms