Untargeted Plasma Metabolomic Profiling in Patients with Major Depressive Disorder Using Ultra-High Performance Liquid Chromatography Coupled with Mass Spectrometry
Open accessAbstract
Major depressive disorder (MDD) is a neuropsychiatric illness with an increasing incidence and a shortfall of efficient diagnostic tools. Interview-based diagnostic tools and clinical examination often lead to misdiagnosis and inefficient systematic treatment selection. Diagnostic and treatment monitoring biomarkers are warranted for MDD. Thus, the emerging field of metabolomics is a promising tool capable of portraying the metabolic repertoire of biomolecules from biological samples in a minimally invasive fashion. Herein, we report an untargeted metabolomic profiling performed in plasma samples of 11 MDD patients, at baseline (MDD1) and at 12 weeks following antidepressant therapy with escitalopram (MDD2), and in 11 healthy controls (C), using ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-(ESI+)-MS). We found two putative metabolites ((phosphatidylserine PS (16:0/16:1) and phosphatidic acid PA (18:1/18:0)) as having statistically significant increased levels in plasma samples of MDD1 patients compared to healthy subjects. ROC analysis revealed an AUC value of 0.876 for PS (16:0/16:1), suggesting a potential diagnostic biomarker role. In addition, PS (18:3/20:4) was significantly decreased in MDD2 group compared to MDD1, with AUC value of 0.785.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Analyses of plasma lipid profile following citalopram and escitalopram administration reveal changes in several types of PC, including increases in PC (36:2), PC (30:0), PC (34:3), PC-O (34:2), PC-O (36:3), LPC (24:0), and SM (24:0) and decreases in PC (36:4), PC (38:6), LPC (20:4), and SM (18:1).
“Analyses of the plasma lipid profile following citalopram and escitalopram administration revealed changes in several types of PC, namely alkyl-PC, lysopPC, and SM (e.g., increases in PC (36:2), PC (30:0), PC (34:3), PC-O (34:2), PC-O (36:3), LPC (24:0), and SM (24:0) and decreases in PC (36:4), PC (38:6), LPC (20:4), and SM (18:1)) [157,158,159].”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [157]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Membrane lipids: where they are and how they behave
van Meer, G., Voelker, D. R., & Feigenson, G. W. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2330 · Cited by 7,157 · see citing works
Genetic Epidemiology of Major Depression: Review and Meta-Analysis
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.10.1552 · Cited by 3,431 · see citing works
Mass spectrometry‐based metabolomics
Dettmer, K., Aronov, P. A., & Hammock, B. D. (2006) · Mass Spectrometry Reviews · doi:10.1002/mas.20108 · Cited by 2,261 · see citing works
Belmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166 · see citing works
Hippocampal volume and depression: a meta-analysis of MRI studies
Videbech, P., & Ravnkilde, B. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.1957 · Cited by 1,590 · see citing works
LMSD: LIPID MAPS structure database
Sud, M., Fahy, E., Cotter, D., Brown, A., Dennis, E. A., Glass, C. K., Merrill, A. H., Murphy, R. C., Raetz, C. R. H., Russell, D. W., et al. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl838 · Cited by 1,388 · see citing works
Clinical diagnosis of depression in primary care: a meta-analysis
Mitchell, A. J., Vaze, A., & Rao, S. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60879-5 · Cited by 1,251 · see citing works
Sen, S., Duman, R., & Sanacora, G. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.005 · Cited by 1,232 · see citing works
Raison, C. L., & Miller, A. H. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.9.1554 · Cited by 1,197 · see citing works
Untreated Depression and Hippocampal Volume Loss
Sheline, Y. I., Gado, M. H., & Kraemer, H. C. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.8.1516 · Cited by 1,180 · see citing works
Hays, R. D. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950130011002 · Cited by 835 · see citing works
Anand, A., Li, Y., Wang, Y., Wu, J., Gao, S., Bukhari, L., Mathews, V. P., Kalnin, A., & Lowe, M. J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.021 · Cited by 787 · see citing works
(2004) · Cited by 780 · see citing works
Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology
Schmidt, H. D., Shelton, R. C., & Duman, R. S. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.151 · Cited by 477 · see citing works
Quehenberger, O., & Dennis, E. A. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1104901 · Cited by 462 · see citing works
Metabolomics: building on a century of biochemistry to guide human health
German, J. B., Hammock, B. D., & Watkins, S. M. (2005) · Metabolomics · doi:10.1007/s11306-005-1102-8 · Cited by 336 · see citing works
Metabolomics tools for identifying biomarkers for neuropsychiatric diseases
Quinones, M. P., & Kaddurah-Daouk, R. F. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.02.019 · Cited by 285 · see citing works
Brain microglia in psychiatric disorders
Mondelli, V., Vernon, A. C., Turkheimer, F., Dazzan, P., & Pariante, C. M. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30101-3 · Cited by 262 · see citing works
Pu, J., Liu, Y., Zhang, H., Tian, L., Gui, S., Yu, Y., Chen, X., Chen, Y., Yang, L., Ran, Y., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0645-4 · Cited by 231 · see citing works
Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder
Roy, B., Dunbar, M., Shelton, R. C., & Dwivedi, Y. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.175 · Cited by 199 · see citing works
Demirkan, A., Isaacs, A., Ugocsai, P., Liebisch, G., Struchalin, M., Rudan, I., Wilson, J. F., Pramstaller, P. P., Gyllensten, U., Campbell, H., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.11.001 · Cited by 163 · see citing works
Plasma lipidomics reveals potential lipid markers of major depressive disorder
Liu, X., Li, J., Zheng, P., Zhao, X., Zhou, C., Hu, C., Hou, X., Wang, H., Xie, P., & Xu, G. (2016) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-016-9768-5 · Cited by 148 · see citing works
Setoyama, D., Kato, T. A., Hashimoto, R., Kunugi, H., Hattori, K., Hayakawa, K., Sato‐Kasai, M., Shimokawa, N., Kaneko, S., Yoshida, S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165267 · Cited by 125 · see citing works
Current understanding of the neurobiology of major depressive disorder.
