On Episode Sensitization in Recurrent Affective Disorders: The Role of Noise

Abstract

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. Neuropsychopharmacology (2003) 28, S13-S20.

Dysregulation of the NF-κB pathway as a potential inducer of bipolar disorder

“…Kraepelin (1921) described in details the episodic nature of the disorder and its progression, characterized as faster recurrences (shorter intervals between episodes of high disease activity) that appeared to be dependent on the episode number. The positive feedback between the disease process and its episodes results in episode sensitization (Huber et al 2003), which may be the key mechanism underlying the long-term course of recurrence in bipolar. Kraepelin also described stress sensitization in which early episodes of unipolar and bipolar disorders are often precipitated by psychosocial stresses, in contrast to later episodes that occur seemingly independently of psychosocial stresses after sufficient number of recurrences (Kraepelin 1921).…”

Stimulus-response curves of a neuronal model for noisy subthreshold oscillations and related spike generation

“…The productive role of stochastic fluctuations and specifically stochastic resonance for sensory encoding and biological systems in general has attracted much attention since the first paper on stochastic resonance in a sensory receptor was published by Moss and coworkers [33],. A multitude of papers than has been demonstrating productive qualitative noise effects in experimental and theoretical studies reaching from the molecular, cellular, systems and even to the behavioural level and disease models [8,12,18,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55].…”

Relating the Bipolar Spectrum to Dysregulation of Behavioural Activation: A Perspective from Dynamical Modelling

“…While some mathematical models of positive feedback and the effects of noise on occurrences of episodes in recurrent affective disorders have already been undertaken [7]–[9], the role of nonlinearity has not been elucidated specifically in these studies. In our model, nonlinearity is inherent in the system, expressed by auto-activation of the BAS, which is a simplification in terms of the modelling process and reduces the number of involved parameters substantially.…”

“…In this model, a stable limit cycle is reached at the onset of the illness, which can be reduced in amplitude upon treatment. Aside from this deterministic approach, there are also a few models dealing with stochasticity in affective disorders and the role of noise in episode sensitisation [7]–[9]. These studies implement aspects of the kindling model, which is used in several neuropsychiatric contexts [10], describing the progression from externally induced disease episodes to autonomously occurring episodes following sensitisation.…”