Novel Phospholipid Signature of Depressive Symptoms in Patients with Coronary Artery Disease
Open accessAbstract
Background Depression in patients with coronary artery disease ( CAD ) is associated with increased cardiovascular morbidity. Given the proinflammatory actions of phospholipids, aberrant phospholipid metabolism may be an etiological mechanism linking CAD and depression. Our primary objective was to identify a phospholipid biomarker panel that characterizes CAD patients with significant depressive symptoms from those without. Methods and Results We performed a targeted lipidomic analysis on CAD patients with significant depressive symptoms (n=37, Center for Epidemiologic Studies Depression score ≥16) and those without (n=49). Phospholipid species were selected using partial least‐square discriminant analysis, and the ability of the resulting model to discriminate between groups was evaluated using receiver operator characteristic curves. Biosignature scores were calculated from this model, and analyses of covariance were performed to compare intergroup differences in biosignature scores, with adjustment for clinical differences between patients. Those with significant depressive symptoms had lower cardiopulmonary fitness, more prevalent history of depression, and a greater number of vascular risk factors. A model of 10 phospholipid species had an area under the curve value of 0.84 (95% confidence interval 0.72‐0.95), sensitivity of 0.73, and specificity of 0.71. This model passed permutation testing (n=1000, P <0.001). Biosignature scores were higher in those with significant depressive symptoms after adjustment for potential confounders (F[1.86]=14.39, P <0.0005). Conclusions The present findings support the role of proinflammatory phospholipid species in the presence of depression in CAD patients from the CAROTID trial (Coronary Artery Disease Randomized Omega‐3 Trial in Depression). Future investigations should aim to replicate findings in larger data sets and clarify possible pathophysiological mechanisms. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00981383.
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?
Elevation of δ-6 desaturase activity in patients with depressive symptoms has been demonstrated.
“The elevation of δ-6 desaturase activity in patients with depressive symptoms has been demonstrated.”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [36]
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
Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association
Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., de Ferranti, S. D., Floyd, J., Fornage, M., Gillespie, C., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000485 · Cited by 12,591 · see citing works
MetaboAnalyst 3.0—making metabolomics more meaningful
Xia, J., Sinelnikov, I. V., Han, B., & Wishart, D. S. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv380 · Cited by 2,680 · see citing works
Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease
Anderson, L., Oldridge, N., Thompson, D. R., Zwisler, A.-D., Rees, K., Martin, N., & Taylor, R. S. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.10.044 · Cited by 1,910 · see citing works
Exercise-based cardiac rehabilitation for coronary heart disease
Heran, B. S., Chen, J. M., Ebrahim, S., Moxham, T., Oldridge, N., Rees, K., Thompson, D. R., & Taylor, R. S. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001800.pub2 · Cited by 1,844 · see citing works
Lichtman, J. H., Bigger, J. T., Blumenthal, J. A., Frasure-Smith, N., Kaufmann, P. G., Lespérance, F., Mark, D. B., Sheps, D. S., Taylor, C. B., & Froelicher, E. S. (2008) · Circulation · doi:10.1161/circulationaha.108.190769 · Cited by 1,482 · see citing works
Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis
Barth, J., Schumacher, M., & Herrmann-Lingen, C. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000146332.53619.b2 · Cited by 1,358 · see citing works
Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications
Felger, J. C., & Lotrich, F. E. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.060 · Cited by 1,180 · see citing works
Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D. E., Tsukumo, D. M. L., Anhe, G., Amaral, M. E., Takahashi, H. K., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2760-08.2009 · Cited by 1,125 · see citing works
Translational biomarker discovery in clinical metabolomics: an introductory tutorial
Xia, J., Broadhurst, D., Wilson, M., & Wishart, D. S. (2012) · Metabolomics · doi:10.1007/s11306-012-0482-9 · Cited by 958 · see citing works
Gromski, P. S., Muhamadali, H., Ellis, D. I., Yun Xu, A., Correa, E. S., Turner, M. L., & Goodacre, R. (2015) · Analytica Chimica Acta · doi:10.1016/j.aca.2015.02.012 · Cited by 914 · see citing works
Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids
Patterson, E., Wall, R., Fitzgerald, G. F., Ross, R. P., & Stanton, C. (2012) · Journal of Nutrition and Metabolism · doi:10.1155/2012/539426 · Cited by 895 · see citing works
Shafer, A. B. (2006) · Journal of Clinical Psychology · doi:10.1002/jclp.20213 · Cited by 837 · see citing works
Ünal, B., Critchley, J., & Capewell, S. (2004) · Circulation · doi:10.1161/01.cir.0000118498.35499.b2 · Cited by 740 · see citing works
Exercise-based cardiac rehabilitation for coronary heart disease
Anderson, L., Thompson, D. R., Oldridge, N., Zwisler, A., Rees, K., Martin, N., & Taylor, R. S. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001800.pub3 · Cited by 558 · see citing works
Phosphoinositide 3-kinase signalling pathways
Cantrell, D. A. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.8.1439 · Cited by 534 · see citing works
Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy
Hibbeln, J., & Salem, N. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.1.1 · Cited by 532 · see citing works
Depression and cardiac disease: epidemiology, mechanisms, and diagnosis.
