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S B Manuck

Publications and source records attributed to S B Manuck.

142 records · Page 8Linked to original sources

Neuropsychological performance of young men who vary in familial risk for hypertension.

Neuropsychological performance was examined as a function of parental history of hypertension. Thirty-five normotensive offspring of two hypertensive parents (PH+/+) were compared to 35 offspring of two normotensive parents (PH-/-) and 35 offspring of one hypertensive and one normotensive parent (PH+/-) on tests of abstract reasoning, attention/mental flexibility, memory, perception, psychomotor skills, and visuospatial/constructional abilities. Results indicated that PH+/+ offspring performed more poorly than PH-/- offspring on tests of visuospatial/constructional and visuoperceptual ability; PH+/- offspring tended to score lower than PH-/- offspring on these tests. These findings were independent of age, education, diastolic blood pressure levels, average alcohol consumption, trait anxiety, and depression. Results of this study may indicate subtle central nervous system involvement associated with familial risk for hypertension.

Adolescent↗

Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys.

Epidemiologic studies link plasma cholesterol reduction to increased mortality rates as a result of suicide, violence, and accidents. Deficient central serotonergic activity is similarly associated with violence and suicidal behavior. We investigated the relationship among dietary and plasma cholesterol, social behavior, and the serotonin system as a possible explanation for these findings. Juvenile cynomolgus monkeys (eight female and nine male) were fed a diet high in fat and either high or low in cholesterol. We then evaluated their behavior over an 8-month period. Plasma lipids and cerebrospinal fluid metabolites of serotonin, norepinephrine, and dopamine were assessed on two occasions, at 4 and 5.5 months after the initiation of behavioral observations. Animals that consumed a low-cholesterol diet were more aggressive, less affiliative, and had lower cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid than did their high-cholesterol counterparts (p < .05 for each). The association among dietary cholesterol, serotonergic activity, and social behavior was consistent with data from other species and experiments and suggested that dietary lipids can influence brain neurochemistry and behavior; this phenomenon could be relevant to our understanding of the increase in suicide and violence-related death observed in cholesterol-lowering trials.

Aggression↗

The pathogenicity of behavior and its neuroendocrine mediation: an example from coronary artery disease.

Although it is frequently hypothesized that perturbations of the body's principal axes of neuroendocrine response, especially the sympathetic-adrenomedullary and pituitary-adrenocortical systems, mediate psychosocial influences on disease, evidence directly supporting this hypothesis is sparse at best and, for most disease entities, nonexistent. In this article, we illustrate a research strategy aimed at elucidating the role of behavior in disease pathogenesis by focusing on a single pathologic process--disease of the coronary vasculature--and emphasizing experimental evidence linking such disease to both behavior and sympathoadrenal activation in nonhuman primates. In cynomolgus monkeys, it is found that several psychosocial variables, e.g., social instability, behavioral dominance (in males), and subordination (in females), promote coronary atherogenesis, either independently or in interaction. Animals exhibiting a heightened cardiac responsivity to stress (reactions of probable sympathetic origin) also develop the most extensive coronary lesions and beta-adrenoreceptor blockade prevents the behavioral exacerbation of atherosclerosis. Social stress causes injury to arterial endothelium (also preventable by adrenoreceptor blockade) and, among chronically stressed animals, impairs endothelium-dependent vasomotor responses of the coronary arteries. It is suggested that similar research programs might elucidate the influence of behavior and neuroendocrine factors on the pathogenesis of other disease states and conditions, including susceptibility to infection.

Animals↗

Stability of individual differences in cellular immune responses to acute psychological stress.

To determine the stability of individual differences in cellular immune reactions to acute mental stress, we correlated enumerative and functional lymphocyte responses to an evaluative speech task across two experimental sessions scheduled 2 weeks apart in 30 young men. Relative to pretask baseline measurements, the speech stressor elicited a diminished proliferative response to phytohemagglutinin and concanavalin A, a decrease in circulating CD19 lymphocytes, and an increase in both CD8 and CD56 lymphocytes across the two occasions of testing. Test-retest correlations were significant for the magnitude of change in proliferative response to PHA (r = .50, p < .005) and in numbers of circulating CD8 and CD56 cells (r = .53, and .42, respectively; p's < .02). Concomitant cardiovascular responses also correlated significantly over the two experimental sessions (heart rate: r = .78, p < .0001; systolic and diastolic blood pressure: r = .79 and .48, p < .0001 and .007). These data provide initial evidence that interindividual variability of cellular immune responses to acute psychological stress is moderately reproducible on retesting and may therefore denote a stable dimension of individual differences.

Adolescent↗

Adrenergic blockade ameliorates cellular immune responses to mental stress in humans.

