Biomedical subjects

Stephen B Manuck

Publications and source records attributed to Stephen B Manuck.

At least 37 records · Page 2Linked to original sources

PubMed2004

Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region.

It was reported recently that exposure to an adverse rearing environment lowers central nervous system (CNS) serotonergic activity in a nonhuman primate (rhesus monkeys), but only among animals having the shorter variant of a functional, biallelic repeat polymorphism in the regulatory region of the serotonin transporter (5-HTT) gene. Because repeat variants of the same core sequence affect transcriptional efficiency of the 5-HTT gene in humans, we examined whether biallelic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) acts analogously to modulate a previously described association between socio-economic status (SES) and CNS serotonergic function. The 5-HTTLPR was genotyped in 139 adult men and women (n = 75 and 64) who were administered a standard neuroendocrine challenge to assess central serotonergic responsivity (plasma prolactin (PRL) response to the serotonin releasing agent, fenfluramine). Socio-economic status was estimated from reported income and years of education. Hierarchical linear regression showed serotonergic responsivity to be predicted by the interaction of 5-HTTLPR genotype and SES (p = 0.018). Individuals of lower income and less education had lower peak PRL concentrations following administration of fenfluramine than did subjects ranking higher on these dimensions, but only among persons possessing at least one 5-HTTLPR short allele. Within genotype, SES covaried moderately with the PRL response to fenfluramine among subjects who were homozygous for the short allele (r18 = 0.50, p < 0.03). A similar association was present at lesser magnitude in heterozygotes (r70 = 0.24, p < 0.05) and absent among subjects homozygous for the long allele (r45 = -0.04, n.s.). Findings were comparable for men and women and persisted on re-analysis restricted to persons without current Axis I psychopathology. We conclude that allelic variation at 5-HTTLPR moderates the influence of social position on CNS serotonergic responsivity.

Adult↗

PubMed2004

Ovarian dysfunction, stress, and disease: a primate continuum.

Menopause is recognized as a period of increased risk for coronary heart disease (CHD) and osteoporosis. Vulnerability to these conditions is often attributed to the naturally occurring estrogen deficiency characteristic of this part of the life cycle. Premenopausal reductions in endogenous estrogen occasioned by functional ovarian abnormalities or failure are hypothesized to be similarly pathogenic and to accelerate development of CHD and osteoporosis prematurely, thereby increasing the health burden of older women. These functional abnormalities, which occur along a continuum from mild, luteal phase progesterone deficiency to amenorrhea, are relatively common and are often attributed to psychogenic factors (stress, anxiety, depression, or other emotional disturbance), exercise, or energy imbalance. Although numerous investigators have commented on these functional deficits, the abnormalities can be difficult to diagnose and are generally unappreciated for the contribution they may make to postmenopausal disease. Studies in nonhuman primates confirm that these deficits are easily induced by psychological stress and exercise, and that they accelerate the development of cardiovascular disease and perhaps bone loss in the presence of a typical North American diet. However, functional reproductive deficits are also reversible and are thus potentially amenable to environmental or behavioral intervention. Data from both women and nonhuman primates support the hypothesis that functional reproductive deficits are adaptive when triggered appropriately but are detrimental when activated in an environment (e.g., sedentary lifestyle, high-fat diet) permissive to the development of chronic disease.

Amenorrhea↗

PubMed2004

Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity.

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69-19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.

Adult↗

PubMed2003

Effects of exercise on cardiovascular outcomes in monkeys with risk factors for coronary heart disease.

OBJECTIVE: Exercise reduces the risk for coronary heart disease. However, the mechanisms mediating the beneficial effects of exercise remain ambiguous. In particular, it is uncertain whether exercise inhibits the development of atherosclerosis, a major pathobiologic process underlying heart disease. METHODS AND RESULTS: To address this question, adult male monkeys were fed an atherogenic diet while assigned to one of four experimental conditions for 34 months: 1) runner/no group disruption, ie, "stable" (n=19); 2) runner plus frequent social group disruption, ie, "unstable" (n=19); 3) sedentary/stable (n=15); or 4) sedentary/unstable (n=18). Neither exposure to exercise nor social group disruption significantly affected the resulting coronary artery atherosclerosis extent or lumen areas (all ANOVA values, P>0.05). When compared with sedentary individuals, exercise animals had lower resting heart rates (119.0+/-3 vs 132.0+/-3 bpm, P=0.002), greater echocardiographically measured left ventricular ejection fractions (77.2+/-0.01% vs 73.8+/-0.01%, P=0.02), greater quantitative angiographically measured dilation of coronary arteries to phenylephrine (2.6+/-1% vs -3.7+/-1% change from baseline diameter, P=0.003), and a reduced cortisol response to an adrenocorticotropin challenge. These measures were not significantly affected by social condition. CONCLUSIONS: Thus, exercise improved some measures of cardiovascular health and reduced stress responsivity but did not inhibit progression of coronary artery atherosclerosis or promote positive artery remodeling. It is concluded that exercise may exert cardioprotective effects without influencing atherosclerosis extent.

