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Biomedical subjects

S B Manuck

Publications and source records attributed to S B Manuck.

At least 37 records · Page 2Linked to original sources
PubMed1998

Recovery from major depression is not associated with normalization of serotonergic function.

BACKGROUND: Plasma prolactin response to fenfluramine, a serotonergic agent, is typically blunted in moderately to severely depressed adults when compared to healthy controls. It is not clear, however, whether this dysregulation represents an acute change during symptomatic depression or a chronic disturbance. METHODS: In the current study, the prolactin responses to D,L-fenfluramine (weight-adjusted oral dose) of 29 adults who had a history of at least one major depressive episode (DSM-III-R criteria), but not during the past year, were compared to the prolactin responses of 58 age-, sex-, and socioeconomic status-matched adults without a lifetime history of major depression. RESULTS: Individuals with a positive history of major depression had significantly lower peak prolactin responses than controls. This finding was not attributable to weight, fenfluramine bioavailability, or baseline prolactin levels. CONCLUSIONS: This is the first investigation to compare men and women with a history of depression but not depressed at the time of the fenfluramine challenge to a similar group of healthy controls. The results are consistent with the hypothesis that central serotonergic activity is persistently disturbed in adults who experience depressive episodes.

Adult↗
PubMed1998

Aggression, impulsivity, and central nervous system serotonergic responsivity in a nonpatient sample.

To test the hypothesis that traits of aggression and impulsivity correlate negatively with central serotonergic system function in a nonpatient population, a standard fenfluramine challenge (for assessment of serotonergic responsivity) and behavioral measurements germane to aggression/impulsivity were administered to a community-derived sample of 119 men and women. In men, peak prolactin responses to fenfluramine correlated significantly with an interview-assessed life history of aggression (r = -.40, p < .002), the Barratt Impulsiveness Scale (r = -.30, p < .03), and traits of Conscientiousness (r = +.30, p < .03), Neuroticism (r = -.31, p < .02) and Angry Hostility (r = -.35, p < .01) on the NEO-Personality Inventory. No significant relationships were observed across all women, although subanalyses restricted to postmenopausal subjects (in whom ovarian influences on prolactin secretion may be mitigated because of diminished estrogen) showed a pattern of behavioral associations somewhat similar to that seen in men. By extending documented relationships between an index of central serotonergic system function and traits of aggression and impulsivity to a more normative range of population variability than is represented in prior literature, this study supports speculation that these associations reflect a basic neurobehavioral dimension of individual differences.

Adult↗
PubMed1998

Cerebral blood flow in hypertensive patients: an initial report of reduced and compensatory blood flow responses during performance of two cognitive tasks.

We asked whether the altered cerebral vasculature associated with essential hypertension might dampen or redirect the regional cerebral blood flow (rCBF) response to cognitive work. Relative rCBF was assessed with [(15)O]water positron emission tomography during a working memory task, a memory span task, and two perceptual control tasks. Unmedicated hypertensive patients and control subjects differed in rCBF response during both memory tasks. Hypertensives showed relatively diminished rCBF responses in right hemisphere areas combined with compensatory activation of homologous areas in the left cerebral cortex. Essential hypertension appears to selectively influence the circulatory reserve of portions of cerebral cortex and secondarily induce recruitment of other cortical areas to process certain tasks.

Aged↗
PubMed1998

Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans.

Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: r=-0.36 and r=-0.29, respectively (P<0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (P</=0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised the lowest quartile were 2.6 times more likely to have a resting systolic/diastolic BP of >135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenesis of hypertension.

Adult↗
PubMed1998

Acute hemoconcentration during psychological stress: assessment of hemorheologic factors.

In this study, we examined the effects of acute psychological stress on hemorheology and hemoconcentration in humans and the associations between stress-induced cardiovascular reactivity and hemorheological changes. Stress-induced changes in hemorheology and hemorheological changes were assessed by measuring plasma viscosity, calculated plasma volume, and total plasma protein. Cardiovascular, hemorheologic, and hematologic variables were assessed in 29 healthy men during a 30-min baseline period and a 5-min speech task. Results indicated that the speech task produced a significant increase in plasma viscosity and total plasma protein and a significant decrease in calculated plasma volume. Significant correlations were observed between changes in blood pressure and heart rate and changes in plasma viscosity, total plasma protein, and calculated plasma volume. These results provide direct evidence that acute psychological stress can produce significant changes in hemorheology and hemoconcentration. The most likely mechanism for the stress-induced hemoconcentration effect is a fluid shift from the vascular to the interstitial spaces through increased blood pressure.

