What does plasma CRP tell us about peripheral and central inflammation in depression?

Felger, Jennifer C.; Haroon, Ebrahim; Patel, Trusharth A.; Goldsmith, David R.; Wommack, Evanthia C.; Woolwine, Bobbi J.; Le, Ngoc-Anh; Feinberg, Rachel; Tansey, Malu G.; Miller, Andrew H.

doi:10.1038/s41380-018-0096-3

Cited by 448Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

What does plasma CRP tell us about peripheral and central inflammation in depression?

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Felger, Jennifer C., Haroon, Ebrahim, Patel, Trusharth A., Goldsmith, David R., Wommack, Evanthia C., Woolwine, Bobbi J., Le, Ngoc-Anh, Feinberg, Rachel +2 more·2020·Molecular Psychiatry

DOI 10.1038/s41380-018-0096-3PMC PMC6291384

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Abstract

Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symptoms of anhedonia. Nevertheless, the relationship between peripheral CRP and other peripheral and central markers of inflammation in depressed patients has not been established. Plasma (n = 89) and CSF (n = 73) was collected from medically stable, currently unmedicated adult outpatients with MDD. Associations among plasma and CSF CRP and plasma and CSF inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF] and IL-1beta) and their soluble receptors/antagonists were examined. Relationships between plasma and CSF inflammatory markers and depressive symptoms including anhedonia and reduced motivation (RM) were also explored. Plasma CRP was correlated with multiple plasma inflammatory markers (all p < 0.05), and a strong correlation was found between plasma and CSF CRP (r = 0.855, p < 0.001). CSF CRP in turn correlated with CSF cytokine receptors/antagonists (all p < 0.05). Principal component analyses revealed clusters of CSF inflammatory markers that were associated with high plasma CRP (>3 mg/L) and correlated with depressive symptom severity. These findings were driven by CSF TNF, which correlated with RM (r = 0.236, p = 0.045), and CSF IL-6 soluble receptor, which correlated with anhedonia (r = 0.301, p = 0.010) in the sample as a whole and particularly females. CRP appears to be a peripheral biomarker that reflects peripheral and central inflammation and seems well-suited for guiding immunotherapies targeting TNF and IL-6 in patients with MDD.

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[25]Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry. 2016; 21(10): 1358– 1365. 26552591 PMC4862934
[26]Haroon E, Fleischer CC, Felger JC, Chen X, Woolwine BJ, Patel T, Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Mol Psychiatry. 2016; 21(10): 1351– 1357. 26754953 PMC4940313
[57]Haroon E, Felger JC, Woolwine BJ, Chen X, Parekh S, Spivey JR, Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings. Brain Behav Immun. 2014. PMC4414678 25500218

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Authors: 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.
Affiliations: Emory University (US)
Atlanta VA Medical Center (US)
Corresponding author: Felger, Jennifer C.
ORCID: Felger, Jennifer C.
Haroon, Ebrahim
Patel, Trusharth A.
Goldsmith, David R.
Woolwine, Bobbi J.
Le, Ngoc-Anh
Miller, Andrew H.
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2018-06-12
Volume: 25
Issue: 6
Pages: 1301-1311
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-018-0096-3
PMC: PMC6291384
OpenAlex: W2808599394
Cited by: 448
References: 77
Citations by year: 2026: 42 · 2025: 70 · 2024: 58 · 2023: 69 · 2022: 63 · 2021: 61 · 2020: 48 · 2019: 29 · 2018: 8
FWCI: 11.62
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Dana Foundation (CADF49143)
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH109637, R01MH107033, R01MH087604, R25MH101079)
National Alliance for Research on Schizophrenia and Depression (BBRF22296)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: C-reactive protein, major depressive disorder, systemic inflammation, neuroinflammation, cerebrospinal fluid biomarkers, interleukin-6, TNF-α, IL-1β, soluble cytokine receptors, anhedonia, reduced motivation, immunotherapy, sex differences
MeSH terms: Adult, Aged, C-Reactive Protein, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Inflammation, Male, Middle Aged, Plasma, Cytokines, Young Adult

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