Decreased heart-period variability in patients with panic disorder: a study of Holter ECG records
Introduction
Patients with panic disorder experience panic attacks, which are associated with several autonomic symptoms, including chest pain, heart pounding, tachycardia and shortness of breath, that suggest autonomic dysfunction. Our previous studies on time and frequency domain measures of heart-rate (HR) variability demonstrated a decreased cardiac vagal function and an exaggerated response to pharmacological challenge with yohimbine in patients with panic disorder, compared to normal controls (Yeragani et al., 1990, Yeragani et al., 1992, Yeragani et al., 1993), suggesting a relatively higher sympathetic function. We have found that sodium lactate produces a significant decrease in cardiac vagal function and a relative increase in sympathetic function in normal controls (Yeragani et al., 1994c), findings similar to the study of George et al. (1989). Compared to controls, patients with panic disorder had an exaggerated vagal withdrawal and higher relative sympathetic activity during lactate and isoproterenol infusions (Yeragani et al., 1994b, Yeragani et al., 1995). A recent report by Kawachi et al. also suggests that higher levels of phobic anxiety are associated with low heart-rate variability (Kawachi et al., 1995).
Recent cardiovascular literature suggests that a decrease in cardiac vagal or an increase in cardiac sympathetic responsiveness is associated with an increase in cardiovascular mortality (Kleiger et al., 1987, Malik and Camm, 1990, Malliani et al., 1991, Odemuyiwa et al., 1991, Bigger et al., 1992, Myerburg et al., 1993). Bigger et al. have shown that decreased ultra-low frequency (ULF:<0.0033 Hz) and very low frequency (VLF: 0.0033–0.04 Hz) powers were independent predictors of cardiac morbidity and sudden death in patients with cardiac illness (Bigger et al., 1992). Two recent reports also suggest that reduced heart-rate variability predicts risk of sudden death in apparently healthy subjects and also in conditions other than coronary artery disease (Molgaard et al., 1991, Fei et al., 1994). This may be especially important because some studies suggest an increased risk for cardiovascular disease in panic disorder patients (Coryell et al., 1986, Weissman et al., 1990, Kawachi et al., 1994a).
Non-invasive measures of cardiac autonomic function provide valuable information about the pathophysiology of anxiety and affective disorders (Yeragani, 1995). Spectral analysis of HR or heart-period (HP) time series in normal subjects reveals a peak at 0.04–0.15 Hz (low frequency: LF), which is related to baroreceptor control, and another at 0.15–0.5 Hz (high frequency: HF), which is related to respiratory sinus arrhythmia (Koepchen, 1984, Pomeranz et al., 1985). The HF power appears to be modulated exclusively by parasympathetic activity in both postures and the LF power, dually by parasympathetic and sympathetic systems (Akselrod et al., 1981, Pomeranz et al., 1985). The ratio of LF/HF power has been used as a measure of relative sympathetic activity in some studies (Pagani et al., 1986, Pagani et al., 1991). Although ULF and VLF powers account for the majority of the total power in 24-h HP time series, the physiological mechanisms of these components are not clearly understood. However, Captopril, an ACE inhibitor, appears to increase the VLF and ULF power in patients with myocardial infarction (Bonaduce et al., 1994). Metoprolol, a beta-blocker, also enhances ULF, VLF and HF powers in patients with coronary artery disease (Niemela et al., 1994). The large portion of 24-h HP power spectrum is composed of frequencies below 0.05 Hz. These lower frequencies have also been related to temperature regulation (Sayers and Mc, 1973, Lindqvist et al., 1990) as well as the renin angiotensin system.
In this study, we investigated HP variability using Holter records in patients with panic disorder and normal controls. Ambulatory monitoring has some unique advantages which include recording of ECG in the subject's usual surroundings, availability of sleep data and a frequency resolution that includes ULF range. Based on our previous findings, we hypothesized that patients with panic disorder would have lower ULF power and higher relative LF power compared to controls.
Section snippets
Subjects
Twenty-three normal subjects [14 females and nine males; age, 35.4±10.2 years (mean±S.D.)] and 29 patients with panic disorder (18 females and 11 males; age, 35.8±7.2 years) participated in this study. This study was approved by the Institutional Review Board at the Wright State University School Of Medicine, Dayton, OH. A signed informed consent was obtained from participants. The subjects were physically healthy with no history of hypertension and their routine blood chemistry and ECG were
Results
There was no significant difference in age, height or weight between patients and controls (Table 1). The patients had significantly higher scores on anxiety measures (Table 1). There were no significant group or interaction effects for the analyses using sex as the grouping factor and ULF, VLF, LF and HF as the dependent factors. HP was also not significantly different between males and females. There was no significant difference in mean HP for the 20-h period. Total power, ULF and VLF powers
Discussion
To our knowledge, this is the first report on HP variability in patients with panic disorder using Holter records. The main findings of this study are decreased total power and absolute ULF power in patients with panic disorder. The total power and absolute and relative ULF powers in the patient group during sleep were significantly lower compared to values in controls. Bigger et al. (1992)and Huikuri et al. (1995)have reported that decreased ULF power is associated with significant
Acknowledgements
This study was in part supported by NIMH grant RO1 MH50752 to V.K.Y.
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