The author has reviewed evidence generated during the past decade at the University of Tennessee and other affective disorders research units in support of a psychobiologic understanding of affective disorders as the final common pathway of various psychologic and biologic factors that impinge on midbrain centers of reward, circadian rhythms, and psychomotor function. In this model, inherited temperamental instability, based on a persistent diencephalic abnormality, provides the fertile soil for the development of major affective episodes. The pathogenesis of full-blown affective episodes is then the product of multiple factors, none of which alone is a necessary or sufficient cause. It is submitted that this unified theory, in bridging psychosocial and biologic factors, provides the most comprehensive etiologic understanding of depressive illness permitted by current data. Clinical implications of the theory are discussed.