Adrenocorticotropic Hormone↗

PubMed2003

Approach to a social stranger is associated with low central nervous system serotonergic responsivity in female cynomolgus monkeys (Macaca fascicularis).

It is widely hypothesized that individual differences in central nervous system (CNS) serotonergic activity underlie dimensional variation in "impulsive" vs. "inhibited" social behavior in both humans and nonhuman primates. To assess relative impulsivity in a social context, a behavioral challenge involving animals' exposure to a social stranger (termed the "Intruder Challenge") was recently validated in adolescent and adult male vervet monkeys (Cercopithecus aethiops sabaeus). Among these animals, monkeys that quickly approached the intruder were found to have lower cerebrospinal fluid (CSF) concentrations of the serotonin (5-HT) metabolite, 5-hydroxyindoleacetic acid, than less impulsive animals. In the present study we extended these observations to determine whether approach to a social stranger, as operationalized by the Intruder Challenge, is similarly associated with diminished CNS serotonergic function in female cynomolgus monkeys (Macaca fascicularis). Study animals were 25 adult monkeys that had been housed for 2 years in stable social groups. In each animal, the rise in plasma prolactin concentration induced by acute administration of the 5-HT agonist, fenfluramine, was used to assess "net" central serotonergic responsivity. When exposed later to an unfamiliar female of the same species in a catch-cage placed for 20 min within the subjects' home enclosure, monkeys that approached to within 1 m of the intruder (median latency to approach=3 min) were found to have significantly smaller prolactin responses to fenfluramine (diminished serotonergic responsivity) compared to "inhibited" animals that failed to approach the intruder (t=2.9, df=23, P<0.009; rpb=-0.51). Neither approach behavior nor the animals' fenfluramine-induced prolactin responses covaried significantly with nondirected expressions of arousal (or anxiety) or with aggressive behaviors exhibited during testing. We conclude that in female cynomolgus monkeys, social impulsivity (vs. inhibition) correlates inversely with individual differences in CNS serotonergic activity, as assessed by neuroendocrine challenge.

Animals↗

PubMed2002

Central nervous system serotonergic responsivity and aggressive disposition in men.

To determine whether normative variability in aggressive behavior correlates negatively with central nervous system (CNS) serotonergic function among men, plasma prolactin (PRL) responses to a standard fenfluramine challenge (administered to assess central serotonergic responsivity) were examined in relation to interview-assessed aggression histories among 118 adult males derived from a nonpatient, community sample. Fenfluramine-induced, peak PRL rises were smaller in subjects whose 'aggression' scores fell above the sample median, compared to their less aggressive counterparts (P<.002). Across subjects, participants' peak PRL responses likewise covaried inversely with aggression history (r(s)=-.32, P<.0005). Additional analyses were conducted on data of 58 subjects who had also been genotyped for a functional polymorphism in the promoter region of the X chromosomal, monoamine oxidase-A (MAO-A) gene. The four variants of this repeat polymorphism were grouped for analysis (alleles '1+4' vs. '2+3') based on prior report of enhanced transcriptional efficiency in MAO-A promoter constructs containing alleles 2 and 3 (repeats of intermediate length). Men in the 2/3 allele group had significantly higher aggression scores (P<.05) and smaller peak PRL responses to fenfluramine (P<.009) than men in the 1/4 allele group. When adjusted by analysis of covariance for concomitant variability in subjects' PRL responses, aggressive disposition no longer varied significantly by genotype. This finding suggests that association of the MAO-A promoter polymorphism with this behavioral phenotype may be mediated, in part, by allele-specific variation in central serotonergic responsivity.

Adult↗

PubMed2002

Stress, immune reactivity and susceptibility to infectious disease.

