Long-Term Bidirectional Hormonal and N europlastic Responses to Stress Implications for the Treatment of Depression

As far back as the works of Emil Kraepelin-who separated the affective disorders from schizophrenia-a prominent role of stressors in the precipitation of early episodes of affective illness was noted (1). Kraepelin spoke of the complex and variegated course of bipolar illness with its waxing and waning of patterns and episodes, and he was among the first to report on a general tendency for increased rapidity of episode cycling (i.e., the well interval between episodes shortened as a function of the number of successive episodes) (Fig. 1). Kraepelin wrote: