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Depression and coronary artery disease
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Symposium abstracts / Journal of Psychosomatic Research 55 (2003) 111–129
substance use disorder, PTSD, or receiving psychiatric care. Forty-five percent had significant depression. BDI scores were significantly higher in patients with PTSD, receiving psychiatric care, or who reported not having a partner. Fifty-four percent of patients had significant anxiety symptoms. Higher anxiety was more likely to be reported by patients who were African American or Hispanic or receiving mental health care. Forty-one percent reported a low or very low QOL. A portion of patients had severe symptoms: aggression (3.9%), depression (11.6%), or anxiety (8.8%); 27.5% reported a very low QOL. Veterans presenting for HCV treatment have a high frequency of clinically significant, active psychological symptoms. It is recommended that patients with severe symptoms (12% in this study) be stabilized with psychiatric intervention before interferon treatment.
Stress and the HPA-axis in aging: description of innovative research (Chair) Spiegel D, Giese-Davis J, Wilhelm FH, O’hara R, GallagherThompson D, (Discussant) Sephton S Recent investigation of the effects of stress and social support on disease progression has shown promise that potentially modifiable environmental factors influence the development of various illnesses. This symposium describes ongoing research that has begun to investigate the role of the hypothalamic – pituitary – adrenal axis (HPA) as a mediator of stress and disease progression in four clinical populations: (1) women with metastatic breast cancer, (2) older adults with depression and cardiovascular disease, (3) individuals with Alzheimer’s disease, and (4) women caring for an elderly family member with significant memory problems. Growing evidence indicates that the cumulative effects of stressors can induce hyperreactivity in the HPA system, producing both direct and indirect effects on endocrine, immune, and cardiovascular systems. The speakers in this symposium will present preliminary results describing the rhythmicity of diurnal variation in salivary cortisol as a useful indicator of HPA dysregulation, as well as the harmful effects of stress in modulating diurnal variation in cortisol in these four important populations.
Emotion regulation may be an important link to circadian cortisol disruption in women with metastatic breast cancer Giese-Davis J, Abercrombie HC, Sephton S, Epel E, Spiegel D Allostatic load, the physiological accumulation of the effects of chronic stressors, has been associated with multiple adverse health outcomes. We found that abnormal diurnal cortisol rhythmicity, one of the prototypes of allostatic load, was strongly predictive of early death in women with metastatic breast cancer. We have found in a second study that 17 women with metastatic breast cancer had significantly more aberrant diurnal cortisol rhythms than did 31 healthy controls. Patients with greater disease severity showed higher mean cortisol levels, smaller waist circumference, and a tendency toward flatter diurnal cortisol rhythms, with peaks occurring later in the day rather than in the morning. Although cortisol slope was not related to psychological or cognitive functioning among patients, controls with aberrant rhythms showed poorer performance on explicit memory tasks, larger waist circumference, lower perceived social support, and a tendency toward higher perceived stress. We also have evidence that diurnal cortisol rhythm was aberrant in repressor and high anxious breast cancer groups and in women expressing less (coded) positive and primary negative affect in their support group. Thus, we have evidence that emotion regulation may be an important link to circadian cortisol disruption in women with metastatic breast cancer.
Depression and coronary artery disease Wilhelm FH, Luce K, Celio CI, Cooke JP, Taylor CB Depression is associated with a higher incidence of coronary artery disease. Although certain pathophysiological mechanisms (e.g., auto-
nomic dysregulation and vascular nonelasticity) have been well documented during baseline, little is known about autonomic and vascular mental stress reactivity in this population. In this preliminary analysis, we assessed how older participants with major depression and cardiac risk factors reacted to a modified Trier Social Stress Test on a variety of cardiovascular and autonomic parameters. Standard parameters indicated that the test was potent: heart rate increased 16 F 6 bpm from baseline, and systolic and diastolic blood pressure increased 45 F 23 and 23 F 10 mm Hg. Rarely assessed parameters such as preejection period (sympathetic control), respiratory sinus arrhythmia (parasympathetic control), vascular compliance, ventricular afterload, and systemic vascular resistance changed similarly, with effect sizes between 0.5 and 2.1. This preliminary data indicate the efficacy of the Trier Social Stress Test for inducing pronounced physiological responses in a variety of systems. Salivary cortisol was collected to further characterize systemic changes under acute stress in depressed patients and their relationship to diurnal cortisol slope. How these measures change after treatment cognitive – behavioral therapy will be evaluated, as well as their relationship with diurnal autonomic function and mood assessed with the LifeShirt system.
