Abstract: Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging).
Abstract: The immature autonomic nervous system (ANS) in premature infants regulates heart rate (HR) and respiration different during quiet sleep (QS) and active sleep (AS). Little information is available about ANS regulation in these subjects. The aim of this study was to investigate changes in autonomic regulation and cardiorespiratory coupling during AS and QS in five very preterm neonates with gestational age (GA) 26-31 weeks, applying univariate and bivariate linear and non-linear dynamics methods to the recorded cardiorespiratory signals. During QS univariate linear indices revealed lower standard deviations and entropies, indicating decreased heart rate (HR) variability. More balanced sympatho-vagal behavior of the ANS was revealed by decreased low frequency (LF), increased high frequency (HF), and a trend toward lower ratio LF/HF in QS. Applied non-linear indices (probabilities, entropies, and fractal measures) quantifying the complexity and scaling behavior of HR regulation processes were significantly altered in QS in comparison to AS. This reflects a lower short-term variability, less complexity, and a loss of fractal-like correlation properties of HR dynamics in QS. One major finding is that cardiorespiratory coupling is not yet completely developed in very preterm neonates with 26-31 weeks GA. Significantly different regulation patterns in bivariate oscillations of HR and respiration during AS and QS could be recognized. These patterns were characterized on the one hand by predominant monotonous regulating sequences originating from respiration independently from HR time series in AS, and to a minor degree in QS, and on the other hand by some prominent HR regulation sequences in QS independent of respiratory regulation. We speculate that these findings might be suitable for monitoring preterm neonates and for detecting disorders in the developing cardiorespiratory system.
Abstract: Alcohol withdrawal syndrome is associated with an increased incidence of cardiac arrhythmias and sudden cardiac death. Heart rate turbulence (HRT) parameters were applied during withdrawal to estimate cardiac regulation during treatment with clomethiazole.
Abstract: Newborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adaptation of their vital functions. However, limited information is available about bivariate couplings of the underlying complex processes controlled by the autonomic nervous system. In this study an animal model of seven newborn piglets (2-3 days old, 1.71 ± 0.15 kg) was used. The aim of this study was to analyze the cardiovascular and cardiorespiratory interactions of autonomous nervous system during sustained hypoxia and the interrelationship of these autonomic time series after induced reoxygenation. For this purpose we applied a new high resolution version of the nonlinear method of Joint Symbolic Dynamics (JSD) for analysis of couplings between heart rate and blood pressure and respiration rate time series, respectively. This new method is characterized by using three defined symbols (JSD3) instead of two and the application of thresholds for the symbol transformation. Our results demonstrate that in contrast to the traditional JSD the comparison of cardiovascular interactions reveals only significant differences between normoxic and hypoxic conditions using JSD3 whereas for cardiorespiratory interactions significant differences were revealed by indices from both JSD2 and JSD3 due to reoxygenation. These results suggest that the application of JSD3 reveals more detailed information about cardiovascular and cardiorespiratory interactions of autonomic regulation and might be useful for monitoring of critical human newborns.
Abstract: Newborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adapting their vital functions. Exposure to hypoxia leads to an increase in the sympathetic tone causing cardio-respiratory response, peripheral vasoconstriction and vasodilatation in privileged organs like the heart and brain. However, there is only limited information available about the time and intensity changes of the underlying complex processes controlled by the autonomic nervous system.
Abstract: Due to recent advances in technology extensive cardiovascular monitoring is widely introduced today. An essential component of cardiovascular monitoring is the analysis of several biosignals as electrocardiogram, blood pressure and other vital signs. This manuscript provides an overview about several application fields of cardiovascular monitoring with the main focus on nonlinear dynamics analysis.
Abstract: Depression has been shown to increase the risk for cardiovascular disease (CVD) more strongly in women than in men. Although the underlying mechanisms are unknown, a putative role of increased sympathetic modulation has been suggested for the association of CVD and depression. The aim of this study was to investigate possible gender-associated differences of autonomic function in healthy volunteers and patients suffering from major depressive disorder (MDD). Linear as well as non-linear measures of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were obtained in each 18 male and 18 female unmedicated patients and respective control subjects. Gender differences were detectable in healthy subjects showing predominant sympathetic modulation in males. This was most obvious in BPV analysis. These gender differences were abolished in patients suffering from MDD, mainly due to altered autonomic modulation in female patients. Our results indicate that BPV is more sensitive to reveal depression-associated changes of autonomic function as compared to HRV. Moreover, female patients contribute most to the overall difference between patients and controls. The shift in the balance of autonomic function in women might account for the increased prevalence of CVD in these patients.
