In the present study, we showed that nonmedicated patients with a first-time diagnosis of MDD had significantly higher QTD, QTcD and PD compared with age- and sex-matched healthy volunteers.
QTD and QTcD were previously investigated in a small-scale study. Nahshoni et al (23
) measured QTD and QTcD in a group of 18 elderly patients with recurrent MDD maintained on antidepressant medication and showed that they had significantly higher QTD and QTcD compared with nine age- and sex-matched healthy subjects. Our results support and extend their findings in a larger group of MDD patients. Because our patients were not using antidepressant medication at the time of ECG measurements, drug side effects can be eliminated as a potential cause of ANS imbalance in these patients. Furthermore, our analysis shows that QTD is affected even in younger or middle-age patients at or near the beginning of their first-ever major depressive episode, suggesting that the toll of stress on the cardiovascular system is immediate. However, at this time we cannot rule out the possibility that elevated QTD could also be a trait marker of depressive personality.
Two studies measured QTD of MDD patients in relation to the effects of electroconvulsive therapy. Tezuka et al (24
) noticed that MDD patients had high QTD at baseline and that QTD peaked immediately after electroconvulsive therapy and returned to baseline within 5 min to 6 min. In a follow-up study they showed that older and younger patients had similar QTD at baseline but QTD was increased significantly more in older patients during the 7 min following electro-convulsive therapy (25
) Although these studies focused on the effects of electroconvulsive therapy and did not include a control group, their observation of high baseline QTD in MDD patients is consistent with our results. It would be interesting to determine whether QTD would further decrease to normal levels in successfully treated MDD patients.
To the best of our knowledge, ours is the first study to show elevated PD in MDD patients compared with a control group. PD was assessed in 30 MDD patients undergoing electroconvulsive therapy and a significant increase in PD was observed after the shock compared with the baseline reading (26
). However, in this study there was no control group to determine the difference at baseline.
There are some limitations to the present study. QT interval measurement is affected by factors such as low T wave amplitude, T wave merging with P or U waves and abnormal morphology of T wave (27
). Consequently, intraobserver and interobserver variability is often high with QTD measurements. We tried to overcome this problem by having a single blinded expert performing all measurements methodically. Because computerized dispersion calculations were not shown to be superior to manual calculations, we opted for manual measurement (28
Heart rate correction of QTD is controversial. Current belief dictates that heart rate does not modify QTD and that QTD should not be corrected for heart rate (27
). Although we calculated QTcD in our study, the results paralleled QTD and did not affect the interpretation of our results.
Potential limitations to the present study include the relatively small sample size and the fact that there is no supporting evidence, such as a biomarker, 24 h Holter or 24 h ambulatory blood pressure monitoring, that would show conclusively that the reason for correlation is indeed ANS disturbances.