Elsevier

Journal of Affective Disorders

Volume 281, 15 February 2021, Pages 351-357
Journal of Affective Disorders

Research paper
Serum Levels of CRP are Associated with Depression in a Middle-aged and Elderly Population with Diabetes Mellitus: A Diabetes Mellitus-Stratified Analysis in a Population-Based Study

https://doi.org/10.1016/j.jad.2020.12.028Get rights and content

Highlights

  • Higher serum CRP levels did associate with increased risk of depression score in subjects with diabetes mellitus.

  • Higher serum CRP levels did associate with increased risk of depressive symptoms in subjects with diabetes mellitus.

  • 3. Higher serum CRP levels in subjects with diabetes mellitus was significantly associated with higher possibility of depression events.

Abstract

Background

The direct relationship between inflammation and depression in patients with diabetes is still unclear. We examined the association between serum C-reactive protein (CRP) levels and the high prevalence of depression in populations (aged ≥49 years) with and without type 2 diabetes.

Methods

Cross-sectional and longitudinal data from 3895 participants obtained from The Irish Longitudinal Study on Ageing (TILDA) were analyzed to determine the association between serum CRP levels and depression, accounting for relevant confounding factors.

Results

Multivariable analyses showed a positive association between serum CRP and depression score, independent of age and gender, BMI, marital status, education, smoking status, alcohol drinking status, systolic BP, diastolic BP, physical activity, self-reported CVDs and laboratory measurements in subjects with diabetes mellitus (coefficient = 0.179, P<0.001) but not in subjects without diabetes mellitus (coefficient = 0.011, P = 0.495). Higher serum CRP levels were associated with an increased risk of depressive symptoms in subjects with diabetes mellitus (OR = 1.301, 95% CI 1.012–1.799, P = 0.011) but not in subjects without diabetes mellitus (OR = 1.004, 95% CI 0.992–1.013, P = 0.344) after adjusting for these same confounding factors. After a follow-up of 4 years, higher serum CRP levels were significantly associated with a higher possibility of depression events in subjects with diabetes mellitus.

Limitations

Time-varying confounding factors may interfere with our results.

Conclusion

We observed a significant positive association between serum CRP levels and the prevalence of depressive symptoms in a middle-aged and elderly population with diabetes after adjustment for a range of lifestyle factors.

Introduction

Existing studies have shown a close association between diabetes and depression. Patients with diabetes have a high risk of depression, which is associated with poor treatment adherence and glycemic control (Anderson et al., 2001, Gonzalez et al., 2008), as well as a high prevalence of diabetes-related complications, including cardiovascular diseases (CVDs) and all-cause mortality (de Groot et al., 2001, van Dooren et al., 2013, Jin-Guo et al., 2010). Therefore, finding controllable risk factors or predictors is of great significance for the prevention and treatment of depression in patients with diabetes.

Recently, some studies have shown the possibility of inflammation being the underlying mechanism of the link between diabetes and depression due to their strong association (Golden et al., 2008). Few studies, however, have investigated the clinical role of inflammation and depression as biological correlates in patients with diabetes. Furthermore, some studies did not determine the association between depression and diabetes in middle-aged and elderly populations (Hood et al., 2012). Previous studies have suggested the role of increased immune system activity and elevated chronic systemic inflammation levels in both diabetes and depression (Raison et al., 2006, Dantzer and Kelley, 2007, Rabinovitch, 1998). Multiple mechanisms are involved in the association between diabetes and inflammation, including alterations of glucose uptake by adipose tissue and an indirect mechanism involving an increase in free fatty acid levels blocking the insulin signaling pathway (Greenberg and McDaniel, 2002).

