Conceived and designed the experiments: XL HL ZY. Performed the experiments: XL JW AP XY HL WG QQ XP HL. Analyzed the data: AP XY ZY OF. Wrote the paper: XL AP XY OF. Other: Management of the field work in Beijing: HL XP.
The authors have declared that no competing interests exist.
Studies in Western populations find that depression is associated with inflammation and obesity. The present study aimed to evaluate the relation of depressive symptoms with inflammatory factors and adipose-derived adipokines in middle-aged and older Chinese.
Data were from 3289 community residents aged 50–70 from Beijing and Shanghai who participated in the Nutrition and Health of Aging Population in China project. Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale (CES-D) score of 16 or higher. Plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, resistin, plasminogen activator inhibitor-1 (PAI-1) and retinol binding protein 4 (RBP4) were measured. Of the 3289 participants, 312 (9.5%) suffered from current depressive symptoms. IL-6 level was higher in participants with depressive symptoms compared to their counterparts in the crude analyses (1.17 vs. 1.05 pg/mL,
We found no evidence that depressive symptoms were associated with inflammatory factors and adipokines in the middle-aged and older Chinese populations. Prospective studies and studies in clinically diagnosed patients are needed to confirm our results and clarify the relation of depression with inflammatory factors and adipokines.
Depression is a mental disorder significantly associated with increased risk of the onset and mortality of cardiovascular diseases (CVD)
To date, numerous studies have suggested that chronic inflammation is an intrinsic part of atherosclerosis
Adipose tissue is now regarded as an endocrine organ and secretes several adipokines, such as adiponectin, resistin, plasminogen activating inhibitor-1 (PAI-1) and retinol binding protein 4 (RBP4)
Therefore, we sought to evaluate the association of clinical relevant depressive symptoms with several inflammatory markers and adipokines in a cross-sectional study of 3289 middle-aged and older Chinese.
The present study is part of the Nutrition and Health of Aging Population in China project and the detailed study design has been described previously
During the home interview, clinically relevant depressive symptoms were measured with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D)
Peripheral venous Ethylene Diamine Tetraacetic Acid (EDTA) blood samples were collected in the morning after at least 8 hours' fasting. The blood samples were centrifuged at 4°C, 3,000 rpm for 15 minutes. After being frozen, the samples were shipped in dry ice to the Institute for Nutritional Sciences and stored at −80°C until analysis. CRP was measured by a particle-enhanced immunoturbidimetric assay (Orion Diagnostica, Espoo, Finland) using microparticles coated with anti-human CRP antibodies. The lower detection limit of the assay was 0.25 mg/L and the detailed assay procedure was described previously
Plasma adiponectin, resistin and active PAI-1 concentrations were measured by Luminex xMAP™ Technology (Linco Research Inc, St Charles, Mo) on a Bio-Rad Multiplex Suspension Array System. The sensitivity of the assay was 145.5, 6.7 and 1.3 pg/mL for adiponectin, resistin and active PAI-1, respectively, with an intra-assay coefficient of variation (CV) of 1.4–7.9% and an inter-assay CV <21%. Adipokines measurements were done simultaneously with IL-6 measurements, therefore the same 96 samples were excluded from analyses.
Plasma RBP4 was measured in duplicate by an in-house developed and validated sandwich ELISA, with an intra-assay CV of 1.8–7.6% and an inter-assay CV of 3.7–8.8%. Detailed assay procedure has been described elsewhere
Total cholesterol, triglycerides, and glucose were measured enzymatically on an automatic analyzer (Hitachi 7080, Japan) with reagents purchased from Wako Pure Chemical Industries (Osaka, Japan). Fasting insulin was determined by radioimmunoassay (Linco Research, MO).
