Michael Lehofer

Increased heart rate in depressed subjects in spite of unchanged autonomic balance

A clinical study was conducted to examine the effects of depression on cardiac autonomic control. Cardiac autonomic control was measured in 26 nonmedicated patients (19 females) suffering from Major Depression, melancholic type, and in 26 age- and sex-matched normal controls. We measured heart rate and high frequency heart rate variability (respiratory sinus arrhythmia), pulsewave velocity and blood pressure, during 10 min of supine rest under controlled conditions. Using a log transformed time domain measure of respiratory sinus arrhythmia (logRSA), we found an inverse linear dependence between cardiac vagal tone and age in the healthy subjects as well as the depressed patients. logRSA was 0.22+/-0.25 in the patients and 0.25+/-0.16 in the control group. While this difference was not significant (P > 0.1), the deviations from the regression line were significantly (P < 0.0005) greater in the patients (0.21+/-0.12) than in the control group (0.09+/-0.07), indicating a more heterogeneous vagal tone in the depressed patients. Heart rate was also significantly (P < 0.03) greater in the depressed patients (76.6+/-12.4) than in the control group (69.5+/-6.9). No between-group differences were found in pulsewave velocity or systolic blood pressure, but diastolic blood pressure was lower in depressed patients (73.5+/-8.7 vs. 80.8+/-9.1). We discuss the possibility that the increased heart rate seen in the absence of vagal tone changes may not be due to altered vagal or sympathetic tone, as measured in this study. Other factors, including altered autonomous heart rate, may be responsible for the higher heart rate in the depressed group.

Major depression and cardiac autonomic control.

We investigated autonomic control of heart rate in patients with major depression, melancholic type. Twenty-three depressed inpatients who were being treated with tricyclic antidepressants and 23 depressed patients who were taking no medications were compared with age- and sex-matched control groups on resting cardiac vagal tone and heart rate. In unmedicated depressed patients, cardiac vagal tone was comparable to that of control subjects, but heart rate was significantly higher. This increase in heart rate may have been due to sympathetic activation caused by anxiety, since the depressed patients were significantly more anxious than the control subjects. Medicated patients exhibited diminished cardiac vagal tone and higher heart rate than unmedicated patients and controls. This was probably due to the anticholinergic effects of the antidepressants. Our findings suggest that cardiac vagal tone is not lower than normal in patients with depression, melancholic type.

Heart rate variability as a prognostic tool in cardiology. A contribution to the problem from a theoretical point of view.

BackgroundRecent clinical studies have proposed standard deviation of heart rate as a diagnostic tool for the outcome of cardiac infarction. Mathematical analysis of heart rate variability shows that heart rate is influenced by different frequency components derived from different parts of the autonomous nervous system. In the experimental part of this study, we investigated the possibility of calculating a variable describing the parasympathetic branch of the autonomous nervous system exclusively. Methods and ResultsIn 60 healthy volunteers, heart rate was measured to 1 millisecond during two different conditions: 5 minutes of rest, and 5 minutes of intermittent handgrip dynamometry; the latter is known to increase sympathetic arousal selectively. Heart rate was found to be lower at rest (65.9±9.7 beats per minute) than during dynamometry (72.8±10.4 beats per minute, P<.001). Respiratory sinus arrhythmia (RSA) calculated from the mean absolute differences between successive heart beats showed no significant change (3.01± 1.62 beats per minute at rest versus 2.97±1.30 beats per minute during dynamometry). In contrast, standard deviation increased from 5.19±1.98 to 9.22±3.56 beats per minute (P<.001). ConclusionsIt can be concluded from these data as well as from other plots presented in this article that RSA is a measure of the parasympathetic vagal tone, whereas standard deviation is increased by both sympathetic and parasympathetic arousal. Clinical evidence and data from physiological experiments are presented to show that a selective measure of vagal tone like RSA may offer advantages over standard deviation as a prognostic tool in cardiology.

Phase‐ and frequency coordination of cardiac and respiratory function

Abstract ECG and respiration (by nose thermistor sensor) were measured in 160 healthy volunteers under resting conditions. Frequency analysis allowed to distinguish fast (center frequency ≈ 0,25 Hertz), medium (center frequency ≈ 0,1 Hertz) and slow waves (center frequency = 0,05 Hertz) of heart rate variability. The fast waves are related to respiratory sinus arrhythmia, which mirrors parasympathetic tone and the slow waves are mainly connected with the sympathetic nervous activities, whereas medium waves are influenced by both the sympathetic and the parasympathetic nervous system. Simultaneously we calculated the heart ‐ respiration coupling by recording a total of ≈ 18.000 respiratory cycles as well as the time from the R‐peak to the onset of the next inspiration. Three distinct peaks of coincidence are related to afferents discharging in the isometric systolic phase (peak I ), to the baroreceptor afferents in the great arterial vessels (peak 2) and afferents excited in the relaxation or diastolic fil...

