The Role of Anxiety in Metabolic Syndrome

Aline Sardinha; Antonio E Nardi


Expert Rev Endocrinol Metab. 2012;7(1):63-71. 

In This Article

MS & Anxiety

Anxiety triggers activation of the human stress system through behavioral and physiological changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. These processes appear to adversely affect autonomic and hormonal regulation, resulting in metabolic abnormalities, inflammation, insulin resistance and endothelial dysfunction.[40] The most accepted underlying mechanism relies on the hypothesis that increased activation of the HPA axis could be pathophysiologically involved in the concomitant occurrence of the typical MS risk factors and stress.

Patients with anxiety disorders normally present with more cortisol in the urine than individuals without psychiatric disorders, while there seems to be no difference in the excretion of catecholamines and serotonin.[41] There is considerable evidence from clinical, cellular and molecular studies that elevated cortisol, particularly when combined with secondary inhibition of sex steroids and growth hormone secretions, causes accumulation of fat in visceral adipose tissues as well as metabolic abnormalities.[41] Glucocorticoid exposure is also followed by stress-induced overeating behavior with increased food intake and leptin-resistant obesity, perhaps disrupting the balance between leptin and neuropeptide Y.[42] A study using a rodent model of social stress found that the consumption of a high-fat diet during social stress enhances the effect of chronic stress on body composition, adding to the body of knowledge about the mechanisms responsible for the development of obesity, diabetes and, ultimately, MS.[43]

Chronic anxiety and psychosocial stress also produces an array of adverse health consequences that are highly comorbid, including emotional eating, affective disorders and MS. The consumption of high caloric diets is thought to provide comfort in the face of unrelenting psychosocial stress, in a pattern observed both in humans and primates.[44] Anxiety disorders are also frequently accompanied by self-destructive and unhealthy behaviors as well as medication and treatment noncompliance.[40] Thus, modern genetic and environmental interactions may explain the explosion in the prevalences of MS and diabetes in psychologically stressed humans.[15]

However, available evidence suggests that there is no independent association between anxiety and MS. In three cross-sectional surveys completed in rural regions of Australia during the 2004–2006 period, MS was associated with depression but not psychological distress or anxiety.[28] A cohort of 5698 participants in Finland presented no clear association of MS with depression or anxiety.[45] More recently, in a study that sought to determine the association between the sympathetic firing pattern and anxiety level in patients with MS and elevated blood pressure, the single-unit sympathetic nerve-firing pattern did not correlate with any aspect of the metabolic profile; however, it was significantly associated with anxiety state and trait and the affective component of the depression scores. These results lead the authors to point to an indirect association; as chronic mental stress modulates the pattern of sympathetic activity, this, in turn, may confer greater cardiovascular risk on individuals with MS and elevated blood pressure.[46] In a sample of 1217 anxiety and depressive disorder patients, MS abnormalities are associated with severity of depression and with tricyclic antidepressant use, but not with anxiety symptom severity.[47] A review article by Goldbacher and Matthews proposed that psychological characteristics, especially depression, hostility and anger, may increase risk for MS, but found no such pattern for anxiety.[48]

The most frequently cited hypothesis explaining the coexistence of anxiety and MS is that they are indirectly related. Anxiety and depressive disorders often occur concomitantly, and their incidence in the general population as well as in chronically ill individuals may be higher than reported.[19] It is also possible that metabolic disorders impact HPA axis activity, as proposed by a study with female MS patients that showed that women with the abdominal obesity phenotype present alterations of HPA axis activity independent of the presence of psychological symptoms.[49]

Some evidence, however, points in the opposite direction. A large cross-sectional study of 4256 male US veterans surprisingly found that generalized anxiety disorder, but not major depressive disorder, was positively associated with MS in models that adjusted for all sociodemographic variables.[50] These authors discussed the potential roles of anxiety and chronic stress, which are prominent in generalized anxiety disorder patients, in MS and suggested that future research focus on these variables. In a community-based sample of 2917 older persons, anxiety symptoms were significantly associated with MS in men (OR per standard deviation [SD]: 1.13; 95% CI: 1.00–1.28), but not in women (OR per SD: 0.98; 95% CI: 0.89–1.08). These outcomes raise the question of whether psychosocial risk factors are associated with MS in an elderly population and whether other variables may also play a role.[34] In all cases, it seems methodologically difficult to show an independent role of anxiety as a risk factor for MS, controlling for the influence of depression and stress (Table 1).


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