Covariates included characteristics associated with depressive symptoms, inflammation and adipokines as suggested by previous publications. The study team was trained to conduct the face-to-face home interviews using a standard questionnaire. Socio-demographic variables included age, gender, geographic location (Beijing/Shanghai), residential region (urban/rural) and educational level (≤9 or >9 years in school). Current smoking status (yes/no) and alcohol drinking status (yes/no) were also assessed. The physical activity level for each individual was classified as low, moderate, and high according to the International Physical Activity Questionnaire (short last 7 day format) scoring protocol
Data were analyzed using Stata 9.2 (StataCorp, College Station, Texas). A two-sided
n | Depressive Symptoms (n = 312) | No Depressive Symptoms (n = 2977) | ||
Age (years) | 3289 | 58.26±6.17 | 58.64±5.99 | 0.285 |
Women | 1831 | 214 (68.6%) | 1617 (54.3%) | <0.001 |
Geographic Location | <0.001 | |||
Beijing | 1641 | 224 (78.2%) | 1397 (46.9%) | |
Shanghai | 1648 | 68 (21.8%) | 1580 (50.1%) | |
Residential Region | 0.135 | |||
Rural | 1649 | 143 (45.8%) | 1697 (50.3%) | |
Urban | 1640 | 169 (54.2%) | 1480 (49.7%) | |
Current Smoker | 920 | 77 (24.7%) | 843 (28.3%) | 0.173 |
Current Alcohol Drinker | 939 | 82 (26.3%) | 857 (28.8%) | 0.351 |
Physical Activity Level | <0.001 | |||
Low | 245 | 46 (14.7%) | 199 (6.7%) | |
Moderate | 1381 | 121 (38.8%) | 1260 (42.3%) | |
High | 1663 | 145 (46.5%) | 1518 (51.0%) | |
Education Level (>9 years in school) | 757 | 52 (16.7%) | 705 (23.7%) | 0.005 |
Anti-inflammatory Drugs | 471 | 85 (27.2%) | 386 (13.0%) | <0.001 |
Presence of Comorbidity | 1295 | 152 (48.7%) | 1143 (38.4%) | <0.001 |
Presence of Obesity | 487 | 54 (17.3%) | 433 (14.5%) | 0.191 |
Body Mass Index (kg/m2) | 3289 | 24.85±3.90 | 24.42±3.55 | 0.064 |
Triglyceride (mmol/L) | 3289 | 1.39±0.97 | 1.39±1.08 | 0.523 |
Total Cholesterol (mmol/L) | 3289 | 4.80±0.99 | 4.69±0.98 | 0.054 |
Fasting Plasma Insulin (pmol/L) | 3285 | 16.53±9.28 | 15.32±9.49 | 0.008 |
Systolic blood pressure (mmHg) | 3289 | 142.8±22.2 | 139.8±22.5 | 0.028 |
Data are presented as n (%) or mean±SD.
Obesity is defined as having a body mass index ≥28 kg/m2.
Data are not normally distributed,
To further examine the associations, we used logistical regression with elevated inflammatory factors or adipokines as a dichotomous outcome variable and current depressive symptoms as a predictor variable. Elevated inflammatory factors or adipokines were defined as having values in the top quartile of each biomarker.
Of the 3289 participants, 312 (9.5%) suffered from current depressive symptoms as indicated by a CES-D score ≥16. The prevalence rates of depressive symptoms were higher in women and participants from Beijing than their counterparts (
Current depressive symptoms were only associated with increased IL-6 level in the crude analyses and this association lost statistical significance after multiple adjustment (
Unadjusted Geometric Mean (95% CI) | Adjusted Geometric Mean (95% CI) | |||||
Depressive Symptoms | No Depressive Symptoms | Depressive Symptoms | No Depressive Symptoms | |||
CRP (mg/L) | 0.79 (0.69–0.91) | 0.70 (0.67–0.73) | 0.107 | 0.78 (0.68–0.90) | 0.80 (0.74–0.86) | 0.803 |
IL-6 (pg/mL) | 1.17 (1.06–1.29) | 1.05 (1.02–1.08) | 0.023 | 1.13 (1.03–1.25) | 1.10 (1.04–1.16) | 0.520 |
Adiponectin (µg/mL) | 13.06 (11.93–14.30) | 12.77 (12.42–13.13) | 0.622 | 11.80 (10.82–12.86) | 12.07 (11.48–12.68) | 0.585 |
Resistin (ng/mL) | 9.64 (8..86–10.50) | 8.97 (8.76–9.19) | 0.110 | 9.59 (8.81–10.44) | 9.23 (8.79–9.70) | 0.362 |
PAI-1 (ng/mL) | 9.06 (7.87–10.43) | 8.80 (8.39–9.24) | 0.713 | 9.07 (7.85–10.49) | 10.32 (9.50–11.21) | 0.068 |
RBP4 (µg/mL) | 38.21 (36.86–39.61) | 38.39 (37.98–38.81) | 0.791 | 38.94 (37.60–40.33) | 39.85 (39.06–40.65) | 0.173 |
Data are presented as Geometric Mean (95% CI).
