Cardiac autonomic function and vascular profile in subclinical hypothyroidism: Increased beat-to-beat QT variability.

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.

Effects of Escitalopram on Autonomic Function in Posttraumatic Stress Disorder Among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF).

OBJECTIVE: Posttraumatic stress disorder is a chronic, debilitating condition that has become a growing concern among combat veterans. Previous research suggests that posttraumatic stress disorder disrupts normal autonomic responding and may increase the risk of cardiovascular disease and mortality. Measures of heart rate variability and QT interval variability have been used extensively to characterize sympathetic and parasympathetic influences on heart rate in a variety of psychiatric populations. The objective of this study was to better understand the effects of pharmacological treatment on autonomic reactivity in posttraumatic stress disorder. DESIGN: A 12-week, Phase IV, prospective, open-label trial of escitalopram in veterans with combat-related posttraumatic stress disorder and comorbid depression. SETTING: An outpatient mental health clinic at a Veterans Affairs Medical Center. PARTICIPANTS: Eleven male veterans of Operations Enduring Freedom and Iraqi Freedom diagnosed with posttraumatic stress disorder and comorbid depression. MEASUREMENTS: Autonomic reactivity was measured by examining heart rate variability and QT interval variability. Treatment safety and efficacy were also evaluated pre- and post-treatment. RESULTS: We observed a reduction in posttraumatic stress disorder and depression symptoms from pre- to post-treatment, and escitalopram was generally well tolerated in our sample. In addition, we observed a decrease in high frequency heart rate variability and an increase in QT variability, indicating a reduction in cardiac vagal function and heightened sympathetic activation. CONCLUSION: These findings suggest that escitalopram treatment in patients with posttraumatic stress disorder and depression can trigger changes in autonomic reactivity that may adversely impact cardiovascular health.

Nonlinear indices of circadian changes in individuals with dementia and aggression.

Nonlinear analyses of actigraphy data were utilized to investigate circadian rest-activity system motor control in nursing-home residents with dementia and with/without aggressive behavior (AB). Significant differences observed between groups in measures of approximate entropy (ApEn) and fractal dimension (FD). ApEn and FD are sensitive to detecting and characterizing discrete changes in central motoric control and temporality of behaviors in dementia. Findings may inform understanding of clinical heterogeneity and possible physiologic sub-classifications of Alzheimer's dementia.

Cardio-respiratory coupling in untreated patients with major depression.

BACKGROUND: Depressive disorders are known to be associated with higher risks of cardiovascular diseases. Several studies have reported an imbalance within the autonomic nervous system (ANS) as one putative cause. Previous investigations showed decreased cardio-respiratory coupling in depressive patients that were treated with nortriptyline. We aimed to compare parameters of heart rate variability and cardio-respiratory coupling between unmedicated patients suffering from major depressive disorder (MDD) and healthy controls in order to further understand autonomic dysfunction in the disease. METHODS: We investigated eighteen unmedicated patients with major depressive disorder and eighteen matched healthy controls. Electrocardiogram and respiratory signals were obtained during a twenty minute resting period. Time- and frequency based parameters of HRV, respiratory sinus arrhythmia (RSA), approximate entropy of heart rate (ApEn(RR)) and respiratory rate (ApEn(Resp)) were calculated. Additionally, cross-ApEn between RR-intervals and respiration time series was determined, reflecting coupling of both signals. RESULTS: Patients showed an increased heart rate and LF/HF-ratio. Respiratory sinus arrhythmia (RSA) and ApEn(RR) were reduced in patients in comparison to controls. Breathing rate, ApEn(Resp) and cross-ApEn did not differ between the two groups. DISCUSSION: Increased heart rate, increased LF/HF-ratio, reduced RSA and reduced ApEn(RR) indicate a decrease of cardiac vagal modulation in depressive patients. No difference of cardio-respiratory coupling was observed. Respiratory parameters and cross-ApEn did not differ between both groups, and thus we conclude that diminished vagal modulation is mainly limited to cardiac modulation.

Nonlinear relationship between electrodermal activity and heart rate variability in patients with acute schizophrenia.

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.

Reduced cardio-respiratory coupling after treatment with nortriptyline in contrast to S-citalopram.

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.

Influence of age on linear and nonlinear measures of autonomic cardiovascular modulation.

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.

The influence of negative mood on heart rate complexity measures and baroreflex sensitivity in healthy subjects.

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.

Reduced cardio-respiratory coupling indicates suppression of vagal activity in healthy relatives of patients with schizophrenia.

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.

Psyche and soma: New insights into the connection.

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.

Heart rate variability, QT variability, and electrodermal activity during exercise.

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.

Increased QT variability in patients with anorexia nervosa--an indicator for increased cardiac mortality?

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.

Autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia.

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.

Gastric dysmotility in major depression.

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.