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.

Heart rate and QT variability in children with anxiety disorders: a preliminary report.

This study compared beat-to-beat heart rate and QT variability in children with anxiety disorders (n = 7) and normal controls (n = 15) by using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with a higher risk for sudden cardiac death. A decrease in heart rate variability is also linked to significant cardiovascular events. Supine detrended QT variability, QT variability corrected for mean QT interval, and QTvi (a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) were significantly higher in children with anxiety compared to controls (P < 0.05). The largest Lyapunov Exponent (LLE) of heart rate time series was significantly lower (P < 0.05) in children with anxiety compared to controls. These findings suggest a relative increase in sympathetic activity and a relative decrease in cardiac vagal activity in children with anxiety disorders, and are discussed in the context of the effects of tricyclics on cardiac autonomic function in children, and the rare occurrence of sudden death during tricyclic antidepressant treatment.

Nonlinear measures of heart period variability: decreased measures of symbolic dynamics in patients with panic disorder.

Time series of heart period are not linear and recent studies illustrated the importance of using nonlinear methods to quantify the complexity of these time series. We compared different techniques to quantify the nonlinear complexity of these time series in patients with panic disorder and normal controls and correlated these measures with spectral powers in different bands of interest. Twenty-four hour ECG was recorded in 23 normal controls and 29 patients with panic disorder by using Holter records. Time series of heart period were analyzed by using approximate entropies, slopes of 1/f scaling, two algorithms to calculate fractal dimension, and word sequences using symbolic dynamics. Measures using symbolic dynamics, especially word count (WC-100), showed highly significant differences between the two groups similar to some of the frequency domain (spectral) measures, while the other techniques were relatively ineffective to distinguish between the two groups. Different nonlinear techniques may relate to different aspects of nonlinear complexity of the time series. These nonlinear techniques were also not uniform in showing the differences between awake and sleep periods. Some correlate with the measures of respiratory sinus arrhythmia and some measures obtained from symbolic dynamics may reflect not only the nonlinear complexity of the time series but also the total variability in the 24 hr HP time series, especially power in the ultra-low frequency band (< 0.0033 Hz). However, word count (WC-100) had only weak correlations with other measures and discriminated best between the two groups and showed that this nonlinear measure was of additional value to the linear measures in classifying the two groups.

Effect of age on QT variability.

Heart rate variability is influenced significantly by age. Recent studies have shown the utility of QT variability to study temporal repolarization lability, and increased QT variability is reportedly associated with sudden death. Because beat-to-beat QT interval variability appears to closely follow heart rate variability, this study investigated the relationship between age and QT variability. We obtained QT variability measures in 34 adults (22-55 years of age) and 15 children (6-14 years of age) using a novel algorithm to compute beat-to-beat QT intervals. QT variability corrected for mean QT interval was significantly inversely correlated with age. Coherence in the band of 0 to 0.5 Hz and high-frequency coherence (0.15-0.5 Hz) were also significantly inversely correlated with age. QTvi (QT variability corrected for mean QT interval over heart rate variability corrected for mean heart rate) was not significantly related to age in supine posture during spontaneous or controlled breathing, whereas there was a modest negative relationship in standing posture. These findings suggest that coherence between QT and heart rate time series appears to be modulated by cardiac vagal activity.

Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder.

This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function.

Effect of posture and isoproterenol on beat-to-beat heart rate and QT variability.

RATIONALE: Recent literature emphasizes the utility of QT variability to study ventricular electrophysiologic function. In this investigation, we sought to test the hypothesis that beat-to-beat fluctuations in QT intervals are mediated by sympathetic activity in normal subjects using postural challenge and isoproterenol infusions. SUBJECTS AND METHODS: We obtained ECG in the supine and standing postures during spontaneous breathing, at 12, 15 and 20 per minute controlled breathing (n = 19), and before and after infusions of isoproterenol, a beta-adrenergic agent, in the supine posture during spontaneous breathing (n = 11) using lead II configuration in healthy human adult subjects. Heart rate (HR) and QT time series data were analyzed by spectral analysis of 256 s of real-time data. Beat-to-beat QT intervals were measured by automated analysis of ECG. A QT variability index (QT(vi)) was calculated for each subject as the logarithm of the ratio of normalized QT variance to normalized HR variance. We also calculated fractal dimensions of QT time series during spontaneous breathing. RESULTS: QT(vi) was significantly higher in the standing than in the supine posture (-1. 93 +/- 0.27 vs. -1.47 +/- 0.41; p = 0.0001), and also during isoproterenol infusions in the supine posture (-1.83 +/- 0.39 vs. -1. 27 +/- 0.43; p = 0.0001). Fractal dimensions of QT time series were also significantly higher during standing (p = 0.00001) and isoproterenol infusions (p = 0.0002). Respiratory rate or tidal volume did not account for the increased QT variability seen in the standing posture. CONCLUSIONS: A change from the supine to the standing posture as well as infusion of isoproterenol significantly increased the absolute as well as normalized QT variability, which appears to be due to an increase in sympathetic activity associated with these conditions.

