Sadness is a natural part of the human experience. However, it is normally short-lived and usually caused by a specific reason. When someone experiences persistent and intense feelings of sadness for extended periods of time, it may signal major depression. Major depression is characterized by at least two weeks of low mood that is present across most conditions. Symptoms of major depression include low self-esteem, loss of interest in daily activities, low energy and pain without a clear cause. Major depression can be an isolating, painful and bewildering illness to live with. It takes time and commitment to find the right treatment, but with the right treatment, people can live a healthy and fulfilling life.