Journal Article↗
PubMed1997

Assessing the observed relationship between low cholesterol and violence-related mortality. Implications for suicide risk.

Health advocacy groups advise all Americans to restrict their dietary intake of saturated fat and cholesterol as an efficacious and safe way to lower plasma cholesterol concentrations and thus reduce the risk of coronary heart disease and other atherosclerotic disorders. However, accumulating evidence suggests that naturally low or clinically reduced cholesterol is associated with increased nonillness mortality (principally suicide and accidents). Other evidence suggests that such increases in suicide and traumatic death may be mediated by the adverse changes in behavior and mood that sometimes accompany low or reduced cholesterol. These observations provided the rationale for an ongoing series of studies in monkeys designed to explore the hypothesis that alterations in dietary or plasma cholesterol influence behavior and that such effects are potentiated by lipid-induced changes in brain chemistry. In fact, the investigations in monkeys reveal that reductions in plasma cholesterol increase the tendency to engage in impulsive or violent behavior through a mechanism involving central serotonergic activity. It is speculated that the cholesterol-serotonin-behavior association represents a mechanism evolved to increase hunting or competitive foraging behavior in the face of nutritional threats signaled by a decline in total serum cholesterol (TC). The epidemiological and experimental data could be interpreted as having two implications for public health: (1) low-cholesterol may be a marker for risk of suicide or traumatic death and (2) cholesterol lowering may have adverse effects for some individuals under some circumstances.

Animals↗
PubMed1997

Exaggerated blood pressure responses during mental stress are associated with enhanced carotid atherosclerosis in middle-aged Finnish men: findings from the Kuopio Ischemic Heart Disease Study.

BACKGROUND: Exaggerated cardiovascular reactivity to mental stress is hypothesized to increase atherosclerotic risk. We examined this hypothesis using cross-sectional data from the Kuopio Ischemic Heart Disease study, a population-based epidemiological sample. METHODS AND RESULTS: 901 Eastern Finnish men from four age cohorts (age, 42 to 60 years) were administered a standardized testing battery to assess cardiovascular reactivity to mental stress. Ultrasound measures of intima-medial thickness (IMT) and plaque height from the common carotid arteries were used as noninvasive markers of atherosclerosis. Diastolic blood pressure (DBP) responses to mental stress were significantly associated with mean IMT (b=.021, P=.006), maximum IMT (b=.026, P=.013), and mean plaque height (b=.017, P=.041). Significant associations were also shown between stress-related systolic blood pressure (SBP) reactivity and mean IMT (b=.0151, P=.042). When examined separately by age, associations with IMT were significant only in the youngest half of the sample (age, 46 and 52 years, n=433; for mean IMT, DBP b=.033, P=.0002, SBP b=.0266, P=.003; for maximum IMT, DBP b=.039, P=.002, SBP b=.032, P=.011). Results remained significant in the younger subjects after adjustment for smoking, lipid profiles, fasting glucose, and resting blood pressure (b=.024, P=.011); results also remained significant in a subgroup of unmedicated younger subjects without symptomatic cardiovascular disease (n=135; for SBP reactivity, b=.031, P=.036; for DBP, b=.037, P=.007). CONCLUSIONS: The tendency to show exaggerated pressor responses to mental stress is a significant independent correlate of atherosclerosis in this population sample of Finnish men. The effect does not appear to be accounted for by the confounding influence of other risk factors or preexisting clinical disease.

Adult↗
PubMed1997

Effects of lovastatin on the immune system.

Laboratory investigations have demonstrated that blockade of HMG-CoA reductase in vitro reduces lymphocyte proliferation in response to mitogens as well as other facets of the immune system, such as natural killer cell cytotoxicity. However, in this randomized and double-blind clinical investigation, treatment with 20-mg lovastatin for 6 months did not significantly alter several enumerative and functional characteristics of circulating immune cells.

Adult↗
PubMed1997

Immune system differences in men with hypo- or hypercholesterolemia.

Substantial epidemiologic evidence indicates that relative hypocholesterolemia in apparently healthy individuals is associated with increased subsequent mortality from cancer and other nonatherosclerotic causes of death. To test a hypothesis potentially underlying these unexplained associations, we evaluated whether individuals with hypo- and hypercholesterolemia differ in various enumerative and functional indices of the immune system. Nineteen healthy adult men with a mean age of 46 years and a mean total cholesterol concentration of 151 mg/dl constituted a low cholesterol group and were compared with 39 men of a similar age whose total cholesterol averaged 261 mg/dl. Relative to the high cholesterol group, hypocholesterolemic men had significantly fewer circulating lymphocytes, fewer total T cells, and fewer CD8+ cells (P's < 0.05). Trends toward fewer CD4+ cells and less IL-2 release in response to PHA were also noted in the low, compared to the high, cholesterol group. The low and high cholesterol groups did not differ in number of B lymphocytes, level of PHA-induced proliferation, number of natural killer (NK) cells, or degree of NK cytotoxicity. These data provide preliminary evidence of immune system differences in healthy individuals with hypo- and hypercholesterolemia.