This study evaluated the sympathoadrenal modulation of behaviorally evoked immune responses by administration of a nonselective adrenoceptor antagonist (labetalol) to subjects exposed to mental stress. In a 2 x 2 factorial design, subjects were assigned to a labetalol or saline condition and, within each condition, were exposed either to acute laboratory stress or no stress (control). Lymphocyte subsets, natural killer (NK) cell cytotoxicity, and T cell proliferation to phytohemagglutinin and concanavalin A were assessed pre-experimentally, at baseline after infusion and after 18 minutes of mental stress (or rest). By comparison with the other three conditions, the saline-stress group showed a greater peripheral NK cell number and cytotoxicity, lower mitogenic response to phytohemagglutinin and concanavalin A, and diminished ratio of CD4:CD8 cells after the stressor. As predicted, immune responses did not differ among the remaining groups (labetalol-stress, saline-rest, labetalol-rest). Group differences in NK cell cytotoxicity were not significant after controlling for differences in NK cell numbers. These findings demonstrate that the occurrence of certain immunologic responses to acute psychological stress are dependent on concomitant activation of the sympathetic nervous system.

Adolescent↗

Stress, reactivity, and disease.

In summary, this work is an ambitious attempt to address some key issues in regard to the clinical importance of reactivity. The authors should be complimented for their efforts in addressing these issues, especially in small children. However, it is necessary to view their data in light of both the studies' strengths and weaknesses and to evaluate the implications of the work in light of existing theory and evidence. From this perspective, we think the work provokes interesting ways to think about reactivity. However, it leaves to subsequent research the task of systematically addressing the many issues that it raises.

Heart Rate↗

Psychosocial factors, sex differences, and atherosclerosis: lessons from animal models.

OBJECTIVE: Premenopausal women, compared with men, are relatively spared from coronary heart disease and the underlying atherosclerosis. Our purpose has been to elucidate the reason for this difference and to explore the role of behavioral factors in this phenomenon. METHODS: Studies employed socially housed cynomolgus macaques (Macaca fascicularis) fed an atherogenic diet and subjected to behavioral observations. Ovariectomy, with or without hormone replacement, was used to test specific hypotheses about estrogen's role in the protection of females from atherosclerosis and coronary heart disease. RESULTS: Female macaques, like women, are resistant to atherosclerosis. However, this resistance is modified by social status-dominant monkeys develop little atherosclerosis, whereas subordinates resemble males in the amount of lesion that occurs. Subordinate females also are characterized by hypercortisolemia, behavioral dysfunction, and impaired ovarian function; the resulting low concentrations of circulating estrogen perhaps explain their accelerated atherosclerosis. Notably, atherosclerosis is exacerbated in ovariectomized monkeys but is suppressed in association with pregnancy, a hyperestrogenic state. Moreover, exogenous estrogen (an oral contraceptive) inhibits atherosclerosis in premenopausal social subordinates. CONCLUSIONS: To the extent that our results apply to women, they highlight the potential importance of behavioral stressors and their effects on estrogen activity in the premenopausal development of atherosclerosis. The triad of hypercortisolism, ovarian impairment, and psychiatric morbidity found in monkeys also occurs in women and may represent a high-risk state for disorders of the cardiovascular system and perhaps, other estrogen-sensitive tissues.

Adrenocortical Hyperfunction↗

Chronic social stress, social status, and susceptibility to upper respiratory infections in nonhuman primates.

OBJECTIVE: The objective of the study was to assess the roles of social stress and social status in susceptibility to upper respiratory infection. METHOD: Sixty male cynomolgus monkeys were randomly assigned to stable or unstable social conditions for 15 months. Two markers of social status, social rank and percent of behaviors that were submissive, were assessed at independent observation periods. Endocrine, immune, and behavioral responses were each assessed (at 3-month intervals) during the 9th through 14th months of the study. At the beginning of the 15th month, all animals were exposed to a virus (adenovirus) that causes a common-cold-like illness. The primary outcome was whether or not an animal developed an infection (shed virus) after viral exposure. RESULTS: Although the social instability manipulation was associated with increased agonistic behavior as indicated by minor injuries and elevated norepinephrine responses to social reorganizations, the manipulation did not influence the probability of being infected by the virus. However, low social status (as assessed by either marker) was associated with a substantially greater probability of being infected. It was also associated with less body weight, greater elevated cortisol responses to social reorganizations, and less aggressive behavior. However, none of these characteristics could account for the relation between social status and infection. CONCLUSIONS: Social stress was not associated with susceptibility to infection. However, animals with lower social status were at higher risk than high social status animals.

Adenoviruses, Simian↗

Serum cholesterol and intellectual performance.

OBJECTIVE: The current investigation sought to determine whether intellectual performance is related to serum lipid concentrations. METHODS: Subjects were 177 healthy, Caucasian adult males and females, aged 25 to 60 years, with widely varying total cholesterol concentrations. Crystallized intelligence was estimated from the Information and Vocabulary subtests of the Wechsler Adult Intelligence Scale, Revised (WAIS-R). Fluid intelligence was estimated from the WAIS-R Block Design subtest, and from a computerized version of the Letter Rotation test. RESULTS: Controlling for age, better performance on both Information and Vocabulary subtests was associated with lower total and low-density lipoprotein (LDL) cholesterol and triglyceride concentrations (r's = -.24 to -.35, p's < .005). In contrast, better performance on Block Design was correlated with higher total and LDL cholesterol (r's = .22 to .23, p's < .005). Letter rotation response latency was unrelated to serum lipids. CONCLUSION: These opposing relationships between serum cholesterol and different dimensions of intellectual performance, on the one hand, may reflect the propensity of knowledgeable individuals to consume low fat diets, and on the other hand, suggest that serum cholesterol concentration may be a correlate of brain nutrients important to mental efficiency.

Adult↗

Active coping and cardiovascular reactivity: a multiplicity of influences.

OBJECTIVE: Active coping enhances cardiovascular response presumably by beta-adrenergically mediated myocardial activation. This study examined impedance-derived hemodynamic parameters underlying blood pressure response to two laboratory tasks requiring active coping, performed either with or without an appetitive (i.e., monetary) incentive. METHOD: Forty-eight healthy, young men completed the Stroop Color-Word Test and Mirror Tracing. Half received no incentive, whereas half were provided with a monetary incentive as an active coping manipulation. Task-related changes in blood pressure, heart rate, systolic time intervals, and hemodynamic parameters were monitored. Psychological responses to the tasks were also obtained. RESULTS: On average, incentive virtually doubled blood pressure response to both Stroop and Mirror Tracing. The change in blood pressure was explained predominantly by a concomitant increase in total peripheral resistance. Heart rate response was also enhanced substantially with incentive. Individuals in the incentive condition reported greater interest in the task, but less perceived control, than persons in the no-incentive condition. CONCLUSIONS: The incentive-related increase in total peripheral resistance, combined with an absence of enhanced stroke volume, cardiac output, or preejection period response, indicates that active coping may, under certain conditions, elevate blood pressure via increased systemic resistance, presumably reflecting alpha-adrenergic activation. Furthermore, the enhanced heart rate associated with incentive may reflect a withdrawal of parasympathetic influence.

Adaptation, Psychological↗

Ambulatory blood pressure responses and the circumplex model of mood: a 4-day study.

BACKGROUND: The relation between mood or emotions and concurrent ambulatory blood pressure responses holds both fundamental and clinical interest. METHODS: The primary sample consisted of 69 normotensive or borderline hypertensive but otherwise healthy adult males. The validation sample consisted of 85 healthy male undergraduate college students. Both samples underwent half-hourly 24-hour ambulatory blood pressure measurements on four separate workdays, 1 week apart. At each ambulatory measurement, subjects recorded their behavior, environment, and mood. The circular mood scale, a circular visual analogue scale based on the circumplex model of mood, was used to reflect the totality of a participant's affective state space. Longitudinal random effects regression models were applied in the data analysis. RESULTS: The results for both samples were quite similar. Sleep and posture had the greatest influence on ambulatory blood pressure and heart rate. The effects of the environmental setting, social setting, and consumption were modest but statistically significant. Independent of these covariates, mood exerted a significant effect on blood pressure and heart rate. Relative to the "mellow" default category, blood pressure increased both for "anxious/annoyed" and "elated/happy" and decreased during "disengaged/sleepy" mood. The range of mood-related blood pressure estimates was 6.0/3.7 mm Hg. CONCLUSIONS: The pattern of blood pressure responses suggests that they were related to the degree of engagement of a mood rather than the degree of unpleasantness. The hypothesis that posits that negative affect-related cardiovascular reactivity mediates the observed correlation between negative affect and disease risk should be reconsidered.

Adolescent↗

Does socioeconomic status relate to central serotonergic responsivity in healthy adults?