Psychological stress is known to affect immune function and to predict infectious disease susceptibility. However, not all individuals who are stressed develop disease. In the present article, we report on a series of studies from our laboratory describing interindividual variability of immune responses to psychological stress. In our initial series of experimental investigations, we demonstrated that acute laboratory stress alters both quantitative and functional components of cellular immunity. An examination of response variability revealed that individuals differ substantially in the magnitude of these immune responses. These differences were found to parallel (and be predicted by) interindividual variability in stress-induced sympathetic nervous system activation. Further investigation revealed that individuals vary consistently in the magnitude of their immune responses to stress, making it conceivable that individual differences in immune reactivity provide a vulnerability factor mediating relationships between stress and disease. In support of this possibility, we have recently reported initial evidence that individual differences in the magnitude of stress-induced reduction of immune function may be of clinical significance, being related to an immune response relevant for protection against infection, antibody response to hepatitis B vaccination.

Animals↗

PubMed2002

Retest reliability of prolactin response to dl-fenfluramine challenge in adults.

Neuropharmacologic probes to assess central nervous system (CNS) serotonergic responsivity (e.g., dl-fenfluramine) stimulate serotonergic neurotransmission, thereby causing proportional release of pituitary-derived hormones into the circulation. Individual differences in these hormonal responses are thus thought to reflect dimensional variability in central serotonergic activity, which may, in turn, underlie variation in serotonin-related traits of personality (e.g., impulsivity, behavioral inhibition, harm avoidance). However, the long-term temporal stability of neuropharmacologic indices of CNS serotonergic responsivity has not previously been tested in nonpsychiatric patients. dl-Fenfluramine was administered here to 57 adults, aged 24-60 years, on two occasions 6 months apart, to examine the retest reliability of fenfluramine-induced prolactin [PRL] response to fenfluramine. Baseline PRL concentration (i.e., before administration of fenfluramine) was highly stable over the 6 months (r = 0.88). Variability in serotonergic responsivity, adjusted for baseline PRL concentration, age, sex, and drug concentration during the challenge, was moderately reproducible (r = 0.50 for peak DeltaPRL and 0.57 for PRL "area under the curve," p <.0001). These findings are consistent with speculation that variability in indices of central serotonergic function reflects a temporally stable dimension of individual differences.

Adult↗

PubMed2002

Central nervous system monoamine correlates of social dominance in cynomolgus monkeys (Macaca fascicularis).

Social dominance is a fundamental component of both human and nonhuman primate sociality. However, its neurobiological correlates remain incompletely understood. We evaluated the association between dominance status and monoamine metabolite concentrations in cisternal cerebrospinal fluid (CSF) in adult male (n = 25) and female (n = 21) cynomolgus macaques (Macaca fascicularis) housed in unisexual social groups. Concentrations of the metabolites of dopamine (homovanillic acid [HVA]), norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]) and serotonin (5-hydroxyindoleacetic acid [5-HIAA]) were assayed. Dominant monkeys, both males and females, had significantly higher CSF HVA concentrations than did subordinates (p values <.05). Among males, but not females, dominants also had lower CSF 5-HIAA than subordinates (p <.05). The Dominance-HVA association observed here is consistent with recent speculation that social extraversion, a dominance-related personality trait in humans, may also reflect heightened central nervous system dopaminergic activity.

Animals↗

PubMed2002

Greater intima-media thickness in the carotid bulb is associated with reduced baroreflex sensitivity.

The aim of this study was to evaluate the association between resting baroreflex sensitivity (BRS) and carotid intima-media thickness (IMT), a putative marker of subclinical atherosclerosis. Participants were 64 men and 18 women (median age, 57 years; range, 40 to 70 years), who did not have a previous history of coronary artery disease or treatment for hypertension. Resting BRS was measured during a 9-min baseline period using the noninvasive sequence technique; carotid IMT was subsequently determined using ultrasonography. Hierarchical multiple regression analyses showed that greater IMT in the carotid bulb (an area with a high density of baroreceptors) was associated with reduced BRS. These findings remained after adjusting BRS for resting mean arterial pressure, age, body mass index, gender, and smoking history, R2 = 0.06, P = .03. In contrast, IMT in the common and internal carotid regions (areas with presumably lower baroreceptor densities) did not account for a significant proportion of the variance in BRS. These results suggest that subclinical atherosclerosis, specifically in a region with high baroreceptor density, is associated with a reduced sensitivity of the baroreflex.

Adult↗

PubMed2002

Variability within alpha- and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge.

