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Background: Some studies suggest that it is important to take the end of "T" wave to quantify QT-interval variability, which signifies cardiac repolarization lability, as there is substantial and important information beyond the peak of the T wave on the surface electrocardiogram.Methods: In this study, we examined the relationship between the variability of beat-to-beat RTe (beginning of R-peak to T-end) and the variability of RTp (R-peak to T-peak) in the following groups: normal controls (n = 26), patients with anxiety (n = 26), and patients with cardiovascular disease with or without diabetes (n = 63). We obtained ECG sampled at 1024 Hz in lead II configuration in supine posture to obtain beat-to-beat interbeat interval (R-R) and RT-interval variability for 256 seconds.Results: We found significant positive correlations (r = 0.8; P < 0.00001) in normal controls and patients with anxiety between the variability of RTeVI and RTpVI (RTe and RTp variability indices, respectively, corrected for the mean of RTe and RTp and the mean and the variance of R-R). These correlations were also statistically significant in the medically ill group but the r values were much smaller (r = 0.45 in various groups). The slopes were also significantly different between the two groups (P < 0.001). Bland-Altman plots also showed better agreement between the two measures in the controls and patients with anxiety compared to the group with cardiovascular disease.Conclusions: These findings have methodological implications for studies comparing people with and without overt cardiovascular illness. While RTe or RTp variability index may be used interchangeably in normal controls and some patients with no overt cardiovascular problems, it may be more prudent to use both RTe and RTp variability indices in patients with cardiovascular illness. These indices, especially RTeVI, may provide different information about cardiac repolarization lability. Future studies should address the importance of the relative usefulness of these two measures especially in cardiac patients before and after successful treatment. [ABSTRACT FROM AUTHOR]

Background: Congestive cardiac failure is associated with increased sympathetic activity and impaired baroreflex function. We sought to test the hypothesis that these patients also have blunted response of beat-to-beat QT interval variability during orthostatic challenge.Methods: We compared beat-to-beat heart rate and QT interval data in 17 patients with congestive cardiac failure and 17 age-matched normal controls in supine normal breathing, supine controlled breathing, and standing controlled breathing conditions. The ECG data were acquired in lead II configuration at a sampling rate of 1000 Hz.Results: Supine controlled breathing was associated with an increase in spectral HF power (0.15-0.5 Hz) of HR and QT interval time series compared to spontaneous breathing condition only in controls. While there were significant changes in HR, HR LF power, HR LF/HF ratios, and QT variability measures in standing posture in controls, there were no such changes in patients.Conclusions: This impairment of postural changes of HR variability is most likely due to an impaired baroreceptor function in patients with congestive heart failure. The etiology of this is likely due to an increased cardiac sympathetic and a decreased vagal function. However, the relationship of postural changes in beat-to-beat QT interval variability and baroreflex need further investigation. [ABSTRACT FROM AUTHOR]

Background: Patients with subclinical hypothyroidism (SH) may have higher incidence of coronary heart disease and autonomic dysfunction., Design of the Study: Prospective case control study., Aim and Objectives: To evaluate beat-to-beat QT variability and vascular stiffness in patients with SH compared to normal controls., Materials and Methods: We compared linear and nonlinear measures of cardiac repolarization liability using beat-to-beat QT intervals derived from the surface electrocardiogram during supine posture and vascular indices including pulse wave velocity and ankle-brachial index (ABI) during supine posture between female patients with SH and age- and sex-matched normal controls. Spectral analysis was done at very low frequency (LF) (0.003-0.04 Hz), Low frequency (LF) (0.04-0.15 Hz), and high frequency (HF) (0.15-0.4 Hz). The HF represents vagal regulation (parasympathetic) and LF represents both parasympathetic and sympathetic regulation., Results: We recruited 58 women with a mean age of 31.83 ± 8.9 years and 49 controls with mean age of 32.4 ± 9.9 years ( P = NS). QT variability index (QTvi) was higher in cases compared to controls ( P = 0.01). The ratio of LF/HF of R-R interval which is an index of sympathovagal tone was significantly more in cases compared to controls ( P = 0.02). The difference in the left minus the right ABI was significant between cases and controls ( P = 0.03)., Conclusions: The cases had lower parasympathetic activity as compared to controls, and there was a predominance of sympathetic activity in cases. QTvi may be an important noninvasive tool in this group of patients to study the risk of cardiovascular mortality.

