Depression and Stress Reactivity in Metastatic Breast Cancer

Abstract

Objective: 

Cancer-related distress due to the psychological and physical challenges of metastatic breast cancer (MBC) may result in symptoms of depression, which negatively affects quality and may influence quantity of life. This study investigated how depression affects MBC stress reactivity, including autonomic (ANS) and hypothalamic–pituitary–adrenal (HPA) axis function.

Method: 

Forty-five nondepressed and 45 depressed patients with MBC underwent a modified Trier Social Stress Test (TSST) while affect, cardiovascular, respiratory, and cortisol responses were measured.

Results: 

At study entry, depressed compared with nondepressed patients had significantly lower log cortisol waking rise levels (p = .005) but no other HPA differences. Positive affect (p = .025) and high-frequency heart-rate variability (lnHF) (p = .002) were significantly lower at TSST baseline in depressed patients. In response to the TSST, depressed patients reported significantly lower positive (p = .050) and greater negative affect (p = .037) and had significantly reduced lnHF (p = .031). In secondary analyses, at TSST baseline both low-frequency (lnLF) (p = .002) and very-low-frequency (lnVLF) (p = .0001) heart rate variability were significantly lower in the depressed group. In secondary analyses during the TSST, those who were depressed had significantly lower lnVLF (p = .008) and did not increase aortic impedance reactivity as much as did the nondepressed during the stressor (p = .005).

Conclusion: 

Depression in patients with MBC was associated with alterations in autonomic regulation, particularly reductions in respiratory sinus arrhythmia, a measure of cardiac vagal control, at baseline and during the TSST. In addition, depression was associated with blunted HPA response to awakening. Both MBC groups had relative cortisol hyporesponsiveness to acute stress.

ANS = autonomic nervous system;

BMI = body mass index;

BP = blood pressure;

BRC = baroreflex control of heart rate;

CO = cardiac output;

CVD = cardiovascular disease;

DBP = diastolic blood pressure;

ECG = electrocardiogram;

HDL = high-density lipoprotein;

HPA axis = hypothalamic–pituitary–adrenal axis;

HR = heart rate;

HRSD = Hamilton Rating Scale of Depression;

HRV = heart rate variability;

ICG = impedance cardiogram;

lnHF = natural log of high-frequency HRV;

lnLF = natural log of low-frequency HRV;

lnVLF = natural log of very low frequency HRV;

LDL = low-density lipoprotein;

MBC = metastatic breast cancer;

MDD = major depressive disorder;

ND = nondepressed;

PANAS = Positive and Negative Affect Schedule;

pCO₂ = partial pressure of carbon dioxide;

PEP = preejection period;

RR interval = time between two consecutive R waves of the ECG;

RSA = respiratory sinus arrhythmia;

RSA_TF = transfer function respiratory sinus arrhythmia;

SBP = systolic blood pressure;

SNRI = serotonin–norepinephrine reuptake inhibitor;

SSRI = selective serotonin reuptake inhibitor;

TSST = Trier Social Stress Test;

VLDL = very-low-density lipoprotein.