Psychological stress can also increase inflammation levels through the innervation of cytokine-producing cells and activation of the sympathetic nervous system and macrophage adrenergic receptors (Pickup, 2004). Depression enhances the production of inflammatory cytokines (Dentino et al., 1999, Lutgendorf et al., 1999). Overproduction of inflammatory cytokines may stimulate corticotrophin-releasing hormone production, a mechanism that leads to hypothalamic-pituitary axis activity. Cytokines induced depressive-like behaviors in studies where healthy participants were given endotoxin infusions to trigger a cytokine release, and then the participants developed classic depressive symptoms (Reichenberg et al., 2001). Based on this evidence, it could be hypothesized that inflammation is the common biological pathway underlying the association between diabetes and depression. One study examined the association between inflammation and elevated depressive symptoms, and they found that higher C-reactive protein (CRP) levels were observed in patients with diabetes with depression than in those without depression (Doyle et al., 2013). However, in that study, obesity was not adjusted for, and thus, that study did not answer the question of whether the association between CRP levels and depression in patients with diabetes could be applicable to the general population. Moreover, that study included only a small sample of patients with diabetes and depression, so the robustness of the results needs to be tested in a larger study population. Additionally, although the associations between CRP and depression in the elderly population have been previously investigated, these findings are heterogeneous, and longitudinal studies based on the general population are limited.

The Irish Longitudinal Study on Ageing (TILDA), a large population-based cohort study of middle-aged and elderly individuals (≥49 years), included detailed information on biochemical detection, depression, and potential confounders, including lifestyle factors and age-related comorbidities. Hence, we can fully elucidate the relationship between CRP and depression by multivariate and stratified analyses of the data collected by TILDA. The present study had two major objectives. The first was to clarify the independent relationships between the serum CRP levels and the depression score after adjusting for relevant confounding factors. The second was to assess the associations of CRP levels with depression events after a follow-up of 4 years. In our study, we hypothesized that high CRP levels were associated with a high prevalence of depression in patients with diabetes and that this association may be modified by taking antidepressant medications or CVDs. The large sample size of our study enabled us to examine the association between serum CRP levels and the prevalence of depression in middle-aged and elderly populations with and without type 2 diabetes that were further stratified by antidepressant medication use and CVDs (≥2).

Section snippets

Study population

Study samples from TILDA were used for the analyses in this study. TILDA, which enrolled middle-aged and elderly adults (age ≥49 years), is a large prospective cohort study conducted in the Republic of Ireland with repeated assessments at 2-year intervals. A nationally representative sample was obtained from all residential addresses in the Republic of Ireland by use of the RANSAM sampling procedure, with a response rate of 62% for wave 1 (2009–2011) (Whelan B and Savva G, 2013). Details on the

Results

In total, 8504 subjects (age ≥ 49 years) were recruited for wave 1 of the TILDA study and visited the health center for the wave 1 assessment, and they had adequate CRP data for analysis. Among these individuals, 3895 visited the wave 3 health center for a complete health assessment and were included in the study after excluding subjects with important missing data (N = 3284), those with malignant tumors or other serious diseases (N = 295) and those without follow-up data (N = 580). Fig. 1 is a

Conclusions

Our results show that serum CRP levels are positively associated with depression after adjustment for a range of lifestyle factors in middle-aged and elderly populations with diabetes. These results may be consistent with the predisposition of depressed participants with diabetes to CVDs in later life after decades of unhealthy lifestyle choices have persisted.

Author statement

This work was supported by grants from the National Natural Science Foundation of China (NSFC 81860070 and 82070350) and JiangXi Province Science Foundation for Distinguished Young Scholar (20202ACBL216001).

Authorship contribution statement

Ying Huang: Methodology and writing-original draft; Yuhao Su: Data curation and analysis; Jinzhu Hu: Writing-review & editing and validation.

Declaration of Competing Interest

None of the authors have conflicts of interest to declare or anything to disclose.

Acknowledgment

We thank all individuals who were responsible for the planning and administering of TILDA and making the datasets of TILDA available on their website. We also acknowledge the reviewers and editors for view our work.

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