Research report
Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia

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Abstract

Background

Depression is known to be associated with altered cardiovascular variability and increased cardiovascular comorbidity, yet it is unknown whether altered cardiac autonomic function in depression is associated with insomnia, a common symptom comorbid with depression. This study aimed to investigate the long-term diurnal profile of autonomic function as measured by heart rate variability (HRV) in both major depression and primary insomnia patients.

Method

A total of 52 non-medicated patients with major depression, 47 non-medicated patients with primary insomnia, and 88 matched controls without insomnia were recruited. Each subject was assessed by means of sleep and mood questionnaires and underwent twenty-four-hour ambulatory electrocardiogram monitoring. Standard HRV analysis and a well-validated complexity measure, multiscale entropy, were applied to comprehensively assess the diurnal profiles of autonomic function and physiologic complexity in our study sample.

Results

Compared with the controls, the patients with major depression and those with primary insomnia exhibited significant reductions in parasympathetic-related HRV indices, and this association was mainly driven by the presence of poor sleep. Both groups of patients also exhibited significant reductions in physiologic complexity during the sleep period as compared with the healthy controls. Alterations in HRV indices were correlated with perceived sleep questionnaire scores but not with depression scales.

Conclusions

Our findings suggest a pivotal role of sleep disturbance in regulating cardiovascular variability in major depression and primary insomnia patients. These findings could highlight the importance of treating insomnia as an independent disease rather than a symptom.

Introduction

Insomnia, which is characterized by a perception of poor sleep quality, is a common symptom comorbid with major depression. Studies have found that both insomnia and depression are independent risks of cardiovascular morbidity and mortality (Mallon et al., 2002, Roose, 2001, Schwartz et al., 1999), suggesting potential cardiac autonomic dysregulation in depression and insomnia.

Using heart rate variability (HRV) as a non-invasive means of assessing autonomic function, reduced HRV measures have been observed in patients suffering from cardiovascular diseases comorbid with depression (Carney et al., 2001, Gehi et al., 2005) . One study further suggested that reduced HRV indices in ischemic heart disease patients with depression could be reversed by the use of anti-depressants (Yeragani et al., 2002). Considering depressive illness itself, conflicting results have been reported (Bar et al., 2004, Jindal and Keshavan, 2007, Moser et al., 1998), but majority of the literature suggests that depression itself is associated with reduced HRV indices, particularly those related to vagal activity (Boettger et al., 2008, Guinjoan et al., 1995, Kemp et al., 2010b, Nahshoni et al., 2004, Tonhajzerova et al., 2010, Udupa et al., 2007, Yeragani, 2000).

Patients with primary insomnia may have no significant symptoms of depression, but insomnia itself has been suggested to be an important risk factor for onset of depression in later life (Sateia and Nowell, 2004). Insomnia has been linked to altered heart rate or autonomic function (Bonnet and Arand, 1998, Jurysta et al., 2009, Monroe, 1967, Nilsson et al., 2001), yet it is unclear how insomnia may affect cardiac autonomic regulation in patients with depression and those with primary insomnia. Furthermore, despite a growing body of clinical research regarding the association of HRV and depression, the factors contributing to altered cardiovascular variability in depressed patients remain largely unknown.

The majority of previous studies investigating autonomic function in depressed patients have utilized short-term electrocardiogram (ECG) recordings, for periods ranging from five minutes to a few hours, with a limited number of studies regarding depression and autonomic function having used long-term ECG monitoring (Boettger et al., 2008, Carney et al., 2001, Yeragani, 2000). In order to elucidate the role of autonomic dysfunction in depression and its relationship with insomnia, twenty-four-hour ECG monitoring covering the sleep period was employed in a sample of non-medicated patients suffering from major depression and another group of subjects with primary insomnia.

We hypothesized that insomnia, as measured by perceived sleep questionnaires, may contribute to altered HRV in the patient group, and applied both standard HRV analysis and a well-validated complexity measure, multiscale entropy (MSE), to comprehensively assess the diurnal profiles of autonomic function and physiologic complexity in our study sample.

Section snippets

Subjects

The study sample consisted of three groups of adult medication-free subjects: patients with major depressive disorder (n = 52; age, 42.7 ± 10.2 years; range, 25–63 years), patients with primary insomnia (n = 47; age, 43.9 ± 10.4 years; range, 23–63 years), and healthy controls (n = 88; age, 41.6 ± 11.7 years; range, 22–64 years). Informed consent was received from all subjects prior to commencement of the study, and the protocol was approved by the Institutional Review Board of Taipei Veterans General Hospital.

Demographic data

The demographic and clinical data are presented in Table 1. The patient groups and control subjects did not differ in terms of the age, BMI, and gender ratio. The depression group rated higher on the PSQI than the insomnia group (p = 0.008), and both patient groups had significantly higher PSQI scores than the control subjects (both p < 0.001). The three groups did not differ in terms of daytime sleepiness, as measured by the ESS.

Diurnal variation of heart rate variability between groups

For the awake HRV (Table 2), significant between-group differences

Discussion

The principle findings of this study were as follows: 1) in comparison with the controls, both the patients with major depression and those with primary insomnia exhibited significant reductions in parasympathetic-related HRV indices; 2) both the patients with major depression and those with primary insomnia exhibited significant reductions in physiologic complexity during the bedtime period as compared with the healthy controls; and 3) alterations in HRV indices were correlated with perceived

Role of funding source

This work was supported by the National Science Council (NSC) of Taiwan (NSC 95-2314-B-075-111); NSC support for Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan; Taipei Veterans General Hospital, Taiwan (V96C1-083, V97C1-132, V97F-005); and the Joint Projects of the Veterans General Hospitals University System of Taiwan (Grant VGHUST100-G1-4). These organizations had no further role in study design; in the collection, analysis and interpretation

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgements

The authors wish to thank Zi-Hui Lin, Shan-Ing Chen and Chen-Ru Wang for their excellent technical assistance.

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