OBJECTIVES: To investigate the association between polymorphic variation in alpha- and beta-adrenoreceptor genes and cardiovascular activity at rest and in response to psychological challenge in a sample in which the heritability of these cardiovascular phenotypes may be established. METHODS: Several common polymorphisms were characterized within ADRA1B (alpha1B), ADRA2A (alpha2A), ADRB1 (beta1) and ADRB2 (beta2) and examined in relation to heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure, both at rest and in response to stress. Participants were 309 European-American, young adult men and women (including 101 monozygotic and 44 dizygotic twin pairs). RESULTS: In the full sample, participants carrying any G allele at base pair (bp) 1165 in ADRB1 exhibited elevated resting SBP and DBP and a larger DBP response to mental challenge compared to homozygotes for the C allele (P < 0.04). An AA genotype at bp 145 in ADRB1 was also associated with higher resting SBP and DBP than AG or GG genotypes (P < 0.03). At bp 46 in ADRB2, GG homozygotes had higher resting DBP than subjects possessing any A allele (P < 0.05). For the same polymorphism, however, AG heterozygotes showed lower SBP than both AA and GG homozygotes (P < 0.05). In a subsample of genetically unrelated individuals, ADRB1 (1165) continued to predict resting SBP, DBP and DBP response to stress (P < 0.03), while ADRB2 (46) was associated with resting SBP (P < 0.04) but not DBP. Finally, the degree of allele sharing at ADRB1 (1165) also predicted variability in SBP and DBP at rest among dizygotic twin pairs (P < 0.04). CONCLUSIONS: These results indicate that some polymorphic variation within adrenoreceptor genes contributes to interindividual variability in resting SBP and DBP and in DBP response to mental challenge.

Adult↗

PubMed2002

Effects of six anti-hypertensive medications on cognitive performance.

OBJECTIVE: To describe and compare the effects of six different antihypertensive medications on cognitive performance. DESIGN: Prospective, randomized, and double-blind with treatment cross-over. SETTING: University hypertension clinic and neuropsychology laboratory. PARTICIPANTS: Ninety-eight Caucasian men between 25 and 55 years of age with mild-to-moderate essential hypertension (88 of whom completed the study), and 32 normotensive men with similar socio-demographic characteristics. INTERVENTIONS: Six-week treatment periods with atenolol, metoprolol, hydrochlorothiazide, methyldopa, enalapril and verapamil, and 2-week placebo baseline and wash-out periods. MAIN OUTCOME MEASURES: In-depth neuropsychological assessments and several mood questionnaires were completed during placebo (baseline) periods and active treatment periods. Practice effects due to repeated neuropsychological testing were estimated from data collected concurrently in the normotensive participants. RESULTS: The antihypertensive treatments lowered blood pressure comparably and did not affect mood or anxiety. Small treatment effects were noted in four of seven domains of cognitive performance. Irrespective of medication type, treatment reduced the simple motor speed (P < 0.001), and slowed completion of two tests measuring perceptuo-motor speed and mental flexibility (P </= 0.05). Manual dexterity declined somewhat with metoprolol and methyldopa (P = 0.01). In contrast, all antihypertensive agents favorably affected performance on several tests that require working memory (P < 0.01). Performance on other tests assessing grip strength, learning and memory, attention and executive function was not affected. CONCLUSION: Short-term treatment with standard antihypertensive medications was associated with some small decrements in psychomotor performance and small improvements in working memory, without notable drug-class differences. Long-term effects await further study.

Adult↗

PubMed2002

Is cardiovascular reactivity associated with atherosclerosis among hypertensives?

Exaggerated cardiovascular reactivity to behavioral challenges among otherwise healthy individuals has been associated with carotid atherosclerosis. We evaluated whether a similar relationship exists among hypertensives, who are at a heightened atherosclerotic risk. Untreated, hypertensive men (n=251; age range, 40 to 70 years; 197 white, 54 black) completed a standardized battery of behavioral challenges while their blood pressure responses to the battery were measured. Mean and maximum carotid intima-media thickness and the occurrence of carotid plaques were subsequently determined using B-mode ultrasonography. Although greater systolic and diastolic responses to the battery were associated with greater mean and maximum intima-media thickness in univariate analyses (P<0.01), only diastolic reactivity showed a unique association with mean and maximum carotid intima-media thickness after multivariate adjustment for age, race, socioeconomic status, smoking and alcohol use, body mass index, lipid profile, glucose and insulin concentrations, and resting blood pressure (P<0.05). Carotid plaque occurrence was associated with greater systolic reactivity (P=0.05) and was marginally associated with greater diastolic reactivity (P=0.07) in univariate analyses, but neither systolic nor diastolic reactivity was uniquely associated with the presence of carotid plaques after multivariate risk-factor adjustment. Among hypertensives, exaggerated behaviorally evoked cardiovascular reactivity appears to be uniquely associated with greater carotid intima-media thickness but not with carotid plaque occurrence.

