[Psychiatric polypharmacy and electroconvulsive therapy in treatment-resistant depression]. / Psychiatrische Polypharmazie und Elektrokonvulsionstherapie bei therapieresistenter Depression.

BACKGROUND: Despite its relevant medical risks, polypharmacy is common particularly among difficult to treat conditions, e.g. treatment refractory depression (TRD). According to numerous guidelines, electroconvulsive therapy (ECT) is the treatment of choice in severe and treatment-resistant major depression due to the high effectiveness; however, to date limited data are available concerning the effects of ECT on the concomitant prescription of psychiatric medication. METHODS: For a retrospective explorative analysis of psychiatric polypharmacy (MED) in TRD, data from 58 inpatient treatments were collected. Due to depressive episodes, all patients received psychopharmacological treatment and cognitive behavioral therapy (MED group). Of the patients 29 also underwent ECT (ECT group). Using a modified drug burden index (mod-DBI), the psychiatric medication was quantified at admission (TP0), start (TP1) and termination of ECT (TP2) and discharge in the ECT group or in comparable periods in the MED group (TP3). Differences in distribution were tested with the t-test and alterations in measurements were tested by means of variance analysis (F-test). RESULTS: Patients treated with ECT showed higher mod-DBI values at TP0, mainly due to more frequent prescription of benzodiazepines (BZD), mood stabilizers (MS) and antipsychotic drugs (AP). At the beginning of the inpatient treatment (TP0-TP1) there was an increase in BZD use (in both groups); in the ECT group MS were reduced and AP increased. In the time interval TP1-TP3, BZD (in both groups) and AP (ECT group) were again less frequently prescribed and MS (ECT and MED group) were increased again. Excluding BZD, there was a significant increase in mod-DBI in both groups, whereas the mod-DBI no longer showed significant differences at TP2 and TP3. CONCLUSION: The data possibly indicate that patients with TRD who receive ECT during inpatient treatment already have a more extensive psychiatric medication at admission. Also, psychiatric medication appears to be increased less prominently when ECT is performed. These findings and the possibly associated long-term benefits should be addressed in future research.

Frequency and correlates of maladaptive responses to paranoid thoughts in patients with psychosis compared to a population sample.

INTRODUCTION: The aims of this study were to identify whether responses to paranoid thoughts distinguish patients with psychotic disorders from people in the population who have paranoid thoughts occasionally and to identify factors that are associated with and might explain the different ways of responding. METHODS: Paranoid thoughts were assessed in patients diagnosed with a psychotic disorder (n = 32) and a population control sample (n = 34) with the Paranoia Checklist. Responses to paranoid thoughts were assessed with the Reactions to Paranoid Thoughts Scale (RePT) and social support, self-efficacy and cognitive insight were assessed as potential correlates of the responses to paranoid thoughts. RESULTS: The patients showed significantly more depressed, physical and devaluating responses to paranoid thoughts and employed less normalising responses than the controls. The differences in normalising responses were explained by perceived social integration, whereas the differences in depressive responses were explained by the overall levels of depression and partly explained by externality and social integration. CONCLUSIONS: Maladaptive responses to paranoid thoughts could be relevant to the pathogenesis and maintenance of persecutory delusions. Interventions aimed at reducing paranoia could benefit from targeting dysfunctional responses to paranoid thoughts and by placing a stronger emphasis on treating depression and improving social integration.

Modeling neuronal activity in relation to experimental voltage-/patch-clamp recordings.

A mechanism-based, Hodgkin-Huxley-type modeling approach is proposed that allows connecting the key parameters of experimental voltage-/patch-clamp data directly to the major control values of the model. The objective of this paper is to facilitate the use of mathematical modeling in supplement to electrophysiological recordings. Typical recordings from current-clamp, whole-cell voltage-clamp, and single-channel patch-clamp experiments are illustrated by means of a simplified computer model designed for life science education. These examples demonstrate that the "rate constants", on which the original Hodgkin-Huxley equations are built up, are difficult, in most experiments even impossible, to extract from experimental data. As the combination of the two exponential rate constants leads to sigmoid activation curves, they can be replaced by sigmoid voltage dependencies, mostly presented in form of Boltzmann functions. Conversely, connecting whole-cell and single-channel patch-clamp simulations, the Boltzmann functions, can be related to exponentially voltage dependent probability factors of ion channel transition rates. The thereby introduced small variability of the activation values suggests that the power functions of the activation variables in the current equations can be neglected. Eliminating the rate constants and the power functions can be physiologically justified and makes the model easier to handle, especially in context with experimental data. Further possibilities of dimension reduction as well as model extensions are discussed. This article is part of a Special Issue entitled Neural Coding 2012.