Chiriţă, A. L., Gheorman, V., Bondari, D., et al. (2015) · PubMed · Cited by 105 · see citing works
MahmoudianDehkordi, S., Ahmed, A. T., Bhattacharyya, S., Han, X., Baillie, R. A., Arnold, M., Skime, M. K., John-Williams, L. S., Moseley, M. A., Thompson, J. W., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01097-6 · Cited by 95 · see citing works
Metabolomics of Major Depressive Disorder and Bipolar Disorder: Overview and Future Perspective
Hashimoto, K. (2018) · Advances in clinical chemistry · doi:10.1016/bs.acc.2017.12.005 · Cited by 80 · see citing works
Lipidomics in Major Depressive Disorder
Walther, A., Cannistraci, C. V., Simons, K., Durán, C., Gerl, M. J., Wehrli, S., & Kirschbaum, C. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00459 · Cited by 77 · see citing works
Faria, R., Santana, M. M., Aveleira, C. A., Simões, C. S. O., Maciel, E. A., Melo, T., Santinha, D. R., Oliveira, M. M., Peixoto, F., Domingues, P. M., et al. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.042 · Cited by 76 · see citing works
ENĂTESCU, V. R., Papavă, I., Enătescu, I., Antonescu, M., Anghel, A., Șeclăman, E. P., Sîrbu, I. O., & Marian, C. (2016) · Psychiatry Investigation · doi:10.4306/pi.2016.13.5.549 · Cited by 73 · see citing works
Self-citationSussulini, A., Prando, A., Maretto, D. A., Poppi, R. J., Tasić, L., Banzato, C. E. M., & Arruda, M. A. Z. (2009) · Analytical Chemistry · doi:10.1021/ac901502j · Cited by 65 · see citing works
Treating depression to remission.
Zajecka, J. (2003) · PubMed · Cited by 44 · see citing works
Metabolic Effects of Antidepressant Treatment
Olguner Eker, O., Ozsoy, S., Eker, B., & Dogan, H. (2017) · Nöro Psikiyatri Arşivi · doi:10.5152/npa.2016.12373 · Cited by 44 · see citing works
Knowles, E. E. M., Huynh, K., Meikle, P. J., Göring, H. H. H., Olvera, R. L., Mathias, S. R., Duggirala, R., Almasy, L. A., Blangero, J., Curran, J. E., et al. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.02.479 · Cited by 43 · see citing works
Bandu, R., Lee, H. J., Lee, H. M., Ha, T. H., Lee, H., Kim, S. J., Ha, K., & Kim, K. P. (2018) · Journal of Mass Spectrometry · doi:10.1002/jms.4070 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review
Pinto, B., Conde, T., Domingues, I., & Domingues, M. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042032 · Cited by 51 · see citing works
“The analysis of plasma lipidome from humans after administration of citalopram and escitalopram revealed an increase in several PC and PC-O species, and to a lesser extent, LPC and SM species, and a decrease in PC(38:6), PC(36:4), PS and sphinganine-1-phosphate (SA1P) [92,93].”
BackgroundInfluentialLipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers
Zorkina, Y., Ushakova, V., Ochneva, A., Tsurina, A., Abramova, O., Savenkova, V., Goncharova, A., Alekseenko, I., Morozova, I., Riabinina, D., et al. (2024) · Metabolites · doi:10.3390/metabo14020080 · Cited by 36 · see citing works
- Authors
- Homorogan, C., Nitusca, D., Enatescu, V., Schubart, P., Moraru, C., Socaciu, C., & Marian, C.
- Affiliations
- Victor Babeș University of Medicine and Pharmacy Timișoara (RO)
- Department of Biochemistry, University of Medicine and Pharmacy Victor Babes Timisoara, 300041 Timisoara, Romania
- Discipline of Psychiatry, Department of Neurosciences, University of Medicine and Pharmacy Victor Babes Timisoara, 300041 Timisoara, Romania
- BIODIATECH, Research Center for Applied Biotechnology in Diagnosis and Molecular Therapy, 400478 Cluj-Napoca, Romania
- Venue
- Metabolites
- Publisher
- MDPI AG
- Published
- 2021-07-20
- Volume
- 11
- Issue
- 7
- Pages
- 466
- ISSN
- 2218-1989 (ISSN-L)
- PMC
- PMC8306682
- OpenAlex
- W3185227475
- Cited by
- 19
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Metabolites (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, plasma metabolomics, untargeted metabolomics, phosphatidylserine, phosphatidic acid, phospholipids, escitalopram, antidepressant response, diagnostic biomarkers, depression diagnosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review