OBJECTIVE: We tested whether low SES was associated with reduced central serotonergic responsivity in a community sample of adult men and women and the extent to which standardized measures of aggression and impulsivity mediate the association. METHODS: A total of 270 adults who were enrolled in a clinical trial on the neurobehavioral effects of lipid lowering were given a neuropharmacologic challenge (plasma prolactin response to orally administered fenfluramine) to measure serotonergic responsivity. Measures of family income and educational attainment were standardized and summed to derive an overall index of SES. Scores from the Brown-Goodwin Life History of Aggression interview, the Barratt Impulsiveness Scale, and the Angry Hostility subscale from the NEO Personality Inventory were also standardized and summed to form an aggression/impulsivity score. RESULTS: Low SES was correlated with low prolactin responses to the fenfluramine challenge in the full sample (r = .15) as well as in whites, men, and women evaluated separately. Although the standardized SES score was correlated inversely with aggression/impulsivity measure (r = -.19, p < .01), the association between SES and prolactin responses remained significant when statistical adjustments were made for age, gender, body mass index, and aggression/impulsivity scores. CONCLUSIONS: Blunted serotonergic responsivity is associated with low social class as measured by annual family income and educational attainment.

Adult↗

Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone.

Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen-deficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n = 17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n = 20), and 3) continuously administered 17-beta estradiol (n = 18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one-half) in animals in both hormone replacement groups (p less than or equal to 0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subfraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women.

Animals↗

Social status, environment, and atherosclerosis in cynomolgus monkeys.

The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis in adult male cynomolgus monkeys (Macaca fascicularis). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment in the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean intimal area measurement, based on all arterial sections, served as a coronary index for each animal. Results indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed in stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (i.e., unstable) subordinates. A similar pattern was observed in the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen in the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences in total serum cholesterol or high density lipoprotein cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an individual behavioral characteristic) is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (i.e., under behavioral challenge).

Animals↗

Behavioral antecedents of coronary heart disease and atherosclerosis.

Over 50 epidemiologic, clinical, and experimental studies of behavioral influences on atherosclerosis and CHD have been reviewed; of these investigations, no more than five were published prior to 1975. Despite some inconsistencies and occasional conceptual and methodologic problems in the studies comprising this relatively young literature, the preponderance of available evidence indicates that psychosocial variables play a significant role in coronary disease. To summarize briefly, the Type A behavior pattern has been found predictive of new CHD in nearly all prospective studies of initially healthy individuals, and therapeutic modification of Type A has been shown to reduce risk of recurrent nonfatal MI. Among most prospective studies of post-MI patients and of persons at heightened risk for CHD due to elevations in traditional risk factors, however, Type A has not been found to predict, respectively, recurrence of MI or initial clinical events. Additionally, Type A individuals have shown more extensive coronary artery atherosclerosis on angiographic examination than Type Bs in a minority of studies, and, generally, only where Type A behavior has been measured by the SI. It is noted that many of these clinical studies may be faulted, though, for their use of small and heterogeneous patient samples and for possible biases in the selection and recruitment of subjects. In contrast to the globally defined Type A pattern, a high potential for hostility and an inability or unwillingness to express anger (anger-in) have emerged as significant predictors or correlates of coronary disease in all epidemiologic and clinical studies in which these variables have been examined. These consistent results suggest that a predisposition to hostility and anger, and the inhibited expression of such feelings, represent a "toxic" component of the Type A pattern. Several recent prospective investigations indicate also that high levels of life stress and possession of poor or inadequate social resources are predictive of CHD. The concepts of life stress, social network, and social support, as well as relationships among these variables, are not well-understood, however, and much additional work is needed to identify specific pathogenic and protective attributes of the social environment. In addition to studies of the psychosocial antecedents of CHD in human beings, there now are several published studies of behavioral influences on the development of coronary lesions in animal models.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteriosclerosis↗

Pathogenesis of carotid bifurcation atherosclerosis in cynomolgus monkeys.

We report here the effect of diet and social environment on the carotid bifurcation atherosclerosis of 60 adult male cynomolgus monkeys (Macaca fascicularis) fed either an atherogenic diet (AD) or a more "prudent" diet (PD). Animals within each dietary condition lived either in unstable social groupings (which had their memberships reorganized on a regular basis) or in stable groupings. The experiment lasted 22 months, after which animals were necropsied and the extent of atherosclerosis was measured both at the carotid bifurcation and at other arterial sites. Carotid bifurcation atherosclerosis (CBA) was significantly more extensive and severe among animals fed the AD diet. Among these animals, all of which were normotensive, lesion extent was positively associated with both plasma cholesterol concentrations and heart rate response to behavioral stress, and negatively associated with the ability to clear glucose. No experimental variables correlated with the CBA of the PD animals; these lesions, some of which were extensive, were probably pre-existing. The social conditions and individual behavior patterns of the animals had no effect on CBA in either group, despite a pronounced effect on the coronary arteries (CA) of the same animals. While the overall correlation between CBA and CA atherosclerosis was not high, animals with extensive CBA almost always had extensive CA atherosclerosis. The factors influencing CBA in the cynomolgus monkey may be similar to those affecting humans.

Animals↗