Major Depressive Disorder

Neuron, Vol. 28, 335–341, November, 2000, Copyright ©2000 by Cell Press

Major Depressive Disorder

Review

Maurizio Fava*‡ and Kenneth S. Kendler†‡ * Department of Psychiatry Massachusetts General Hospital—ACC 812 15 Parkman Street Boston, Massachusetts 02114 † Department of Psychiatry Virginia Commonwealth University P.O. Box 980126 Richmond, Virginia 23298

Depression describes both a transient mood state experienced by virtually all individuals at some time in their life as well as a clinical or biobehavioral syndrome, usually called Major Depressive Disorder (MDD). MDD is a medical condition that includes abnormalities of affect and mood, neurovegetative functions (such as appetite and sleep disturbances), cognition (such as inappropriate guilt and feelings of worthlessness), and psychomotor activity (such as agitation or retardation). It is one of the oldest, well-recognized medical disorders, having been clearly described in medical texts dating back to ancient Greece. When MDD occurs with an individual who has also had a history of episodes of mania, this is called Bipolar Disorder (previously termed Manic-Depressive Illness). In this review, we will be focusing on MDD when it occurs without a history of mania, where it is often called Unipolar Depressive Disorder. Current diagnostic criteria for MDD (see for example the American Psychiatric Association’s DSM-IV manual) represent a clinical and historical consensus about the most important symptoms and signs of depressive illness. However, affected individuals display quite a wide variation in clinical symptoms and signs. Furthermore, the current diagnostic conventions are, to some degree, arbitrary. Debate continues as to whether MDD is best conceptualized as a disease or as the extreme of a continuum of increasingly disturbed affective regulation. This review outlines our current understanding of this common and frequently disabling disorder and explores the challenges we face in determining the...