Adult↗
PubMed1997

Lymphocyte subset redistribution during acute laboratory stress in young adults: mediating effects of hemoconcentration.

Acute psychological stress is known to alter the distribution of circulating lymphocyte subsets and also to cause a reduction of plasma volume. Data were reanalyzed from 4 previously reported studies (E. A. Bachen et al., 1995; T. B. Herbert et al., 1994; A. L. Marsland, S. B. Manuck, T. V. Fazzari, C. J. Stewart, & B. S. Rabin, 1995; A. L. Marsland, S. B. Manuck, P. Wood, et al., 1995) to determine the extent to which changes in the concentration of lymphocyte subsets are attributable to such hemoconcentration. Meta-analytic procedures showed circulating concentrations of T-suppressor/cytotoxic (CD8) and natural killer (NK) cells to increase following acute laboratory challenge, whereas T-helper (CD4) and B- (CD19) cell populations did not change. Adjustments for concomitant hemoconcentration reduced the magnitude of stress-related increases in CD8 and NK cells significantly and revealed a decrease in CD4 and CD19 cell concentrations from baseline to stress measurements. These data provide evidence (a) that increases in circulating numbers of CD8 and NK cells following acute stress are partially attributable to hemoconcentration and (b) that CD4 and CD19 cell concentrations decrease during acute stress when hemoconcentration is taken into account.

Adult↗
PubMed1997

Psychological stress and the progression of carotid artery disease.

BACKGROUND: We examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis. METHODS: Using duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease. RESULTS: Atherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (beta = 0.46), a history of hypertension (beta = 0.20), use of lipid level-lowering agents (beta = 0.18), a longer history of smoking (beta = 0.13), a larger cholesterol:high-density lipoprotein ratio (beta = 0.13), a smaller change in heart rate during the task (beta = -0.12), and a higher resting systolic blood pressure (SBP; beta = 0.11) were associated significantly with a greater plaque area (R2 = 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (beta = 0.28), a higher total cholesterol: high-density lipoprotein ratio (beta = 0.23), a shorter resting preejection period (beta = -0.19), and a lower body mass index (beta = -0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2 = 0.24). CONCLUSIONS: These results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.

Adult↗
PubMed1997

Behaviorally elicited heart rate reactivity and atherosclerosis in ovariectomized cynomolgus monkeys (Macaca fascicularis).

It has been hypothesized that atherogenesis is accelerated among individuals who exhibit heightened cardiovascular reactions to psychologic stress. We have reported previously that the coronary atherosclerosis of cholesterol-fed, male and reproductively intact (premenopausal) female cynomolgus monkeys was exacerbated in animals that experienced the largest heart rate (HR) reactions to a fear-eliciting laboratory stressor. In this article, we report a similar relationship among 20 female monkeys that were rendered estrogen-deficient (by ovariectomy) and subsequently treated with replacement of both estrogen and progesterone. At the beginning of a 30-month study period, animals were fitted with ECG telemetry devices, and their HRs were recorded under baseline and stressed conditions. Stress HR measurements were obtained during a standard challenge involving threatened capture and physical handling of the animals. As part of a related experiment, monkeys were then ovariectomized and, for the remainder of the study, administered 17 beta-estradiol (continuously) and progesterone (cyclically) by subcutaneous Silastic implant (Dow Corning). Animals consumed a cholesterol-containing diet throughout, and HR measurements were repeated in the 24th month. At necropsy, the magnitude of animals' HR responses to stress correlated significantly with intimal area measurements in the left anterior descending and circumflex coronary arteries (r = .59 and r = .57, respectively; P < .009). This association was due to a marked exacerbation of coronary atherosclerosis in animals comprising the upper third of the reactivity distribution. Although total and HDL cholesterol concentrations also covaried with HR reactivity, the greater atherosclerosis of "high" HR reactors persisted after statistical adjustment for concomitant variability in plasma lipids. HR reactivity was unrelated to blood pressure, body weight, or social behavior.

