Lipid metabolism and insulin resistance in depressed patients: Significance of weight, hypercortisolemia and antidepressant treatment

Despite lower cholesterol in major depression, cardiovascular risk is increased. We studied cholesterol, lipoproteins, insulin sensitivity and saliva cortisol in 78 depressed patients before and after treatment with amitriptyline or paroxetine. In normal-weight patients, cortisol is correlated with insulin resistance, while in over-weight patients, insulin resistance parameters loaded with body mass index [BMI] and were unrelated to cortisol. In obese patients, there was a negative relationship between cortisol and total cholesterol, LDL-cholesterol, apolipoprotein B and LDL-/HDL-cholesterol ratio. Under treatment, there was an increase of HDL cholesterol and, to a lesser extent, of LDL cholesterol, resulting in a modest reduction of LDL/HDL cholesterol ratio. LDL triglyceride content (a measure of LDL atherogenicity) was reduced compared to baseline. Triglyceride rich lipoproteins decreased in responders to paroxetine and increased in responders to amitriptyline, paralleling weight changes in both groups. In addition to BMI and insulin sensitivity, cortisol is an independent determinant of plasma lipids in major depression. The inverse correlation of cortisol and cholesterol may be explained by direct influence of cortisol on lipoprotein synthesis and proposes a mechanism for the known paradox of low cholesterol and increased cardiovascular risk in depression. Pharmacological treatment of depression exerts a mainly beneficial effect on lipid regulation.