Progress in Neuro-Psychopharmacology and Biological Psychiatry
Heart rate variability in drug-naïve patients with panic disorder and major depressive disorder
Introduction
When parasympathetic activity to the heart is reduced, sympathetic tone is unopposed, thereby increasing the risk of developing lethal cardiovascular disease. Previous studies demonstrated that both patients with panic disorder (PD) (Yeragani et al., 1993, Klein et al., 1995) and those with major depressive disorder (MDD) (Rechlin et al., 1994, Guinjoan et al., 1995, Agelink et al., 2002, Udupa et al., 2007) have diminished parasympathetic activity, or an imbalance between the two systems. It is thought that this mechanism contributes to the increased rates of cardiovascular disease in patients with MDD and PD (Penninx et al., 2001, Gorman and Sloan, 2000). In fact, increased rates of cardiovascular disease indeed have been reported (Weissman et al., 1990, Lett et al., 2004, Salomon et al., 2009, Rudisch and Nemeroff, 2003).
Power spectral analysis of electrocardiogram (ECG) R–R intervals is one of the most useful methods for the detection of autonomic instabilities in various clinical disorders (Berntson et al., 1997). It is generally accepted that the high-frequency (HF; 0.15–0.40 Hz) component is mediated by cardiac parasympathetic tone, which is dependent on respiration. The measurement of augmented HF power during regular deep breathing (Driscoll and Dicicco, 2000) is of importance, because respiratory sinus arrhythmia is primarily parasympathetically mediated and allows assessment of cardiac vagal responsiveness. The relationship of low-frequency (LF; 0.05–0.15 Hz) power to cardiac sympathetic innervation and function, however, has been controversial. A recent study demonstrated that LF power reflects baroreflex function, rather than cardiac sympathetic innervations (Moak et al., 2007), and cannot be used to assess sympathetic outflow to the heart (Baumert et al., 2009, Jardine et al., 2002). This would imply that the previously mentioned simplified concept, which states that the ratio of LF power to HF power (LF/HF) reflects cardiac sympathovagal balance (Perini and Veicsteinas, 2003), is also controversial.
Using heart rate variability, the involvement of cardiac autonomic system in patients with MDD (Gorman and Sloan, 2000, Rechlin et al., 1994, Guinjoan et al., 1995, Agelink et al., 2002, Udupa et al., 2007, Yeragani et al., 1991, Licht et al., 2008) and PD (Gorman and Sloan, 2000, Yeragani et al., 1993, Klein et al., 1995, Ito et al., 1999, Garakani et al., 2009, Yeragani and Rao, 2003) has been studied extensively. Nevertheless, the results have been somewhat inconsistent, probably because of methodological differences, clinical heterogeneity of subjects and differences in medicament therapy. Especially psychotropic drugs are known to alter cardiac autonomic activity in diverse ways (Garakani et al., 2009, Yeragani et al., 1992, Bär et al., 2008). One previous study demonstrated that tricyclic antidepressants and selective serotonin reuptake inhibitors induced different alterations in cardiac autonomic activity (Yeragani and Rao., 2003). Therefore, findings from drug-naïve patients must be relevant for the neurophysiological nature of MDD and PD as well. To our knowledge, however, no previous study has made a direct comparison of power spectral analyses of heart rate variability among drug-naïve (i.e. no history of treatment) patients with MDD and PD. In the present study, we therefore compare cardiac autonomic responses to deep breathing among drug-naïve patients with MDD and PD with those of healthy controls. We hypothesized that patients with MDD and PD would have diminished cardiac autonomic responses to regular deep breathing (10–12 breaths/min: 0.17–0.20 Hz) compared to healthy controls.
Section snippets
Subjects
As shown in Table 1, the PD group consisted of 11 men and 6 women, and the MDD group consisted of 9 men and 6 women. All patients were recruited from the psychiatric outpatient clinic of Kanazawa University Hospital. They fulfilled the DSM-IV criteria for PD or MDD. In the PD group, the mean age (± SD) was 29.4 ± 9.5 years (range: 16–52) and the mean duration of disease (± SD) was 59.2 ± 102.1 weeks (range: 1.5–380). Their mean state score (± SD) on the Spielberger State–Trait Anxiety Inventory (STAI:
Results
In the comparison of R–R interval, the two-way ANOVA (subject group × condition) showed a significant main effect of condition (F = 30.73; p < 0.001), and there was no interaction effect between group and condition (Table 3). As shown in Table 2, deep breathing shortened the R–R interval in all three groups.
In the comparison of LF power, there was no significant main effect, but a significant interaction effect was observed between group and condition (F = 3.40; p = 0.042) (Table 3). As shown in Fig. 1A,
Discussion
In previous studies on heart rate variability, many authors have reported reduced parasympathetic activity (Rechlin et al., 1994, Agelink et al., 2002) and increased sympathetic activity (Agelink et al., 2002, Udupa et al., 2007) during resting conditions in patients with MDD. However, this imbalance has not always been observed during resting conditions (Yeragani et al., 1991, Moser et al., 1998). This inconsistency may have been due to the clinical heterogeneity of subjects or the differences
Conclusions
We have found lower LF power in the MDD group during resting condition as compared to the control and PD groups. In addition, we have found that the MDD group had a lower response to regular deep breathing in LF power and in LF/HF ratio as compared to the control group. The results indicate that the deep breathing revealed diminished cardiac autonomic reactivity in drug-naïve MDD patients.
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