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., (Copyright © 2011 Society for Psychophysiological Research.)

Objective: 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., Method: We assessed linear and nonlinear heart rate variability (HRV) parameters as well as measures of QT variability in 20 female patients with anorexia nervosa and 20 controls. In patients, parameters were correlated with serum electrolytes., Results: QT variability was significantly increased in the patient group and correlated negatively with serum potassium concentrations. HRV measures showed a shift of autonomic balance towards vagal predominance., Discussion: The increase in QT variability might at least in part account for the higher risk of cardiac arrhythmias in patients with anorexia nervosa. Once validated in a prospective study design, parameters of QT variability might serve as surrogate markers for arrhythmia risk stratification in anorexia nervosa. Supplementation with potassium might normalize QT variability abnormalities., (© 2009 by Wiley Periodicals, Inc.)

Objective: 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., Methods: Fifty-two patients suffering from major depression were included. Patients were examined unmedicated in the acute stage and after 5weeks of treatment. Twenty-six were reinvestigated after they received S-citalopram and 26, after nortriptyline. We used non-linear measures of heart rate variability and also a novel measure to examine cardio-respiratory coupling to assess cardiac vagal modulation., Results: There were significant decreases of non-linear measures of heart rate variability in the nortriptyline group in addition to reduced cardio-respiratory coupling in comparison to the group of patients that received S-citalopram. We observed a significant association between the severity of the disease and vagal withdrawal prior to treatment., Conclusions: These findings indicate that S-citalopram influences autonomic modulation on different regulatory levels to a lesser extent than nortriptyline. Our results have implications for treatment of patients with depression as some of them may already have a higher risk for cardiovascular mortality. In addition, it underlines the beneficial use of SSRIs in patients with cardiac diseases., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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.

Background: 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., Methods: Linear and nonlinear measures of heart rate variability and complexity as well as measures of QT interval variability and baroreflex sensitivity were obtained from a total of 131 healthy, medication-free participants from a continuous age range between 20 and 90 years, who were allocated to three different age groups., Results: Heart rate variability and complexity significantly decreased with age, while regularity of heart rate time series increased. In addition, QT interval variability linearly increased with age, while baroreflex sensitivity showed a pronounced decrease. Overall, concerning effects of ageing, linear and nonlinear parameters showed equal differentiation between groups., Conclusion: These data indicate a shift of autonomic balance toward sympathetic predominance in higher age groups, limiting the reactiveness of the cardiovascular system to adjust to different demands and increasing the risk for developing tachyarrhythmias.

Previous studies have observed reduced vagal modulation in patients with acute schizophrenia and their first-degree relatives, thus suggesting a genetic predisposition. To investigate vagal modulation, we analyzed the coupling between heart rate and breathing as a putative measure of central autonomic function in 19 patients, 19 of their relatives and 19 matched control subjects. The interaction of heart rate and breathing was investigated in all groups applying the non-linear parameter cross-ApEn, indicating the asynchrony between both time series. In addition, measures of the time and frequency domain of heart rate variability (HRV) were obtained. The main finding of our study is a significantly increased cross-ApEn value, indicating reduced central vagal modulation both in relatives and patients suffering from schizophrenia. Non-linear measures of HRV proved to more sensitively differentiate relatives from control subjects. Furthermore, we observed a correlation between psychopathology and breathing, indicating that positive symptoms are associated with a higher degree of regularity in the breathing pattern. Our results suggest that autonomic dysfunction previously described for patients suffering from schizophrenia is also present in first-degree relatives. This might relate to changes of brainstem activity in patients and relatives, and a common genetic background in patients and their family members can be assumed., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Various measures of autonomic function have been developed, and their applicability and significance during exercise are controversial., Methods: Physiological data were therefore obtained from 23 sport students before, during, and after exercise. Measures of R-R interval variability, QT variability index (QTvi), and electrodermal activity (EDA) were calculated. We applied an incremental protocol applying 70%, 85%, 100%, and 110% of the individual anaerobic threshold for standardized comparison., Results: Although HR increased stepwise, parasympathetic parameters such as the root mean square of successive differences were not different during exercise and do not mirror autonomic function satisfactorily. Similar results were observed with the approximate entropy of R-R intervals (ApEnRR). In contrast, the increase in sympathetic activity was well reflected in the EDA, QTvi, and ApEn of the QT interval (ApEnQT)/ApEnRR ratio., Conclusion: We suggest that linear and nonlinear parameters of R-R variability do not adequately reflect vagal modulation. Sympathetic function can be assessed by EDA, QTvi, or ApEnQT/ApEnRR ratio.

