To the best of our knowledge, this is the first meta-analysis that examines the association between depression and MetS, using data from both cross-sectional and cohort studies. We found that depression and MetS were significantly correlated in cross-sectional studies, and a bidirectional association was observed in prospective cohort studies.
Most of the cross-sectional studies reported a higher prevalence of depression in participants with MetS compared with those without. However, the prevalence varied significantly by sex, study design, subject sources, and assessment methods of depression and MetS. Therefore, we did not pool the prevalence; instead, pooled the OR, a measure of association that was more consistent across studies. Our estimated crude OR was 1.42 (95% CI 1.28–1.57), suggesting that MetS and depression are significantly related. The effect size remained significant in the pooled ORs of studies adjusting for potential confounders, such as sociodemographic factors and lifestyle factors: the pooled adjusted OR of depression by MetS status was 1.27 (1.07–1.51), and the pooled adjusted OR of MetS by depression status was 1.34 (1.18–1.51).
We found that the association was somewhat stronger in cross-sectional studies that identified depression using a self-reported symptom scale rather than a structured clinical diagnostic interview or clinician diagnosis. One possible explanation is that estimates may differ depending on the use of dimensionally versus categorically based depression assessment tools (23
). Categorically based tools—particularly structured psychiatric interviews—would explicitly exclude individuals with subsyndromal depressive symptoms from case status. By contrast, use of self-reported symptom cutoff scores would allow inclusion of many people with clinically significant depressive symptoms who would not meet formal criteria for DSM diagnosis, yet abundant evidence indicates that subsyndromal depressive symptoms, like clinical syndromes, are significantly associated with morbidity, adverse functional outcomes, and excess health care use (24
). Thus, inclusion of people with subsyndromal depression in the reference category may have weakened estimates of studies using categorically based depression definitions. However, this is in opposition to cohort studies of MetS predicting depression: participants with MetS were more likely to develop clinical diagnosed depression than self-reported symptoms (OR = 2.18 vs. 1.36). Nevertheless, only two studies used clinical diagnosed depression (16
), and the definition of MetS in the Almeida et al. (25
) study was stringent (meeting all four criteria of high waist circumference and self-reported treatment of dyslipidemia, diabetes, and hypertension). Thus, this result should be interpreted cautiously. We also found that the association was stronger in studies that defined MetS using the IDF criterion instead of the NCEP ATP-III criterion. The major distinction between the two criteria is that the IDF criterion specifies an obligatory component of central obesity, which is optional in the NCEP ATP-III criterion. Depression was significantly associated with central obesity (26
), which might explain why the association was stronger when the IDF definition was used.
Cross-sectional studies do not provide the temporal relationship between depression and MetS. We thus conducted a further meta-analysis to investigate the association between depression and MetS in prospective cohort studies. This observed bidirectional association between depression and MetS was consistent with results from the cross-sectional studies and also in agreement with two recent meta-analyses that show a reciprocal association between depression and diabetes (2
) and between depression and obesity (27
The interplay between depression and MetS is likely to be mediated through multiple mechanisms. First, depression has been positively associated with central obesity (26
), chronic inflammation (28
), and insulin resistance (29
), which are underlying etiological mechanisms for MetS (2
). Second, depression has known neuroendocrine effects (e.g., dysregulation of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system activation) (3
), which could influence MetS risk by affecting abdominal fat accumulation, glucose metabolism, and blood pressure regulation (30
). Third, depressed individuals tend to have poor diet and sleep disturbance and engage in less physical activity (31
), and these behaviors are known risk factors for the development of MetS. Fourth, conventional medication treatment for depression may exert direct effects on various components of MetS and partially explain the observed association (32
). In the opposite direction, individuals with MetS have increased levels of inflammatory cytokines (e.g., C-reactive protein and interleukin 6) (5
) and leptin resistance (33
), which may also be involved in depressive mood (34
). Other metabolic disturbances, such as insulin-glucose homeostasis and mitochondrial respiration, are also indicated in the pathophysiology of depression (36
). Another potential explanation is that vascular damage in the brain might predispose to depression in the elderly according to the vascular depression hypothesis (37
). MetS, as a cluster of vascular risk factors, could lead to subclinical vascular damage (38
), which in turn may produce depressive symptoms. Furthermore, MetS is associated with a sedentary lifestyle and a negative self-perception due to stigmatization of obesity (a component of MetS), which can lead to an increased risk of depression (27
). Taken together, the potential mechanisms are complex and may involve several shared physiological pathways, such as obesity and inflammation. Certainly, more studies are needed to explore the mechanisms underlying this reciprocal relation, which will be crucial for the prevention and treatment of both conditions.
This meta-analysis has strengths and limitations. The primary strength is that this is the first meta-analysis that explicitly examines the bidirectionality of the depression-MetS relationship on the basis of a comprehensive literature search. We contacted authors for unpublished data and found no indication of publication bias in all the analyses. However, the meta-analysis was limited to English-language publications, and we may have missed some articles of other languages. We also observed robust and consistent associations across different subgroups via sensitivity analyses and subgroup analyses. Yet as a major limitation, there was evidence of heterogeneity across the studies used for the analysis of association between MetS and risk of depression in both study designs. This heterogeneity may be attributable to the differences in study design, sample size, analysis strategies, participants’ characteristics, and diagnostic criteria of depression and MetS definition criteria. To account for the heterogeneity, we chose random-effects models for the meta-analyses, but the results were not materially changed when we used fixed-effect models. Furthermore, few cohort studies examine the association between baseline depression and future risk of MetS and, thus, more investigations along this line are needed.
In spite of these limitations, our results have significant implications for both clinical care and public health. Mounting evidence suggests that depression is associated with increased risks of diabetes (2
) and CVD (3
). MetS is regarded as an intermediate condition that frequently proceeds to the clinical manifestations of diabetes and CVD, although MetS is not usually diagnosed in clinical settings. Our results suggest that the association between depression and diabetes/CVD might start at an early stage before individuals meet the diagnostic criteria of diabetes or CVD. Therefore, we argue that in patients with depression, the cardiometabolic risk factors and MetS status should be carefully monitored, and proper treatment and lifestyle changes could be advised if the patients are at a higher risk of diabetes/CVD. On the other hand, for people with MetS who are already susceptible to diabetes/CVD, early detection of depression may inform appropriate preventive strategies. Collaborative care for patients with depression and diabetes/CVD recently has been demonstrated to be effective in control of both depression and comorbidities (40
). Certainly, more studies are still needed to evaluate whether early screening and collaborative care for patients with depression and MetS (or its components) could reduce the future risk of diabetes and vascular diseases.