Animals↗
PubMed1997

Self-reported levels of anxiety do not predict neuropsychological performance in healthy men.

It is widely believed that even mild to moderately severe levels of anxiety have a negative impact on neuropsychological performance. To test that possibility, we used scores from Spielberger's State and Trait Anxiety scales to predict performance on measures of attention, learning, memory, mental flexibility, and eye-hand coordination. Two samples of healthy young and middle-aged men were studied. Sample 1 consisted of 125 university students (M age = 20.37); Sample 2 consisted of 50 men recruited from the community (M age = 40.64). Results of multiple regression analyses revealed no significant associations in either sample, after controlling for age, education, and average alcohol consumption. These findings suggest an absence of relationship between self-reported symptoms of anxiety and neuropsychological function in healthy men.

Journal Article↗
PubMed1997

Using ethological principles to study psychosocial influences on coronary atherosclerosis in monkeys.

Studies with male cynomolgus monkeys suggest that atherosclerosis is potentiated among individuals that are habitually successful in their aggressive encounters with social strangers, thereby retaining dominant social status in an unstable environment. Further, the increased risk of atherosclerosis experienced by such animals is related, in part, to the autonomic (sympathetic) adjustments they make while responding to the demands of retaining dominant status. These data provide clear support for the hypothesis that psychosocial factors influence disease pathogenesis via neuroendocrine mediation. Additionally, they provide initial evidence in favor of Jim Henry's suggestion that the pattern of neuroendocrine response to environmental challenge depends on the type and degree of control an animal can exert in such circumstances (Henry & Stephens 1977).

Animals↗
PubMed1996

D,L-fenfluramine challenge test: experience in nonpatient sample.

The plasma prolactin response to a single-dose fenfluramine challenge is increasingly utilized in psychiatric research as an indirect and noninvasive measure of central serotonergic activity. However, the influences of age, gender, and body weight on prolactin response and characterization of physical and psychological symptoms evoked by fenfluramine remain poorly studied. In the current study, 83 nonpatient male and female volunteers, 25-60 years old, were administered a standardized fenfluramine challenge test (60 mg). Serial blood samples for plasma drug concentration and plasma prolactin concentration were obtained and side effects reported by participants were recorded. Analyses revealed that both plasma drug concentration and prolactin response were correlated with weight-relative dose (r = 0.43 and r = 0.38, respectively; p < 0.001). No significant relationship was noted between prolactin response and either age or gender. Symptoms during fenfluramine challenge were reported by 90% of subjects, most commonly fatigue, headache, lightheadedness, and difficulty concentrating. Overall side effect severity was related to weight-relative dose (r = 0.26; p < 0.05) and prolactin response (r = 0.42; p < 0.001). We conclude that fenfluramine challenge results should be reported as change in plasma prolactin relative to dose, and that in nonpatient samples the test is associated with frequent side effects.

Adult↗
PubMed1996

Absence of enhanced sympathoadrenal activity and behaviorally evoked cardiovascular reactivity among offspring of hypertensives.

To determine whether offspring of hypertensives show enhanced sympathetic nervous system activity, we evaluated several indices of sympathoadrenal activation and cardiovascular responsiveness to behavioral stimuli among 90 normotensive, young adult men having either one or two hypertensive parents (PH+(-), PH++) or normotensive parents only (PH--) (n = 30/group). Measurements included heart rate (HR) and blood pressure (BP) reactions to three mental stressors (the Stroop test, mental arithmetic, mirror tracing), a cold pressor test, postural adjustment (60 degrees upright tilt), isometric exercise and bicycle ergometry, as well as the 24-h excretion of catecholamines (epinephrine [E], norepinephrine [NE]) and venous plasma catecholamine concentrations, both at rest (seated and supine) and in response to the Stroop test and upright tilt. The three groups did not differ in age, education, body mass index (BMI), estimated aerobic fitness, resting HR, cardiac preejection period (PEP) and PEP:LVET (left ventricular ejection time) ratio, 24-h Na or K excretion, or fasting lipids, insulin or plasma renin activity. Resting systolic and diastolic BP varied as a function of parental hypertension, and were significantly higher in PH++ than among PH-- subjects (P < .05). No significant group difference was observed on any measure of plasma or urinary catecholamines, nor did offspring of hypertensives (PH++ or PH+-) showed greater HR or BP reactions than PH-- subjects to any of the several laboratory challenges. In sum, we find no evidence of enhanced sympathetic activity or heightened cardiovascular responsiveness among normotensive young adults who are familially predisposed to essential hypertension.

Adolescent↗