Background: Somatic symptoms of the gastrointestinal tract occur frequently in major depressive disorder (MDD) and might be associated with the known autonomic imbalance in the disease. Hence, we have investigated gastric electrical activity in patients suffering from major depression before and after treatment by means of electrogastrography (EGG) to investigate a putative association with either the disease state and its symptoms or its relation to the treatment., Methods: EGG readings before and after ingestion of a test meal of 27 patients suffering from major depression were recorded before and after treatment with antidepressants and compared with age-matched controls. Abdominal symptoms were rated by a specific Autonomic Nervous Symptom-score., Results: We found a significantly increased amount of tachygastria before and after medication, indicating increased sympathetic modulation. A significant difference was observed for the instability coefficients before and after medication, indicating gastric dysmotility in our patients prior to treatment. The elevated approximate entropy measure points to increased complexity and dysregulation. Furthermore, we have observed a correlation between subjective sensation of sweating and dry mouth with the sympathetic parameter tachygastria., Discussion: Our results suggest that major depression is associated with gastric dysrhythmia possibly caused by increased sympathetic modulation. Linear and non-linear EGG measures emphasize a possible role of the autonomic nervous system in the development of gastric symptoms. The treatment with antidepressants seems to increase the activity of the sympathetic nervous system, without aggravating gastric symptoms. The association of increased sympathetic modulation with somatic symptoms was indicated by correlation analysis with these symptoms., (Copyright 2009 Elsevier Inc. All rights reserved.)

The interaction of Psyche and Soma are well known and this interaction happens through a complex network of feedback, medication, and modulation among the central and autonomic nervous systems, the endocrine system, the immune system, and the stress system. These systems, which were previously considered pristinely independent, in fact, interact at myriad levels. Psychoneuroimmunology (PNI) is an emerging discipline that focuses on various interactions among these body systems and provides the underpinnings of a scientific explanation for what is commonly referred to as the mind-body connection. This article reviews the relevant literature with an emphasis on Indian research.

Background: 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., Aim: To study the effect of negative emotion on heart rate variability and complexity measures as well as on baroreceptor sensitivity, as these parameters reflect cardiac autonomic function., Patients and Methods: We studied 20 healthy female controls before and after neutral MIP and 20 healthy female subjects before and after negative MIP. We investigated measures of valence of mood, heart rate variability and complexity and the baroreceptor sensitivity index., Results: While there was a significant difference in the valence of mood between the neutral and the negative effect condition, there were no significant differences in any of the heart rate or baroreceptor sensitivity measures between the two groups., Conclusions: Our findings did not show any significant influence of acute negative MIP on heart rate variability and complexity measures and baroreceptor sensitivity, even though depressive disorder and stress are associated with decreased heart rate variability. These findings are discussed in the context of clinical depression and anxiety and the increased risk for cardiac mortality. In contrast to the presented results here, we have previously shown that MIP in healthy subjects alters pain perception and thalamic activity.

Recent studies applying functional magnetic resonance imaging have focused on the description of cerebral substrates of changes in cardiac function during diverse autonomic maneuvers or stressful cognitive tasks. These studies might be limited by the indistinguishable neuronal activity due to cognitive processes, which are known to influence autonomic function, and the 'baseline' activity in the central autonomic network. We therefore investigated 26 healthy volunteers in the magnetic resonance scanner to simultaneously obtain functional brain images and RR intervals (intervals between ventricular depolarizations) of the high-resolution electrocardiogram. The mean RR interval length within each functional scan was computed, which was finally convolved with the canonical hemodynamic response function to obtain a regressor for the functional time series. The resulting individual contrast image indicated a positive covariation of the blood oxygen level-dependent signal and RR interval length in the ventromedial prefrontal cortex (vmPFC). Furthermore, a reduced mean cross-approximate entropy value was shown for the interaction between the vmPFC and individual RR intervals. This suggests reduced asynchrony between the heart rate and vmPFC activity in contrast to other brain areas. Our findings confirm data obtained in animals describing the vmPFC as an important forebrain structure of the central autonomic network and an influence of the vmPFC in the cortical generation of efferent vagal activity. This finding needs to be investigated in diseases with known suppression of efferent vagal modulation.

