Cholesterol And Lipids In Depression: Stress, Hypothalamo-Pituitary-Adrenocortical Axis, And Inflammation/Immunity

There are many different ways to classify lipids. Here, we focus on lipid profiles in depression, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very-low density lipoprotein (VLDL) cholesterol, and the ratios of TC/HDL and LDL/HDL (atherogenic index). Several studies have discussed the relationship between serum cholesterol and suicide, violence, anxiety disorders, depressive disorders, and schizophrenia [1-3]. Some of these papers suggested that low or lowering cholesterol levels could cause or worsen depressive symptoms and increase the risks of suicide and violence death. There are many reports that discussed the relationships between the lipid profiles, depression, and suicide from the viewpoints of decreased serotonergic transmission on suicide behavior [4, 5], lower serum cholesterol and serotonin levels [6, 7], serum cholesterol levels and polymorphism in the promoter region of the serotonin transporter gene for depression and suicide [8-10], low serum cholesterol and suicide risk [11, 12], and serotonergic receptor function [13, 14]. These studies supported the hypothesis that reduced cholesterol levels resulted in reduced central serotonin transmission. Major depression is associated with altered changes in hypothalamo-pituitary-adrenocortical (HPA) axis activity and immune and endocrine systems. Because these systems can affect each other reciprocally, interactions between the lipid profiles and the neuroendoimmune systems in depression should be addressed [15-20]. Penttinen has suggested that low cholesterol concentration and suicidal behavior are connected with interleukin 2, which caused decreased serum cholesterol level and increased serum TG level [15]. In major depression, activation of the inflammatory response system and increased concentrations of proinflammatory cytokines, prostaglandin E₂, and negative immuno-regulatory cytokines in peripheral blood have been reported [16]; Myint and Kim suggested one neurodegeneration hypothesis of depression that involved cytokine-serotonin interaction through the enzyme indoleamine-2,3-dioxygenase [16]. Some authors also discussed brain-immune interactions [17], glucocorticoid receptors in major depression [18], physiopathology of depression in HPA axis [19], and neurobiological consequences of adverse early-life experiences [20]. In clinical practice, depressive symptoms were common in patients with physical illness, including cardiovascular disease, diabetes mellitus, end-stage renal disease, and women in pregnancy, following delivery or menopause. However, data that specifically addressed serum lipid profiles in patients with depressive disorders and physical illnesses were still scarce. In this review we discuss the relationships between serum lipid profile levels, major depression, and suicide attempts, as well as the interactions between lipid profiles, stress, HPA axis, and inflammation/immunity in depressive disorders. The conclusion emphasizes the importance of integrated data between clinical phenotypes and molecular mechanisms in depressive disorders.