Heart Disease Risk Factors in Major Depression
Condition: Adrenal Gland Hyperfunction; Cardiovascular Disease; Involutional Depression
MeSH terms: Cardiovascular Diseases; Heart Diseases; Adrenocortical Hyperfunction; Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      A series of studies in patients with major depression have consistently demonstrated a
      doubling of the mortality rate at any age, independent of suicide. In addition, the relative
      risk for clinically significant coronary artery disease in patients with major depression is
      also 2 or more in studies that independently controlled for risk factors such as smoking,
      hypertension, etc. The principal long-term goals of the CNE include the determination of the
      mechanisms that underlie enhanced susceptibility to premature ischemic heart disease in
      patients with major depression, documenting the age at which demonstrable pathophysiologic or
      predictive changes begin to occur, and charting their rate of progression. Our long-term goal
      is to use our understanding of underlying mechanisms to enhance our capacity to predict who
      with major depression is most likely to develop premature ischemic heart disease, to
      determine what the mechanisms underlying this susceptibility are, and to develop improved
      means for treatment and prevention.

      Depressed patients are known to manifest a variety of neuroendocrine changes that predispose
      to coronary artery disease including hypercortisolism, decreased secretion of growth hormone
      and a deficiency of sex steroids. A final common denominator of these neuroendocrine
      abnormalities is insulin resistance. Insulin resistance promotes several changes that would
      favor hypertension and increased coronary artery disease including increased sodium
      retention, increased activity of the sympathetic nervous system, proliferation of vascular
      smooth muscle and deposition of highly metabolically active visceral fat. The latter induces
      additional risk factors for coronary disease, including dyslipidemia, hypercoagulation, and
      enhanced inflammation. It is a matter of public health importance to document the frequency
      and severity of insulin resistance in patients with major depression compared to a closely
      matched group of healthy controls. To accurately quantify insulin resistance in each patient
      and control, we will apply the hyperinsulinemic euglycemic glucose clamp procedure. This is
      the gold standard method for measuring the insulin sensitivity since it reflects the direct
      human body glucose metabolic response to a known insulin infusion. Moreover, it is essential
      to use this technique in patients with major depression as data indicate that other
      alternative procedures give unreliable results in the context of hypercortisolism.
    

Detailed description: 
      A series of studies in patients with major depression have consistently demonstrated a
      doubling of the mortality rate at any age, independent of suicide. In addition, the relative
      risk for clinically significant coronary artery disease in patients with major depression is
      also 2 or more in studies that independently controlled for risk factors such as smoking,
      hypertension, etc. The principal long-term goals of the CNE include the determination of the
      mechanisms that underlie enhanced susceptibility to premature ischemic heart disease in
      patients with major depression, documenting the age at which demonstrable pathophysiologic or
      predictive changes begin to occur, and charting their rate of progression. Our long-term goal
      is to use our understanding of underlying mechanisms to enhance our capacity to predict who
      with major depression is most likely to develop premature ischemic heart disease, to
      determine what the mechanisms underlying this susceptibility are, and to develop improved
      means for treatment and prevention.

      Depressed patients are known to manifest a variety of neuroendocrine changes that predispose
      to coronary artery disease including hypercortisolism, decreased secretion of growth hormone
      and a deficiency of sex steroids. A final common denominator of these neuroendocrine
      abnormalities is insulin resistance. Insulin resistance promotes several changes that would
      favor hypertension and increased coronary artery disease including increased sodium
      retention, increased activity of the sympathetic nervous system, proliferation of vascular
      smooth muscle and deposition of highly metabolically active visceral fat. The latter induces
      additional risk factors for coronary disease, including dyslipidemia, hypercoagulation, and
      enhanced inflammation. It is a matter of public health importance to document the frequency
      and severity of insulin resistance in patients with major depression compared to a closely
      matched group of healthy controls. To accurately quantify insulin resistance in each patient
      and control, we will apply the hyperinsulinemic euglycemic glucose clamp procedure. This is
      the gold standard method for measuring the insulin sensitivity since it reflects the direct
      human body glucose metabolic response to a known insulin infusion. Moreover, it is essential
      to use this technique in patients with major depression as data indicate that other
      alternative procedures give unreliable results in the context of hypercortisolism.
    

Keywords: Cardiovascular Disease; Glucose Clamp; Hypercortisolism; Insulin Sensitivity; Major Depression Disorder; Inflammation; Coagulation; Metabolic; Insulin; Cytokine; Depression; Volunteer; Healthy Volunteer