Ansgar Conrad

Depression and stress reactivity in metastatic breast cancer

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; RSATF = 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.

Psychophysiological and Cortisol Responses to Psychological Stress in Depressed and Nondepressed Older Men and Women With Elevated Cardiovascular Disease Risk

Objective: The objective of this study was to compare psychophysiological and cortisol reactions to psychological stress in older depressed and nondepressed patients at risk for cardiovascular disease (CVD). Methods: Forty-eight depressed participants and 20 controls with elevated cardiovascular risk factors underwent a psychological stress test during which cardiovascular variables were measured. Salivary cortisol was collected after each test segment. Traditional (e.g., lipids) and atypical (e.g., C-reactive protein) CVD risk factors were also obtained. Results: At baseline, the groups did not differ on lipid levels, flow-mediated vasodilation, body mass index, or asymmetric dimethylarginine. However, the depressed patients had significantly higher C-reactive protein levels. Contrary to our hypothesis, there were no differences in baseline cortisol levels or diurnal cortisol slopes, but depressed patients showed significantly lower cortisol levels during the stress test (p = .03) and less cortisol response to stress. Compared with nondepressed subjects, depressed subjects also showed lower levels of respiratory sinus arrhythmia (RSATF) during the stress test (p = .02). Conclusions: In this sample, older depressed subjects with elevated risk for CVD exhibited a hypocortisol response to acute stress. This impaired cortisol response might contribute to chronic inflammation (as reflected in the elevated C-reactive proteins in depressed patients) and in other ways increase CVD risk. The reduced RSATF activity may also increase CVD risk in depressed patients through impaired autonomic nervous system response to cardiophysiological demands. ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ADMA = asymmetric dimethylarginine; ANS = autonomic nervous system; BMI = body mass index; BP = blood pressure; BRC = baroreflex control; CAD = coronary artery disease; CBT = cognitive behavioral therapy; CHD = coronary heart disease; CO = cardiac output; CON = nondepressed control; CPM = cycles per minute; CVD = cardiovascular disease; DBP = diastolic blood pressure; DISH = Depression Interview and Structured Hamilton; ECG = electrocardiogram; FMVD = flow-mediated vasodilation; HDL = high-density lipoprotein; HPA = hypothalamic–pituitary–adrenal axis; HR = heart rate; HRSD = Hamilton Rating Scale of Depression; HRV = heart rate variability; LDL = low-density lipoprotein; MDD = major depressive disorder; MI = myocardial infarction; NO = nitric oxide; PANAS = Positive and Negative Affect Schedule; pCO2 = partial pressure of carbon dioxide; PEP = preejection period; PSS = Perceived Stress Scale; RSA = respiratory sinus arrhythmia; RSATF = transfer function respiratory sinus arrhythmia; SBP = systolic blood pressure; SVR = systemic vascular resistance; TSST = Trier Social Stress Test; VLDL = very-low-density lipoprotein.

Muscle tension in generalized anxiety disorder: A critical review of the literature

BACKGROUND Generalized anxiety disorder (GAD) is a prevalent, disabling, and often chronic disorder. With a typical recovery rate of only about 40% with current psychological treatments a better understanding of potential psychophysiological mechanisms is vital. METHODS Since the most discriminative somatic symptom of GAD compared to other anxiety disorders is muscle tension this review qualitatively examines the literature on muscle tension as it relates to GAD and muscle relaxation therapy for GAD patients. RESULTS Muscle tension in GAD is poorly understood. Experimental studies refute the often-assumed direct relationship between anxiety and muscle tension. However, muscle relaxation therapies have been as effective as cognitive interventions directly addressing the defining symptom worry. CONCLUSIONS Muscle tension in its objective and subjective representations may play a role in GAD through various pathways that are testable. Future research needs to better examine the different aspects and functions of muscle tension in GAD.

Change point analysis for longitudinal physiological data: detection of cardio-respiratory changes preceding panic attacks.

