The modern idea of depression appears similar to the much older concept of melancholia. The name melancholia derives from "black bile," one of the "four humours" postulated by Galen.

Clinical depression was originally considered to be a chemical imbalance in transmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms.[2] Since these suggestions, many other causes for clinical depression have been proposed.