HPA impairment in AD O’hara R, Miller T, Noda A, Taylor J, Yesavage J, Bailey A, Hall S, Murphy G Hypercortisolemia and reduced negative feedback inhibition of cortisol secretion are noted concomitants of Alzheimer’s disease. Investigations of the relationship between dementia severity and cortisol levels have yielded mixed findings. Variations in age of onset and stage of illness may impact the relationship between hypercortisolemia and disease progression. It has been suggested that the apolipoprotein E4 allele, a genetic risk factor for AD, negatively impacts HPA axis function in AD patients. We report on an investigation of the impact of APOE genotype on the relationship between cortisol and cognition in 55 patients with Alzheimer’s disease. Overall, we observed elevated levels of cortisol to be associated with lower MMSE scores. This relationship was also observed in a longitudinal follow-up of a subset of these patients who were followed for up to 5 years. However, contrary to our prediction, we observed a significant relationship between cortisol levels and cognition in AD patients negative for the apolipoprotein E4 allele, while no relationship was observed in the AD patients positive for the E4 allele. The implications of these findings for investigations of the pathophysiological impact of HPA impairment in AD and in age-associated cognitive decline will be discussed.
Caregiving and adverse outcomes Gallagher-Thompson D, Singer LS, Depp CA; Long CE, Thompson LW Caregiving for a dementing family member has been associated with adverse health outcomes and higher mortality. A growing body of research has identified compromised immune function, increased cardiac reactivity, and differences in neuroendocrine function compared to matched noncaregiver controls. Activation of the HPA axis was hypothesized to mediate chronic stress in caregivers. We report on an investigation of cortisol dysregulation in Latina and Anglo caregivers. In a pilot study, we compared 42 caregivers and 38 sociodemographically comparable female controls. We found significant differences between caregivers and controls in terms of both absolute levels as well as the rate of decay in cortisol. As predicted, caregivers had higher concentrations of cortisol in their saliva at all time points and showed atypical diurnal variation in cortisol regardless of their ethnicity. For example, the overall slope of change for caregivers was 0.075 and for controls was 0.11. These data provide support for negative physiological effects of the chronic demands of caregiving and were the basis for a psychoeducational intervention targeting stress reduction for this population. We are currently examining the effects of 2
Symposium abstracts / Journal of Psychosomatic Research 55 (2003) 111–129
substance use disorder, PTSD, or receiving psychiatric care. Forty-five percent had significant depression. BDI scores were significantly higher in patients with PTSD, receiving psychiatric care, or who reported not having a partner. Fifty-four percent of patients had significant anxiety symptoms. Higher anxiety was more likely to be reported by patients who were African American or Hispanic or receiving mental health care. Forty-one percent reported a low or very low QOL. A portion of patients had severe symptoms: aggression (3.9%), depression (11.6%), or anxiety (8.8%); 27.5% reported a very low QOL. Veterans presenting for HCV treatment have a high frequency of clinically significant, active psychological symptoms. It is recommended that patients with severe symptoms (12% in this study) be stabilized with psychiatric intervention before interferon treatment.
Stress and the HPA-axis in aging: description of innovative research (Chair) Spiegel D, Giese-Davis J, Wilhelm FH, O’hara R, GallagherThompson D, (Discussant) Sephton S Recent investigation of the effects of stress and social support on disease progression has shown promise that potentially modifiable environmental factors influence the development of various illnesses. This symposium describes ongoing research that has begun to investigate the role of the hypothalamic – pituitary – adrenal axis (HPA) as a mediator of stress and disease progression in four clinical populations: (1) women with metastatic breast cancer, (2) older adults with depression and cardiovascular disease, (3) individuals with Alzheimer’s disease, and (4) women caring for an elderly family member with significant memory problems. Growing evidence indicates that the cumulative effects of stressors can induce hyperreactivity in the HPA system, producing both direct and indirect effects on endocrine, immune, and cardiovascular systems. The speakers in this symposium will present preliminary results describing the rhythmicity of diurnal variation in salivary cortisol as a useful indicator of HPA dysregulation, as well as the harmful effects of stress in modulating diurnal variation in cortisol in these four important populations.
