Depression is defined in diagnostic literature as a mood disorder characterized by depressed mood, loss of interest or pleasure in activities, significant changes in weight, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, difficulty concentrating, and suicidal ideation and/or attempts. Research suggests a link between depressed mood and monoamine depletion, elevated cortisol, and inflammation, but existing laboratory evidence is inconclusive. Current treatments for depression include selective serotonin reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT), and lifestyle changes; however, more severe forms of the disorder can require other medication, sometimes in combination with electroconvulsive therapy (ECT). Disagreement persists over how to define and classify depression, in part due to its ambivalent relationship to melancholia, which has existed as a medical concept in different forms since antiquity. Melancholia was reconfigured in 19th-century medicine from traditional melancholy madness into a modern mood disorder. In the early 20th century, melancholia gradually fell out of use as a diagnostic term with the introduction of manic-depressive insanity and unipolar depression. Following the publication of DSM-III in 1980 and the introduction of SSRIs a few years later, major depressive disorder became ubiquitous. Consumption of antidepressants have continued to rise year after year, and the World Health Organization notes depression as the leading cause of disability worldwide. At present, internationally recognized systems of classification favor a single category for depressive illness (alongside a circular mood disorder, bipolar I and II), but this view is challenged by clinicians and researchers who argue for the reinstatement of melancholia as a separate and distinct mood disorder with marked somatic and psychotic features.