Huffman, J. C., Celano, C. M., Beach, S. R., Motiwala, S. R., & Januzzi, J. L. (2013) · Cardiovascular Psychiatry and Neurology · doi:10.1155/2013/695925 · Cited by 445 · see citing works
Phosphoinositide 3-kinase signalling pathways
Domin, J. (2006) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781860948091_0003 · Cited by 444 · see citing works
Lopresti, A. L., Maker, G. L., Hood, S. D., & Drummond, P. D. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.09.017 · Cited by 371 · see citing works
Immune regulation of central nervous system functions: from sickness responses to pathological pain
Watkins, L. R., & Maier, S. F. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01443.x · Cited by 367 · see citing works
Dietary Fat Intake and the Risk of Depression: The SUN Project
Sánchez‐Villegas, A., Verberne, L. D. M., de Irala, J., Ruiz‐Canela, M., Toledo, E., Serra‐Majem, L., & Martínez‐González, M. Á. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016268 · Cited by 246 · see citing works
Measurement of Red Cell Lifespan and Aging
Franco, R. S. (2012) · Transfusion Medicine and Hemotherapy · doi:10.1159/000342232 · Cited by 236 · see citing works
The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder
Varghese, F. P., & Brown, E. S. (2001) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v03n0401 · Cited by 236 · see citing works
Older Age and the Underreporting of Depressive Symptoms
Lyness, J. M., Cox, C., Curry, J., Conwell, Y., King, D. A., & Caine, E. D. (1995) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1995.tb07325.x · Cited by 213 · see citing works
Assies, J., Lieverse, R., Vreken, P., WANDERS, R. J. A., Dingemans, P. M. A. J., & Linszen, D. H. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00986-0 · Cited by 188 · see citing works
Su, K. (2009) · Neurosignals · doi:10.1159/000198167 · Cited by 168 · see citing works
Arachidonic acid metabolism: role in inflammation.
Samuelsson, B. O. (1991) · PubMed · Cited by 151 · see citing works
Serine Phospholipid-specific Phospholipase A That Is Secreted from Activated Platelets
Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H., & Inoue, K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.4.2192 · Cited by 143 · see citing works
Gałecki, P., Gałecka, E., Maes, M., Chamielec, M., Orzechowska, A., Bobińska, K., Lewiński, A., & Szemraj, J. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.01.016 · Cited by 141 · see citing works
Sphingosylphosphorylcholine—biological functions and mechanisms of action
zu Heringdorf, D. M. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(02)00154-3 · Cited by 135 · see citing works
Sundaram, J. R., Chan, E. S., Poore, C. P., Pareek, T. K., Cheong, W. F., Shui, G., Tang, N., Low, C., Wenk, M. R., & Kesavapany, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5177-11.2012 · Cited by 127 · see citing works
Assies, J., Pouwer, F., Lok, A., Mocking, R. J. T., Bockting, C., Visser, I., Abeling, N. G. G. M., Durán, M., & Schene, A. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010635 · Cited by 124 · see citing works
Phosphatidylserine-Mediated Cellular Signaling
Kay, J. G., & Grinstein, S. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-6331-9_10 · Cited by 112 · see citing works
Role of Depression and Inflammation in Incident Coronary Heart Disease Events
Shimbo, D., Chaplin, W. F., Crossman, D. J., Haas, D. C., & Davidson, K. W. (2005) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.05.064 · Cited by 110 · see citing works
Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E. (2009) · Hormone and Metabolic Research · doi:10.1055/s-0029-1202852 · Cited by 89 · see citing works
Effect of linoleic acid on endothelial cell inflammatory mediators
Young, V. M., Toborek, M. J., Yang, F., McClain, C. J., & Hennig, B. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90241-4 · Cited by 88 · see citing works
Depressive Symptoms and Sex Affect Completion Rates and Clinical Outcomes in Cardiac Rehabilitation
Caulin‐Glaser, T., Maciejewski, P. K., Snow, R. J., Lalonde, M., & Mazure, C. M. (2007) · Preventive Cardiology · doi:10.1111/j.1520-037.2007.05666.x · Cited by 67 · see citing works
