This study is the first to show that major depression predicts increased risk for developing the metabolic syndrome during a 7-year follow-up period in a sample of White and African-American middle-aged women. Results also suggest that women with a lifetime history of recurrent depression may have the greatest risk of developing the metabolic syndrome. Our findings are consistent with previous longitudinal studies documenting an association of depressive symptoms with increased risk for developing the metabolic syndrome in women (15
), as well as the cross-sectional evidence for an association between major depression and prevalence of the metabolic syndrome in women (7
). Although each of the aforementioned studies provides indirect support for a link between depression and risk of the metabolic syndrome, conclusions drawn from these studies are tempered by cross-sectional data (7
), self-reports (9
), or the measurement of depressive symptoms as opposed to clinical depression (15
). The current investigation extends prior findings by using a well-validated, standardized interview measure of clinical depression and demonstrating consistent effects in African-American and White women. In addition, the availability of multiple measurements for both depression and the metabolic syndrome permitted investigation of the direction of this association. Results of exploratory analyses suggest that the metabolic syndrome may not be a risk factor for the onset of major depression in this sample of middle-aged women. Finally, the current findings suggest that a lifetime history of depression is associated with increased risk of the metabolic syndrome as a unified construct, but not its individual components.
Several notable behavioral and pathophysiological factors may link depression with the metabolic syndrome. First, poor diet and sleep, physical inactivity, and smoking are all more common among individuals with depression (33
), and emerging evidence suggests that these behaviors are also associated with the metabolic syndrome (37
). In the current investigation, the association between depression and the metabolic syndrome was not attenuated by daily caloric intake, physical activity, or smoking. However, with the exception of smoking, we examined only baseline measures of these lifestyle variables as diet and physical activity are notoriously difficult to measure. Second, a history of alcohol abuse or dependence may be an important link as well. It was a significant predictor of the metabolic syndrome and attenuated the association of major depression and the metabolic syndrome in the survival model and GEE models of women with no metabolic syndrome at baseline. Consistent with data showing a positive association between a lifetime history of heavy alcohol use and the metabolic syndrome (40
), results of the current study suggest that excessive alcohol consumption, independent of depression, may be an important factor in the development of the metabolic syndrome in women. Excessive alcohol consumption has also been linked to components of the metabolic syndrome, including hypertension (43
) and increased central (44
) and visceral (41
Plausible physiological mechanisms linking depression with the metabolic syndrome include dysregulation of the hypothalamic-pituitary adrenal (HPA) axis and autonomic nervous system (ANS) via such pathways as an accumulation of visceral adiposity and impaired insulin sensitivity (47
), as well as aberrant serotonergic functioning (48
). Although anxiety disorders are also associated with HPA dysregulation, they are characterized by hypocortisolemia and increased glucocorticoid receptors, as opposed to the hypercortisolemia associated with depression and the metabolic syndrome (49
). Similar mechanisms may link heavy alcohol use with the metabolic syndrome, as heavy drinkers have been shown to exhibit dysregulation of the HPA axis and ANS (50
Given our data and the recent report that depressive symptoms and the metabolic syndrome predict clinical events in women with suspected CAD (9
), it is possible that the metabolic syndrome may be one pathway linking depression with disease in women. Further research is needed to better understand the underlying biobehavioral mechanisms by which depression may influence risk for the metabolic syndrome over time, and investigate whether the metabolic syndrome is a mechanism linking depression with CAD and diabetes. In addition, future studies of the effect of psychological and behavioral interventions for depression on the development or remediation of the metabolic syndrome are warranted.
The current investigation has several limitations. First, it only evaluates the role of depression in middle-aged women and not in men. Some evidence suggests that the findings for depression may be stronger in women than in men (7
); thus, these findings should not be generalized to men. Second, it should be kept in mind that the sample has a higher rate of major depression than anticipated, possibly because of the close and confidential relationship between participants and interviewers. Third, because of a relatively small number of incident cases of metabolic syndrome, the current study could not fully evaluate the role of comorbid conditions.
On the other hand, this investigation is the first to show that major depression is a significant predictor of the prevalence and onset of the metabolic syndrome in middle-aged women. Depression is one of the most prevalent psychiatric disorders in women, with lifetime prevalence rates in middle-aged women estimated at approximately 22% (51
). In addition to impairment in mental health and social functioning, depression has significant physical health consequences and increases a woman’s risk for CAD and Type 2 diabetes, two diseases for which the metabolic syndrome is a putative risk factor. Questions regarding a woman’s history or current experience of depression may be a useful way to help identify women who are at high risk for developing the metabolic syndrome and, subsequently, aid in early prevention or treatment of CAD and diabetes. In addition, psychological and behavioral interventions targeting depression in women may be a valuable tool for the prevention and treatment of the metabolic syndrome. A better understanding of the relationship between depression and the metabolic syndrome as well as underlying mechanisms may have substantial implications for the development of interventions designed to reduce the risk of disease in women.