Genetic disposition to inflammation and response to antidepressants in major depressive disorder
Open accessAbstract
Background Inflammation may play an important role in depression and its treatment. A previous study found that increased C-reactive protein (CRP), a marker of systemic inflammation, is associated with worse response to the serotonergic antidepressant escitalopram and better response to the noradrenergic antidepressant nortriptyline. It is unclear whether this reflects genetic disposition to inflammation.Methods We analyzed genotype data and weekly Montgomery-Åsberg Depression Rating Scale scores (MADRS) from 755 unrelated individuals obtained over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. We calculated a polygenic risk score for CRP level based on genome-wide meta-analysis results from the CHARGE Consortium.Results A higher polygenic risk score for CRP was associated with slightly better response to escitalopram and slightly worse response to nortriptyline, reflected in a statistically significant interaction between polygenic risk score and drug (beta = 1.07, 95% CI = 0.26-1.87, p = 0.0093).Discussion A differential association between CRP-PRS and antidepressant drug that is in a direction opposite to that found with serum CRP measurement suggests that previously observed effect of inflammation on antidepressant efficacy may be driven by state factors distinct from genetic influences on systemic inflammation.
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?
Anti-inflammatory action of SSRI and SNRIs has been hypothesized through which they can indirectly reduce depressive symptoms, although findings are still contradictory.
“Indeed, anti-inflammatory action of SSRI and serotonin and noradrenaline inhibitors (SNRIs) has been hypothesized through which they can indirectly reduce depressive symptoms [124,125,126], even though the findings are still contradictory [77].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [77]
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
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
Self-citationRush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643 · see citing works
Population Structure and Eigenanalysis
Patterson, N., Price, A. L., & Reich, D. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020190 · Cited by 5,280 · see citing works
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879 · see citing works
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848 · see citing works
eQTLGen, Wray, N. R., 23andMe, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0090-3 · Cited by 3,005 · see citing works
Self-citationMaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes
Li, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20533 · Cited by 1,843 · see citing works
Nanni, V., Uher, R., & Danese, A. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020335 · Cited by 1,480 · see citing works
Self-citationData quality control in genetic case-control association studies
Anderson, C. A., Pettersson, F. H., Clarke, G. M., Cardon, L. R., Morris, A. P., & Zondervan, K. T. (2010) · Nature Protocols · doi:10.1038/nprot.2010.116 · Cited by 1,318 · see citing works
PRSice: Polygenic Risk Score software
Euesden, J., Lewis, C. M., & O’Reilly, P. F. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu848 · Cited by 1,149 · see citing works
Self-citationBaumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084 · see citing works
Depression: A Global Public Health Concern
Marcus, M., Yasamy, M. T., van Ommeren, M., Chisholm, D., & Saxena, S. (2012) · PsycEXTRA Dataset · doi:10.1037/e517532013-004 · Cited by 997 · see citing works
A mechanism converting psychosocial stress into mononuclear cell activation
Bierhaus, A., Wolf, J., Andrassy, M., Rohleder, N., Humpert, P. M., Petrov, D., Ferstl, R., von Eynatten, M., Wendt, T., Rudofsky, G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438019100 · Cited by 926 · see citing works
Pace, T. W. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., & Heim, C. M. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1630 · Cited by 810 · see citing works
Inflammation and clinical response to treatment in depression: A meta-analysis
Strawbridge, R., Arnone, D., Danese, A., Papadopoulos, A., Herane Vives, A., & Cleare, A. J. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.06.007 · Cited by 666 · see citing works
