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Depression Sure, we all feel sad or blue from time to time. But, when you feel sad for long periods and the feelings become intense, the depressed mood and its associated physical symptoms can keep you from living a normal life. Depression is an extremely complex disease. No one knows exactly what causes it, but it can occur for a variety of reasons. Some people experience depression during a serious medical illness. Others may have depression with life changes such as a move or the death of a loved one. Still others have a family history of depression. Those who do may experience depression and feel overwhelmed with sadness and loneliness for no known reason.