Cardiac autonomic dysfunction has been reported in patients suffering from schizophrenia. The aim of the present study was to evaluate gastric electrical activity in unmedicated patients suffering from acute schizophrenia in relation to their symptoms. Electrogastrography was performed before and after test meal ingestion in 26 patients suffering from schizophrenia and 26 matched controls. The non-linear measure approximate entropy (ApEn) was calculated for the first time from the obtained signal in addition to standardized measures. Results were correlated with the scales for the assessment of positive symptoms and negative symptoms. In addition, autonomic and abdominal symptoms were assessed by the autonomic symptom score. We found a significantly increased amount of tachygastria and arrhythmia within the signal of the activity of the gastric pacemaker before and after test meal digestion in patients compared to controls, indicating increased sympathetic modulation within the enteric nervous system. A significant difference was observed for slow wave, which represents the dominant frequency of gastric pacemaker activity, indicating gastric dysmotility in our patients. The elevated ApEn measure points to increased complexity and dysregulation. In addition, we have observed a correlation between delusions and tachygastria. Sympathetic function seems to be altered in the enteric nervous system of patients suffering from schizophrenia. Future studies need to explore the influence of the disease on different branches of the autonomic nervous system and clinical consequences of enteric dysfunction. Our findings point to a possible systemic autonomic imbalance that needs to be studied in respect to the neurobiology of schizophrenia.

Introduction: Though increased risk of sudden death in patients with schizophrenia is well-documented, the mechanisms remain unclear. Recent studies report two known risk factors for sudden cardiac death and other arrhythmias in schizophrenia, i.e., decreased RR interval variability (RRV) and increased QT interval variability (QTV). However, these studies did not control for the effects of medication. Herein, we report the results of our study comparing RRV and QTV in first episode neuroleptic-naive psychosis patients with healthy matched controls., Methods: 24 patients with first episode neuroleptic naïve psychosis were matched with 26 healthy controls on age and gender. After an overnight fast, all participants underwent an electrocardiogram recording in the morning., Results: In comparison with matched controls, patients with first episode neuroleptic-naïve psychosis had significantly increased QTV corrected for RRV, and decreased RRV., Conclusions: The observed alterations in RRV and QTV may reflect impaired cardiac autonomic function that could underlie risk for abnormal ventricular repolarization and thereby increase the risk of sudden death and other arrhythmias. Our data suggest that RRV and QTV alterations may be independent of medication effects in first episode psychosis patients.

Altered amygdala activity in patients with schizophrenia can influence respiratory patterns and consequently cardiovascular parameters. Hence, we examined respiration and heart rate time series complexity as well as coupling of both signals. Electrocardiograms and respiratory signals were obtained from 25 unmedicated patients with schizophrenia and controls. Approximate entropy (ApEn) was calculated for heart and respiratory rates as well as cross-ApEn reflecting coupling of both signals. Coupling was decreased indicating diminished vagal modulation at the brain stem level. Regularity of breathing correlated with disease severity. These data might reflect a lack of inhibitory control over brainstem centers in schizophrenia.

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.

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.

Background: 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., Methods: 20 patients suffering from acute alcohol withdrawal syndrome and 20 controls were included. For patients, heart rate and respiration were recorded on admission, after medication and at discharge. From these data, complexity measures (symbolic dynamics, approximate entropy) of heart rate modulation and respiration as well as parameters for cardio-respiratory coupling (coherence, cross-approximate entropy) which relate to vagal function were calculated., Results: Heart rate modulation was significantly less complex in patients acutely admitted for alcohol withdrawal. Furthermore, coupling between beat-to-beat (RR) intervals and respiration time series was significantly diminished. Of the parameters assessed, cross-approximate entropy showed a trend for correlation with symptom severity., Conclusion: These data indicate diminished vagal function in acute alcohol withdrawal. Applying the methods described thus allows a sensitive detection of vagal neuropathy in this disease.

