Sex differences in the association of baseline c-reactive protein (CRP) and acute-phase treatment outcomes in major depressive disorder: Findings from the EMBARC study
Open accessAbstract
Peripheral inflammation is associated with poor response to antidepressant treatments. However, whether sex differentially affects this association remains unknown. Participants of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) with baseline plasma samples were included in this study (n = 220; male n = 75, female n = 145). Depression severity [Hamilton Rating Scale for Depression 17-item (HAMD-17)] was measured at baseline and weeks- 1, 2, 3, 4, 6, and 8. Plasma c-reactive protein (CRP) was measured with commercially-available ELISA kits at baseline, week-1, and week-8. Sex difference in prediction of baseline-to-week-8 HAMD-17 change by baseline CRP was tested with sex-by-baseline-CRP-by-time interaction in mixed model analysis. Additionally, changes in CRP from baseline-to-week-8 CRP and its association with HAMD-17 changes over that period were also evaluated. Covariates included body mass index, site, smoking status, and age. There was a significant sex difference in association of baseline-to-week-8 HAMD-17 reduction with baseline CRP (p = 0.033). Higher baseline CRP was associated with lower baseline-to-week-8 HAMD-17 reduction in females (p < 0.0001) but not in males (p = 0.632). Additionally, CRP was significantly reduced (p = 0.041, effect size = 0.254) from baseline-to-week-8, but there were no sex differences in this reduction (p = 0.249). Baseline-to-week-8 changes in HAMD-17 and CRP were not significantly associated either overall (p = 0.348) or based on sex (p = 0.370). In a large study of depressed outpatients, we replicated previous findings that elevated baseline CRP levels are associated with worse antidepressant treatment outcomes. However, this effect was limited only to females. These findings emphasize the importance of studying sex differences in biological mechanisms linking inflammation and depression.
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In an RCT, elevated baseline CRP levels were associated with the worst antidepressant treatment outcome only in female samples.
“A recent RCT evaluated the sex differences in the association between CRP levels and the response to antidepressant treatments [97]. Participants were assessed with HAMD-17 at baseline and at weeks 1, 2, 3, 4, 6, and 8 after the treatment. Elevated baseline CRP levels were associated with the worst antidepressant treatment outcome only in female samples [97].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [97]
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- Authors
- Jha, M. K., Minhajuddin, A., Chin-Fatt, C., Greer, T. L., Carmody, T. J., & Trivedi, M. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Trivedi, Madhukar H.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 113
- Pages
- 165-171
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC6506231
- OpenAlex
- W2922705509
- Cited by
- 40
- References
- 40
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 3 · 2019: 2
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Hersh Foundation
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- sex differences, C-reactive protein, major depressive disorder, antidepressant response, peripheral inflammation, acute phase response, depression severity, plasma biomarkers, outpatients
- MeSH terms
- Acute Disease, Adult, Antidepressive Agents, C-Reactive Protein, Major Depressive Disorder, Double-Blind Method, Female, Follow-Up Studies, Humans, Inflammation, Male, Psychiatric Status Rating Scales, Sex Factors, Treatment Outcome
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