Dehghan, A., Dupuis, J., Barbalić, M., Bis, J. C., Eiríksdóttir, G., Lu, C., Pellikka, N., Wallaschofski, H., Kettunen, J., Henneman, P., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.948570 · Cited by 512 · see citing works
Rational Inferences about Departures from Hardy-Weinberg Equilibrium
Wittke‐Thompson, J. K., Pluzhnikov, A., & Cox, N. J. (2005) · The American Journal of Human Genetics · doi:10.1086/430507 · Cited by 427 · see citing works
Uher, R., Tansey, K. E., Dew, T., Maier, W., Mors, O., Hauser, J., Dernovsek, M. Z., Henigsberg, N., Souery, D., Farmer, A., et al. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14010094 · Cited by 418 · see citing works
Self-citationGenome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project
Uher, R., Perroud, N. A., Ng, M., Hauser, J., Henigsberg, N., Maier, W., Mors, O. N., Placentino, A., Rietschel, M., Souery, D., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09070932 · Cited by 350 · see citing works
Self-citationMeasuring depression: comparison and integration of three scales in the GENDEP study
Uher, R., FARMER, A. E., Maier, W., Rietschel, M., Hauser, J., Marušić, A., Mors, O. N., Elkin, A., Williamson, R. J., Schmael, C., et al. (2007) · Psychological Medicine · doi:10.1017/s0033291707001730 · Cited by 290 · see citing works
Self-citationKöhler-Forsberg, O., Buttenschøn, H. N., Tansey, K. E., Maier, W., Hauser, J., Dernovsek, M. Z., Henigsberg, N., Souery, D., Farmer, A., Rietschel, M., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.02.020 · Cited by 283 · see citing works
Self-citationSELF-REPORT AND CLINICIAN-RATED MEASURES OF DEPRESSION SEVERITY: CAN ONE REPLACE THE OTHER?
Uher, R., Perlis, R. H., Placentino, A., Dernovšek, M. Z., Henigsberg, N., Mors, O. N., Maier, W., McGuffin, P., & FARMER, A. E. (2012) · Depression and Anxiety · doi:10.1002/da.21993 · Cited by 264 · see citing works
Self-citationContribution of Common Genetic Variants to Antidepressant Response
Tansey, K. E., Guipponi, M., Hu, X., Domenici, E., Lewis, G., Malafosse, A., Wendland, J. R., Lewis, C. M., McGuffin, P., & Uher, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.030 · Cited by 245 · see citing works
Self-citationKathiresan, S., Larson, M. G., Vasan, R. S., Guo, C., Gona, P. N., Keaney, J. F., Wilson, P. W. F., Newton‐Cheh, C., Musone, S. L., Camargo, A. L., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.591271 · Cited by 228 · see citing works
Jha, M. K., Minhajuddin, A., Gadad, B. S., Greer, T., Grannemann, B., Soyombo, A., Mayes, T. L., Rush, A. J., & Trivedi, M. H. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.023 · Cited by 206 · see citing works
Prins, B. P., Abbasi, A., Wong, A., Vaez, A., Nolte, I., Franceschini, N., Stuart, P. E., Guterriez Achury, J., Mistry, V., Bradfield, J. P., et al. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1001976 · Cited by 199 · see citing works
Aschbacher, K., Epel, E., Wolkowitz, O. M., Prather, A. A., Puterman, E., & Dhabhar, F. S. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.10.010 · Cited by 112 · see citing works
Pistis, G., Porcu, E., Vrieze, S. I., Sidore, C., Steri, M., Danjou, F., Busonero, F., Mulas, A., Żołędziewska, M., Maschio, A., et al. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.216 · Cited by 96 · see citing works
Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy
Steimer, W., Müller, B., Leucht, S., & Kissling, W. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(01)00423-5 · Cited by 92 · see citing works
Sas, A. A., Vaez, A., Jamshidi, Y., Nolte, I. M., Kamali, Z., Spector, T. D., Riese, H., & Snieder, H. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.08.008 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
C-Reactive protein as a biomarker for major depressive disorder?
Orsolini, L., Pompili, S., Tempia Valenta, S., Salvi, V., & Volpe, U. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031616 · Cited by 171 · see citing works
Han, L. K. M., Verhoeven, J. E., Tyrka, A. R., Penninx, B. W. J. H., Wolkowitz, O. M., Månsson, K. N. T., Lindqvist, D., Boks, M. P., Révész, D., Mellon, S. H., et al. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.04.004 · Cited by 104 · see citing works
Meerman, J. J., ter Hark, S. E., Janzing, J., & Coenen, M. J. H. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.02.015 · Cited by 58 · see citing works
Is Autophagy Involved in the Diverse Effects of Antidepressants?