Objective: 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., Methods: We assessed heart rate variability and baroreflex sensitivity parameters as well as pupillographic measures in 28 unmedicated patients with schizophrenia and compared these measures to those of 28 controls. In addition, cardiovascular and pupillographic parameters were correlated in both groups., Results: The obtained cardiovascular parameters indicated decreased parasympathetic modulation. Patients showed a significantly increased resting pupil diameter as well as reduced relative amplitude, suggesting a dominance of sympathetic control and a lack of parasympathetic modulation at the pupil. Intriguingly, the parasympathetic latency of the pupil constriction was similar in both groups and correlated with several cardiovascular parameters. These correlations were in the opposite direction in patients compared to controls. Furthermore, shorter latencies of the pupil constriction were associated with symptom severity in patients., Conclusions: Overall, we found evidence for an autonomic dysregulation at the pupil and heart in patients with schizophrenia. Future studies are warranted to describe this complex interaction at different levels of the autonomic system., Significance: The interrelationship of both the systems indicates that the autonomic dysfunction affects the regulation in different branches of the autonomic network as well as their interaction in schizophrenia.

Background: Depressed patients frequently complain about vegetative symptoms. The aim of the present study was to evaluate gastric electrical activity in patients suffering from major depression in relation to their symptoms., Methods: Electrogastrography (EGG) was performed before and after a test meal ingestion in 21 patients suffering from major depression and control subjects. A structured interview was used to assess the severity of clinical as well as abdominal symptoms., Results: Patients presented with significantly elevated proportions of tachygastria. Significant differences were found for the parameter arrhythmia, the coefficient of dominant frequency and slow wave after the test meal ingestion. A positive correlation was found between tachygastria and ANS score as well as tachygastria and the item "sweating"., Limitations: Further studies are warranted to include more patients and to investigate interaction with specific antidepressive drugs., Discussion: This is the first study demonstrating an increased amount of tachygastria in patients suffering from major depression which might be caused by increased sympathetic modulation. The correlation of tachygastria with the amount of gastric symptoms underlines the clinical significance of this finding.

Objectives: Cardiac mortality is known to be increased in depressive patients. However, the underlying mechanisms remain elusive to date. Decreased heart rate variability (HRV) has been discussed as contributing to increased cardiac mortality, but studies examining patients suffering from major depressive disorder (MDD) have revealed inconsistent results. This study aimed to investigate long-term and broad band parameters of heart rate regulation in MDD, which have been shown to be more sensitive for the assessment of autonomic dysfunction., Methods: A total of 18 non-medicated patients suffering from MDD and 18 matched control subjects without cardiac disease were recruited and 24-h ambulatory electrocardiograms were recorded. Data were recorded during three distinct time intervals linear and nonlinear parameters as well as autonomic information flow (AIF) were calculated., Results: The power law slope was significantly reduced in the patient group for all intervals investigated and correlated with symptom severity, whereas standard deviation of the 5-min NN intervals (SDANN) and area under the AIF curve (INT(NN)) showed significant differences between groups in the morning hours only. Analysis of standard HRV parameters in the time and frequency domain revealed no significant differences between groups., Conclusions: The evidence for decreased complexity of cardiac regulation in depressed patients presented here might be useful as an indicator of the increased cardiac mortality known in depression, especially since these parameters are capable of predicting cardiac mortality in other diseases. The importance of these parameters for patients at risk should be evaluated in future prospective studies.

Patients with schizophrenia have been reported to experience sudden cardiac death 3 times more likely than individuals from the general population. One important factor related to an increased risk of cardiac arrhythmias and sudden death is the prolongation of the QTc interval. This study examined whether acute psychosis might influence the beat-to-beat variability of the QT interval, which reflects effectively cardiac repolarization lability. High resolution electrocardiographic recordings were performed in 25 unmedicated patients suffering from acute schizophrenia and matched controls. From these, parameters of beat-to-beat heart rate and QT variability measures such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the scale for the assessment of positive symptoms (SAPS) and negative symptoms (SANS). QTvi was significantly higher in patients with schizophrenia compared to controls. While QTvi correlated with the degree of delusions and hallucinations, no correlation with electrolyte concentrations was found. Approximate entropy of heart rate was decreased indicating reduced complexity and decreased vagal tone. In conclusion, increased QT variability in patients with schizophrenia indicates abnormal cardiac repolarization lability, which can result in serious cardiac arrhythmias. The correlation of positive symptoms with QT variability might indicate high sympathetic cardiac activity in these patients, which might be associated with increased cardiovascular mortality.

