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Selective serotonin reputake inhibitors (SSRIs) such as Prozac and Luvox sometimes work wonders for depression, but sometimes they don't work at all. For some people the answer to depression is controlling depression, sometimes with very simple drugs.u

There's growing evidence that depression can be caused by an inflamed brain.

Dr. Gholam Khandaker and his colleagues at the University of Cambridge in the UK reviewed the results of 20 clinical studies involving over 5,000 patients treated for chronic inflammatory diseases with medications designed to control the release of cytokines, a group of proteins that cells use to send signals to each other. Some cytokines carry a signal to cells to release inflammatory substances that cause heat, pain, redness, and swelling. The anti-cytokine drugs used to treat inflammatory diseases like rheumatoid arthritis, Khandaker and associates learned, are also about as effective as selective serotonin reuptake inhibitors (SSRIs) in treating depression.

How Can an Inflamed Brain Cause Depression?

The cytokines send signals to particular kinds of cells. Specifically, it is cells in the immune system that are activated by the cytokines that send a signal for the release of substances that cause inflammation. In the immune system, inflammation isn't a bad thing. The immune system uses inflammation to get rid of infectious microorganisms, and to break down dead tissue or old tissue in bones and joints that needs to be remodeled to accommodate changes in the way the body distributes weight. We all need some inflammation. However, inflammation has effects on the brain as well as on the rest of the body.

When our bodies are fighting infection it is natural for us to want to curl up and be left alone. That's because the immune system is fighting infection in two different ways. White blood cells called macrophages release cytokines not just to fight germs but also to recruit other white blood cells to travel to the site of the infection and join the attack. When these macrophages reach the brain, however, a second set of cells called microglial cells come into play. The microglia release a different set of cytokines just in the brain that enable the kinds of behaviors that help a sick person recover faster. These cytokines trigger fatigue, loss of appetite, and loss of energy. These changes in behavior give the person time to rest, or at least to stay out of circulation to avoid spreading the disease to others.

In Modern Life, Immune Signals Keep Coming

This system served humans well when they lived in primitive communities. Eight hundred years ago, staying indoors when you had the flu might have saved you from going to the market and catching Black Plague. However, it's not just infections that can trigger the release of inflammatory cytokines. Obesity and diabetes also cause the release of cytokines. If you become obese, you tend also to become depressed, so you don't want to get out and exercise, and so you might start taking more comfort in eating alone than in engaging in other activities with friends and family. If you become diabetic, your cytokines might keep you from the physical activity that helps you regulate your blood sugar levels, and the side of high blood sugar levels is even more insulin resistance that raises your blood sugar levels higher and makes your cytokine levels even worse. PTSD (post-traumatic stress syndrome) similarly releases cytokines that can cause depression, obesity, anxiety, and inflammatory diseases to spiral downward with ever-worsening symptoms.

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