نوسان ضربان قلب کوتاه مدت در بیماران مسن تر با افسردگی تازه تشخیص داده شده

Dysfunction of the autonomic nervous system has been considered to be a risk factor for major depressive disorder (MDD) and cardiovascular disease (CVD). The aim of this study was to evaluate short-term heart rate variability (HRV) in elderly patients with newly diagnosed MDD. Thirty MDD patients over 60 years old newly diagnosed by a structured interview were enrolled, free from antidepressants. Socio-demographic data, blood tests, and heart rate variability (HRV) obtained from 5-min ECG were gathered. The MDD group showed significantly lower very low frequency power, low frequency power, high frequency power, and total power in frequency domain. In time domain analysis, the MDD group showed a significantly smaller standard deviation of the NN, root mean square of the differences of the successive NN, and NN50/total number of all NNs. These findings demonstrated a lower HRV in older patients who were newly diagnosed with depression without a history of CVD and antidepressants effect, compared with the control subjects. Low HRV may be an important predictor of both MDD and CVD in elderly. The use of HRV in elderly depressive patients could be a meaningful screening method for risk of CVD.

Depression is a common and disabling health problem worldwide. The estimated lifetime prevalence of major depressive disorder (MDD) is 16.2%, and the disease causes remarkable psychosocial impairments (Kupfer et al., 2012). Depression is associated with various medical conditions and is a leading cause of disability, accounting for 40.5% of the years lived with disability worldwide (Whiteford et al., 2013). Medical illness is a risk factor for depression, and the prevalence of depression increases with increasing illness severity (Li and Rodin, 2011). Co-morbid depression has been associated with 20–40% of cardiovascular disease (CVD) patients (Gonzalez et al., 1996). A meta-analysis of prospective studies reported a dose–response relationship between the severity of depression and the risk of CVD (Ferketich et al., 2000, Rugulies, 2002 and Williams et al., 2002). Depression is associated with many unhealthy behaviors, such as smoking and drinking to excess, which increase the risk of future CVD. CVD patients who are depressed might have a greater sympathetic response to stress, which may lower the threshold for hypertension and facilitate the progression of the atherosclerotic process (Li and Rodin, 2011). CVD may impair social functioning and has a significant burden of illness, which may increase the risk of developing depression (Alexopoulos et al., 2002). Although the exact mechanism underlying the association between depression and CVD is not clear, one possible hypothesis is that autonomic dysfunction might be a co-risk factor for both illnesses (Carney et al., 2002 and Grippo and Johnson, 2002). Measurement of heart rate variability (HRV) is regarded as a non-invasive and highly sensitive method to evaluate autonomic nervous system (ANS). Low HRV has been associated with the development of CVD and MDD (Carney et al., 2005); furthermore, lower HRV could predict cardiac events in healthy adults and mortality in CVD patients (Vaishnav et al., 1994 and Dekker et al., 2000). Many previous studies have revealed that lower HRV was associated with unfavorable health outcomes in depressed patients (Veith et al., 1994, Lehofer et al., 1997 and Moser et al., 1998). There is a significant negative correlation between the severity of depression and HRV (Kemp et al., 2010). A systematic meta-analysis revealed that individuals with more severe depression are likely to have a lower HRV compared with individuals with less severe depression (Kemp et al., 2010). Elderly depressed patients have a significant coherent deficit in autonomic tone indicated by lower LF-HRV and total power spectral density compared with non-depressed individuals (Vasudev et al., 2011), which indicate a remarkable deficit in autonomic tone in patients with late-life depression. However, these findings are needed to confirm by other studies because of methodological limitations, such as lack of structured interview for diagnosis and including just frequency domain analysis of HRV test (Vasudev et al., 2011). Considering the fact that the ANS changes increase with aging, it is difficult to demonstrate that elderly depressed patients display decreased HRV against a background of decreased HRV with aging. It is quite possible that depression in elderly patients further reduces HRV, which potentially results in an increased risk of cardiovascular morbidity and mortality. It is notable, however, that previous reports on these phenomena had several limitations. First, most studies were performed in previously diagnosed depressed patients who were taking anti-depressants. The use of antidepressants may have an effect on the ANS status evaluated by HRV (Licht et al., 2008). Some psychotropic drugs are known to alter cardiac autonomic activity in diverse ways (Glassman et al., 2003). A recent study showed antidepressant effect was significant in lowering HRV in depressive elderly, while depression per se did not affect in lowering HRV ( O׳Regan et al., 2014). Second, studies on the association between HRV and depression have generally been conducted with patients with known CVD. The research results from those subjects can hardly discern the effect of depression on the lowering of HRV from CVD. Last but not least, there were inconsistent results about the association of the lowering of HRV and late-life depression. Vasudev et al. reported that the patients with previous and current late-life depression showed significant changes in HRV compared to controls ( Vasudev et al., 2011). However, the other study did not show the differences in the time domain or frequency domain measures of HRV between depressed elderly and normal control ( Jindal et al., 2008 and O׳Regan et al., 2014). The inconsistency among the previous studies could draw from the methodological limitations, such as the use of psychotropics and CVD history of subjects. Therefore, we have performed a study on newly diagnosed and treatment-naive elderly MDD patients without co-morbid CVD to identify whether elderly depression is associated with the lowering of HRV.

There were no significant differences in the socio-demographic data or lifestyle characteristics, such as the exercise and alcohol drinking/smoking habits, between the two groups (Table 1 and Table 2). Blood pressure (depression group vs. control group: systolic 124.3±12.4 vs. 119.3±14.5, respectively; diastolic 75.7±9.7 vs. 71.7±8.7, respectively), the mean body mass index (25.7±3.0 vs. 24.5±2.6, respectively), HbA1c level (6.0±0.6 vs. 6.0±1.0, respectively), total cholesterol level (192.3±35.0 mg/dl vs. 196.3±33.8 mg/dl, respectively), LDL level (121.2±32.5 vs. 120.5±27.7, respectively), HDL level (49.0±11.0 vs. 59.5±15.1, respectively) and TG level (130.0±71.6 vs. 100.0±45.9, respectively) were not significantly different between the two groups.