Major depression with ischemic heart disease: Effects of paroxetine and nortriptyline on long-term heart rate variability measures

Background: Studies have linked depression to sudden death and serious cardiovascular events in patients with preexisting cardiac illness. Recent studies have shown decreased vagal function in cardiac patients with depression and depressed patients without cardiac illness. Methods: We compared 20-hour, sleeping, and awake heart period variability measures using spectral analysis, fractal dimension, and symbolic dynamics in two patient groups with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of paroxetine or nortriptyline treatment. Results: Spectral measures showed decreases in awake and sleeping total power (TP: 0.0-0.5 Hz), ultra low frequency power (ULF: 0-0.0033 Hz), very low frequency power (VLF: 0.0033-0.04 Hz), and low-frequency power (LF: 0.04-0.15 Hz) for nortriptyline condition and a decrease in high-frequency power (HF: 0.15-0.5 Hz) for the awake condition in patients who received nortriptyline. A measure of nonlinear complexity, WC-100, significantly increased after paroxetine during the awake condition. Conclusions: These findings suggest that nortriptyline has stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Paroxetine may have some cardio-protective effects, especially in cardiac patients

Major depression with ischemic heart disease: Effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate

Depression is associated with increased cardiovascular mortality in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate variability (HRV) or heart period variability has been linked to sudden death in patients with cardiac disease as well as in normal controls. Recent studies have shown decreased vagal function in cardiac patients with depression as well as in depressed patients without cardiac illness. In this study, we compared 20 h awake and sleep heart period nonlinear measures using quantification of nonlinearity and chaos in two groups of patients with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of treatment with paroxetine or nortriptyline. Patients received paroxetine, 20-30 mg/day or nortriptyline targeted to 190-570 nmol/l for 6 weeks. For HRV analysis, 24 patients were included in the paroxetine treatment study and 20 patients in the nortriptyline study who had at least 20,000 s of awake data. The ages of these groups were 60.4 +/- 10.5 years for paroxetine and 60.8 +/- 13.4 years for nortriptyline. There was a significant decrease in the largest Lyapunov exponent (LLE) after treatment with nortriptyline but not paroxetine. There were also significant decreases in nonlinearity scores on S-netPR and S-netGS after nortriptyline, which may be due to a decrease in cardiac vagal modulation of HRV. S-netGS and awake LLE were the most significant variables that contributed to the discrimination of postparoxetine and postnortriptyline groups even with the inclusion of time and frequency domain measures. These findings suggest that nortriptyline decreases the measures of chaos probably through its stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Nortriptyline was also associated with a significant decrease in nonlinearity scores, which may be due to anticholinergic and/or sympatholytic effects. As depression is associated with a strong risk factor for cardiovascular mortality, one should be careful about using any drug that adversely affects cardiac vagal function. Copyright (C) 2002 S. Karger AG, Basel

Twenty-four-hour QT interval variability: Increased QT variability during sleep in patients with panic disorder

Recent studies on beat-to-beat QT interval variability (QTV) have shown that it can be used as a noninvasive measure of cardiac repolarization lability. It is also a predictor of sudden cardiac death and is higher in patients with anxiety and depression. This study examined the diurnal measures in QTV in 32 normal adults and 22 patients using 24-hour electrocardiogram records. We obtained 8 5-min segments of ECG sampled at 1,000 Hz from the 24-hour records. Our results show that QTV measures at nighttime are significantly higher in patients with panic disorder compared with controls. These findings demonstrate blunted diurnal changes in ventricular repolarization lability in patients resulting in a higher QT variability index during sleep. We speculate that these effects may relate to a relative increase in cardiac sympathetic activity in patients with panic disorder, and may contribute to the increased risk for cardiac mortality in patients with anxiety. Copyright (C) 2002 S. Karger AG, Basel

Heart rate time series: decreased chaos after intravenous lactate and increased non-linearity after isoproterenol in normal subjects

