Abstract
Autonomic nervous system (ANS) dysregulation in depression is associated with symptoms associated with the ANS. The beat-to-beat pattern of heart rate defined as heart rate variability (HRV) provides a noninvasive portal to ANS function and has been proposed to represent a means of quantifying resting vagal tone. We quantified HRV in bipolar depressed (BDD) patients as a measure of ANS dysregulation seeking to establish HRV as a potential diagnostic and prognostic biomarker for treatment outcome. Forty-seven BDD patients were enrolled. They were randomized to receive either escitalopram–celecoxib or escitalopram-placebo over 8 weeks in a double-blind study design. Thirty-five patients completed the HRV studies. Thirty-six healthy subjects served as controls. HRV was assessed at pretreatment and end of study and compared with that of controls. HRV was quantified and corrected for artifacts using an algorithm that incorporates time and frequency domains to address non-stationarity of the beat-to-beat heart rate pattern. Baseline high frequency-HRV (i.e., respiratory sinus arrhythmia) was lower in BDD patients than controls, although the difference did not reach significance. Baseline low-frequency HRV was significantly lower in BDD patients (ln4.20) than controls (ln = 5.50) (p < 0.01). Baseline heart period was significantly shorter (i.e., faster heart rate) in BDD patients than controls. No significant change in HRV parameters were detected over the course of the study with either treatment. These findings suggest that components of HRV may be diminished in BDD patients.
Highlights
Compared to major depressive disorder (MDD) and anxiety disorders, bipolar disorder (BD) is less prevalent, but it represents a significant mental health concern worldwide
There were negative correlations between treatment resistance severity and baseline respiratory sinus arrhythmia (RSA), LF-heart rate variability (HRV), and heart period (HP), with significance reached in the negative relationship between treatment resistance severity and RSA
In another study of bipolar patients studied during a euthymic state, Cohen et al reported that time domains of HRV (HR, HP) were decreased compared to healthy controls (HCs); HF-HRV was significantly increased [39]
Summary
Compared to major depressive disorder (MDD) and anxiety disorders, bipolar disorder (BD) is less prevalent, but it represents a significant mental health concern worldwide. Manic episodes represent the distinguishing feature for a diagnosis of BD type I versus other mood disorders, bipolar depression (BDD) causes significant distress and dysfunction for patients and their families and poses major treatment challenges. Because it is often difficult to distinguish BDD from an episode of MDD prior to a distinct episode of mania, it poses significant diagnostic challenges to the clinician. Episode length and frequency of episodes may be relatively similar between depression and mania in BD, clinical evidence suggests that BD patients are less likely to fully recover from a major depressive episode than from a manic, hypomanic, or even minor depressive episode [2] it is imperative to consider BDD patients as being susceptible to treatment resistance.
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