Increased QT variability in patients with panic disorder and depression.

This study investigated beat-to-beat QT variability in patients with panic disorder and depression, and normal control subjects using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden death. QT(vm) (QT variability normalized for mean QT interval) and QT(vi) (a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) were significantly higher in patients with panic disorder and depression in supine as well as standing postures (P=0.002 and 0.0001 for QT(vm) and QT(vi), respectively). In another analysis, QT(vi) was significantly higher in patients with panic disorder compared to control subjects in supine as well as standing postures during spontaneous breathing as well as 12, 15 and 20 per minute breathing (P=0.005). These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression and the utility of QT(vi) as a noninvasive measure of temporal repolarization lability.

Effects of paroxetine on heart period variability in patients with panic disorder: a study of holter ECG records.

We investigated cardiac autonomic function in 16 patients with panic disorder before and after treatment with paroxetine using Holter ECG records. Our previous data suggest a relative increase in sympathetic activity in patients with panic disorder, especially during sleep. Data for 20 h and awake and sleep periods were analyzed using spectral analysis to quantify absolute and relative heart period variability in ultra low (ULF: <0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. We also obtained fractal dimensions (FD) for the 20-hour, awake and sleep time series of RR intervals. Paroxetine treatment (19.7 +/- 4.7 mg/day for 105 +/- 37 days) resulted in a significant improvement in the frequency and intensity of panic attacks and also on the state anxiety inventory. Paroxetine treatment produced a significant decrease of 20-hour absolute HF power, awake absolute LF power and sleep absolute HF power. There was also a significant decrease of FDs after treatment with paroxetine for the sleep period. The decrease in LF and HF powers, and sleep FD is likely due to the antimuscarinic effect of paroxetine. The decrease in day-time LF power may also be due to a decrease in relative cardiac sympathetic activity after paroxetine treatment.

The current status of tardive dystonia.

Tardive dystonia (TDt), a persistent dystonia associated with exposure to neuroleptic drugs, is an uncommon disorder. It differs from tardive dyskinesia (TDk) in epidemiology, clinical features, risk factors, pathophysiology, course, prognosis, and treatment outcome. TDt seems to develop faster and is more painful, distressing, and disabling than tardive dyskinesia. In this article, evidence is reviewed on the face, descriptive, construct, and predictive validity of this iatrogenic complication of antipsychotic drugs. It is suggested that TDt should not be lumped together with TDk. It deserves a separate nosological status as an independent diagnostic category. The subclassification of TDt into various subtypes based on coexistence of other movement disorders is suggested.

Wernicke-Korsakoff amnestic syndrome secondary to malnutrition in a patient with schizoaffective disorder.

OBJECTIVE: The authors identify a rare case of Wernicke-Korsakoff amnestic syndrome and highlight its occurrence in the absence of alcohol dependence. METHOD: A longitudinal case history of a patient with schizoaffective disorder who developed Wernicke-Korsakoff syndrome secondary to malnutrition. RESULTS: Refusal to eat based on persecutory delusions in chronic psychotic patients can cause malnutrition and result in Wernicke-Korsakoff syndrome. CONCLUSIONS: With increasing managed-care demands for outpatient treatment of chronic psychotic patients, physicians may see more cases of Wernicke-Korsakoff syndrome in psychiatric populations.

Fractal dimension and approximate entropy of heart period and heart rate: awake versus sleep differences and methodological issues.

