A key sign of depression is either depressed mood or loss of interest in activities you once enjoyed. For a diagnosis of depression, these signs should be present most of the day either daily or nearly daily for at least two weeks. In addition, the depressive symptoms need to cause clinically significant distress or impairment. They cannot be due to the direct effects of a substance, for example, a drug or medication. Nor can they be the result of a medical condition such as hypothyroidism.