Adult↗

PubMed2002

The association between racial identity and hypertension in African-American adults: elevated resting and ambulatory blood pressure as outcomes.

OBJECTIVES: This study investigated the association between Black racial identity attitudes and hypertension. It was hypothesized that racial identity attitudes characterized, in part, by an intense focus on African Americans as a group and a general rejection of White individuals and culture (termed transitional identity), would be associated with elevated blood pressure. It was also hypothesized that the experience of stress and hostility or cynical mistrust associated with transitional identity would account for this association. METHODS: Participants were 126 non-obese African-American men and women (mean age 53.8 years) with normal blood pressure or minimally treated hypertension, recruited from among individuals enrolled in a study of risk factors for atherosclerosis in southwestern Pennsylvania. Participants completed assessments of racial identity, hostility, perceived stress, and race-focused situational appraisal. Physiological measures included resting and daytime ambulatory systolic blood pressures (SBP) and diastolic blood pressures (DBP), as well as nocturnal declines in blood pressure. RESULTS: Transitional racial identity attitudes significantly predicted resting SBP (P<.03) and DBP (P<.002), as well as ambulatory SBP (P<.001) and DBP (P <.0004), when adjusting for demographic variables. Transitional identity remained a significant predictor of resting DBP (P<.01) and ambulatory SBP (P<.02) and DBP (P<.006), when hostility and perceived stress were also controlled. CONCLUSIONS: Results suggest that transitional racial identity may be an important correlate of elevated blood pressure in African Americans and that this association cannot be fully accounted for by measures of perceived stress or hostility.

Adult↗

PubMedDate not supplied

Covariation of psychosocial characteristics associated with cardiovascular disease: genetic and environmental influences.

OBJECTIVE: Three psychosocial characteristics associated with cardiovascular disease (CVD)-depression, hostility, and social support-tend to correlate with one another. However, the causes of each characteristic and why they tend to co-occur are not completely understood. Therefore, the current study used a twin design to examine the relative contributions of genetic and environmental influences to the variation and covariation of these three psychosocial characteristics. METHODS: The sources of variation and covariation among the Beck Depression Inventory, the Cook-Medley Hostility Scale, and the Interpersonal Support Evaluation List were examined in a young adult community sample of 157 monozygotic and 75 dizygotic twin pairs. RESULTS: Phenotypic confirmatory factor analysis indicated that a single latent factor could account for their moderate intercorrelations. Twin analyses indicated that the Beck Depression Inventory and Interpersonal Support Evaluation List were each influenced by genetic and nonshared environmental factors, whereas the Cook-Medley Hostility Scale was influenced by familial (genetic and/or shared environmental) and nonshared environmental factors. Bivariate associations between these scales were largely determined by common genetic effects and, to a lesser degree, common nonshared environmental effects. Covariation among the three scales could be explained by a single common genetic factor and a common nonshared environmental factor. Environmental factors shared within families did not contribute to covariation among the psychosocial characteristics. CONCLUSIONS: The results challenge the conventional approach of examining these psychosocial variables as independent risk factors for cardiovascular disease and argue for the importance of investigating specific causes for their covariation.

Adult↗

PubMedDate not supplied

Reactivity and vulnerability to stress-associated risk for upper respiratory illness.

