COMMENTARIES

Psychosocial Stress Factors and the Metabolic Syndrome: Evidence for Their Relationship and the Role of Cortisol

Nicole Vogelzangs, M.Sc. and Brenda Penninx, Ph.D., Department of Psychiatry and EMGO Institute,
VU University Medical Center, AJ Ernststraat 887, 1081 HL
Amsterdam, The Netherlands
Tel: +31 20 788 5632
Fax: +31 20 788 5664
E-mail: nicolev@ggzba.nl

Cardiovascular disease (CVD) and diabetes are among the most common life-threatening diseases causing distress and disability [1]. In the recent history of psychosomatic research, psychosocial stress factors have repeatedly been found to be risk factors for CVD and diabetes. For instance, depression and anxiety have been shown to increase the risk of new CVD events, new coronary heart disease (CHD) events, cardiac mortality [2-4], and diabetes [5]. In addition to these psychiatric diagnoses, lack of emotional support and experience of major stressful life events have also been shown to subsequently increase the risk of CVD, CHD, and diabetes [6,7].

Are Psychosocial Stress Factors Associated with the Metabolic Syndrome?

Emerging evidence suggests that part of the link between such psychosocial factors and CVD and diabetes may operate through the metabolic syndrome [8], a clustering of cardiovascular risk factors including abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, and hyperglycemia [9]. Psychosocial factors, such as life events, depression, and anxiety, have been linked to individual components of the metabolic syndrome, including insulin resistance, high blood pressure, abdominal obesity, and lipid abnormalities [10,11] and recent studies have also directly linked psychosocial factors with the metabolic syndrome. Kinder et al. [12] found that young women, but not men, with a history of depression were twice as likely to have the metabolic syndrome. McCaffery et al. [13] found an association between depressive symptoms and metabolic risk in adult male twins and Chandola et al. [14] related work stress with an increased risk of the metabolic syndrome. Räikkönen et al. [15,16] reported prospective associations between depressive symptoms, tension, anger, and stressful life events with the metabolic syndrome in a population-based cohort of middle-aged women.

      In our recent study [17] among a large cohort of 2,917 community-dwelling black and white older persons (the Health ABC study), we showed that distinct psychosocial factors were associated with an increased prevalence of the metabolic syndrome. We found that the odds of the metabolic syndrome increased by 13% per experienced life event in the past year. In addition, not receiving adequate emotional support increased the odds of having the metabolic syndrome by 35%. Depressive symptoms were also associated with the metabolic syndrome, but only in white and not in black persons and anxiety symptoms increased the probability of the metabolic syndrome in men, but not in women. Moreover, when these psychosocial factors were combined into a psychosocial risk index, a higher score on the psychosocial risk index was associated with a higher odds of the metabolic syndrome.

The Role of Cortisol in the Association between Psychosocial Factors and the Metabolic Syndrome

Although the association between psychosocial factors with the metabolic syndrome might help explain the relationship between psychosocial factors and CVD/diabetes, it still leaves the question unanswered why psychosocial stress then would be associated with the metabolic syndrome. Although poor life style habits might explain part of this association, more biological explanations have also been suggested. Psychosocial stress factors have typically been linked with increased levels of cortisol and hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis [18]. As suggested by Björntorp [19], a hyperactive HPA-axis can cause accumulation of fat in visceral adipose tissues as well as metabolic abnormalities, i.e. the metabolic syndrome. He describes that cortisol binds to glucocorticoid receptors which have a high density in visceral fat depots; there it activates lipoprotein lipase and inhibits lipid mobilization, which leads to an accumulation of triglycerides in the visceral area. It is also suggested that these effects are even more pronounced when combined with low levels of sex steroid hormones, which have also been associated with depressive symptoms [20]. Therefore, a combination of depression and hypercortisolemia could increase the risk for metabolic syndrome even more.

      Using data from the InChianti study [21], a community-based study in 867 persons aged 65 and over, we showed that depressed mood and high levels of 24-hour urinary cortisol (per 48 µg increase = 1 SD), each individually, increased the probability of the metabolic syndrome by about 20%. However, when combining these two factors, we found an interaction between depressed mood and urinary cortisol in predicting the metabolic syndrome. Specifically, depressed persons who had high levels of urinary cortisol (highest tertile in our sample: > 111 µg), had a 84% increased probability of the metabolic syndrome compared to non-depressed persons with normal cortisol levels, which suggests that hypercortisolemic depression constitutes a specific risk factor for the metabolic syndrome.

Concluding Remarks

Recent interest in the role of the metabolic syndrome in the association between psychosocial factors and CVD and diabetes has resulted up until now in a handful of studies investigating the relationship between psychosocial factors and the metabolic syndrome. These studies have found that different psychosocial risk factors, such as life events, emotional support, anxiety, and depressive symptoms, can be associated with the metabolic syndrome in diverse populations. Moreover, this association appeared to be even stronger for persons experiencing multiple stress factors. Although some of these studies suggest that psychosocial stress longitudinally precedes the metabolic syndrome, it is very well possible that this association also exists in the other direction. More prospective studies are needed to fully understand the direction of the association between psychosocial factors and the metabolic syndrome. In addition, some evidence exists that cortisol might play an important role in explaining this association. Future studies should deepen our understanding of the role of cortisol and other possible underlying mechanisms. Such information could be important when trying to prevent and treat CVD, diabetes, depression, or anxiety.

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