Statistical methods for detecting changes in longitudinal time series of psychophysiological data are limited. ANOVA and mixed models are not designed to detect the existence, timing, or duration of unknown changes in such data. Change point (CP) analysis was developed to detect distinct changes in time series data. Preliminary reports using CP analysis for fMRI data are promising. Here, we illustrate the application of CP analysis for detecting discrete changes in ambulatory, peripheral physiological data leading up to naturally occurring panic attacks (PAs). The CP method was successful in detecting cardio-respiratory changes that preceded the onset of reported PAs. Furthermore, the changes were unique to the pre-PA period, and were not detected in matched non-PA control periods. The efficacy of our CP method was further validated by detecting patterns of change that were consistent with prominent respiratory theories of panic positing a relation between aberrant respiration and panic etiology.

Does improving mood in depressed patients alter factors that may affect cardiovascular disease risk

To determine if improvement in mood would ameliorate autonomic dysregulation, HPA dysfunction, typical risk factors and C-reactive protein in depressed patients with elevated cardiovascular disease risk (CVD), 48 depressed participants with elevated cardiovascular risk factors were randomized to a cognitive behavioral intervention (CBT) or a waiting list control (WLC) condition. Twenty non-depressed age and risk-matched controls were also recruited. Traditional risk factors (e.g., lipids, blood pressure) and C-reactive protein were assessed pre- and post-treatment six months later. Subjects also underwent a psychophysiological stress test while cardiovascular physiology was measured. Salivary cortisol was measured during the day and during the psychological stress test. At post-treatment, the CBT subjects were significantly less depressed than WLC subjects. There was no significant difference in change scores on any of the traditional risk factors or C-reactive protein, cortisol measures, or cardiovascular physiology, except for triglyceride levels and heart rate, which were significantly lower in treatment compared to control subjects. The normal controls exhibited no change in the variables measured during the same time. A significant improvement in mood may have little impact on most traditional or atypical risk factors, cortisol or cardiophysiology.

The psychophysiology of generalized anxiety disorder: 1. Pretreatment characteristics

Generalized anxiety disorder (GAD) patients have been reported to have more muscle tension than controls, which has provided a rationale for treating them with muscle relaxation therapies (MRT). We tested this rationale by comparing 49 GAD patients with 21 controls. Participants underwent 5-min relaxation tests, during which they either just sat quietly (QS) or sat quietly and tried to relax (R). GAD patients reported themselves to be more worried during the assessment than the controls, had higher heart rates and lower end-tidal pCO2, but not higher muscle tension as measured by multiple EMGs. QS and R did not differ on most psychological and physiological measures, indicating that intention to relax did not affect speed of relaxation. In the GAD group, self-reported anxiety was not associated with electromyographic or autonomic measures. We conclude that GAD is not necessarily characterized by chronic muscle tension, and that this rationale for MRT should be reconsidered.

The psychophysiology of generalized anxiety disorder: 2. Effects of applied relaxation

Muscle relaxation therapy assumes that generalized anxiety disorder (GAD) patients lack the ability to relax but can learn this in therapy. We tested this by randomizing 49 GAD patients to 12 weeks of Applied Relaxation (AR) or waiting. Before, during, and after treatment participants underwent relaxation tests. Before treatment, GAD patients were more worried than healthy controls (n=21) and had higher heart rates and lower end-tidal pCO2, but not higher muscle tension (A. Conrad, L. Isaac, & W.T. Roth, 2008). AR resulted in greater symptomatic improvement than waiting. However, 28% of the AR group dropped out of treatment and some patients relapsed at the 6-week follow-up. There was little evidence that AR participants learned to relax in therapy or that a reduction in anxiety was associated with a decrease in activation. We conclude that the clinical effects of AR in improving GAD symptoms are moderate at most and cannot be attributed to reducing muscle tension or autonomic activation.

Physiological evaluation of psychological treatments for anxiety

Classification of mental disorders has been greatly influenced by a medical model postulating biological abnormalities that underlie its divisions. Particularly in anxiety disorders, physiological symptoms are part of the Diagnostic and Statistical Manual criteria. Therefore, successful therapy should influence physiological as well as cognitive–verbal expressions of anxiety. Nevertheless, despite the well-known limitations of self-report, physiological outcome measures have only occasionally been employed. We searched the literature for treatment studies that attempted to make a physiological argument for the efficacy of a psychological treatment for anxiety. Our search found only a few methodologically sound examples, where normalization of self-report and physiological measures corresponded. The most convincing studies dealt with the treatment of specific phobias and post-traumatic stress disorder.