Emotion regulation may be an important link to circadian cortisol disruption in women with metastatic breast cancer Giese-Davis J, Abercrombie HC, Sephton S, Epel E, Spiegel D Allostatic load, the physiological accumulation of the effects of chronic stressors, has been associated with multiple adverse health outcomes. We found that abnormal diurnal cortisol rhythmicity, one of the prototypes of allostatic load, was strongly predictive of early death in women with metastatic breast cancer. We have found in a second study that 17 women with metastatic breast cancer had significantly more aberrant diurnal cortisol rhythms than did 31 healthy controls. Patients with greater disease severity showed higher mean cortisol levels, smaller waist circumference, and a tendency toward flatter diurnal cortisol rhythms, with peaks occurring later in the day rather than in the morning. Although cortisol slope was not related to psychological or cognitive functioning among patients, controls with aberrant rhythms showed poorer performance on explicit memory tasks, larger waist circumference, lower perceived social support, and a tendency toward higher perceived stress. We also have evidence that diurnal cortisol rhythm was aberrant in repressor and high anxious breast cancer groups and in women expressing less (coded) positive and primary negative affect in their support group. Thus, we have evidence that emotion regulation may be an important link to circadian cortisol disruption in women with metastatic breast cancer.
Depression and coronary artery disease Wilhelm FH, Luce K, Celio CI, Cooke JP, Taylor CB Depression is associated with a higher incidence of coronary artery disease. Although certain pathophysiological mechanisms (e.g., auto-
nomic dysregulation and vascular nonelasticity) have been well documented during baseline, little is known about autonomic and vascular mental stress reactivity in this population. In this preliminary analysis, we assessed how older participants with major depression and cardiac risk factors reacted to a modified Trier Social Stress Test on a variety of cardiovascular and autonomic parameters. Standard parameters indicated that the test was potent: heart rate increased 16 F 6 bpm from baseline, and systolic and diastolic blood pressure increased 45 F 23 and 23 F 10 mm Hg. Rarely assessed parameters such as preejection period (sympathetic control), respiratory sinus arrhythmia (parasympathetic control), vascular compliance, ventricular afterload, and systemic vascular resistance changed similarly, with effect sizes between 0.5 and 2.1. This preliminary data indicate the efficacy of the Trier Social Stress Test for inducing pronounced physiological responses in a variety of systems. Salivary cortisol was collected to further characterize systemic changes under acute stress in depressed patients and their relationship to diurnal cortisol slope. How these measures change after treatment cognitive – behavioral therapy will be evaluated, as well as their relationship with diurnal autonomic function and mood assessed with the LifeShirt system.
HPA impairment in AD O’hara R, Miller T, Noda A, Taylor J, Yesavage J, Bailey A, Hall S, Murphy G Hypercortisolemia and reduced negative feedback inhibition of cortisol secretion are noted concomitants of Alzheimer’s disease. Investigations of the relationship between dementia severity and cortisol levels have yielded mixed findings. Variations in age of onset and stage of illness may impact the relationship between hypercortisolemia and disease progression. It has been suggested that the apolipoprotein E4 allele, a genetic risk factor for AD, negatively impacts HPA axis function in AD patients. We report on an investigation of the impact of APOE genotype on the relationship between cortisol and cognition in 55 patients with Alzheimer’s disease. Overall, we observed elevated levels of cortisol to be associated with lower MMSE scores. This relationship was also observed in a longitudinal follow-up of a subset of these patients who were followed for up to 5 years. However, contrary to our prediction, we observed a significant relationship between cortisol levels and cognition in AD patients negative for the apolipoprotein E4 allele, while no relationship was observed in the AD patients positive for the E4 allele. The implications of these findings for investigations of the pathophysiological impact of HPA impairment in AD and in age-associated cognitive decline will be discussed.
Caregiving and adverse outcomes Gallagher-Thompson D, Singer LS, Depp CA; Long CE, Thompson LW Caregiving for a dementing family member has been associated with adverse health outcomes and higher mortality. A growing body of research has identified compromised immune function, increased cardiac reactivity, and differences in neuroendocrine function compared to matched noncaregiver controls. Activation of the HPA axis was hypothesized to mediate chronic stress in caregivers. We report on an investigation of cortisol dysregulation in Latina and Anglo caregivers. In a pilot study, we compared 42 caregivers and 38 sociodemographically comparable female controls. We found significant differences between caregivers and controls in terms of both absolute levels as well as the rate of decay in cortisol. As predicted, caregivers had higher concentrations of cortisol in their saliva at all time points and showed atypical diurnal variation in cortisol regardless of their ethnicity. For example, the overall slope of change for caregivers was 0.075 and for controls was 0.11. These data provide support for negative physiological effects of the chronic demands of caregiving and were the basis for a psychoeducational intervention targeting stress reduction for this population. We are currently examining the effects of 2