On the impact of episode sensitization on the course of recurrent affective disorders

Sensitization of an organism by recurrent disease episodes is postulated as : a key mechanism governing the progressive long-term course of affective d isorders. The particular significance is that episode sensitization could u nderly the transition from externally triggered disease episodes to autonom ous episode generation. Functionally, this transition might be explained by positive feedback between a disease episode and the activity state of an o rganism which includes the introduction of a memory trace fur generated dis ease episodes. Here we consider the functional consequences of episode sens itization for the course of recurrent affective disorders. We use a computa tional approach and extend our previously introduced model for the course o f affective disorders by a feedback mechanism for episode sensitization. De pending on sensitization timescale and amount, triggered episodes leave the model in a sustained sensitized state or induce autonomous disease progres sion. Runaway activation can end in saturation. Remarkably, however, over a broad parametric range the progression ends in intermediate states: with f luctuating disease patterns. This behavior results from the model's nonline ar dynamics and represents a situation where the feedback intermittently ch anges between positive and negative directions. Our simulations strongly su pport episode sensitization as an important disease mechanism for affective disorders From a nonlinear standpoint, this mechanism offers an explanatio n not only for autonomous disease progression but also for occurence and st ability of irregular rapid-cycling disease states. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.