Generalized anxiety and C-reactive protein levels: a prospective, longitudinal analysis
Open accessAbstract
Background: Generalized anxiety disorder (GAD) is highly co-morbid with depression. Depression is associated with elevated levels of the inflammation marker C-reactive protein (CRP), cross-sectionally and over time. To date, no studies have looked at the association between CRP and GAD. Method: A total of nine waves of data from the prospective population-based Great Smoky Mountains Study (n=1420) were used, covering children in the community aged 9–16, 19 and 21 years old. Structured interviews were used at each assessment to assess GAD symptoms, diagnosis and cumulative episodes. Blood spots were collected and assayed for high-sensitivity CRP levels. Results: GAD was associated with increased levels of CRP in bivariate cross-sectional analyses. These bivariate associations, however, were attenuated after accounting for demographic, substance-use and health-related covariates. In longitudinal models, there was little evidence that CRP predicted later GAD. Associations from GAD to later CRP were attenuated in models adjusted for health-related coavariates and there was evidence that the GAD–CRP association was mediated by body mass index (BMI) and medication use. Conclusions: Similar to depression, GAD was associated with elevated levels of CRP, but the effect of GAD on CRP levels was explained by the effect of GAD on health-related behaviors such as BMI and medication use. This study suggests differences in the association between inflammation and depression and GAD.
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Children with GAD and stable coronary heart disease patients with GAD have higher rates of CRP compared with controls.
“Other evidence in children with GAD (Copeland et al, 2012) and stable coronary heart disease patients with GAD (Bankier et al, 2008) also found higher rates of CRP in individuals with GAD compared with controls.”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Copeland et al, 2012
The Results > Cross-sectional Associations section (page unavailable) reports higher CRP with GAD in bivariate analyses, but the association became nonsignificant after adjustment for health-related covariates. The Abstract > Methods (page unavailable) describes assessments at ages 9–16, 19, and 21; the reported association is for that combined sample, not specifically for children. The coronary heart disease finding is attributed to a different citation and is not assessed here. (LLM, conf=0.82)
Experimental — accuracy not yet measuredC-reactive protein increases over time in agoraphobia.
“| C-reactive protein | Increased in GAD | Bankier et al (2008),Copeland et al (2012), and Wagner et al (2015) |”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Copeland et al (2012)
The Results (Longitudinal Associations; page unavailable) report that GAD symptoms predicted later CRP levels in a simple model, but the association weakened after adjustment for health-related factors. The paper studies generalized anxiety disorder, not agoraphobia, so it does not support the condition named in the quoted claim. The printed citing sentence names GAD instead. (LLM, conf=0.86)
Experimental — accuracy not yet measuredParticipants with CRP values above 10 mg/L in any measurement were removed from statistical analysis because such values probably indicate acute inflammatory or infectious states rather than low-grade systemic inflammation.
“Participants with CRP values above 10 mg/L in any of the measurements were removed from statistical analysis (N = 5) since such values probably indicate acute inflammatory or infectious states and not low-grade systemic inflammation associated with cardiovascular and metabolic risk (Copeland et al., 2012; Wagner et al., 2015; Pearson et al., 2003).”
From Inflammatory markers changes following acceptance-based behavioral psychotherapy in generalized anxiety disorder patients: Evidence from a randomized controlled trial (2024) · cites this paper as Copeland et al., 2012
The Methods and Materials > Assessment passage says CRP observations above 10 mg/L were removed because they indicate frank infection, while lower values reflect chronic low-grade inflammation associated with cardiovascular and metabolic risk. It reports removing 190 observations, not excluding participants who had an elevated value in any measurement. The citing paper’s N = 5 is not a figure reported for this exclusion in Copeland et al. (LLM, conf=0.89)
Experimental — accuracy not yet measuredMany but not all studies have found an association between anxiety and CRP.
“Many [35– 41], but not all [42] studies have found an association between anxiety and CRP.”
C-reactive protein is increased in generalized anxiety disorder (GAD).
“| C-reactive protein | Increased in GAD | Bankier et al (2008),Copeland et al (2012), and Wagner et al (2015) |”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Copeland et al (2012)
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References 63 · Cited by 123
Research works printed but not linked: 2
- AMERICAN PSYCHIATRIC ASSOCIATION Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) 1994 American Psychiatric Press, Inc Washington, DC
- MCDADE W STALLINGS JF WORTHMAN CM Psychosocial stress and cell-mediated immune function: Validation of a blood spot method for Epstein-Barr virus antibodies American Journal of Physical Anthropology 1997 24 Suppl 164 65
- Authors
- Copeland, W. E., Shanahan, L., Worthman, C., Angold, A., & Costello, E. J.
- Affiliations
- Duke University (US)
- University of North Carolina at Chapel Hill (US)
- Emory University (US)
- Duke Medical Center (US)
- Corresponding author
- Copeland, W. E.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2012-04-30
- Volume
- 42
- Issue
- 12
- Pages
- 2641-2650
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC3449031
- OpenAlex
- W2138797763
- Cited by
- 123
- References
- 63
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 14 · 2020: 17 · 2019: 8 · 2018: 11 · 2017: 8 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 6 · 2012: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH-63671, R01MH063970, R01MH048085, MH-63970, R03MH094605, K23MH080230, R01MH063671)
- National Institute on Drug Abuse (DA/MH11301, R01DA011301)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- generalized anxiety disorder, C-reactive protein, inflammation, depression, body mass index, medication use, mediation, children and adolescents, Great Smoky Mountains Study
- MeSH terms
- Adolescent, Anxiety Disorders, C-Reactive Protein, Child, Cross-Sectional Studies, Depressive Disorder, Female, Humans, Longitudinal Studies, Male, North Carolina, Prospective Studies, Somatoform Disorders, Statistics as Topic, Comorbidity, Young Adult
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