ABSTRACT
Robert M. Post, Andrew M. Speer, Gabriele S. Leverich, and Susan R.B. Weiss National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland Terence A. Ketter Stanford University School of Medicine, Stanford, California
The fundamental phenomenological observations underlying the sensitization and kindling hypotheses were inherent in Emil Kraepelin’s early classification and description of manic-depressive illness [1]. He noted, amidst a variegated pattern of the illness and its inherent unpredictability, a general tendency for the well intervals between depressive episodes to shorten over time (ie, a general trend for cycle acceleration) (Fig. 1). He also laid the fundamental groundwork for the stress sensitization component of the hypothesis with his observations that initial episodes of manic or depressive illness were often precipitated by psychosocial stressors, but subsequent episodes of affective illness would recur in a highly similar form of ‘‘quite without external occasion’’ [Ref. 1, p. 181] (Fig. 2).
