Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women

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Abstract

Objective

Depression is a risk factor for morbidity and mortality in a variety of populations, and anxiety has also been associated with risk of mortality among cardiac patients. Dysfunction of the autonomic nervous system may be involved in this risk. The primary goal of this study was to evaluate the relationship between levels of self-reported symptoms of depression and anxiety and 24-hour urinary catecholamine excretion.

Method

Ninety-one women aged 47–55 years were evaluated. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and state anxiety was assessed with the state anxiety portion (SAI) of the Spielberger State–Trait Anxiety Inventory (STAI). Twenty-four hour urine collections were assayed for epinephrine (EPI), norepinephrine (NE) and cortisol (CORT). EPI, NE and CORT were indexed by body surface area to control for individual differences in body size.

Results

Higher levels of depression symptoms were associated with increased 24-hour NE excretion (r=.27, P=.009), with depressed women (n=17, BDI scores ≥10) exhibiting an approximately 25% higher rate of urinary NE excretion than women with BDI scores <10 (n=74), P=.007. Higher levels of state anxiety were also related to greater NE excretion (r=.28, P=.01), and CORT excretion was related to both depression (r=.23, P=.02) and anxiety (r=.22, P=.04). Depression and anxiety symptoms were unrelated to urinary EPI excretion.

Conclusions

The current findings that higher levels of depression and anxiety symptoms are related to increased 24-hour urinary NE and CORT excretion among women suggests that depression and anxiety may be associated with increased sympathetic nervous system (SNS) activity, and are consistent with the possibility that SNS activity may play a role in the increased mortality associated with depression in community-dwelling older adults.

Introduction

Over the last 10 years, depression has emerged as a risk factor for mortality in general medical patients [1], [2], community-dwelling older men and women [3], [4], [5], and post-myocardial infarction (MI) patients [6], [7], [8], [9], [10], [11]. Several studies have also reported that anxiety is related to mortality among cardiac patients [12], [13], [14]. Although the mechanisms responsible for depression- and anxiety-related mortality have not been identified, growing evidence suggests that dysregulation of the autonomic nervous system may be involved. For example, clinically depressed coronary artery disease (CAD) patients have an increased prevalence of ventricular tachycardia, when compared with nondepressed CAD patients [15]. In addition, post-MI patients with both symptoms of depression and frequent premature ventricular contractions are at greater risk of cardiac mortality than patients with symptoms of depression without frequent premature beats [7].

Excessive sympathetic activation is known to provoke cardiac arrhythmias and sudden cardiac death [16], [17], and may also lead to increased risk of morbidity and mortality through promotion of vascular injury and inhibition of normal healing [18]. Depressed psychiatric patients have been shown to exhibit increased levels of plasma norepinephrine (NE) [19], urinary NE [20] and increased levels of cortisol (CORT) [21], [22], [23], [24], [25], suggesting a relationship between depression and overactivity of the hypothalamic–pituitary–adrenocortical axis and the sympathetic nervous system (SNS). However, not all studies have found an effect of depression on NE [21], [26], [27], [28]. Although this may be explained in part by reduced power to detect an effect of depression due to small sample sizes [21], this is unlikely to fully explain the discrepant findings. Another possibility is that the depression–SNS relationship is contingent on the presence of psychological stress. The rate of urinary catecholamine excretion averaged over a 24-hour period may be an appropriately sensitive measure of real life stress [29], or aggregated sympathetic responses over the day [20], [30], which may enhance our ability to observe a relationship between depression symptoms and NE.

The primary purpose of this investigation was to evaluate the relationship between symptoms of depression and anxiety and rates of 24-hour urinary catecholamine excretion among healthy women. Few studies have examined the relationship between depression and urinary catecholamines among women (e.g. Ref. [31]), despite previous findings of a higher prevalence of depression among women [32], [33], [34], as well as the documented risk of depression-related mortality among women [10], [35]. We hypothesized that women reporting higher levels of depression on the Beck Depression Inventory (BDI; [36]) and higher levels of anxiety on the state anxiety portion (SAI) of the Spielberger State–Trait Anxiety Inventory (STAI; [37]) would exhibit higher 24-hour urinary NE excretion. In keeping with previous research [21], [22], [23], [24], [25], we also hypothesized that women reporting more depressive symptoms would exhibit greater 24-hour CORT excretion.

Section snippets

Participants

A total of 91 women, aged 47–55 years (M=50.2, S.D.=2.0) are included in the current report. Duke University Medical Center's Internal Review Board approved the study protocol, and all participants provided verbal and written consent prior to participation. These data are from a larger study comparing pre- and postmenopausal women with respect to a number of cardiovascular parameters, and the participants completed procedures not reported here (e.g. a laboratory mental stress testing protocol).

Results

BDI scores ranged from 0 to 21 (M=5.8, S.D.=4.9). The distribution was positively skewed, with a median BDI score of 5 and 19% of the BDI scores ≥10. State anxiety scores ranged from 20 to 66 (M=31.5, S.D.=10.3). Scores on the SAI were significantly and positively related to BDI scores (r=.50, P=.0001). Scores on the SAI (r=.54, P< .0001) and BDI (r=.37, P=.0004) were also related to the mean subjective stress (i.e. negative emotions) ratings made in ambulatory diaries completed on the day of

Discussion

Higher levels of depression and anxiety symptoms were associated with increased 24-hour NE excretion, but not with increased levels of urinary EPI. The positive relationship between depression and urinary NE was observed when depression scores were treated continuously, as well as when clinical cutoffs for depression scores were used to create groups higher and lower in depression. Women with BDI scores of 10 and greater exhibited about a 22% higher rate of creatinine-adjusted urinary NE

Acknowledgements

This research was supported by grants HL 53724 from the National Institutes of Health (NIH), by M01-RR-30 General Clinical Research Centers Program, National Center for Research Resources, NIH, and by MH19109 from the National Institute of Mental Health (NIMH).

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