1. Investigations that assess cardiac autonomic function include non-linear techniques such as fractal dimension and approximate entropy in addition to the common time and frequency domain measures of both heart period and heart rate. This article evaluates the differences in using heart rate versus heart period to estimate fractal dimensions and approximate entropies of these time series.2. Twenty-four-hour ECG was recorded in 23 normal subjects using Holter records. Time series of heart rate and heart period were analysed using fractal dimensions, approximate entropies and spectral analysis for the quantification of absolute and relative heart period variability in bands of ultra low (<0.0033 Hz), very low (0. 0033-0.04 Hz), low (0.04-0.15 Hz) and high (0.15-0.5 Hz) frequency.3. Linear detrending of the time series did not significantly change the fractal dimension or approximate entropy values. We found significant differences in the analyses using heart rate versus heart period between waking up and sleep conditions for fractal dimensions, approximate entropies and absolute spectral powers, especially for the power in the band of 0.0033-0.5 Hz. Log transformation of the data revealed identical fractal dimension values for both heart rate and heart period. Mean heart period correlated significantly better with fractal dimensions and approximate entropies of heart period than did corresponding heart rate measures.4. Studies using heart period measures should take the effect of mean heart period into account even for the analyses of fractal dimension and approximate entropy. As the sleep-awake differences in fractal dimensions and approximate entropies are different between heart rate and heart period, the results should be interpreted accordingly.

Decreased heart-period variability in patients with panic disorder: a study of Holter ECG records.

This study investigated cardiac autonomic function in patients with panic disorder and normal controls using Holter ECG records. A decrease in ultra-low frequency power (< 0.0033 Hz) is known to be associated with an increased risk for cardiovascular mortality in humans. Twenty-four-hour ECG was recorded in 29 patients with panic disorder and 23 normal controls using Holter records. Data for 20 h and also 20000 s of awake and 20000 s of sleep periods were analyzed using spectral analysis to quantify absolute and relative heart-period variability in ultra low (ULF: < 0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. The patients with panic disorder had significantly lower total and absolute ULF power, which was more pronounced during sleep. The patients also had significantly lower relative ULF power and significantly higher relative LF power during sleep. There was a significant increase of relative LF power from awake to sleep period only in the patient group. The decrease in total and ULF power may increase the risk of mortality and sudden arrhythmic death in patients with panic disorder if they experience a cardiac event. The higher relative LF power during sleep also suggests a possible higher sympathetic drive in the patients during sleep.

Effect of age on long-term heart rate variability.

OBJECTIVE: Previous studies on short-term time series of heart rage suggest an inverse relationship between age and spectral powers of heart rate variability in various frequency bands. In this study, we examined the relationship between age (6-61 years) and long-term heart rate variability. METHODS: We obtained 24-h Holter ECG in 33 healthy human subjects (11 children and 22 adults). The heart rate data were analyzed by using spectral analysis and fractal dimensions of the time series. RESULTS: We found a significant negative correlation between age and very low frequency (VLF, 0.0033-0.04 Hz), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) powers and fractal dimensions during awake as well as sleep periods, and a positive correlation between age and LF/HF ratios. Age and ultra-low frequency (ULF, < 0.0033 Hz) were modestly and negatively correlated only during the awake period. CONCLUSIONS: Sleep ULF power is not significantly affected by age, whereas VLF, LF and HF powers and fractal dimensions of heart rate significantly decrease with age during awake as well as sleep periods.

Analysis of 24-hour ECG in patients with panic disorder.

Previous evidence suggests an increased cardiovascular morbidity in patients with panic disorder. In this study, we compared 24-hour ECG in patients with panic disorder (n = 22; age: 36.1 +/- 7.6 years) and healthy controls (n = 21; age: 34.6 +/- 10.0 years). The QTc intervals during the day or night were not significantly different between patients and controls. Ventricular ectopic beats were also not significantly different between the two groups. These results do not suggest any overt cardiac arrhythmias in this age group of patients with panic disorder.

Psychosensory features in mood disorder: a preliminary report.

The purpose of this study was to determine the prevalence of psychosensory features in mood disorder patients, and to investigate the relationship between psychosensory features and classic psychopathology. We evaluated 50 mood disorder patients (39 bipolar, 11 schizoaffective) for the presence of psychosensory features and psychopathology. We assessed psychosensory features separately using the Profile of Psychomotor Symptoms. We obtained additional information regarding each patient's psychiatric and drug history, family history, and electroencephalogram. Seven (14.0%) experienced three or more recent psychosensory features, and 12 (24.0%) reported three or more past psychosensory features. The presence of alcohol and drug abuse, number of medications, and electroencephalographic abnormality had no effect on the prevalence of psychosensory features. Psychosensory features significantly (rs = .53, P < .001) correlated with hallucinations, but not with other psychopathology (P > NS). Psychosensory features are not uncommon in mood disorders and have a strong relationship with hallucinations. Our findings also suggest that the presence of psychosensory features in mood disorder suggests episode severity and not a specific subgroup.

