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Elevated C-Reactive Protein in Patients With Depression, Independent of Genetic, Health, and Psychosocial Factors: Results From the UK Biobank
Abstract
OBJECTIVE: The authors investigated the pathways (genetic, environmental, lifestyle, medical) leading to inflammation in major depressive disorder using C-reactive protein (CRP), genetic, and phenotypic data from the UK Biobank. METHODS: This was a case-control study of 26,894 participants with a lifetime diagnosis of major depressive disorder from the Composite International Diagnostic Interview and 59,001 control subjects who reported no mental disorder and had not reported taking any antidepressant medication. Linear regression models of log CRP level were fitted to regress out the effects of age, sex, body mass index (BMI), and smoking and to test whether the polygenic risk score (PRS) for major depression was associated with log CRP level and whether the association between log CRP level and major depression remained after adjusting for early-life trauma, socioeconomic status, and self-reported health status. RESULTS: CRP levels were significantly higher in patients with depression relative to control subjects (2.4 mg/L compared with 2.1 mg/L, respectively), and more case than control subjects had CRP levels >3 mg/L (21.2% compared with 16.8%, respectively), indicating low-grade inflammation. The PRS for depression was positively and significantly associated with log CRP levels, but this association was no longer significant after adjustment for BMI and smoking. The association between depression and increased log CRP level was substantially reduced, but still remained significant, after adjustment for the aforementioned clinical and sociodemographic factors. CONCLUSIONS: The data indicate that the "genetic" contribution to increased inflammation in depression is due to regulation of eating and smoking habits rather than an "autoimmune" genetic predisposition. Moreover, the association between depression and increased inflammation even after full adjustment indicates either the presence of yet unknown or unmeasured psychosocial and clinical confounding factors or that a core biological association between depression and increased inflammation exists independently from confounders.
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“Furthermore, MDD patients showed more frequently a low-grade inflammation state (i.e., CRP > 3 mg/L) than control subjects (21.1% compared with 16.8%, respectively) [83].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [83]
In the citing paper
“A study recruiting 26,894 participants with a lifetime diagnosis of MDD, evaluated using the Composite International Diagnostic Interview (CIDI), were compared with 59,000 healthy control subjects regarding CRP levels [83]. CRP levels were significantly higher in patients with depression than in the control group (2.4 mg/L compared with 2.1 mg/L, p < 0.001).”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [83]
Citations
Cites
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534
An atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255
The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
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
The global prevalence of common mental disorders: a systematic review and meta-analysis 1980–2013
Steel, Z., Marnane, C., Iranpour, C., Chey, T., Jackson, J. W., Patel, V., & Silove, D. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyu038 · Cited by 2,846
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2 (2011) · Nature · doi:10.1038/nature10251 · Cited by 2,697
Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., et al. (2015) · Nature Genetics · doi:10.1038/ng.3359 · Cited by 2,603
Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0326-7 · Cited by 2,565
Self-citationElevated C-reactive protein levels in overweight and obese adults
Visser, M. (1999) · JAMA · doi:10.1001/jama.282.22.2131 · Cited by 2,494
Genetics of rheumatoid arthritis contributes to biology and drug discovery
the RACI consortium, Okada, Y., the GARNET consortium, Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., et al. (2014) · Nature · doi:10.1038/nature12873 · Cited by 2,310
