Depression May Induce Metabolic Syndrome

By Bruce Jancin

NEW ORLEANS -- Psychological stress as manifested in depressive symptoms may be implicated in the etiology of metabolic syndrome, Viola Vaccarino, M.D., said at the annual scientific sessions of the American Heart Association.

The most likely mechanism involves depression-related neurohormonal activation, including a ratcheting up of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. This in turn induces insulin resistance, a key component of metabolic syndrome. The proximate cause of the insulin resistance may be the elevated cortisol levels known to result from the neuroendocrine activation that accompanies depression, explained Dr. Vaccarino of Emory University, Atlanta.

Metabolic syndrome consists of a constellation of traits: low HDL cholesterol, high triglycerides, hypertension, elevated fasting blood glucose (which serves as a proxy for insulin resistance), and abdominal obesity.

The presence of any three or more of these components defines a patient who has metabolic syndrome, according to National Cholesterol Education Program guidelines, which have identified metabolic syndrome as an important secondary therapeutic target because of its association with increased cardiovascular risk.

In a step toward unraveling the complex etiology of metabolic syndrome, Dr. Vaccarino reported on the relationship between depressive symptoms and insulin resistance in 91 male twin pairs aged 47-57 years who were enrolled in the Vietnam Era Twin Registry, an ongoing study examining the role of depression in cardiovascular disease. All 182 participants were free of symptomatic cardiovascular disease. Thirty-nine of the twin pairs were discordant for lifetime history of major depression.

The investigators used the Beck Depression Inventory (BDI) to measure subjects' current level of depressive symptoms. They found a strong, graded, direct relationship between depressive symptoms and insulin resistance as measured by the Homeostatic Model Assessment (HOMA).

The 10% of subjects with a BDI of 14 or more, indicating moderate to severe depressive symptoms, had greater insulin resistance as shown in a higher mean HOMA score than the 24% with mild to moderate depressive symptoms and a BDI of 6-13, who in turn were more insulin resistant than individuals with a BDI below 6.

On the other hand, lifetime history of major depression as assessed using the Structured Clinical Interview for DSM-IV wasn't associated with insulin resistance in the absence of current depressive symptoms. This suggests that it is state, rather than trait depression, that's important in development of metabolic syndrome, she said.

The observed association between current depressive symptoms and insulin resistance wasn't explained by differences in the standard cardiovascular risk factors or diabetes.

Body mass index wasn't associated with depressive symptoms. But interestingly, Dr. Vaccarino said, abdominal obesity was. That is, the greater a subject's waist-to-hip ratio, the higher his BDI score.

This argues against sedentary lifestyle as being the mediator between depressive symptoms and insulin resistance, since lack of physical activity would be expected to result in an increased body mass index without specifically promoting centralized weight gain. Abdominal obesity is often a neuroendocrine phenomenon that can be induced by high cortisol levels, she said.

Dr. Vaccarino emphasized that the twin study should be viewed as cross-sectional, hypothesis-generating research. The links it found between depressive symptoms, insulin resistance, and metabolic syndrome require confirmation in prospective studies.