Abstract: We investigated to what degree tonic skin conductance levels (SCL) and cardiac autonomic dysfunction are interrelated in schizophrenia. Heart rate variability (HRV) and SCL were simultaneously assessed in 18 unmedicated patients and 18 controls matched for age, sex, weight, and smoking habits. For comparison to prior studies, phasic sympathetic skin responses (SPR) were also recorded. Compared to controls, patients had prolonged SPR latency and reduced SPR amplitude with a right-greater-than-left asymmetry, which was inversely correlated with positive symptoms. An autonomic imbalance was reflected in linear and nonlinear measures of HRV and increased SCL. Patients showed a stronger nonlinear association between SCL and heart rate than controls. HRV and SCL findings were strongly affected by group differences in breathing rate. Stronger HRV-SCL coupling in patients may suggest augmented sympathetic modulation in schizophrenia.
Abstract: Endothelial dysfunction (EF) is a central phenomenon in a variety of conditions associated with increased cardiovascular morbidity. Here, we investigated EF during acute alcohol withdrawal syndrome before and 24h after medication. We aimed to analyze microcirculation, applying the post-occlusive reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as markers of EF. Additionally, we explored whether segmentation of spectral analysis data may disclose more detailed information on dynamic blood flow behavior.
Abstract: Cardiac mortality is known to be increased in patients with major depression. Several studies have reported an imbalance within the autonomic nervous system (ANS) of patients with major depressive disorder (MDD) as one putative cause. Since a heritability of autonomic modulation was demonstrated in healthy subjects, we aimed to investigate autonomic modulation in first-degree relatives of patients with MDD to find potential autonomic imbalances.
Abstract: Recent studies revealed cardiac autonomic dysfunction in patients with acute schizophrenia, which appears to be mainly related to reduced vagal and increased sympathetic modulation. To understand the significance of cardiac autonomic function in patients with schizophrenia, we extended these studies to relatives of patients. In this study, we assessed cardiac autonomic modulation in healthy first-degree relatives of patients with schizophrenia (n = 36) to investigate a putative genetic influence. Data were compared with control subjects matched for age, gender, and physical activity as well as to patients suffering from schizophrenia. First-degree relatives showed an attenuated, yet identical pattern in autonomic dysfunction as patients with decreased vagal modulation of heart rate, decreased baroreflex sensitivity, but no difference in blood pressure variability could be detected. The patients' relatives also showed a similar pattern in regards to QT variability. In addition, the subgroup comparison of offspring vs. siblings showed a significant difference in heart rate variability suggesting a higher degree of heritability in offspring. In conclusion, the pattern of autonomic dysfunction seen in patients and relatives might indicate underlying disease-inherent genetic vulnerability, especially because autonomic parameters are heritable. In addition, these findings may be of value to identify the high-risk group of patients' relatives in regards to serious cardiovascular events so that early preventive measures can be taken.
Abstract: In addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation.
Abstract: Major depressive disorder is associated with increased cardiac mortality. A decrease in vagal modulation related to reduced heart rate variability might contribute to increased mortality among many other factors. We sought to examine the hypothesis that nortriptyline treatment will be associated with a decrease in heart rate variability and coupling between heart rate and respiration compared to treatment with S-citalopram.
Abstract: Electroconvulsive therapy (ECT) is an established treatment option for major depressive disorder when other treatments have failed. However, the underlying mechanisms responsible for these therapeutical effects are insufficiently understood to date. Furthermore, treatment outcome is difficult to predict. Recent research suggested an important role of autonomic modulation for successful treatment. We aimed to examine putative associations between autonomic modulation and response to ECT treatment and hypothesized a role for vagal modulation prior to therapy. Twenty-four patients with MDD who received ECT were assessed by means of heart rate and blood pressure variability analysis as well as baroreflex sensitivity measurements before, during and after a course of ECT. Autonomic parameters from the complete study population revealed that ECT did not significantly alter basic autonomic modulation after six sessions. Analyses showed a significant association of the reduction of HAMD scores during therapy when compared with baseline autonomic function as reflected in SDNN(RR) (p<0.004), Forbword(RR) (p<0.025) and compression entropy Hc(RR) (p<0.0003). A significant correlation was observed when overall HAMD reduction and changes of LFnu(RR) (p<0.026) or HFnu(RR) (p<0.026) during the course of therapy were analyzed. Our findings suggest that high levels of parasympathetic modulation at baseline might be associated with a beneficial effect upon ECT treatment. Adding to this, levels of parasympathetic activity seemed to increase in patients who respond to ECT treatment. Given these findings can be confirmed in future studies, autonomic modulation might be used as a predictor for therapeutic efficacy of ECT.
Abstract: Age has been identified as an independent risk factor for cardiovascular diseases. In addition, autonomic imbalance toward sympathetic preponderance has been shown to facilitate the occurrence of heart disease. Here, we aimed to assess autonomic modulation of cardiovascular parameters during normal ageing applying well-established linear and novel nonlinear parameters.
