Major depressive disorder (MDD) (also known as clinical depression, major depression, unipolar depression, or unipolar disorder; or as recurrent depression in the case of repeated episodes) is a mental disorder characterized by a pervasive and persistent low mood that is accompanied by low self-esteem and by a loss of interest or pleasure in normally enjoyable activities. The term “depression” is used in a number of different ways. It is often used to mean this syndrome but may refer to other mood disorders or simply to a low mood. Major depressive disorder is a disabling condition that adversely affects a person’s family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression commit suicide, and up to 60% of people who commit suicide had depression or another mood disorder. The diagnosis of major depressive disorder is based on the patient’s self-reported experiences, behavior reported by relatives or friends, and a mental status examination. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. The most common time of onset is between the ages of 20 and 30 years, with a later peak between 30 and 40 years. Typically, people are treated with antidepressant medication and, in many cases, also receive counseling, particularly cognitive behavioral therapy (CBT). Medication appears to be effective, but the effect may only be significant in the most severely depressed. Hospitalization may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy (ECT). The course of the disorder varies widely, from one episode lasting weeks to a lifelong disorder with recurrent major depressive episodes. Depressed individuals have shorter life expectancies than those without depression, in part because of greater susceptibility to medical illnesses and suicide. It is unclear whether or not medications affect the risk of suicide. Current and former patients may be stigmatized. The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and has left many aspects of depression as the subject of discussion and research. Proposed causes include psychological, psycho-social, hereditary, evolutionary and biological factors. Long-term substance abuse may cause or worsen depressive symptoms. Psychological treatments are based on theories of personality, interpersonal communication, and learning. Most biological theories focus on the monoamine chemicals serotonin, norepinephrine and dopamine, which are naturally present in the brain and assist communication between nerve cells. This cluster of symptoms (syndrome) was named, described and classified as one of the mood disorders in the 1980 edition of the American Psychiatric Association’s diagnostic manual.