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Myung W, Choi H, Lee C, Lee JR, Carroll BJ, Kim DK. Association Between Levels of High-Sensitivity C-Reactive Protein and General Psychological Distress Symptoms. JAMA Psychiatry. 2016;73(11):1199–1201. doi:10.1001/jamapsychiatry.2016.2167
The inflammatory marker high-sensitivity C-reactive protein (hs-CRP) is associated with symptoms of depression.1-3 A recent study reported that elevated levels of hs-CRP in the general population are associated with specific depressive symptoms of low energy, sleep disturbance, and appetite disturbance3; however, common general psychological distress symptoms (GPDS) were not investigated. We tested the association between levels of hs-CRP and GPDS in the general population.
We combined data on urban (n = 144 312) and rural (n = 6711) individuals from the Korean Genome and Epidemiology Study, conducted from January 1, 2004, to December 31, 2013, as well as those enrolled in the health check-up program at Samsung Medical Center (n = 63 014) from January 1, 2010, to December 31, 2014. A total of 214 037 ethnic Korean participants (mean [SD] age, 52.3 (9.7) years; male to female ratio, 4.0:6.0) were analyzed. Plasma levels of hs-CRP were measured using standard procedures (median, 0.61 mg/L; interquartile range, 0.37-1.25 mg/L) (to convert to nanomoles per liter, multiply by 9.524), and were log-transformed and standardized. General psychological distress symptoms were assessed using a validated 18-item scale (Table).4 We coded items as dichotomous variables with positive responses indicating clinically salient symptoms. This study was approved by the ethics review board of Samsung Medical Center. Written informed consent was obtained from all participants.
We first examined cross-sectional associations between levels of hs-CRP and each symptom. After initially adjusting for age and sex (model 1A), we included smoking status, alcohol consumption status, body mass index (calculated as weight in kilograms divided by height in meters squared), and certain chronic illnesses (Table) as covariates (model 1B). In model 2, we further adjusted for the sum of the remaining GPDS item scores to assess independent associations of levels of hs-CRP with individual symptoms. Multivariable logistic regression was used in each cohort and pooled with random effects meta-analysis. Holm-Bonferroni correction was used.
In model 1A, all items had positive associations with levels of hs-CRP (Table). After adjustment for smoking, alcohol consumption, body mass index, and chronic illnesses (model 1B), item 11 (able to start new work) lost significance (odds ratio [OR], 1.008; 95% CI, 0.998-1.017). When the associations were adjusted for age, sex, and the sum of the other symptoms (model 2A), only 7 items showed positive associations with levels of hs-CRP (feeling of well-being and health: OR, 1.084; 95% CI, 1.072-1.095; feeling refreshed after sleep: OR, 1.046; 95% CI, 1.030-1.062; loss of sleep because of worry: OR, 1.030; 95% CI, 1.013-1.047; able to concentrate: OR, 1.020; 95% CI, 1.006-1.035; self-managing as well as most people would: OR, 1.113; 95% CI, 1.056-1.174; restless and ill-tempered: OR, 1.031; 95% CI, 1.011-1.051; and loss of self-confidence: OR, 1.037; 95% CI, 1.019-1.055). In addition, items 11 and 14 showed negative associations with levels of hs-CRP (able to start new work: OR, 0.967; 95% CI, 0.955-0.979; and able to face problems: OR, 0.975; 95% CI, 0.962-0.988). When the associations were adjusted for all other covariates (model 2B), only 6 of the 18 items remained positive (feeling of well-being and health: OR, 1.072; 95% CI, 1.053-1.091; feeling refreshed after sleep: OR, 1.043; 95% CI, 1.025-1.061; loss of sleep because of worry: OR, 1.027; 95% CI, 1.009-1.044; self-managing as well as most people would: OR, 1.109; 95% CI, 1.054-1.167; restless and ill-tempered: OR, 1.028; 95% CI, 1.009-1.048; and loss of self-confidence: OR, 1.035; 95% CI, 1.017-1.053).
We found that levels of hs-CRP were associated with all 18 GPDS items (model 1A). Most of these associations were preserved after adjustment for smoking, alcohol consumption, body mass index, and chronic illnesses (model 1B). Moreover, we found that controlling for scores of all other symptoms substantially reduced the range of items associated with levels of hs-CRP (models 2A and 2B). These findings suggest that inflammation may have independent effects on only some of the individual GPDS items.
The items associated with subjective perception for health and functioning (items 1, 8, and 16) showed robust significance across the 4 models. However, core symptoms of clinical depression (items 3, 6, and 15: fatigue and loss of appetite, loss of energy, and depressed mood, respectively) showed nonsignificant associations when adjusting for other GPDS items (models 2A and 2B). Thus, the association with inflammation was more obvious in subjective distress symptoms than in core depressive symptoms. In comparison with the previous report3 that claims linkage between hs-CRP and specific symptoms of depression, our results confirm only the association with disturbed sleep; associations between lack of energy and changes in appetite with levels of hs-CRP were not replicated. Reasons for these differences could include incomplete coverage of symptoms of depression in the GPDS, rating of symptoms by frequency rather than by true severity in the earlier study,5 different symptom measures, and different statistical approaches (covariates and multiple-test correction), as well as variation in participant characteristics (range of levels of hs-CRP, symptom prevalence, and race/ethnicity).2 The cross-sectional design of both previous reports2,3 and of our study is another limitation.
In conclusion, we found several specific associations of GPDS with levels of hs-CRP in the general population. Our findings suggest that a broader range of psychosocial distress symptoms should be considered in future studies of the association between inflammation and psychiatric illness.6
Corresponding Author: Doh Kwan Kim, MD, PhD, Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea (firstname.lastname@example.org).
Published Online: September 21, 2016. doi:10.1001/jamapsychiatry.2016.2167
Author Contributions: Drs Myung and Choi should be considered co–first authors. Drs Choi and Kim had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Myung, Choi, Kim.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Myung, C. Lee, J.R. Lee.
Critical revision of the manuscript for important intellectual content: Choi, Carroll, Kim.
Statistical analysis: Myung.
Obtaining funding: Kim.
Study supervision: Choi, Kim.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grant NRF-2014R1A2A1A10052419 from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology. This study was provided with data from the Korean Genome and Epidemiology Study that was supported by the Korea Center for Disease Control and Prevention, Republic of Korea.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Seonwoo Kim, PhD, Samsung Biomedical Research Institute provided advice on statistical analyses. She was not compensated for her contributions.
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