CRP, C-reactive protein; CI, confidence interval; IL-6, interleukin-6; PAI-1, plasminogen activator inhibitor-1; RBP4, retinol binding protein 4.
Adjusted for geographic location, residential area, age, sex, body mass index, smoking status, drinking status, physical activity level, educational level, comorbidity status, log-insulin, log-triglyceride, log-total cholesterol, log-systolic blood pressure, and use of anti-inflammatory drugs.
We confirmed in logistical regression analyses that depressive symptoms were not associated with elevated levels of any of these biomarkers (
Risk of Elevated Biomarkers | ||
CRP (≥1.51 mg/L) | 0.99 (0.74–1.31) | 0.920 |
IL-6 (≥1.60 pg/mL) | 1.01 (0.77–1.34) | 0.931 |
Adiponectin (≥21.72 µg/mL) | 1.02 (0.76–1.37) | 0.909 |
Resistin (≥14.01 ng/mL) | 1.14 (0.86–1.49) | 0.363 |
PAI-1 (≥19.45 ng/mL) | 0.79 (0.58–1.08) | 0.138 |
RBP4 (≥46.85 µg/mL) | 0.95 (0.71–1.27) | 0.714 |
Data are presented as odd ratio (95% CI).
CRP, C-reactive protein; IL-6, interleukin-6; PAI-1, plasminogen activator inhibitor-1; RBP4, retinol binding protein 4.
Adjusted for geographic location, residential area, age, sex, body mass index, smoking status, drinking status, physical activity level, educational level, comorbidity status, log-insulin, log-triglyceride, log-total cholesterol, log-systolic blood pressure, and use of anti-inflammatory drugs.
Elevated inflammatory factors or adipokines were defined as having values in the top quartile of each biomarker.
In a sample of 3289 community residents from Beijing and Shanghai, we found no evidence that depressive symptoms were associated with increased levels of various inflammatory factors (CRP and IL-6) and adipokines (adiponectin, resistin, PAI-1 and RBP4). To the best of our knowledge, the present study is the first to simultaneously investigate the association of depressive symptoms with inflammatory factors and adipokines in Chinese populations.
The relation between depression and inflammation has been widely studied with inconsistent results reported. Two studies found null relation
Previous studies have found that depression is positively associated with obesity
The association between depression and adipose-derived adipokines is a sparsely studied area and the direction remains unclear. Leo et al.
The main strength of our study is that we used data from a large population-based sample of both genders and from both northern and southern China, which is representative of populations of this age. Furthermore, we carefully controlled for various covariates known to be related to inflammation, adipokines and depression in the analyses.
Admittedly, certain limitations should be considered in interpreting our results. Firstly, the validity of the findings based on the self-reported measure of depression (CES-D) is inferior to the psychiatric diagnostic interview, which is the gold standard. However, the sensitivity of the CES-D to detect major depression is high
In conclusion, depressive symptoms are not associated with inflammatory factors (CRP and IL-6) and adipokines (adiponectin, resistin, PAI-1, RBP4) in the middle-aged and older Chinese populations. Therefore, the relationship between depression and CVD is unlikely to be explained through direct effects on inflammatory factors and adipokines. Further studies, particularly prospective studies and studies in clinically diagnosed patients, are needed to confirm the results. Studies in different populations and age groups are also warranted.
The authors want to express their sincere appreciation to the study participants and to the researchers and the healthcare professionals from the Centers for Disease Control and Prevention in Beijing and in Shanghai.