Depression and heart rate variability

I

Depression and Heart Rate Variability Vikram K. Yeragani, Richard Balon, Robert Pohl, and C. Ramesh Key Words:

D e p r e s s i o n , anxiety, heart rate variability, a u t o n o m i c , c a r d i o v a s c u l a r

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Introduction Since there is evidence suggesting an increased incidence of cardiovascular morbidity in patients with major depression and phobic anxiety (Dalack et al 1990: Kawachi et al 1994), we have been conducting studies on cardiac autonomic function in these disorders using noninvasive techniques such as spectral analysis of heart rate (HR). Low frequency (LF:0.01-0.05 Hz) power has been related to renin angiotensin and thernmregulatory mechanisms, midfrequency (MF:0.07-0.15 Hz) power to baroreceptor control, and high-frequency (HF:0.16-0.5 Hz) power to respiratory sinus arrhythmia (Malliani et al 1991). Our previous findings suggest that patients with panic disorder have decreased variance of heart rate time series, higher standing r e l a m e midfrequency power, and higher increases in standing midfrequency power when challenged v, ith yohimbine (Yeragani et al 1992, 1993). We have also found that patients with panic disorder have exaggerated vagal withdrawal and higher sympathovagal ratios during sodium lactate and isoproterenol infusions (Yeragani et al 1994, 1995). In a previous report on time domain measures of heart rate variability, we did not find any significant differences in the standard deviation of heart rate between patients with depression and normal controls (Yeragani et al 199l). However, the data acquisition and determination of R-R intervals were done manually, and we did not use spectral analysis of HR in this study. In the present relx)rt, we compare heart rate variability data on 16 patients with major depression with no current or past history of panic attacks, and 29 patients with panic disorder without a current history of major depression. The data on these 16 patients with depression have not been published elsewhere. However.

we presented the data on some of these patients with panic disorder in an earlier report (Yeragani et al 1993).

Methods Subjects Sixteen patients with major depression without a history of panic attacks (7 men, 9 women) and 29 patients with panic disorder without a current history of major depression (13 men, 16 women) participated in this study. The study was approved by the Institutional Review Board and the procedures of the study were explained to each subject, and a written informed consent was obtained prior to the studies. All subjects were healthy and there was no history of any significant physical illness, especially cardiovascular disease or diabetes. The diagnoses were made according to the DSM III-R criteria. The patients were not taking an~ psychotropic medication for at least 2 weeks prior to the postural study.

Procedure All subjects were instructed not to smoke or drink caffeinated beverages at least for 3 hours prior to the postural tests and the experiments were conducted in the morning. After 10 rain of ~upine rest the electrocardiogram (ECG) was recorded for 10 min in supine posture and for 20 min after they actively stood up (no passive tilt was used). The subjects were asked to breathe normally and no attention was paid to their breathing. There were twO sets of data used in this study: supine and standing.

Recording and Analysis of the ECG Signal From the Wright State UniversitySchool ol Medicineand the VA MedicalCenter Dayton, OH (VKY): and Wayne State / niversit.,, School of Medicine. [)etroit. MI (RB. RP. CR). Address reprint requests to VK. Yeragani. M.D.. Profe,,sor of P~,ychiatr). 116-A. VA Medical Center. Dayton. OH 45428 Received October 17, 1994: revised June 2t~. Iq95 © 1995 Socict3, nl Biological Py3cNalr~

The ECG was recorded using limb leads using a Hewlett Packard 78352 A patient monitor and a 78173 A ECG monitor (Palo Alto, CA). The ECG signal from the ECG monitor was recorded on to a PC at a sampling rate of 500 Hz. R-R intervals were found by 0006-3223195/$09.50 SSDI l)006-3223(95)00365-N

Brief Reports

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taking the time difference between points of maximum derivative of successive QRS complexes. We performed the analyses after playing the original data back so that we could visually inspect and use artifact free data. We have used 260 sec of continuous real time data during supine and standing conditions. According to the method described by Berger et al (1986), we obtained a smoothed instantaneous heart rate series sampled at 4 Hz. The power spectrum was obtained as the magnitude squared of the fast Fourier transform using a rectangular data window. The power spectra were then integrated over the following frequency bands; low frequency (LF:0.01-0.05 Hz), midfrequency (MF: 0.07-0.15 Hz), and high frequency (HF:0.2-0.5 Hz). The direcl current (DC) component was removed during the computation ot the power spectrum. Both absolute and relative powers were obtained. Absolute power is the actual value of power in a particular frequency band. Relative power in a particular frequency band is its percentage of total power.