Influence of age on the parasympatholytic property of tricyclic antidepressants

Clinical evidence indicates that parasympatholytic effects of tricyclic antidepressants increase with age. The aim of the present study was to determine the possible physiological reason for this phenomenon. Subjects included 23 patients (14 female) with major depression, melancholic type, and 23 age- and sex-matched healthy control subjects. Cardiac vagal tone was measured at rest using both spectral analysis and a time domain beat-to-beat method. Results of the spectral and time domain methods for the estimation of vagal tone used in this study were highly correlated in control subjects as well as in medicated depressed subjects. Both patients and control subjects showed an age-related decline in cardiac vagal tone. Tricyclic antidepressants decreased vagal tone significantly by 25-49% depending on age (20-60 years), although the age difference was not significant. The greater effect of tricyclic antidepressants on parasympathetic activity typically seen in older age groups may reflect the fact that predrug levels of vagal tone are already low in older patients. Measurement of vagal tone prior to drug administration may therefore be of prognostic value for anticholinergic side effects.

Reduced dopamine D3 receptor expression in blood lymphocytes of smokers is negatively correlated with daily number of smoked cigarettes: A peripheral correlate of dopaminergic alterations in smokers

The mesolimbic dopaminergic system is known to mediate rewarding effects of nicotine administration, and dysfunctions of this system may underlie failure to stop cigarette smoking. Expression of dopamine receptors in peripheral blood lymphocytes (PBLs) has been indicated as a peripheral correlate of brain status. Dopamine receptor D(3) (DRD3) and D(4) (DRD4) mRNA expression in PBLs was measured by real-time polymerase chain reaction in smokers (n=26) and former smokers (n=14), compared with nonsmoking control subjects (n=35). A significant (p=.032, Bonferroni corrected) 30% reduction of DRD3 mRNA expression in PBLs was found in smokers but not former smokers in comparison with controls. DRD3 mRNA expression in PBLs in smokers but not former smokers was negatively correlated with daily number of cigarettes consumed (Pearson correlation coefficient r=-.54, p=.005). These data suggest a selective inhibiting effect of smoking on DRD3 mRNA expression and, with the known involvement of DRD3 in reward mediation, indicates a vicious-cycle explanation for the motivation for continued smoking.

Nervousness and pain sensitivity: II. Changed relation in ex-addicts as a predictor for early relapse

We recently demonstrated a coupling between nervousness and pain sensitivity in healthy volunteers, and we defined a mean ratio of nervousness/log pain threshold of 1.95 +/- 1.47 for healthy humans. Because in another study former opiate addicts were found to exhibit a persistent opioid independent analgesia, we wondered whether nervousness is also changed in these patients, or if the balance between nervousness and pain sensitivity is altered. Forty unmedicated former opiate addicts during long-term rehabilitation and 40 age-matched control subjects were included in the study. The subjects rated their nervousness prior to a cold pressor test on a Visual Analog Scale. It turned out that the average nervousness rating was higher than in the control subjects and that a distinct subgroup of pain sensitive ex-addicts exhibited a higher ratio of nervousness vs. pain threshold. In this group the risk for relapse was three to four times higher than in the other ex-addicts.

Nervousness and pain sensitivity: I. A positive correlation.

Neuroanatomical studies suggest a close interrelationship between brainstem centers regulating arousal and pain sensitivity. Nervousness, as assessed with a Visual Analog Scale, and pain sensitivity, as assessed with a cold pressor test, were used to clarify whether a physiological association of nervousness and pain sensitivity can be found in healthy subjects. Forty healthy volunteers were included in the study. We demonstrate a significant positive correlation between self-rated nervousness and pain threshold. These data suggest that there is a coupling between nervousness and endogenous pain control. Based on the results, a nervousness-pain-threshold quotient was calculated as a possible measure of the interrelationship of the endogenous pain control system to autonomic activity. A different nervousness-pain-threshold quotient, indicating a different coupling, may provide information on changes in accessory neurophysiologic functions.

Long-term imprisonment leads to cognitive impairment

The effects of long-term imprisonment on cognitive functions are investigated in a longitudinal study. Twenty-four serious offenders in an Austrian penitentiary underwent concentration and memory performance measurements via a questionnaire presented to them under controlled conditions in two sessions at a 42 month interval. The difference in the parameters indicated cognitive impairment after this period that was highly significant (P < 0.01); this can be interpreted as a direct consequence of imprisonment.

Baseline plasma epinephrine levels predict Wisconsin Card Sorting Test scores in healthy volunteers

The present study was undertaken to further explore the potential neuropsychological information associated with baseline plasma levels of catecholamines and dopamine D3 receptor (DRD3) mRNA expression in peripheral blood lymphocytes (PBL). Baseline plasma norepinephrine and epinephrine levels and PBL DRD3 mRNA expression were compared with performance in the Wisconsin Card Sorting Test (WCST) in n=79 healthy volunteers (mean+/-S.D. age: 24.1+/-3.2 years, 34 males). After correction for multiple testing, we found that baseline plasma epinephrine levels predicted WCST total number of errors (Spearmans rho=-0.36, p<0.05), number of perseverative responses (Spearmans rho=-0.36, p<0.05) and percent conceptual level responses (Spearmans rho=0.37, p<0.05). Plasma norepinephrine levels and PBL DRD3 mRNA expression did not predict WCST scores, but PBL DRD3 mRNA expression correlated negatively with plasma epinephrine levels (Spearmans rho=-0.45, p<0.001). Further studies should be undertaken to explore possible neurophysiological links between plasma epinephrine levels and the neurobiology underlying cognitive performance.