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., & Schatzberg, A. F. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.65 · Cited by 2,269
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617
PRSice-2: Polygenic Risk Score software for biobank-scale data
Choi, S. W., & O’Reilly, P. F. (2019) · GigaScience · doi:10.1093/gigascience/giz082 · Cited by 1,538
Raison, C. L., & Miller, A. H. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.9.1554 · Cited by 1,197
The Effects of Physical Activity on Serum C-Reactive Protein and Inflammatory Markers
Kasapis, C., & Thompson, P. D. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.12.077 · Cited by 1,149
Genome-wide meta-analyses identify multiple loci associated with smoking behavior
The Tobacco and Genetics Consortium (2010) · Nature Genetics · doi:10.1038/ng.571 · Cited by 1,098
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,027
Bentham, J., Morris, D. L., Graham, D. S. C., Pinder, C. L., Tombleson, P., Behrens, T. W., Martin, J. J., Fairfax, B. P., Knight, J. C., Chen, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3434 · Cited by 1,004
Osimo, E. F., Pillinger, T., Rodriguez, I. M., Khandaker, G. M., Pariante, C. M., & Howes, O. D. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.02.010 · Cited by 937
Self-citationCortés, A., Hadler, J., Robinson, P. C., Leo, P., Cremin, K., Pryce, K., Harris, J., Bradbury, L. A., Kenna, T., Yang, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2667 · Cited by 872
Penninx, B. W., Milaneschi, Y., Lamers, F., & Vogelzangs, N. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-129 · Cited by 839
Osimo, E. F., Baxter, L. J., Lewis, G., Jones, P. B., & Khandaker, G. M. (2019) · Psychological Medicine · doi:10.1017/s0033291719001454 · Cited by 774
Wootton, R. E., Richmond, R. C., Stuijfzand, B. G., Lawn, R. B., Sallis, H. M., Taylor, G. M. J., Hemani, G., Jones, H. J., Zammit, S., Davey Smith, G., et al. (2020) · Psychological Medicine · doi:10.1017/s0033291719002678 · Cited by 587
Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study
Benros, M. E., Waltoft, B. L., Nordentoft, M., Østergaard, S. D., Eaton, W. W., Krogh, J., & Mortensen, P. B. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1111 · Cited by 572
Lippard, E. T. C., & Nemeroff, C. B. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19010020 · Cited by 527
What does plasma CRP tell us about peripheral and central inflammation in depression?
Felger, J. C., Haroon, E., Patel, T. A., Goldsmith, D. R., Wommack, E. C., Woolwine, B. J., Le, N.-A., Feinberg, R., Tansey, M. G., & Miller, A. H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0096-3 · Cited by 448
Musselman, D. L., Miller, A. H., Porter, M. R., Manatunga, A. K., Gao, F., Penna, S., Pearce, B. D., Landry, J. C., Glover, S. G., McDaniel, J. S., et al. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.8.1252 · Cited by 444
Ligthart, S., Vaez, A., Võsa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.09.009 · Cited by 421
The childhood experience of care and abuse questionnaire (CECA.Q): Validation in a community series
Bifulco, A. T., Bernazzani, O., Moran, P. M., & Jacobs, C. (2005) · British Journal of Clinical Psychology · doi:10.1348/014466505x35344 · Cited by 403
Treatment-resistant depression and peripheral C-reactive protein.
Chamberlain, S. R., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D. N. C., Drevets, W. C., Cowen, P. J., Harrison, N. A., Pointon, L., Pariante, C. M., et al. (2019) · British Journal of Psychiatry · doi:10.1192/bjp.2018.66 · Cited by 400
Smıth, D. J., Nicholl, B. I., Cullen, B., Martin, D. J., Haq, Z. U., Evans, J. J., Gill, J. M. R., Roberts, B. A., Gallacher, J., Mackay, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075362 · Cited by 360
The UK-PSC Consortium, Ji, S.-G., The International IBD Genetics Consortium, The International PSC Study Group, Juran, B. D., Mucha, S., Folseraas, T., Jostins, L., Melum, E., Kumasaka, N., et al. (2017) · Nature Genetics · doi:10.1038/ng.3745 · Cited by 357
Davis, K. A. S., Coleman, J. R. I., Adams, M. J., Allen, N. E., Breen, G. D., Cullen, B., Dickens, C. M., Fox, E., Graham, N., Holliday, J., et al. (2020) · BJPsych Open · doi:10.1192/bjo.2019.100 · Cited by 351
