On episode sensitization in recurrent affective disorders: the role of noise

Episode sensitization is postulated as a key mechanism underlying the long-term course of recurrent affective disorders. Functionally, episode sensitization represents positive feedback between a disease process and its disease episodes resulting in a transition from externally triggered to autonomous episode generation. Recently, we introduced computational approaches to elucidate the functional properties of sensitization. Specifically, we considered the dynamics of episode sensitization with a simple computational model. The present study extends this work by investigating how naturally occurring, internal or external, random influences ("noise") affect episode sensitization. Our simulations demonstrate that actions of noise differ qualitatively in dependence on both the model's activity state as well as the noise intensity. Thereby induction as well as suppression of sensitization can be observed. Most interestingly, externally triggered sensitization development can be minimized by tuning the noise to intermediate intensities. Our findings contribute to the conceptual understanding of the clinical kindling model for affective disorders and also indicate interesting roles for random fluctuations in kindling and sensitization at the neuronal level.