Rein, T. (2019) · Cells · doi:10.3390/cells8010044 · Cited by 45 · see citing works
Diniz, B. S., Mulsant, B. H., Reynolds, C. F., Blumberger, D. M., Karp, J. F., Butters, M. A., Mendes‐Silva, A. P., Vieira, É. L. M., Tseng, G. C., & Lenze, E. J. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.19678 · Cited by 43 · see citing works
Zou, T., Zhang, J., Liu, Y., Zhang, Y., Sugimoto, K., & Mei, C. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00131 · Cited by 37 · see citing works
Tomasi, J., Lisoway, A. J., Zai, C. C. H., Harripaul, R., Müller, D. J., Zai, G. C., McCabe, R. E., Richter, M. A., Kennedy, J. L., & Tiwari, A. K. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.09.002 · Cited by 36 · see citing works
Li, X., Wang, H., Li, C., Wu, J., Lü, J., Guo, J., & Tu, Y. (2021) · The Anatomical Record · doi:10.1002/ar.24778 · Cited by 31 · see citing works
Pharmacogenetics and Depression: A Critical Perspective
Corponi, F., Fabbri, C., & Serretti, A. (2019) · Psychiatry Investigation · doi:10.30773/pi.2019.06.16 · Cited by 32 · see citing works
Self-citationPharmacogenomic scores in psychiatry: systematic review of current evidence
Sharew, N. T., Clark, S. R., Schubert, K. O., & Amare, A. T. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02998-6 · Cited by 33 · see citing works
Segura, À. G., Martínez-Pinteño, A., Gassó, P., Rodríguez, N., Bioque, M., Cuesta, M. J., González‐Peñas, J., García‐Rizo, C., Lobo, A., González-Pinto, A. M., et al. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2022.05.021 · Cited by 21 · see citing works
Pharmacogenomics polygenic risk score: Ready or not for prime time?
Singh, S., Stocco, G., Theken, K. N., Dickson, A. L., Feng, Q., Karnes, J. H., Mosley, J. D., & Rouby, N. M. E. (2024) · Clinical and Translational Science · doi:10.1111/cts.13893 · Cited by 23 · see citing works
Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities
Zhai, S., Mehrotra, D. V., & Shen, J. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad470 · Cited by 23 · see citing works
Pan, Y., Luo, R., Zhang, S., Liu, Y., Wang, Y., Feng, S., & Li, H. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.06.080 · Cited by 17 · see citing works
Zong, L., Ge, M., Wang, J., Kuang, D., Wei, H., Wang, Z., Hu, Z., Zhao, C., Jin, Q., Chen, M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-52442-4 · Cited by 17 · see citing works
Taylor, R., Coleman, J. R. I., Lawrence, A. J., Strawbridge, R., Zahn, R., & Cleare, A. J. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.04.074 · Cited by 10 · see citing works
The Pharmacogenomics of Selective Serotonin Reuptake Inhibitors
García‐Marín, L. M., Rabinowitz, J. A., Ceja, Z., Alcauter, S., Medina-Rivera, A., & Rentería, M. E. (2022) · Pharmacogenomics · doi:10.2217/pgs-2022-0037 · Cited by 11 · see citing works
Pharmacogenetics and the Response to Antidepressants in Major Depressive Disorder
Bertollo, A. G., Mocelin, R., & Ignácio, Z. M. (2025) · Pharmaceuticals · doi:10.3390/ph18091360 · Cited by 9 · see citing works
Harrington, Y. A., Fortaner-Uyà, L., Paolini, M., Poletti, S., Lorenzi, C., Spadini, S., Melloni, E. M. T., Agnoletto, E., Zanardi, R., Colombo, C., et al. (2024) · Genes · doi:10.3390/genes15121517 · Cited by 8 · see citing works
Memantine can protect against inflammation-based cognitive decline in geriatric depression
Dyk, K. V., Siddarth, P., Rossetti, M. M., Ercoli, L. M., Milillo, M. M., & Lavretsky, H. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100167 · Cited by 8 · see citing works
