The defining features of major depressive disorder (MDD) are marked and persistent dysphoria plus additional cognitive signs and symptoms (anhedonia, sleep disturbance, weight/appetite changes, motor agitation/retardation, anergia, excessive guilt or worthlessness, poor concentration or indecisiveness, and recurrent thoughts of death or suicide) (1). MDD is distinct from normal sadness by its persistence (i.e., ≥2 weeks), additional signs and symptoms, and substantial associated impairment. The definition of MDD excludes other conditions typified by substantial depressive symptoms (other psychiatric disorders, drug/alcohol dependence, and somatic diseases). The lifetime prevalence of MDD is ∼15% (2-4) and is twofold higher in women (5) with a course typified by recurrence of illness (6). It is associated with considerable morbidity (7-9), excess mortality from suicide and other causes (10-13), and substantial direct and indirect costs (14). A WHO study projected MDD to be the second leading cause of disability worldwide by 2020 (15).