OBJECTIVE: We tested the hypothesis that the greater a person's laboratory stress-elicited elevation in cortisol, the greater the life stress-related risk for upper respiratory infection (URI). We also tested the prediction that the greater the laboratory stress-elicited rise in natural killer cell (NK) cytotoxicity, the smaller the life stress-related URI risk. Finally, we explored whether sympathetic nervous system (SNS) and enumerative immune reactivities to laboratory stress moderate the relation between life stress and URI. METHODS: At baseline, 115 healthy subjects were administered a negative stressful life events checklist and were tested to assess their SNS (blood pressure, heart rate, and catecholamines), HPA (cortisol), and immune (NK cell cytotoxicity and lymphocyte subsets) reactivities to laboratory speech tasks administered 2 weeks apart. Responses were averaged across the two laboratory assessments to create reactivity scores. After these assessments were completed, participants were followed weekly for 12 consecutive weeks. At each follow-up they completed a measure of perceived stress experienced over the last week. They were also instructed to contact the study coordinator if they had a cold or flu at any time during follow-up. A health care worker verified reported illnesses. RESULTS: In a traditional prospective analysis, high cortisol reactors with high levels of life events had a greater incidence of verified URI than did high reactors with low levels of life events and low reactors irrespective of their life event scores. Using hierarchical linear modeling, CD8(+) number, Natural Killer (NK) cell number, and NK cell cytotoxicity, each interacted with weekly perceived stress levels in predicting concurrent occurrences of self-reported URIs. For these outcomes, low immune reactors were more likely to experience an URI during high stress than low stress weeks. High immune reactors did not exhibit differences in weekly URIs as a function of weekly stress level. The SNS reactivity markers did not moderate the association of stress and URI incidence in either analysis. CONCLUSIONS: Acute HPA and immune responses to laboratory stressors are markers of how vulnerable people are to the increased risk for URI associated with stressors in the natural environment.

Adolescent↗

PubMedDate not supplied

Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress.

OBJECTIVE: Previous studies suggest that hemoconcentration may be one mechanism by which acute psychological stress causes elevations of serum total cholesterol and its subfractions. Alternatively, such elevations may result from sympathetically mediated changes in lipid metabolism. This study evaluated these two hypotheses by manipulation of sympathetically mediated responses to stress using a nonselective adrenoceptor antagonist, labetalol. METHOD: In a 2 x 2 factorial design, 52 healthy male participants were randomly assigned to a stress or no-stress condition and, within each condition, were administered either labetalol or saline. Participants assigned to stress completed three cognitive and evaluative tasks lasting a total of 18 minutes. Indices of hemoconcentration (hematocrit and hemoglobin), heart rate, blood pressure, and serum lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, and triglycerides) were assessed at preinfusion and infusion baselines and after mental stress (or rest). RESULTS: Labetalol reduced sympathetic activation, as shown by a substantial reduction in heart rate elevation during stress, but did not alter changes in blood pressure or in hemoconcentration, as indicated by equivalent increases in hematocrit and hemoglobin in the two stressed groups. Labetalol blocked stress-induced increases in free fatty acid concentrations and lowered triglyceride levels but did not influence rises in total, HDL, or LDL cholesterol among stressed subjects. However, arithmetic correction for hemoconcentration eliminated the increases in total, HDL, and LDL cholesterol. CONCLUSIONS: These findings suggest that elevations in total cholesterol and its HDL and LDL subfractions during acute stress are caused by accompanying hemoconcentration, whereas concomitant rises in free fatty acids and triglycerides result from the direct metabolic effects of sympathetic activation.

Adolescent↗

PubMedDate not supplied

Allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cardiovascular reactivity in young adult male and female twins of European-American descent.

OBJECTIVE: To examine the effect of length variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on individual differences in cardiovascular response to psychological challenge. METHODS: Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) responses to computerized versions of two psychological challenges, the Stroop Color-Word Interference Test and mental arithmetic, were measured among 131 monozygotic (MZ) and 60 dizygotic (DZ) male or female (same-sex) European-American twin pairs. Among the 382 participants, 140 were homozygous for the "long" allele (l/l) at 5-HTTLPR, 61 were homozygous for the "short" allele (s/s), and 181 participants had one long and one short allele (l/s). Association and sib-pair analyses were performed to characterize genetic associations. RESULTS: In the full sample, 5-HTTLPR was associated with HR reactivity to psychological challenge, albeit in interaction with sex. Task-elicited HR responses of women homozygous for the short allele were significantly greater than among: a) men of the same genotype; and b) women having either one (l/s) or two (l/l) long alleles at 5-HTTLPR. SBP and DBP responsivity was unrelated to genotype. These results were corroborated on reanalysis in two genetically independent subsamples. Variability at 5-HTTLPR also predicted HR reactivity in sib-pair analyses among DZ twins. CONCLUSIONS: These results suggest that the commonly observed sex difference in HR reactivity may be, in part, genetically mediated and perhaps occur only among individuals homozygous for the short allele at 5-HTTLPR.

Adult↗