Abstract: Decreased cardiac vagal function is linked with increased cardiac mortality and depression is associated with decreased heart rate variability. We have previously shown that the Mood Induction Procedure (MIP) in healthy subjects alters pain perception and thalamic activity during pain perception.
Abstract: Increased mortality in anorexia nervosa is associated with autonomic dysfunction and prolongation of the QT interval. In this study, we examined the relative importance of repolarization abnormalities and vagal modulation of heart rate. In particular, we hypothesized that patients with anorexia nervosa show increased QT interval variability, particularly since this measure has been shown to correlate with serious cardiac arrhythmias.
Abstract: Methods from nonlinear dynamics (NLD) have shown new insights into heart rate (HR) variability changes under various physiological and pathological conditions, providing additional prognostic information and complementing traditional time- and frequency-domain analyses. In this review, some of the most prominent indices of nonlinear and fractal dynamics are summarized and their algorithmic implementations and applications in clinical trials are discussed. Several of those indices have been proven to be of diagnostic relevance or have contributed to risk stratification. In particular, techniques based on mono- and multifractal analyses and symbolic dynamics have been successfully applied to clinical studies. Further advances in HR variability analysis are expected through multidimensional and multivariate assessments. Today, the question is no longer about whether or not methods from NLD should be applied; however, it is relevant to ask which of the methods should be selected and under which basic and standardized conditions should they be applied.
Abstract: To investigate cardiac autonomic dysfunction in patients with major depressive disorder (MDD). Research in this area has faced several limitations because of the heterogeneity of the disease, the influence of medication, and methodological shortcomings.
Abstract: Information on autonomic modulation can be derived from different organs that are innervated by the sympathetic and the parasympathetic nervous system, when assessing e.g. heart rate or blood pressure fluctuations or the pupil's reaction to light. Correlations between parameters from different target organs might reveal information on hierarchically higher centres of autonomic integration. Here, we obtained parameters of heart rate variability, blood pressure variability, baroreflex function and light reaction pupillography from 50 individuals and tested the hypothesis that these are associated. Pupil diameter and constriction latency significantly correlated with parameters of heart rate variability, but not with those of blood pressure variability. In contrast, relative amplitude significantly correlated with blood pressure variability only. In conclusion, the different branches of the autonomic nervous system examined here are not associated unequivocally but show a distinct pattern of interrelations in healthy subjects. Examinations as described here might add to the diagnosis of autonomic dysfunction and reveal differential patterns in certain disease states.
Abstract: To investigate the effect of depression and medication on the autonomic nervous system (ANS) we compared 25 patients suffering from depression with 72 matched control subjects (CON). From every patient three times ECG and non-invasive blood pressure were recorded in: acute non-mediated state (T1), medicated state (T2) and clinical recovered state (T3). Cardiac autonomic regulation was evaluated by linear and nonlinear analysis methods. The results show that non-medicated depressed patients differ significantly from CON (p0.05). In the medicated state considerably high significant differences between depressed patient and CON were found (p0.0001). After an 18 months follow-up a normalization of autonomic parameters was achieved in depressed patients. These results show that depression influences autonomic parameters significantly and that medical treated clinical recovered patients approximate to healthy controls in autonomic regulation.
Abstract: Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias. We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated. In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment. This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.
Abstract: Cardiac autonomic dysregulation has been reported in patients with schizophrenia. However, there are no definite data examining whether other branches of the autonomic nervous system are compromised as well and how they interrelate with cardiac function. In this study, we tested the hypothesis that the autonomic dysregulation at the heart is reflected in the regulation of the pupillary light reflex.
Abstract: Chronic alcoholism represents a risk factor for cardiac arrhythmias. One underlying mechanism is a sympathetically dominated autonomic imbalance. This is especially apparent during acute withdrawal from alcohol. Since linear analysis of heart rate variability may not be entirely adequate to detect such autonomic dysfunction in acute alcohol withdrawal, we applied novel non-linear parameters and measures for cardio-respiratory coupling.
Abstract: Cardiovascular mortality is significantly increased in patients suffering from schizophrenia. The mechanisms currently discussed contain unhealthy lifestyle with obesity and smoking, increased incidence of diabetes, adverse pro-arrhythmic effects of antipsychotic medication and altered autonomic function. It is therefore likely that the adaptation of the heart rate to different requirements is faulty in schizophrenia. One way to detect adaptive capabilities and thus stability of regulation is to measure complexity of heart rate fluctuations, with more complex heart rate fluctuations indicating better adaptability of the underlying system.
Abstract: Heart rate variability (HRV), blood pressure variability (BPV), and the assessment of baroreflex sensitivity are widely accepted methods for analyzing and characterizing cardiovascular regulation and for an enhanced risk evaluation in different diseases. As a result of the complexity of the investigated regulatory systems, univariate analyses do not often provide a convenient description of pathological changes in the cardiovascular regulation. Therefore, the application of a multivariate approach is preferable.
