We know that declining insulin activity in the brain, due to insulin resistance, may play a role in the development of major depression. Interestingly, Lithium (used to treat bipolar disorders) mimics some of the effects of insulin in the brain. Omega-3-Fatty Acids have been shown to improve metabolic syndrome and depression. Cortisol levels are commonly elevated in patients with Metabolic Syndrome and/or major depression. Depression is a stressor on the body and 50-70% of patients with depression have hypercortisolemia. These high levels of cortisol lead to decreased serotonin activity in the brain. Low levels of serotonin are associated with depression, anxiety and violence.
Metabolic Syndrome and hypercortisolemia result in elevated fasting blood sugars, impaired glucose uptake into the cells for energy, hyperlipidemia, high blood pressure and deposition of visceral fat. Elevated levels of visceral fat increase inflammation that makes depression, insulin resistance and metabolic syndrome worse. In a vicious cycle, high levels of visceral fat maintain high levels of cortisol through several enzymatic reactions.
Both major depression and metabolic syndrome are inflammatory processes. Patients with either or both processes have high levels of inflammatory cytokines (substances which promote the inflammatory process). And did you know that patients with major depression may have twice the levels of inflammatory cytokines than those without depression? These high levels of cytokines increase cortisol through stimulation of the brain and adrenal glands and exacerbates metabolic syndrome and depression. The areas of the brain that are involved in major depression are very sensitive to inflammatory cytokines. Depression and Metabolic Syndrome are the result of chemistry, nutrition and emotional trauma gone awry.
There is an increasing risk of developing depression if the patient is obese. The risk is higher for overweight women than it is for men. When the patient has abdominal obesity, the risk of depression is elevated in both men and women. Adiponectin is a hormone released by fatty tissue which decreases appetite and elevates mood. Levels of adiponectin are LOW in obesity, depression and metabolic syndrome. Patients have less depression when they lose weight. Insulin sensitivity, glucose tolerance and lipid levels also improve. Furthermore, when patients with depression are treated with anti-depressants, their metabolic syndrome improves.
Finally, remember what I wrote about lowering cholesterol and making less sex hormones several blogs back? Cholesterol is the precursor to the sex hormones and to cortisol. When levels are pushed too low, the patient has decreased libido and low levels of sex hormones. Well, a study was published which revealed an increased risk of suicide in patients treated with medication and diet to lower cholesterol. One study showed that both men and women had a rate of suicide that was three times higher if they were in the lowest 25% of cholesterol levels than those that were in the highest 25%. Animal studies reveal that lowering cholesterol levels in the brain decreased the number of serotonin receptors. This can lead to major depression.
In the next post, we will look at the remainder of the metabolic implications of insulin resistance and depression.