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 disorders. The particular significance is that episode sensitization could underly the transition from externally triggered disease episodes to autonomous episode generation. Functionally, this transition might be explained by positive feedback between a disease episode and the activity state of an organism which includes the introduction of a memory trace for generated disease episodes. Here we consider the functional consequences of episode sensitization for the course of recurrent affective disorders. We use a computational approach and extend our previously introduced model for the course of affective disorders by a feedback mechanism for episode sensitization. Depending on sensitization timescale and amount, triggered episodes leave the model in a sustained sensitized state or induce autonomous disease progression. Runaway activation can end in saturation. Remarkably, however, over a broad parametric range the progression ends in intermediate states with fluctuating disease patterns. This behavior results from the model's nonlinear dynamics and represents a situation where the feedback intermittently changes between positive and negative directions. Our simulations strongly support episode sensitization as an important disease mechanism for affective disorders. From a nonlinear standpoint, this mechanism offers an explanation not only for autonomous disease progression but also for occurence and stability of irregular rapid-cycling disease states.