Association of CRP Genetic Variation and CRP Level With Elevated PTSD Symptoms and Physiological Responses in a Civilian Population With High Levels of Trauma
Open accessAbstract
OBJECTIVE: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma. METHOD: Cross-sectional data and DNA samples were collected from 2,698 individuals recruited from an inner-city public hospital that serves a primarily African American, low-socioeconomic-status population. A subgroup of 187 participants participated in further interviews, testing, and physiological measures; of these, 135 were assessed using the fear-potentiated startle paradigm to assess fear-related phenotypes of PTSD. RESULTS: One SNP within the CRP gene, rs1130864, was significantly associated with increased PTSD symptoms (N=2,692), including "being overly alert" as the most significant individual symptom (N=2,698). Additionally, CRP genotype was associated with the odds of PTSD diagnosis (N=2,692). This SNP was also associated with increased CRP level (N=137), and high CRP levels (>3 mg/L) were positively associated with PTSD symptoms (N=187) and fear-potentiated startle to a safety signal (N=135). CONCLUSIONS: Together, these data indicate that genetic variability in the CRP gene is associated with serum CRP level and PTSD symptom severity, including that of hyperarousal symptoms. Elevated CRP levels were also associated with exacerbated fear-related psychophysiology and PTSD symptom ratings and diagnosis. These findings suggest a potential mechanism by which an increased proinflammatory state may lead to heightened PTSD symptoms.
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Inflammatory markers are elevated not only in a subgroup of patients with depression but also in patients with other neuropsychiatric disorders including anxiety disorders and schizophrenia.
“inflammatory markers are elevated not only in a subgroup of patients with depression30,31 but also in patients with other neuropsychiatric disorders including anxiety disorders and schizophrenia32,33.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [32]
The Introduction identifies PTSD as an anxiety disorder and reports elevated inflammatory cytokines in people with PTSD; the Results also associate higher CRP with PTSD symptoms and diagnosis. This supports the anxiety-disorder example, but our copy does not address schizophrenia. The depression portion is attached to different citations in the citing sentence. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHeightened peripheral CRP concentrations are associated with higher PTSD symptoms and greater odds for a PTSD diagnosis.
“More recently, heightened peripheral CRP concentrations were associated with higher PTSD symptoms and greater odds for a PTSD diagnosis (Michopoulos et al, 2015c).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Michopoulos et al, 2015c
A single SNP in the CRP gene, rs1130864, is associated with heightened peripheral concentrations of CRP, augmented PTSD symptoms, and increased odds of a PTSD diagnosis in traumatized individuals.
“This study determined that a single SNP in the CRP gene, rs1130864, was associated with heightened peripheral concentrations of CRP, augmented PTSD symptoms, and increased odds of a PTSD diagnosis in traumatized individuals (Michopoulos et al, 2015c).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Michopoulos et al, 2015c
Inflammation has been associated with antidepressant treatment non-responsiveness.
“inflammation has been associated with antidepressant treatment non-responsiveness9,32,35–37.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [32]
The Introduction links inflammation with PTSD and notes a similar association with depression, but it does not discuss antidepressant treatment response. Searches for antidepressant non-responsiveness and treatment-resistant depression found no passage addressing that association in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredCRP concentration is correlated with PTSD symptom severity and duration, such that PTSD patients with high CRP had greater symptom severity and duration than those with low CRP.
“Michopoulos et al (2015) and Heath et al (2013) reported that CRP concentration was correlated with PTSD symptom severity and duration, such that PTSD patients with high, compared with low, CRP had greater symptom severity and duration (Heath et al, 2013;Michopoulos et al, 2015).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Michopoulos et al, 2015
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- Authors
- Michopoulos, V., Rothbaum, A. O., Jovanovic, T., Almli, L. M., Bradley, B., Rothbaum, B. O., Gillespie, C. F., & Ressler, K. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- From the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta; the Atlanta VA Medical Center, Atlanta; the Howard Hughes Medical Institute, Bethesda, Md.; and the Yerkes National Primate Research Center, Atlanta.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2015-04-01
- Volume
- 172
- Issue
- 4
- Pages
- 353-362
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4440454
- OpenAlex
- W2163146990
- Cited by
- 203
- References
- 61
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 22 · 2023: 17 · 2022: 19 · 2021: 16 · 2020: 27 · 2019: 10 · 2018: 20 · 2017: 22 · 2016: 19 · 2015: 13
- FWCI
- 21.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (K23MH082256, MH082256, MH 071537, F31MH085445, F32MH070129, R01MH096764, R01MH071537, MH096764, R56MH071537, MH070129)
- National Center for Research Resources (M01-RR00039, M01RR000039)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD071982)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- C-reactive protein, CRP gene polymorphisms, post-traumatic stress disorder, hyperarousal symptoms, fear potentiation, fear-potentiated startle, systemic inflammation, proinflammatory state, trauma exposure, African American adults, low socioeconomic status
- MeSH terms
- Adult, Asian, Black or African American, C-Reactive Protein, Cross-Sectional Studies, Fear, Female, Genotype, Hispanic or Latino, Humans, Male, Middle Aged, Reflex, Startle, Stress Disorders, Post-Traumatic, Linear Models, Logistic Models, Polymorphism, Single Nucleotide, White People
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 ›
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