Speech abnormalities in tardive dyskinesia.

The authors assessed tardive dyskinesia and the structure and physiology of speech apparatus, phonation, and articulation speech abnormalities in 27 chronically ill male psychiatric patients. Tardive dyskinesia was associated with impairment in phonation, intelligibility, and rate of speech production. Patients with and without tardive dyskinesia had similar rates of structural and physiological abnormalities of speech apparatus. The authors conclude that tardive dyskinesia is associated with substantial impairment in speech.

DSM-III and DSM-III-R: what are American psychiatrists using and why?

The purpose of this study was to determine whether American psychiatrists have switched from DSM-III to DSM-III-R as their primary diagnostic reference, and to examine what factors predicted the continued use of DSM-III. In 1989, we conducted a mail survey of practicing psychiatrists (N = 454), residency program directors (N = 128), residents (N = 1,331), and researchers (N = 196) regarding their training in, use of, and opinions about DSM-III and DSM-III-R. Approximately 30% of practitioners continued to use DSM-III as their primary diagnostic reference, although this was less frequently true of researchers and residents. In none of the four groups did a majority believe that DSM-III-R was needed, despite the fact that the majority of each group indicated that it was an improvement over DSM-III. The most commonly perceived reasons for publishing DSM-III-R were that it corrected problems with DSM-III and new research indicated changes were warranted. Compared with DSM-III-R users, DSM-III users more frequently believed that the 7-year interval between the two editions was too short, that DSM-III-R was not needed, and that the revised manual was little better than the original. Thus, 2 years after the publication of DSM-III-R 90% of psychiatrists were using DSM-III-R, at least in part, although a substantial minority continued to use DSM-III as their primary diagnostic manual. Even among DSM-III-R users, many believed that the revised manual was not needed. The perceived need for DSM-III-R was associated with the reasons ascribed to its publication; therefore, acceptance of DSM-IV may be partially a function of how its development is promoted and justified. That nearly one third of a random sample of practicing psychiatrists continued to use DSM-III supports concerns that the publication of DSM manuals every 6 or 7 years will divide the psychiatric community into subgroups using different diagnostic criteria.

Are schizophrenia and affective disorder related? preliminary data from a family study.

OBJECTIVE: Most investigators presume that schizophrenia and affective disorder are separate diseases. Others have proposed alternatives to this Kraepelinian view. These alternatives were addressed by preliminary analyses of data from a family study of psychopathology. METHOD: The authors identified 1,895 first-degree relatives of 166 patients with DSM-III schizophrenia, 71 patients with affective disorder, and 85 medical comparison probands; 949 relatives were blindly diagnosed. RESULTS: The risks for schizophrenia and affective disorder (unipolar melancholia and bipolar disorder combined) were significantly higher in the relatives of the schizophrenic probands and the relatives of the probands with affective disorder than in the relatives of the comparison probands. The morbid risk for nonmelancholic depressions was not significantly higher. Among the relatives of the schizophrenic probands, the risk for affective disorder was highest among the relatives of the patients with "core" schizophrenia, who were younger at illness onset, had chronic illness, had severe emotional blunting, and showed few affective features. CONCLUSIONS: Despite limitations, these preliminary analyses, consistent with other studies, suggest some familial relationship between schizophrenia and severe forms of affective disorder.

Consumers' attitudes toward DSM-III and DSM-III-R: a 1989 survey of psychiatric educators, researchers, practitioners, and senior residents.

To understand how DSM-III and DSM-III-R are used and perceived by educators, researchers, practitioners, and trainees, in the spring of 1989 we surveyed all US psychiatric residency training directors (N = 197), 337 active psychiatrist researchers, a nationwide random sample of 952 practicing psychiatrists, and all PGY-3 and -4 residents. We describe the factors influencing the use of DSM-III and DSM-III-R and the perceptions of strengths and weaknesses of the DSMs from various perspectives (training, research, and practice). A modest increase in the acceptance of the DSM system was noted in comparing the results from the current survey and a similar 1984 survey about DSM-III. The implications of these findings for the development of DSM-IV are discussed.