The present cross-sectional examination of a general population of Japanese demonstrated a higher prevalence of elevated depressive symptoms in male subjects with MetS compared to those without it. This association remained significant even after controlling for the effects of age, marital status, history of cardiovascular disease, smoking habit, alcohol intake, and regular exercise. Furthermore, the prevalence of elevated depressive symptoms rose with the number of MetS components. In female subjects, on the other hand, there was no clear association between MetS and depressive symptoms.
Although a number of observational studies have investigated the association between MetS and depressive symptoms, their conclusions have been inconsistent [11–29]. With regard to cross-sectional studies, a French study demonstrated elevated depressive symptoms in men and women with MetS . The PPP-Bonita Study also showed close associations of MetS and its components with depressive symptoms in Finnish men and women . With respect to longitudinal design research, the Whitehall II study demonstrated that the presence of MetS was associated with 38% increased risks of future depressive symptoms in men and women in London . The Health in Men Study showed that MetS was a strong predictor of the future development of depression in elderly Australian men . A positive association between MetS and the incidence of depression was also reported in an office-based study of 956 Japanese men . On the other hand, a cohort study from France demonstrated no significant association between MetS and depressive symptoms in elderly subjects aged about 70–90 years old . A recent systematic review and a meta analysis including all these studies, however, demonstrated a clear relationship between MetS and depression. Our findings from the Hisayama Study suggest that the concept of a link between MetS and depression is likely to be applicable to Japanese men.
Several population-based observational studies have reported the association between MetS and depression separately for men and women. A cross-sectional study in France demonstrated that depression and depressive symptoms were associated with MetS, irrespective of gender . A cross-sectional study in Poland showed that MetS was observed more frequently among male subjects with depressive symptoms than those without, while there were no associations among women . A cross-sectional study in the United States reported that women with a history of major depressive episode were twice as likely to have metabolic syndrome compared with those without such a history, but men with history of depression were not significantly more likely to have MetS . A cohort study in Finland found that MetS was not associated with depression or anxiety in either men or women . Therefore, there has been significant inconsistency in gender differences in the link between MetS and depression in Western populations. With regard to Asian populations, on the other hand, a cohort study of Japanese male employees showed a positive relationship between MetS and depression . A cross-sectional study of Japanese subjects in Takarazuka City demonstrated that the mean depression score was higher for men with MetS than those without it, while depression was not associated with MetS in women . In the present study of Japanese subjects, MetS was associated with elevated depressive symptoms in men but not in women. In Asian populations, MetS may be associated with depressive symptoms only in men.
One of the mechanisms underlying the association between MetS and depressive symptoms is thought to be the stress-induced hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which is common in depression [30–32] and could lead to metabolic alterations [33–35]. Chronic stress has also been shown to increase the risk of metabolic disorders through elevated sympathetic activity . Another potential mechanism is that cerebral small vessel disease associated with MetS  can increase the risk of late-life depression [38, 39]. It is also possible that behavioral factors associated with depressive symptoms, such as physical inactivity and poor diet, contribute to central adiposity and metabolic disorders.
Another important finding from the present analysis is the lack of associations between MetS and depressive symptoms in women. This finding is consistent with a previous cross-sectional study. The SOPKARD project demonstrated clear associations between MetS and depressive symptoms in Polish men but not in Polish women . The reason for this discrepancy has not been clearly resolved, but it may be attributable to heterogeneity in genetic factors, hormonal factors, socio-economic factors and social roles between men and women.
There were several limitations to this study. Because of the cross-sectional nature of the study, we were unable to determine whether or not there was a causal association between MetS and the development of depressive symptoms. In addition, we were unable to address the potential mechanisms underlying the reported associations, the self-reported covariates had somewhat limited accuracy, and the study lacked definite diagnosis of depression based on structured interviews with psychiatrists using standard criteria.