Ilene C. Siegler

Depression and Long-Term Mortality Risk in Patients With Coronary Artery Disease *

Previous research has established that patients with coronary artery disease (CAD) have an increased risk of death if they are depressed at the time of hospitalization. Follow-up periods have been short in these studies; therefore, the present investigation examined this phenomenon over an extended period of time. Patients with established CAD (n = 1,250) were assessed for depression with the Zung Self-Rating Depression Scale (SDS) and followed for subsequent mortality. Follow-up ranged up to 19.4 years. SDS scores were associated with increased risk of subsequent cardiac death (p = 0.002) and total mortality (p < 0.001) after controlling for initial disease severity and treatment. Patients with moderate to severe depression had a 69% greater odds of cardiac death and a 78% greater odds of mortality from all causes than nondepressed patients. Increased risk was not confined to the initial months after hospitalization. Patients with high SDS scores at baseline still had a higher risk of cardiac death > 5 years later (p < 0.005). Compared with the nondepressed, patients with moderate to severe depression had an 84% greater risk 5 to 10 years later and a 72% greater risk after > 10 years. Patients with mild depression had intermediate levels of risk in all models. The heightened long-term risk of depressed patients suggests that depression may be persistent or frequently recurrent in CAD patients and is associated with CAD progression, triggering of acute events, or both.

A path model of chronic stress, the metabolic syndrome, and coronary heart disease.

Objective We tested a theoretical stress model cross-sectionally and prospectively that examined whether relationships of chronic stress, psychophysiology, and coronary heart disease (CHD) varied in older adult men (N = 47), older adult women not using hormone replacement therapy (HRT) (N = 64), and older adult women using HRT (N = 41). Method Structural equations examined relationships of CHD with 1) chronic stress (caring for a spouse with Alzheimer’s disease and patient functioning), 2) vulnerability (anger and hostility), 3) social resources (supports), 4) psychological distress (burden, sleep problems, and low uplifts), 5) poor health habits (high-caloric, high-fat diet and limited exercise), and 6) the metabolic syndrome (MS) (blood pressure, obesity, insulin, glucose, and lipids). Results Caregiver men had a greater prevalence of CHD (13/24) than did noncaregiver men (6/23) (p < .05) 27 to 30 months after study entry. This was influenced by pathways from caregiving to distress, distress to the MS, and the MS to CHD. In men, poor health habits predicted the MS 15 to 18 months later, and the MS predicted new CHD cases over 27 to 30 months. In women, no “caregiving-CHD” relationship occurred; however, 15 to 18 months after study entry women not using HRT showed “distress-MS” and “MS-CHD” relationships. In women using HRT, associations did not occur among distress, the MS, and CHD, but poor health habits and the MS were related. Conclusions In older men, pathways occurred from chronic stress to distress to the metabolic syndrome, which in turn predicted CHD. Older women not using HRT showed fewer pathways than men; however, over time, distress, the MS, and CHD were related. No psychophysiological pathways occurred in older women using HRT.

Personality at Midlife: Stability, Intrinsic Maturation, and Response to Life Events

Although developmental theories and popular accounts suggest that midlife is a time of turmoil and change, longitudinal studies of personality traits have generally found stability of rank order and little or no change in mean levels. Using data from 2,274 men and women in their 40s retested after 6 to 9 years, the present study examined two hypotheses: (a) that retest correlations should be no higher than about .60 and (b) that there should be small decreases in Neuroticism, Extraversion, and Openness, and small increases in Agreeableness and Conscientiousness. The study also explored the effects of recalled life events on subsequent personality scores. Results did not support the first hypothesis; uncorrected retest correlations uniformly exceeded .60. This was true for all personality traits, including facets of Agreeableness and Conscientiousness not previously included in longitudinal studies. The hypothesized decreases in Neuroticism, Extraversion, and Openness were found, but Conscientiousness showed a small decrease instead of the predicted increase. Life events in general showed very little influence on the levels of personality traits, although some effects were seen for changes in job and marital status that warrant further research.

Characteristics of socially isolated patients with coronary artery disease who are at elevated risk for mortality.

Objectives Social isolation has been linked to poor survival in patients with coronary artery disease (CAD). Few studies have closely examined the psychosocial characteristics of CAD patients who lack social contact. Methods Social isolation was examined as a predictor of mortality in 430 patients with significant CAD. More isolated patients were compared with their less isolated counterparts on factors that might help explain the association between isolation and survival. Results The mortality rate was higher among isolated individuals. Those with three or fewer people in their social support network had a relative risk of 2.43 (p = .001) for cardiac mortality and 2.11 (p = .001) for all-cause mortality, controlling for age and disease severity. Adjustments for income, hostility, and smoking status did not alter the risk due to social isolation. With the exception of lower income, higher hostility ratings, and higher smoking rates, isolated patients did not differ from nonisolated patients on demographic indicators, disease severity, physical functioning, or psychological distress. Isolated patients reported less social support and were less pleased with the way they got along with network members, but they did not report less satisfaction with the amount of social contact received. Conclusions Patients with small social networks had an elevated risk of mortality, but this greater risk was not attributable to confounding with disease severity, demographics, or psychological distress. These findings have implications for mechanisms linking social isolation to mortality and for the application of psychosocial interventions.