Table 1. Heart Rate (bpm) Variability Measures

Statistical A n a l y s i s

Discussion

BMDP statistical software (Berkeley, CA) was used to perform the analyses. Analysis of covariance (ANCOVA) for repeated measures was used to compare the supine and standing conditions between patients and controls for heart rate, and low frequency, midfrequency, and high-frequency powers with age as a covariate. Standing relative MF power was compared using Mann-Whitney test as the distributions were not normal. Probability values of <- 0.(15 (two-tailed) were considered significant.

These results suggest a relative increase in cardiac sympathetic activity in patients with panic disorder compared to patients with depression, a finding similar to our previous comparison of normal controls and patients with panic disorder (Yeragani et al 1993). Our previous report (Yeragani et al 1993) showed a decreased standing LF power in patients with panic disorder compared to controls, and in the current study this difference between panic and depressed patients did not reach statistical significance. However, the standing relative MF power, which is one of the measures of relative cardiac sympathetic activity, is significantly higher in patients with panic disorder. It will be important to investigate the LF, MF, and HF powers in age matched populations, and also to include a group of patients with current symptoms of both depression and panic disorder. This study is also limited by the lack of an age-matched control group. These studies are especially important in view of the recent findings of Kawachi et al (1994) suggesting an increased risk of sudden death in patients with phobic anxiety, and since an increase in cardiac sympathetic activity may play a role in fatal cardiac arrhythmias.

Results The patients with depression were older compared to the panic group (32.4 _+ 8.2 vs 37.3 + 8,6 years: t -- 1.9; p = 0.07). There were no significant differences between patients with panic disorder and depression for the supine or standing absolute LF. MF, and HF powers after the age was covaried out (Table l i. However, the relative MF power was significantly higher in patients with panic disorder compared to the patients with depression (39 -+ 15 vs. 27 + 19: p = 0.025: Mann-Whitney test). There was no significant correlation between age and relative MF power.

Supine

Standing

Heart rate LF power" MF power HF power Heart rate LF power MF power HF power

Panic disorder (Mean - SD)

Depression (Mean 4- SD)

70.0 4- 7.0 9.7 4- 7.6

68.4 +- 9.6 10.4 + 8.4

8.6 -+ 7.0

5.6 + 8.0

6.3 89.2 20.9 21.1

+- 8.6 ± 8.6 ± 15.1 4- 19.4

2.2 L 2.2

5.0 -+ 9.6 89.4 + 17.6 30.2 4- 36.4 17.7 4- 21.2 2.6 -+ 2.0

" Units fi~r p o w e r are bpm 2.

References Berger RD, Akselrod S, Gordon D, Cohen R ( 1986): An efficient algorithm for spectral analysis of heart rate variability. IEEE Trans Biomed Engg 33:900-904. Dalack GW, Roose SP (1990): Perspectives on the relationship between cardiovascular disease and affective disorder. J Clin Psychiatry 5 l(suppl):4-9. Kawachi I, Colditz G, Ascherio A, Rimm EB, Giovannucci E, Stampfer M J, Willett WC ( 1994): Prospective study of phobic anxiety and risk of coronary, heart disease in men. Circulation 89:1992-1997. Malliani A, Pagani M, Lombardi F. Cerutti S (1991): Cardiovascular neural regulation explored in the frequency domain Circulation 84:482-492.

Yeragani VK, Pohl RB, Balon R, Ramesh C, Glitz D, Jung I, Sherwood P (1991): Heart rate variability in patients with depression. Psychiatr>' Res 37:35-46. Yeragani VK, Berger RD, Pohl RB, Srinivasan K, Balon R, Ramesh C, Weinberg P, Berchou R (1992): Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: A study of power spectral analysis of heart rate. J Cardiovasc Pharmacol 20:609-618. Yeragani VK, Pohl RB, Berger R, Balon R, Ramesh C, Glitz D, Srinivasan K, Weinberg P (1993): Decreased heart rate variability in panic disorder patients: A study of power spectral analysis of heart rate. Psychiatry Res 46:89-103.

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Yeragani VK, Srinivasan K. Balon R, Ramesh C, Berchou R (1994): Lactate sensitivity and cardiac cholinergic function in panic disorder. Am J Psychiat~' 151 : 1226-1228.

Brief Reports

Yeragani VK, Pohl R, Srinivasan K, Balon R, Ramesh C, Berchou R (1995): Effect of lsoproterenol infusions on heart rate variability in patients with panic disorder. Psychiatry Res 56:289-293.