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The Depression-Inflammation Connection

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The dramatic rise in depression diagnoses over the last two decades is a great challenge to modern medicine. I believe that part of the "depression epidemic" is false -- a creation of aggressive disease-mongering by pharmaceutical companies to promote antidepressant sales. However, it's equally clear that within that trend, there has been a real rise in depression rates.

The reasons for the increase are complex, but one important theory deserves special consideration, because I believe it offers new possibilities for prevention and treatment. At the center of this theory are cytokines -- proteins made by immune cells that govern responses to foreign antigens and germs.

Cytokines have varied effects. One type -- the interleukins -- controls inflammation and produces fever. Another type governs how red and white blood cells in the bone marrow mature. Because of such powerful effects, some cytokines have proved useful as medical treatments, though they can be quite toxic. In 1980, scientists succeeded in inserting a gene for human interferon into bacteria -- this made it possible to mass-produce and purify these proteins. Since then, synthetic, injectable forms of interferon have been in wide use as treatments for several cancers (skin cancers, some leukemias), chronic viral hepatitis and multiple sclerosis.

A commonly-reported side effect of interferon therapy is severe depression; in fact, some patients have committed suicide. Long-term activation of the immune system, as in autoimmune disease, also seems to go along with depression. The reverse is also true: Depression seems to involve changes in various aspects of immunity, particularly those having to do with cytokines. People with rheumatoid arthritis, scleroderma, systemic lupus (SLE) and other forms of autoimmunity are often depressed. And when proinflammatory cytokines are administered to animals, they elicit "sickness behavior": The animals become listless, lose interest in eating, grooming, socializing and sex, and show increased sensitivity to pain, changes strikingly similar to those in humans with major depression.

Loss of interest in food and ability to take pleasure in eating make sense as a short-term response to infection -- it frees up energy used for digestion and makes it available for immune defense. Once the immune system gains the upper hand, it can turn down the cytokines, allowing brain centers that control appetite and taste to resume normal activity. Malignant tumors, however, even when they are relatively small, often stimulate prolonged cytokine responses that do more harm than good. For example, they permanently suppress appetite. This leads to extreme wasting (cachexia) that all too many cancer patients suffer. Given that dramatic effect on the brain and body, consider the impact of prolonged cytokine responses on parts of the brain associated with thoughts and emotions.

The reason I find the cytokine hypothesis of depression so compelling is that it fits right in with my belief that doing everything we can to contain unnecessary inflammation -- by adhering to an anti-inflammatory diet, for example -- is the best overall strategy for attaining optimum health.

Inflammation is the cornerstone of the body's healing response. It is the process by which the immune system delivers more nourishment and more defensive activity to an area that is injured or under attack. But inflammation is so powerful and so potentially destructive that it must stay where it is supposed to be and end when it is supposed to end; otherwise it damages the body and causes disease. Cytokines are the principal chemical mediators of the inflammatory response. Anything you can do to keep them within their proper bounds will reduce your risks of chronic disease and also, it now appears, protect you from depression.

How to control inappropriate inflammation is a big subject, but dietary choices are perhaps the most important way to keep excessive cytokine production in check. The anti-inflammatory food pyramid consists of foods that can help control inflammation, as well as provide the vitamins, minerals and fiber required for optimal health. Prudent exercise regimes and stress-reduction techniques can also be helpful.

My new book, "Spontaneous Happiness," from which this article is adapted, provides detailed information about therapies and lifestyle changes that can control inflammation. It also explores other methods to improve mood states. Depression is a serious problem, but as our understanding of the mechanisms behind it improves, I believe we can make significant progress in developing simple, safe, effective therapies to treat it.

Andrew Weil, M.D., is the founder and director of the Arizona Center for Integrative Medicine and the editorial director of www.DrWeil.com. Become a fan on Facebook, follow Dr. Weil on Twitter, and check out his Daily Health Tips Blog.