Serotonin-Related Gene Polymorphisms and Central Nervous System Serotonin Function *

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover—indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)—in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity×genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender×genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

Hostility patterns and health implications: correlates of Cook-Medley Hostility Scale scores in a national survey.

Correlated Cook-Medley Hostility Scale (Ho) scores with sociodemographic variables in a national survey of 2,536 adults. Multiple regression models revealed that Ho scores were associated with race (p less than .0001), years of education (p less than .001), sex (p less than .001), occupation (p = .0002), and income (p = .0025). Higher scores were found in non-Whites, men, and those of lower socioeconomic status. There was a Race x Income interaction (p less than .005), such that the greatest Ho score differences between the races occurred among those with the lowest incomes. Age was related to Ho scores in a curvilinear fashion: higher scores in the youngest and oldest age groups than in the middle-aged groups (p = .025). Marital status was unrelated to Ho scores. These patterns of hostility are similar to the patterns of health indicators in the population. Because hostility has been found to be associated with adverse health outcomes, hostility may account for some of the demographic variations in health status. However, it is argued that research must first establish the generality of the hostility-health relationship across subgroups of the population.

Depressive Symptoms and Survival of Patients With Coronary Artery Disease

Objective Multiple studies have shown that high levels of depressive symptoms increase the mortality risk of patients with established coronary disease. This investigation divided depressive symptoms into groups to assess their relative effectiveness in predicting survival. Methods Questionnaires about the presence of depressive symptoms were administered to 1250 patients with significant coronary disease while they were hospitalized for diagnostic coronary angiography. Follow-up for mortality due to cardiac disease was conducted annually for up to 19.4 years. Factor analysis was used to divide items on the Zung Self-Rating Depression Scale into four groups: Well-Being, Negative Affect, Somatic, and Appetite. In addition, responses to a single item regarding feelings of hopelessness were available for 920 patients. Results Well-Being and Somatic symptoms significantly predicted survival (p ≤ .01). Negative Affect items were also related to survival (p = .0001) and interacted with age. A 2-SD difference in the Negative Affect term was associated with a relative risk of 1.29 for patients >50 years old and 1.70 for younger ones. Only Negative Affect remained significant in a model with the other symptom groups. Hopelessness also predicted survival with a relative risk of 1.5. Both the Hopelessness and Negative Affect items remained as independent predictors in the same model. All models controlled for severity of disease and treatment. With one exception (income and Hopelessness), results were essentially unchanged by additional controls for age, gender, and income. Conclusions Depressive symptoms differentially predicted survival, with depressive affect and hopelessness being particularly important. These effects were independent of disease severity and somatic symptoms and may be especially important in younger patients.

Depressive symptoms, menopausal status, and climacteric symptoms in women at midlife.

Objective Previous studies have found increased rates of depression in women aged 45 to 54 years, but the factors that influence these rates are not understood. It was assessed whether higher rates of depressive symptoms were associated with menopausal status, climacteric symptoms, and use of hormone replacement therapy. Design Cross-sectional survey. Setting Community sample. Methods Data are from 581 women ages 45 to 54 years who were interviewed by telephone between October 1998 and February 1999. Measures Depression was measured with the abbreviated CES-D, a depressive symptoms screening measure. Women’s reported perception of menopausal stage, frequency of periods in the preceding 12 months, and history of oophorectomy were used to classify their menopausal status into four categories: (1) no indication of menopause; (2) close to menopause; (3) had begun menopause; and (4) had completed menopause. Results There were 168 women (28.9%) who reported a high level (≥10) of depressive symptoms when the abbreviated CES-D was used. In a logistic-regression analysis, significant factors associated with increased depressive symptoms included physical inactivity, inadequate income, use of estrogen/progesterone combination, and presence of climacteric symptoms (trouble sleeping, mood swings, or memory problems). Menopausal status was not associated with depressive symptoms. Conclusions In this sample of women age 45 to 54 years, climacteric symptoms but not menopausal status were associated with higher rates of depressive symptoms.

Central nervous system serotonin function and cardiovascular responses to stress.

Objective The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. Methods Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. Results Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. Conclusions These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.

Trust, Health, and Longevity

Scores on the Rotter Interpersonal Trust Scale were evaluated as predictors of psychological well-being, functional health, and longevity in a sample of 100 men and women who were between 55 and 80 years old at baseline (mean age 66.8). Cross-sectionally, high levels of trust were associated with better self-rated health and more life satisfaction. Follow-up over approximately 8 years found baseline levels of trust to be positively related to subsequent functional health, but not to subsequent life satisfaction. Mortality follow-up after 14 years demonstrated that those with high levels of trust had longer survival (p = .03), a finding that was somewhat weakened by controlling for baseline health ratings. These findings illustrate the health protective effects of high levels of trust and suggest the potential usefulness of the trust concept for understanding successful aging.