Cordell, H. J., Han, Y., Mells, G. F., Li, Y., Hirschfield, G. M., Greene, C. S., Xie, G., Juran, B. D., Zhu, D., Qian, D. C., et al. (2015) · Nature Communications · doi:10.1038/ncomms9019 · Cited by 287
Khandaker, G. M., Zuber, V., Rees, J. M. B., Carvalho, L. A., Mason, A. M., Foley, C. N., Gkatzionis, A., Jones, P. B., & Burgess, S. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0395-3 · Cited by 287
Genetic Contributions of Inflammation to Depression
Barnes, J., Mondelli, V., & Pariante, C. M. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.169 · Cited by 237
Tylee, D. S., Sun, J., Hess, J. L., Tahir, M. A., Sharma, E., Malik, R., Worrall, B. B., Levine, A. J., Martinson, J. J., Nejentsev, S., et al. (2018) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32652 · Cited by 219
Coleman, J. R. I., Peyrot, W. J., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., Hübel, C., Gaspar, H. A., Kan, C., der Auwera, S. V., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0546-6 · Cited by 206
Metabolic and inflammatory markers: associations with individual depressive symptoms
Lamers, F., Milaneschi, Y., de Jonge, P., Giltay, E. J., & Penninx, B. W. J. H. (2017) · Psychological Medicine · doi:10.1017/s0033291717002483 · Cited by 202
Wittenberg, G. M., Stylianou, A., Zhang, Y., Sun, Y., Gupta, A., Jagannatha, P. S., Wang, D., Hsu, B. L., Curran, M. E., Khan, S. A., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0471-8 · Cited by 194
Duivis, H. E., de Jonge, P., Penninx, B. W., Na, B. Y., Cohen, B. E., & Whooley, M. A. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10081163 · Cited by 191
Nikkheslat, N., Zunszain, P. A., Horowitz, M. A., Barbosa, I. G., Parker, J. A., Myint, A.-M., Schwarz, M. J., Tylee, A. T., Carvalho, L. A., & Pariante, C. M. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.02.002 · Cited by 147
Cattaneo, A., Ferrari, C., Uher, R., Bocchio‐Chiavetto, L., Riva, M. A., & Pariante, C. M. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw045 · Cited by 130
Plant, D. T., Pawlby, S., Sharp, D., Zunszain, P. A., & Pariante, C. M. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.155 · Cited by 108
Hruby, A., & Jacques, P. F. (2019) · Current Developments in Nutrition · doi:10.1093/cdn/nzz019 · Cited by 83
Kovács, D., Eszlári, N., Petschner, P., Pap, D., Vas, S., Kovacs, P. L., Gonda, X., Juhász, G., & Bagdy, G. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.02.012 · Cited by 67
Cohen‐Woods, S., Fisher, H. L., Ahmetspahic, D., Douroudis, K., Stacey, D., Hosang, G. M., Korszun, A., Owen, M. J., Craddock, N. J., Arolt, V., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.08.023 · Cited by 40
Sforzini, L., Pariante, C. M., Palacios, J. E., Tylee, A. T., Carvalho, L. A., Viganò, C. A., & Nikkheslat, N. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.07.023 · Cited by 26
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Metadata
- Authors
- Pitharouli, M. C., Hagenaars, S. P., Glanville, K. P., Coleman, J. R. I., Hotopf, M., Lewis, C. M., & Pariante, C. M.
- Affiliations
- National Health Service (GB)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2021-06
- Volume
- 178
- Issue
- 6
- Pages
- 522-529
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W3161566379
- Cited by
- 218
- References
- 51
- Citations by year
- 2026: 42 · 2025: 34 · 2024: 41 · 2023: 41 · 2022: 36 · 2021: 24
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Medical Research Council (MR/S015132/1, MR/N015746/1, MC_PC_17228)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, C-reactive protein, low-grade inflammation, polygenic risk score, genetic predisposition to depression, smoking, body mass index, early trauma, socioeconomic status
- MeSH terms
- Adverse Childhood Experiences, C-Reactive Protein, Depressive Disorder, Major, Major Depressive Disorder, Female, United Kingdom, Health Status, Humans, Inflammation, Male, Middle Aged, Psychology, Smoking, Social Class, Linear Models, Case-Control Studies, Biological Specimen Banks, Genetic Predisposition to Disease
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