Feinstein, R. E., Blumenfield, M., Orlowski, B., Frishman, W. H., & Ovanessian, S. (2006) · Cardiology in Review · doi:10.1097/01.crd.0000200977.41695.43 · Cited by 65 · see citing works
Horrobin, D. F. (2001) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.182 · Cited by 49 · see citing works
Lee, L. H.-W., Shui, G., Farooqui, A. A., Wenk, M. R., Tan, C. H., & Ong, W. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114570900995x · Cited by 43 · see citing works
Lysophosphatidylserine has Bilateral Effects on Macrophages in the Pathogenesis of Atherosclerosis
Nishikawa, M., Kurano, M., Ikeda, H., et al. (2014) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.25650 · Cited by 42 · see citing works
Tsuboi, H., Watanabe, M., Kobayashi, F., Kimura, K., & Kinae, N. (2013) · Clinical Nutrition · doi:10.1016/j.clnu.2012.07.011 · Cited by 42 · cited 1× · see citing works
“These results are consistent with those of Tsuboi and colleagues, who reported positive correlations between serum PA levels and depressive symptom severity.(32) Although the serum fraction reflects recent dietary intake rather than long-term trends, our replication of this association in a different blood fraction su…”
ResultKurano, M., Dohi, T., Nojiri, T., Kobayashi, T., Hirowatari, Y., Inoue, A., Kano, K., Matsumoto, H., Igarashi, K., Nishikawa, M., et al. (2015) · BBA Clinical · doi:10.1016/j.bbacli.2015.08.003 · Cited by 34 · see citing works
Lowering dietary n-6 polyunsaturated fatty acids
Alashmali, S. M., Hopperton, K. E., & Bazinet, R. P. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000255 · Cited by 27 · see citing works
Cribb, L., Murphy, J., Froud, A., Oliver, G., Bousman, C., Ng, C. H., & Sarris, J. J. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1327685 · Cited by 24 · see citing works
Lanctôt, K. L., Mazereeuw, G., Herrmann, N., Xu, H., Blanchard, A. P., Figeys, D., OH, P. I., & Bennett, S. A. L. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s87111 · Cited by 19 · see citing works
Self-citationKomori, T. (2015) · Mental Illness · doi:10.4081/mi.2015.5647 · Cited by 19 · see citing works
Postle, A. D. (2012) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32834fb003 · Cited by 15 · see citing works
Komori, T. (2015) · Mental Illness · doi:10.1108/mi.2015.5647 · Cited by 12 · see citing works
Mazereeuw, G., Herrmann, N., David, W. L., Hillyer, L. M., OH, P. I., & Lanctôt, K. L. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.12.009 · Cited by 11 · see citing works
Self-citationMazereeuw, G., Herrmann, N., Xu, H., et al. (2015) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
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
“This further supports the association between depression and chronic inflammation [68].”
BackgroundResultInfluentialLipids 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
- Chan, P., Suridjan, I., Mohammad, D., Herrmann, N., Mazereeuw, G., Hillyer, L. M., Ma, D. W. L., Oh, P. I., & Lanctôt, K. L.
- Affiliations
- University of Toronto (CA)
- Sunnybrook Hospital (CA)
- University of Guelph (CA)
- Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada
- University Health Network (CA)
- Corresponding author
- Lanctôt, Krista L.
- Venue
- Journal of the American Heart Association
- Published
- 2018-05-15
- Volume
- 7
- Issue
- 10
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC6015327
- OpenAlex
- W2802241866
- Cited by
- 15
- References
- 51
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research (114913_1)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- depression, coronary artery disease, phospholipids, lipidomics, biomarkers, inflammation, depressive symptoms, cardiovascular risk, cardiorespiratory fitness, vascular risk factors, omega-3 fatty acids
- MeSH terms
- Affect, Aged, Aged, 80 and over, Coronary Artery Disease, Cross-Sectional Studies, Depression, Female, Humans, Male, Middle Aged, Phospholipids, Predictive Value of Tests, Risk Factors, Reproducibility of Results, Biomarkers, Case-Control Studies, Randomized Controlled Trials as Topic, Inflammation Mediators, Metabolomics
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