In this study, we reanalyzed our previous heart rate time series data on the effects of intravenous sodium lactate (ns9) and intravenous isoproterenol (ns11) using non-linear techniques. Our prior findings of significantly higher baseline non-linear scores (NL: S ) and significantly lower largest Lyapunov exponents in supine posture in netGS patients with panic disorder compared to control subjects prompted this study. We obtained the largest Lyapunov exponent (LLE), and a measure of non-linearity (NL: S ) of heart rate time series. LLE quantifies predictability netGS and NL quantifies the deviation from linear processes. There was a significant increase in NL score, (S ) after netGS isoproterenol infusions and a significant decrease in LLE (an increase in predictability indicating decreased chaos ), after intravenous lactate in supine posture in normal control subjects. Increased NL scores in supine posture after intravenous isoproterenol may be due to a relative increase in cardiac sympathetic activity or a decrease in vagal activity at least in certain circumstances, and an overall decrease in LLE may indicate an impaired cardiac autonomic flexibility after intravenous sodium lactate, as LLE is diminished by autonomic blockade by atropine. Band analysis of LLE (LFyHF )( LF: 0.04 – 0.15 Hz and HF: 0.15 – 0.5 Hz) showed an increase of these ratios during either condition with a higher sympathovagal interaction after the drug administration. These findings may throw new light on the association of anxiety and significant cardiovascular events. 2002 Elsevier Science Ireland Ltd. All rights reserved

Platelet Serotonin Transporter Function and Heart Rate Variability in Patients with Panic Disorder

Many studies showed abnormal serotonin transporter (5-HTT) function and heart rate variability (HRV) in panic disorder patients. The present study investigated the relationship between HRV power spectral analysis findings and platelet serotonin uptake in panic disorder patients. Short-term HRV over 5 min and platelet serotonin transporter uptake parameters (Vmax and Km) were measured both in 45 patients with panic disorder and in 30 age-matched normal healthy control subjects. Low frequency power (LF) normalized unit (nu) and LF/high frequency power (HF) were significantly higher, whereas HF and HF nu were lower in the patient group than in the control group. Vmax and Km were all significantly lower (i.e., reflects decreased 5-HTT function) in patients with panic disorder than in normal controls. In the patient group, Km was negatively correlated with LF/HF and LF nu whereas no such correlations between them were found in the control group. By multivariate analysis based on multiple hierarchical linear regression, a low Km independently predicted an increased LF nu even after controlling for age, sex, and body mass index in the patient group. These results suggest that impaired 5-HTT function is closely related to dysregulation of autonomic nervous system in panic disorder

The pNNx Heart Rate Variability Statistics: An Application to Neuroautonomic Dysfunction of Clozapine-Treated Subjects

