To our knowledge, this is the first study to report the association between MetS and the onset of depressive symptoms across different age-groups in a prospective, multicentric, elderly general-population cohort. MetS was associated with an almost doubling of the odds for new-onset depressive symptoms in the age-group 65–70 years, even in subjects without apparent CVD pathologies, whereas for older age-groups the association was not significant.
Several cross-sectional studies have shown an association between the MetS and depression in young adults (16
) and middle-aged populations (17
). Although in several studies the assumption has been that depression predicts the MetS, depression also could be a consequence of the MetS. To date, this direction of the association has been prospectively investigated in the middle-aged population (3
), and a “two-way street” between depression and the MetS is now evidenced. Our observation of an elevated risk of developing depressive symptoms in both pre-elderly men and women with MetS is consistent with a previous report (6
) carried out in a large, middle-aged British population that included men and women. Another prospective study (3
) carried out in the middle-aged population has suggested a sex-specific association by finding an association in women but not in men and was in accordance with a previous study (4
) reporting an association between MetS and depressive symptoms in a cohort of middle-age women. The absence of a relationship in men may, however, result from the lack of statistical power as a result of the lower prevalence of MetS combined with the lower incidence of depressive symptoms in men compared with women. In our study, no evidence of an interaction with sex was found in the MetS/depressive symptoms relationship. Our results are in line with those reported by Almeida et al. (5
), which was a study carried out on a large cohort of Australian older men (12,216 men aged 65–84 years), indicating that MetS was associated with an increase in the risk of incident depression.
MetS has gained clinical currency as a robust predictor of cardiovascular morbidity (8
), which may consequently raise the prevalence of “vascular depression” (9
). It is therefore crucial to determine whether the association between the MetS and depressive symptoms is not driven by depressive symptoms generated by manifest CVD. To our knowledge, very few studies have investigated this question (20
). The present data provide evidence that the observed MetS/depression association may be independent of past, current, and incident CVDs and thus constitutes a novel finding.
Regarding the specific components of MetS, our data showed that the low HDL cholesterol component was associated with increased odds of new-onset depressive symptoms in those aged 65–70 years. Corresponding associations in that age-group were not observed for other MetS components. These data are in agreement with recent findings on the importance of dyslipidemia in the etiology of late-life depression (21
) and also may imply that the association observed between MetS and depressive symptoms may be partially driven by HDL cholesterol in the pre-elderly participants. Additional work is needed to assess whether a better management of HDL cholesterol would reduce the incidence of depressive symptoms in this age-group.
The reason why MetS would predict new-onset depressive symptoms until age 70 years but not after remains unclear. MetS, as an entity, is an empirical concept (8
), and it is possible that its clinical utility is less relevant in late-elderly subjects than in young elders. Another explanation would be that the MetS/depression relationship in older-aged subjects is masked by the higher disability, morbidity, and mortality rate associated with older age, because poor health is associated with both the MetS (12
) and late-onset depression (14
) in our previous work carried out in the 3C study and other cohorts. Finally, our results also may reflect the fact that the late onset of late-life depression (after age 70 years) did not share the same etiology, and therefore the same risk factors, as the onset of depressive symptoms in middle-aged and pre- and “young” elderly subjects (7
). Additional work is needed to further investigate whether the MetS/depressive symptoms relationship is different before and after age 70 years.
The longitudinal and multicentric design and the large sample size, which included >4,000 elderly subjects from the general population, constitute the major strengths of this investigation. Furthermore, to strengthen the assumption that participants included in the present analyses are free of depressive symptoms, we made the choice to also exclude all participants who were diagnosed at baseline as having current or past major depressive episodes based on the MINI Psychiatric Interview, which was administered in the entire 3C study cohort only at baseline. The limitations of the present report included, first, the classification of the clinical level of depression using the CES-D. This instrument has, however, been validated in the elderly general population, with a cutoff point of 16, which corresponds to clinically significant levels of depressive symptomatology and warrants clinical intervention (13
). A second drawback involves reliance on the NCEP-ATP III in defining MetS, whereas other definitions also exist (8
). However, the NCEP-ATP III is the most widely used definition, thus allowing us to compare our results with other studies. Furthermore, as the diagnosis of type 2 diabetes by a general practitioner was not assessed in the 3C study at baseline, we considered participants who reported the use of antidiabetes drugs as having type 2 diabetes to compute MetS according to NCEP-ATP III criteria. Third, the design of our study, an observational epidemiological study with MetS only assessed at baseline, does not permit us to conclude that there is a causal link between MetS and depressive symptoms. Furthermore, the description of factors associated with the MetS condition suggests that participants with MetS at baseline constitute a vulnerable population and thus the possibility that unmeasured confounders may partly explain the observed associations remains. However, our results were robust to adjustments for a large range of sociodemographic, health behavior, and health status factors, making it less probable that they were attributable to confounding or obtained by chance. Additional investigation is needed to establish MetS as an etiological factor for depression in pre-elderly subjects; especially, it remains to be shown whether a better management of MetS or its reversion is associated with lower incidence of depressive symptoms.
Despite these limitations, by exploring MetS/depressive symptoms across different age-groups in the elderly, our findings suggest that the MetS/depressive symptoms link evidenced until now in middle-aged subjects can probably be extended to young elderly populations but not to the oldest ones. At this stage, it is too early to present MetS as a predictor of depression, but under the hypothesis that prevention and treatment of MetS may be important for the prevention of depressive symptoms in middle age (6
), results of our study would suggest that such intervention studies also would be justified in order to prevent depressive symptoms in populations between 65 and 70 years of age.