ter Hark, S. E., Vos, C. F., Aarnoutse, R. E., Schene, A. H., Coenen, M. J. H., & Janzing, J. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.03.057 · Cited by 8 · see citing works
Fond, G. B., Godin, O., Schürhoff, F., Berna, F. S., Aouizerate, B., Capdevielle, D., Chéreau, I., d’Amato, T., Dubertret, C., Dubreucq, J., et al. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.004 · Cited by 7 · see citing works
Serretti, A., Fabbri, C., Fanelli, G., Baune, B. T., Minelli, A., Serretti, A., Dierssen, M., Maron, E., Potier, M.-C., Gennarelli, M., et al. (2025) · Neuroscience Applied · doi:10.1016/j.nsa.2025.105530 · Cited by 4 · see citing works
Self-citationChang, T.-Y., Zhuang, T.-Y., Yang, Y.-C., Hsu, C.-C., & Cheng, W. (2025) · Environmental Health and Preventive Medicine · doi:10.1265/ehpm.25-00106 · Cited by 3 · see citing works
Serretti, A., Souery, D., Kasper, S., Bartova, L., Zohar, J., Montgomery, S., Ferentinos, P. P., Rujescu, D., Ferri, R., Fanelli, G., et al. (2025) · Genomic psychiatry : · doi:10.61373/gp025r.0092 · Cited by 2 · see citing works
Ye, J., Zhao, J., Li, H., & He, J. (2025) · Sensors · doi:10.3390/s25237162 · Cited by 2 · see citing works
Pharmacogenomic scores in psychiatry: Systematic review of existing evidencePreprint
Sharew, N. T., Clark, S. R., Schubert, K. O., & Amare, A. T. (2024) · medRxiv · doi:10.1101/2024.04.05.24305376 · Cited by 2 · see citing works
Progress in Biomarkers to Improve Treatment Outcomes in Major Depressive Disorder
Vaccarino, S. R., Ceniti, A. K., Rotzinger, S., & Kennedy, S. H. (2024) · Cambridge University Press eBooks · doi:10.1017/9781108973922.024
- Authors
- Zwicker, A., Fabbri, C., Rietschel, M., Hauser, J., Mors, O., Maier, W., Zobel, A., Farmer, A., Aitchison, K. J., McGuffin, P., Lewis, C. M., & Uher, R.
- Affiliations
- Dalhousie University (CA)
- King's College London (GB)
- Heidelberg University (DE)
- Poznan University of Medical Sciences (PL)
- Aarhus University Hospital (DK)
- University of Bonn (DE)
- University of Alberta (CA)
- Corresponding author
- Uher, Rudolf
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 105
- Pages
- 17-22
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2887725539
- Cited by
- 28
- References
- 32
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 1 · 2022: 7 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by-nc-nd)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Funders
- European Commission Framework 6 (LSHB-CT-2003-503428)
- U.K. Medical research council and GlaxoSmithKline (G0701420)
- Canada Research Chairs Program (231397)
- Canadian Institutes of Health Research (124976, 142738, 148394)
- Nova Scotia Health Research Foundation
- Dalhousie Medical Research Foundation
- National Institute for Health Research (NIHR) Biomedical Research Centre at South London
- Maudsley NHS Foundation Trust and King's College London
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- major depressive disorder, C-reactive protein, systemic inflammation, antidepressant response, escitalopram, nortriptyline, polygenic risk score, state factors
- MeSH terms
- Adult, C-Reactive Protein, Major Depressive Disorder, Female, Humans, Inflammation, Male, Middle Aged, Nortriptyline, Pharmacogenetics, Meta-Analysis as Topic, Citalopram, Selective Serotonin Reuptake Inhibitors, Risk Assessment, Adrenergic Uptake Inhibitors, Genetic Predisposition to Disease, Genome-Wide Association Study
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