Objective The percentage Of Successive normal cardiac interbeat intervals greater than 50 msec (pNN50) is a widely used heart rate variability measure, which is useful in identifying the neuroautonomic dysfunction of psychiatric disorders. However, pNN50 is only one member of a larger family of pNNx statistics, where x is greater than 0 msec. The potential application of the general pNNx statistics has not yet been explored in the psychiatric field. The authors examined the pNNx statistics in clozapine-treated subjects and normal controls to evaluate the usefulness of the general pNNx statistics. Methods Sixty-one schizophrenic patients treated with clozapine and fifty-nine normal controls were evaluated. probability values for the differences between the groups at each pNN value (range: pNN1-pNN100) were calculated using data obtained from a 30-minute electrocardiogram. Results The conventional pNN50 and pNNx values with x<50 msec were all significantly lower in the patient group (p<0.05). The distinction between the two groups was more prominent at pNN values less than 50 msec than that observed at pNN50. The maximum separation between groups occurred at pNN5 (68.2 +/- 19.1 vs 22.5 +/- 20.5, p<10(-22)). Conclusion The pNNx with x<50 msec provided more robust discrimination between the groups than the conventional pNN50, suggesting the importance of analyzing very small variations of interbeat interval in discriminating normal and pathological heart rate patterns. The results also Suggest that the general pNNx statistics may be applied and useful in evaluating the neuroautonomic dysfunction in patients treated with clozapine, complementing the traditionally Computed pNN50 value. Psychiatry Invest 2009;6:294-298This study was supported in part by the Brain Korea 21 project for Medicine, Dentistry, and Pharmacy (Seoul National University) and by Grant No. 04-2006-0540 from Seoul National University Hospital.Duschek S, 2009, HYPERTENS RES, V32, P938, DOI 10.1038/hr.2009.115Lollgen D, 2009, MUSCLE NERVE, V39, P536, DOI 10.1002/mus.21242Siepmann M, 2008, APPL PSYCHOPHYS BIOF, V33, P195, DOI 10.1007/s10484-008-9064-zBar KB, 2008, J CLIN PSYCHOPHARM, V28, P694, DOI 10.1097/JCP.0b013e31818a6d25Bar KJ, 2008, PSYCHIAT RES, V157, P255, DOI 10.1016/j.psychres.2007.04.021Bar KJ, 2007, CLIN NEUROPHYSIOL, V118, P2009, DOI 10.1016/j.clinph.2007.06.012Bar KJ, 2007, SCHIZOPHR RES, V95, P115, DOI 10.1016/j.schres.2007.05.034Kim JH, 2006, EUR NEUROPSYCHOPHARM, V16, P459, DOI 10.1016/j.euroneuro.2005.11.003Mujica-Parodi LR, 2005, NEUROPSYCHOBIOLOGY, V51, P10, DOI 10.1159/000082850KIM W, 2005, J KOREAN NEUROPSYCHI, V44, P176Tank J, 2004, HYPERTENSION, V43, P1035, DOI 10.1161/01.HYP.0000125729.90521.94Kim JH, 2004, PROG NEURO-PSYCHOPH, V28, P371, DOI 10.1016/j.pnpbp.2003.11.007Mueck-Weymann M, 2004, CLIN AUTON RES, V14, P15, DOI 10.1007/s10286-004-0123-0Yeragani VK, 2003, PSYCHIAT RES, V121, P185, DOI 10.1016/S0165-1781(03)00235-XAgelink MW, 2003, PHARMACOPSYCHIATRY, V36, P166Mietus JE, 2002, HEART, V88, P378Yeragani VK, 2002, BIOL PSYCHIAT, V52, P418Eschweiler GW, 2002, PHARMACOPSYCHIATRY, V35, P96Goldberger AL, 2002, P NATL ACAD SCI USA, V99, P2466, DOI 10.1073/pnas.012579499Ansakorpi H, 2002, J NEUROL NEUROSUR PS, V72, P26MALASPINA D, 2002, CNS SPECTRUMS, V7, P53Mueck-Weymann M, 2002, DEPRESS ANXIETY, V16, P93, DOI 10.1002/da.10037Cohen H, 2001, BRIT J PSYCHIAT, V179, P167Haapaniemi TH, 2001, J NEUROL NEUROSUR PS, V70, P305Cohen H, 2001, CLIN NEUROPHARMACOL, V24, P106Agelink MW, 2001, J CLIN PSYCHOPHARM, V21, P8Toichi M, 1999, INT J PSYCHOPHYSIOL, V31, P147Malaspina D, 1997, BIOL PSYCHIAT, V41, P612Korpelainen JT, 1996, STROKE, V27, P2059HALL RCW, 1995, PSYCHOSOMATICS, V36, P267RECHLIN T, 1994, BIOL PSYCHIAT, V35, P888*AM PSYCH ASS, 1994, DIAGN STAT MAN MENT, P273HUIKURI HV, 1990, AM J CARDIOL, V65, P391BIGGER JT, 1988, AM J CARDIOL, V61, P208KAY SR, 1987, SCHIZOPHRENIA BULL, V13, P261EWING DJ, 1984, BRIT HEART J, V52, P396GUY W, 1976, ECDEU ASSESSMENT PSY

Effects of Aesthetic Chills on a Cardiac Signature of Emotionality

Previous studies have shown that a cardiac signature of emotionality (referred to as EK, which can be computed from the standard 12 lead electrocardiogram, ECG), predicts inter-individual differences in the tendency to experience and express positive emotion. Here, we investigated whether EK values can be transiently modulated during stimulation with participant-selected music pieces and film scenes that elicit strongly positive emotion. The phenomenon of aesthetic chills, as indicated by measurable piloerection on the forearm, was used to accurately locate moments of peak emotional responses during stimulation. From 58 healthy participants, continuous EK values, heart rate, and respiratory frequency were recorded during stimulation with film scenes and music pieces, and were related to the aesthetic chills. EK values, as well as heart rate, increased significantly during moments of peak positive emotion accompanied by piloerection. These results are the first to provide evidence for an influence of momentary psychological state on a cardiac signature of emotional personality (as reflected in EK values). The possibility to modulate ECG amplitude signatures via stimulation with emotionally significant music pieces and film scenes opens up new perspectives for the use of emotional peak experiences in the therapy of disorders characterized by flattened emotionality, such as depression or schizoid personality disorder

Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis

Background: Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis.Method: Studies comparing resting state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis. Results: Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterised by lower HRV (high frequency: Hedges’ g = -.29. 95%CI: -.41 to -.17, p < 0.001; time domain: Hedges’ g = -0.45, 95%CI: -0.57 to -0.33, p < .001) than controls. Panic Disorder (n=447), Post-Traumatic Stress Disorder (n=192), Generalized Anxiety Disorder (n=68), and Social anxiety disorder (n=90), but not Obsessive Compulsive Disorder (n=40), displayed reductions in high frequency HRV relative to controls (all ps < .001). Conclusions: Anxiety disorders are associated with reduced HRV, findings associated with a small to moderate effect size. Findings have important implications for future physical health and wellbeing of patients, highlighting a need for comprehensive cardiovascular risk reduction