Objective: 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., Methods: We calculated novel non-linear measures for beat-to-beat interval complexity from short-term ECG recordings in 20 unmedicated patients suffering from acute schizophrenia and compared them to those obtained from matched controls., Results: Data from all mathematical models applied, i.e. joint symbolic dynamics, compression entropy, fractal dimension and approximate entropy, revealed significantly reduced complexity of heart rate time series in acute schizophrenia. When using heart rate as a covariate, only fractal dimension remained significantly altered, thus appearing to be a relatively more important heart rate independent parameter., Conclusions: Complexity of heart rate modulation is significantly reduced in acute, untreated schizophrenia, thus indicating an increased risk for cardiovascular events in these patients., Significance: These data might eventually add to the currently discussed monitoring of physical health in patients with schizophrenia, possibly providing a promising tool for cardio-arrhythmic risk stratification.

Objective: Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal., Methods: High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations., Results: Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations., Conclusion: Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.

Decreased vagal activity has been described in acute schizophrenia and might be associated with altered cardiovascular regulation and increased cardiac mortality. The aim of this study was to assess baroreflex sensitivity in the context of psychopathology. Twenty-one acute, psychotic, unmedicated patients with a diagnosis of paranoid schizophrenia were investigated after admission to the hospital. Results were compared with 21 healthy volunteers matched with respect to age and sex. Cardiovascular parameters obtained included measures for heart rate variability, baroreflex sensitivity, as well as cardiac output, left ventricular work index, and total peripheral resistance. All parameters investigated were analyzed using linear and novel nonlinear techniques. Positive and negative symptoms were assessed to estimate the impact of psychopathology on autonomic parameters. Subjects with acute schizophrenia showed reduction of baroreflex sensitivity accompanied by tachycardia and greatly increased left ventricular work index. Nonlinear parameters of baroreflex sensitivity correlated with positive symptoms. For heart rate variability, mainly parameters indicating parasympathetic modulation were decreased. Vascular pathology could be excluded as a confounding factor. These results reflect a dysfunctional cardiovascular regulation in acute schizophrenic patients at rest. The changes are similar to adaptational regulatory processes following stressful mental or physical tasks in healthy subjects. This study suggests that hyperarousal in acute schizophrenia is accompanied by decreased efferent vagal activity, thus increasing the risk for cardiovascular mortality. Future studies are warranted to examine the role of the sympathetic system and possible autonomic differences in hyperarousal induced by anxiety and/or external stressful events.

Background: Anxiety symptoms are associated with a marked increase in sudden cardiac death, suggesting an abnormality in cardiac autonomic function. Our previous studies show a relationship between R amplitude variability and sympathetic function., Methods: We examined the effects of beta-adrenergic stimulation on R and T amplitude variability in panic disorder patients by infusing the beta-adrenergic agonist isoproterenol in 6 panic disorder patients and 11 normal subjects. The ECG signal was analyzed before the infusion and 5 min after the infusion was started. The outcome measures were the R and T detrended variance normalized for mean amplitudes (R(vm) and T(vm)) and the R(vi) and T(vi), measures which are normalized for the inter-beat interval variability in addition., Results: Patients with panic disorder had significantly more variability in R and T amplitude than normal controls and the R amplitude variability was increased further by beta-adrenergic stimulation with isoproterenol, which was more pronounced in the patients., Conclusions: The isoproterenol-associated increase in R amplitude variability occurred in controls in the absence of significant anxiety. However, the increase in R amplitude variability was greater in patients with panic disorder, suggesting a greater sensitivity to beta-adrenergic effects of isoproterenol or to isoproterenol-induced anxiety., ((c) 2007 S. Karger AG, Basel.)

Objective: This study aimed to further investigate autonomic function in schizophrenic patients using long-term electrocardiographic (ECG) recordings., Methods: Twenty unmedicated patients suffering from an acute episode of paranoid schizophrenia and 20 matched control subjects were recruited and 24-h ambulatory electrocardiograms were recorded. In order to investigate complexity of heart rate fluctuations related to different physiological time scales, linear heart rate variability (HRV) as well as autonomic information flow (AIF) parameters were calculated from day and night time intervals., Results: While heart rates were increased, root mean successive square difference (RMSSD), a measure for vagal function as well as standard deviation of 5-min mean NN-intervals (SDANN), reflecting parasympathetic and sympathetic tone, were decreased in schizophrenia. Furthermore, a decrease of vagal information flow was apparent during night time (decreased mean high frequency peak decay (PD(mHF))). In addition, increased INT(NN) (area under the AIF curve) as well as decreased beat decay (BD(NN)) and mean very low frequency PD (PD(mVLF)) indicated reduced complexity in patients during day and night time., Conclusions: HRV and AIF parameters indicate altered diurnal autonomic variation in schizophrenia., Significance: Reduced vagal modulation and loss of complexity might both contribute to the increased risk for sudden cardiac death in schizophrenia.

