Redford B. Williams

Hostility, CHD Incidence, and Total Mortality: A 25-Year Follow-Up Study of 255 Physicians

High levels of hostility as assessed by a MMPI scale (Ho) have been found associated with increased levels of arteriographically documented coronary atherosclerosis. In this study we examined the relationship between hostility and subsequent health status in a 25-year follow-up of 255 medical students who completed the MMPI while in medical school. High Ho scores were found to be predictive of both clinical coronary disease incidence and total mortality.

Vulnerability genes or plasticity genes

The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility’ is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the absence of adversity. Recent G × E findings consistent with this perspective and involving monoamine oxidase-A, 5-HTTLPR (5-hydroxytryptamine-linked polymorphic region polymorphism) and dopamine receptor D4 (DRD4) are reviewed for illustrative purposes. Results considered suggest that putative ‘vulnerability genes’ or ‘risk alleles’ might, at times, be more appropriately conceptualized as ‘plasticity genes’, because they seem to make individuals more susceptible to environmental influences—for better and for worse.

The Cook-medley hostility scale: item content and ability to predict survival.

&NA; Previous studies have identified the MMPI‐based Cook and Medley hostility scale (Ho) as a predictor of health outcomes. To achieve a better understanding of the construct measured by this scale, Ho items were classified on an a priori basis. Six subsets were identified: Cynicism, Hostile Attributions, Hostile Affect, Aggressive Responding, Social Avoidance, and Other. Study 1 examined the correlations of these subsets with scales of the NEO Personality Inventory in two samples of undergraduates. Good convergent and discriminant validity were demonstrated, but there was some evidence that items in the Social Avoidance and Other categories reflect constructs other than hostility. Study 2 examined the ability of the Ho scale and the item subsets to predict the 1985 survival of 118 lawyers who had completed the MMPI in 1956 and 1957. As in previous studies, those with high scores had poorer survival (chi 2 = 6.37, p = 0.012). Unlike previous studies, the relation between Ho scores and survival was linear. Cynicism, Hostile Affect, and Aggressive Responding subsets were related to survival, whereas the other subsets were not. The sum of the three predictive subsets, with a chi 2 of 9.45 (p = 0.002), was a better predictor than the full Ho scale, suggesting that it may be possible to refine the scale and achieve an even more effective measure of those aspects of hostility that are deleterious to health.

Type A behavior, hostility, and coronary atherosclerosis.

&NA; Type A behavior pattern was assessed using the structured interview and hostility level was assessed using a subscale of the Minnesota Multiphase Personality Inventory in 424 patients who underwent diagnostic coronary arteriography for suspected coronary heart disease. In contrast to non‐Type A patients, a significantly greater proportion of Type A patients had at least one artery with a clinically significant occlusion of 75% or greater. In addition, only 48% of those patients with very low scores (less than or equal to 10) on the Hostility scale exhibited a significant occlusion; in contrast, patients in all groups scoring higher than 10 on the Hostility scale showed a 70% rate of significant disease. The essential difference between low and high scorers on the Hostility scale appears to consist of an unwillingness on the part of the low scorers to endorse items reflective of the attitude that others are bad, selfish, and exploitive. Multivariate analysis showed that both Type A behavior pattern and Hostility score are independently related to presence of atherosclerosis. In this analysis, however, Hostility score emerged as more related to presence of atherosclerosis than Type A behavior pattern. These findings confirm previous observations of increased coronary atherosclerosis among Type A patients. They suggest further that an attitudinal set reflective of hostility toward people in general is over and above that accounted for by Type A behavior pattern. These findings also suggest that interventions to reduce the contribution of behavioral patterns to coronary disease risk might profitably focus especially closely on reduction of anger and hostility.

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.

Components of type A, hostility, and anger-in: relationship to angiographic findings

&NA; Previous research has linked the Type A coronary‐prone behavior pattern to angiographically documented severity of coronary atherosclerosis (CAD). The present study sought through component scoring of the Type A Structured Interview (SI) to determine what elements of the multidimensional Type A pattern are related to coronary disease severity in a selected group of patients with minimal or severe CAD. Multivariate analyses controlling for the major risk factors showed no relationship between global Type A and extent of disease. Of all attributes measured, only Potential for Hostility and Anger‐In were significantly and positively associated with the disease severity, including angina symptoms and number of myocardial infarctions. Further analysis revealed that Potential for Hostility and Anger‐In were interactive in their association, such that Potential for Hostility was associated with disease endpoints only for patients who were high on the Anger‐In dimension. These findings support previous research in suggesting that anger and hostility may be the critical aspects of the Type A pattern in predisposing individuals to risk of CAD.

Social support, Type A behavior, and coronary artery disease

&NA; The interaction of Type A behavior and social support in relation to the degree of coronary artery disease (CAD) severity was investigated. One hundred thirteen patients undergoing diagnostic coronary angiography received the Type A structured interview (SI) and completed a battery of psychometric tests, including the Perceived Social Support Scale (PSSS). Statistical analyses revealed a Type by social support interaction, such that the probability of significant CAD was inversely related to the level of social support for Type As but not Type Bs. Type As with low levels of social support had more severe CAD than Type As with high levels of social support. On the other hand, this relationship was not present for Type Bs. These results are consistent with the hypothesis that social support moderates the long‐term health consequences of the Type A behavior pattern.

Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression

Dysregulation of central serotonin neurotransmission has been widely suspected as an important contributor to major depression. Here, we identify a (G1463A) single nucleotide polymorphism (SNP) in the rate-limiting enzyme of neuronal serotonin synthesis, human tryptophan hydroxylase-2 (hTPH2). The functional SNP in hTPH2 replaces the highly conserved Arg441 with His, which results in approximately 80% loss of function in serotonin production when hTPH2 is expressed in PC12 cells. Strikingly, SNP analysis in a cohort of 87 patients with unipolar major depression revealed that nine patients carried the mutant (1463A) allele, while among 219 controls, three subjects carried this mutation. In addition, this functional SNP was not found in a cohort of 60 bipolar disorder patients. Identification of a loss-of-function mutation in hTPH2 suggests that defect in brain serotonin synthesis may represent an important risk factor for unipolar major depression.

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.

Situational determinants of cardiovascular and emotional reactivity in high and low hostile men.

&NA; Various epidemiologic studies have found that high scores on the Cook and Medley Hostility (Ho) scale are associated with increased risk of coronary heart disease (CHD), severity of atherosclerosis, and all‐cause mortality. One plausible biological mechanism suspected of contributing to increased risk of CHD is sympathetic nervous system‐mediated hyperresponsivity to environmental stressors. The present study evaluated cardiovascular reactivity among young men with high versus low Ho scores during performance of an anagram task with or without harassment. Compared to performing the task alone, harassment led to increased cardiovascular arousal that was more pronounced for the high Ho subjects than the low Ho subjects. Moreover, harassment produced increases in self‐rated anger, irritation, and tension, but it was only among those subjects with high Ho scores that increased anger and irritation were associated with enhanced cardiovascular arousal. While suggesting a role for anger‐ and irritation‐induced cardiovascular arousal in pathogenesis of CHD, these findings indicate that situation characteristics mediate the relationship between Ho scores and cardiovascular reactivity, and that there may be a differential biological link between anger/irritation and cardiovascular responses in men with high and low Ho scores.