Serum cholesterol and serotonergic function in major depressive disorder

Studies have revealed a relationship between serum cholesterol levels and serotonergic (5HT) function in healthy young adults. Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy adults, while MDD patients with elevated cholesterol have a poorer prognosis for treatment response. The goal of the present study is to examine (1) the relationship between serum cholesterol levels and central 5HT function by way of the cortisol and prolactin response to the 5HT-selective agonist DL-fenfluramine in MDD patients and (2) differences in 5HT-function between MDD patients who present with and without elevated cholesterol. Fasting serum cholesterol levels were measured in 21 outpatients with MDD. After oral administration of 60 mg of DL-fenfluramine in these patients, cortisol and prolactin responses were measured to test whether cholesterol levels predicted the degree of cortisol or prolactin response. Cortisol and prolactin responses were compared between patients with and without elevated cholesterol levels, defined as ≥200 mg/dl. MDD patients with elevated cholesterol levels were more likely to demonstrate an attenuated cortisol response. There was no relationship between cholesterol levels and cortisol or prolactin response. Excess cholesterol may adversely affect the function of membrane-bound serotonergic structures, and this may explain why MDD patients with elevated cholesterol are more likely to exhibit attenuated neuroendocrine responses, less likely to respond to treatment and more likely to relapse.