Objectives: Several psychiatric conditions are associated with frequent fluctuations of affect. In this study, we propose a new technique to uniformly score depression and mania objectively and use a new mathematical technique to model the frequent fluctuations in mood using simulated data. Our main aim is to examine the usefulness of this measure for evaluating treatment effects or course of illness, especially in bipolar or unipolar affective illness to quantify mood fluctuations., Methods: We use a prototypical model, which takes into account the mean, the standard deviation (SD) and the coefficient of variation (CV = SD*100/mean) of the mood scores of the subjects over a user-defined period. We utilize simulated data of subjects for euthymia, minor depression, minor mania, severe depression, severe mania and cyclic bipolar illness (manic depression, MDP). We propose an objective method to quantify the mood of the subjects at weekly intervals (the interval can be user-defined) using a scale of 1-9 (1-4 = degrees of depression, 5 = euthymia, 6-9 = degrees of mania). These scores can be sampled according to the convenience and feasibility of the measurements, which can be derived from various clinical scales or by observation of the subjects in hospitals or other environments. We derive a new mathematical technique to arrive at a normalized measure for each of these conditions of simulated data in addition to the mean, SD and approximate entropy (ApEn)., Results: We utilize three sets of data, one to train the model to classify the condition of the subjects and the other two to test the reliability of the technique. We are able to successfully classify the condition of the subjects over a 52-timepoint period (length can be days or weeks depending upon the sampling rate). The New Index (NI) correlates significantly only with the mean (r(2) = 0.78), but not with the SD or ApEn score., Conclusions: These results indicate that it may be beneficial to reduce data according to the techniques we propose so that there is greater uniformity within which to compare future studies to evaluate treatment effects, not only in rapid-cycling MDP but also in other affective disorders. This method may be suitable for the meta-analysis of several studies, although different scales have been used in each of those studies. Our measure derived from simulated data has shown sufficient deviation of all the abnormal states from the euthymic state. The advantages and pitfalls of these techniques are further discussed to evaluate affect in various disorders. However, future prospective studies must address the importance of this measure in comparison with mean, SD and ApEn scores or other nonlinear measures of these time series. We are evaluating other nonlinear dynamic models, which may provide a continuous measure with which to identify different degrees of fluctuation of mood.

Decreased vagal function is associated with vascular dysfunction. In this study, we compared vascular indices and correlated heart rate and QT variability measures with vascular indices in patients with anxiety disorders and normal controls. We compared age- and sex-matched controls (n=23) and patients with anxiety (n=25) using the Vascular Profiler (VP-1000; Colin Medical Instruments, Japan), approved by the US Food and Drug Administration. Using this machine, we obtained ankle and brachial blood pressure (BP) in both arms (brachial), both legs (ankle), and carotid artery, and lead I electrocardiogram (ECG) and phonocardiogram. Using these signals, pulse-wave velocity (PWV), and arterial stiffness index % and preejection period can be calculated. We also obtained ECG sampled at 1000 Hz in lead II configuration in supine posture to obtain beat-to-beat interbeat interval (R-R) and QT interval variability for 256 s. Patients with anxiety had significantly higher carotid mean arterial pressure (MAP) %, brachial-ankle PWV (BAPWV), arterial stiffness index %, MAP, and diastolic BP of the extremities compared to controls. We found significant negative correlations (r values from .4 to .65; P<.05 to .007) between R-R interval high-frequency (0.15-0.5 Hz) power (which is an indicator of cardiac vagal function), and increased BAPWV and systolic BP of the extremities only in patients. We were unable to find such correlations in controls. We also found significant positive correlations between QT variability index (a probable indicator of cardiac sympathetic function) and MAP of the extremities and BAPWV only in the patient group. These findings suggest an important association between decreased vagal and increased sympathetic function, and decreased arterial compliance and possible atherosclerotic changes and increased BP in patients with anxiety.