Noise-induced precursors of tonic-to-bursting transitions in hypothalamic neurons and in a conductance-based model.

The dynamics of neurons is characterized by a variety of different spiking patterns in response to external stimuli. One of the most important transitions in neuronal response patterns is the transition from tonic firing to burst discharges, i.e., when the neuronal activity changes from single spikes to the grouping of spikes. An increased number of interspike-interval sequences of specific temporal correlations was detected in anticipation of temperature induced tonic-to-bursting transitions in both, experimental impulse recordings from hypothalamic brain slices and numerical simulations of a stochastic model. Analysis of the modelling data elucidates that the appearance of such patterns can be related to particular system dynamics in the vicinity of the period-doubling bifurcation. It leads to a nonlinear response on de- and hyperpolarizing perturbations introduced by noise. This explains why such particular patterns can be found as reliable precursors of the neurons' transition to burst discharges.

Aspects of Piaget's cognitive developmental psychology and neurobiology of psychotic disorders - an integrative model.

Psychological, neurobiological and neurodevelopmental approaches have frequently been used to provide pathogenic concepts on psychotic disorders. However, aspects of cognitive developmental psychology have hardly been considered in current models. Using a hypothesis-generating approach an integration of these concepts was conducted. According to Piaget (1896-1980), assimilation and accommodation as forms of maintenance and modification of cognitive schemata represent fundamental processes of the brain. In general, based on the perceived input stimuli, cognitive schemata are developed resulting in a conception of the world, the realistic validity and the actuality of which is still being controlled and modified by cognitive adjustment processes. In psychotic disorders, however, a disproportion of environmental demands and the ability to activate required neuronal adaptation processes occurs. We therefore hypothesize a failure of the adjustment of real and requested output patterns. As a consequence autonomous cognitive schemata are generated, which fail to adjust with reality resulting in psychotic symptomatology. Neurobiological, especially neuromodulatory and neuroplastic processes play a central role in these perceptive and cognitive processes. In conclusion, integration of cognitive developmental psychology into the existing pathogenic concepts of psychotic disorders leads to interesting insights into basic disease mechanisms and also guides future research in the cognitive neuroscience of such disorders.

Oscillations, resonances and noise: basis of flexible neuronal pattern generation.

Modulation of neuronal impulse pattern is examined by means of a simplified Hodgkin-Huxley type computer model which refers to experimental recordings of cold receptor discharges. This model essentially consists of two potentially oscillating subsystems: a spike generator and a subthreshold oscillator. With addition of noise the model successfully mimics the major types of experimentally recorded impulse patterns and thereby elucidate different resonance behaviors. (1) There is a range of rhythmic spiking or bursting where the spike generator is strongly coupled to the subthreshold oscillator. (2) There is a pacemaker activity of more complex interactions where the spike generator has overtaken part of the control. (3) There is a situation where the two subsystems are decoupled and only resonate with the help of noise.

Interactions of temperature and angiotensin II in paraventricular neurons of rats in vitro.

We recorded extracellular impulse activity of hypothalamic paraventricular neurons ( n=75) in rat brain slices during application of angiotensin II (ANG II, 10(-9)-10(-6) M) and/or temperature changes (32-42 degrees C). ANG II, with a threshold concentration of 10(-8) M, increased the firing rate in more than 80% of the neurons with strongest excitations occurring in bursting neurons. Increasing the temperature also raised the discharge rate in the majority of the neurons, often together with enhanced burst discharges. When ANG II was applied during ongoing sinusoidal temperature changes, its effects were more pronounced at elevated temperatures. These electrophysiological data illustrate that stimulus-encoding properties at the neuronal level can contribute to the interactions between osmoregulatory and thermoregulatory mechanisms including mutual sensitization when different stimuli (here: ANG II and temperature changes) are applied simultaneously.