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

Department of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmannstrasse 8, D-35033 Marburg, Germany.
Neuropsychopharmacology (Impact Factor: 7.05). 08/2003; 28 Suppl 1(7):S13-20. DOI: 10.1038/sj.npp.1300141
Source: PubMed


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.

Download full-text


Available from: Hans Albert Braun
  • Source
    • "Kraepelin (1921) described in detail 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 a sufficient number of recurrences (Kraepelin, 1921). "
    [Show abstract] [Hide abstract]
    ABSTRACT: A century of investigations enhanced our understanding of bipolar disorder although it remains a complex multifactorial disorder with a mostly unknown pathophysiology and etiology. The role of the immune system in this disorder is one of the most controversial topics in genetic psychiatry. Though inflammation has been consistently reported in bipolar patients, it remains unclear how the immunologic process influences the disorder. One of the core components of the immune system is the NF-κB pathway, which plays an essential role in the development of innate and adaptive immunity. Remarkably, the NF-κB pathway received only little attention in bipolar studies, as opposed to studies of related psychiatric disorders where immune dysregulation has been proposed to explain the neurodegeneration in patient conditions. If immune dysregulation can also explains the neurodegeneration in bipolar disorder, it will underscore the role of the immune system in the chronicity and pathophysiology of the disorder and may promote personalized therapeutic strategies. This is the first review to summarize the current knowledge of the pathophysiological functions of NF-κB in bipolar disorder.
    Full-text · Article · Aug 2015 · Journal of Psychiatric Research
  • Source
    • "Networks of synchronous neurons (Pereira et al., 2007; Batista et al., 2013; Wu et al., 2013; Shi et al., 2009; Torrealdea et al., 2009) in particular, have become of great interest due to a multitude of related neurological pathologies. These include Parkinson's disease (Park et al., 2011), epilepsy (Heilman and Quattrochi, 2004; Huber et al., 2003), seizures (Takeshita and Bahar, 7506), depression (Johnstone, 2007), schizophrenia (Brenner et al., 2003) and sleep disorders (Fulcher et al., 2014). In addition, neural firing regime transitions in the context of synchronization are ubiquitous and of relevance to a number of physiological functions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Central pattern generators are neuron networks that produce vital rhythmic motor outputs such as those observed in mastication, walking and breathing. Their activity patterns depend on the tuning of their intrinsic ionic conductances, their synaptic interconnectivity and entrainment by extrinsic neurons. The influence of two commonly found synaptic connectivities - reciprocal inhibition and electrical coupling - are investigated here using a neuron model with subthreshold oscillation capability, in different firing and entrainment regimes. We study the dynamics displayed by a network of a pair of neurons with various firing regimes, coupled by either (i) only reciprocal inhibition or by (ii) electrical coupling first and then reciprocal inhibition. In both scenarios a range of coupling strengths for the reciprocal inhibition is tested, and in general the neuron with the lower firing rate stops spiking for strong enough inhibitory coupling, while the faster neuron remains active. However, in scenario (ii) the originally slower neuron stops spiking at weaker inhibitory coupling strength, suggesting that the electrical coupling introduces an element of instability to the two-neuron network.
    Full-text · Article · Nov 2014 · Biosystems
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oscillations of the membrane potential are a prominent feature of several neurons in the central and peripheral nervous system. Evidences exist that neurons combine intrinsic oscillations with stochastic influences to obtain sensitive encoding. Here we investigated the responses of oscillatory neurons with respect to different activity states and noise levels as well as different measures of the responses. For that we used a computational approach and studied systematically the responses of a physiologically motivated neuronal oscillator model. With subthreshold activation of the model, noise mediates oscillation-coupled spike generation. In this situation noise-tuning results in maximum curves for the coherence of oscillations and spikes (coherence resonance) whereas the mean spike frequencies increase monotonically. In contrast, with suprathreshold activation, noise suppresses oscillation-coupled spike generation. In this situation, noise tuning leads to a minimum curve for the mean spike frequency whereas the coherence measure decreases monotonically. In conclusion, our study shows interesting effects on neuronal responses depending on the level of stimulation and noise intensity. In addition, the study demonstrates how such dynamical behaviors might fulfill different purposes depending on the actual encoding strategy used.
    No preview · Article · May 2003 · Proceedings of SPIE - The International Society for Optical Engineering
Show more