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Biomedical subjects

M F Muldoon

Publications and source records attributed to M F Muldoon.

At least 19 recordsLinked to original sources
PubMed2006

Hypertension labelling was associated with poorer self-rated health in the Third US National Health and Nutrition Examination Survey.

Individuals labelled as having hypertension tend to report poor self-rated health (SRH), but it is unclear whether this association is independent of actual hypertension, socioeconomic status and adiposity, and extends across racial and ethnic groups. In a cross-sectional study we compared hypertensive and normotensive individuals (N = 19,057) who varied in whether they had ever been labelled hypertensive. Blood pressure was measured in participants' homes and mobile examination centres in the United States as part of the Third National Health and Nutrition Examination Survey, 1988-1994. The main outcome measure was global SRH. Hypertensive labelling was associated with poorer SRH and was independent of established SRH predictors, antihypertensive medication use, body mass index, and hypertension status (adjusted odds ratio (OR) = 1.79, 95% confidence interval (CI), 1.61-1.99). Hypertension was also associated with poorer SRH (OR = 1.26; 95% CI 1.09-1.46) but this association was eliminated by adjustment for hypertensive labelling (OR 1.06; 95% CI 0.92-1.22). These effects were consistent across non-Hispanic white, non-Hispanic black, and Hispanic subgroups. Individuals labelled hypertensive are more likely to have lower SRH and this labelling effect predominates over that of actual hypertension. Public health efforts to increase the number of individuals screened for high blood pressure may successfully detect the presence of hypertension but may also reduce health-related quality of life as measured by global SRH.

Adiposity↗
PubMed2005

Reduced cerebral blood flow response and compensation among patients with untreated hypertension.

OBJECTIVE: To determine whether memory performance in hypertensive subjects induces diminished parietal and prefrontal blood flow activation relative to normotensive subjects but compensatory amygdala/hippocampal activation. METHODS: Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects performed in two memory and one sensorimotor task while global and regional cerebral blood flow (rCBF) was assessed with [15O]water and PET. Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained. RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive subjects were less than in normotensive subjects in the posterior parietal area, as expected; blunted responses were also shown within the middle posterior arterial watershed and thalamus. Relative to all other participants, hypertensive subjects that performed relatively well on verbal memory showed an enhanced rCBF response in the right amygdala/hippocampus. Furthermore, hypertensive, but not normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area that was significantly correlated with task-induced prefrontal rCBF. No confounding influences were identified from carotid artery or MRI measures. CONCLUSIONS: Memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow (rCBF) response, particularly in parietal cortex. Potentially compensatory rCBF responses appear to occur in midbrain and correlate with prefrontal rCBF.

Adaptation, Physiological↗
PubMed2001

Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials.

OBJECTIVE: To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality). DESIGN: Meta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments. STUDIES REVIEWED: 19 out of 21 eligible trials that had data available on non-illness mortality. INTERVENTIONS REVIEWED: Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years. MAIN OUTCOME MEASURE: Deaths from suicides, accidents, and violence in treatment groups compared with control groups. RESULTS: Across all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P=0.20). The odds ratios were 1.28 (0.94 to 1.74; P=0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P=0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P=0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P=0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P=0.23). CONCLUSION: Currently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs.

Accidents↗
PubMed2001

The nature of the association between diet and serum lipids in the community: a twin study.

Diet is commonly thought to be an environmental influence on serum lipid concentrations. This study evaluated whether total caloric and fat intake predict total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for environmental, as compared with genetic, reasons among 137 monozygotic and 67 dizygotic young adult twins. When genetic influences were controlled by correlating differences between monozygotic co-twins, a significant association remained between diet and TC, LDL, and HDL, suggesting that these dietary and serum lipid measures correlate for environmental reasons. Twin structural equation modeling confirmed these results. Overall, these results provide additional support for the hypothesis that diet is an environmental influence on TC, LDL, and HDL.

Adolescent↗
PubMed2000

Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults.

The apolipoprotein E genotype (APOE) is an established risk factor for Alzheimer disease, with the age-at-onset occurring earlier in individuals having at least one APOE epsilon 4 allele, relative to the APOE epsilon 3 or APOE epsilon 2 isoforms. Moreover, nondemented older adults with the APOE epsilon 4 allele also show diminished cognitive performance, particularly on tests of learning and memory, and an accelerated decline in memory performance with increasing age. The current investigation extends the study of the APOE epsilon 4 allele and cognitive performance to healthy, middle-aged adults. A community sample of 220 non-Hispanic Caucasian men and women, aged 24-60 (average age = 46), were genotyped for the APOE polymorphism and completed a battery of neuropsychological tests. Multivariate analyses were conducted on measures of verbal learning and memory (e. g., learning a list of words and recalling them 30 min later), visual memory (e.g., reproducing a previously copied figure from memory), and attention span (e.g., repeating long lists of digits), after adjustments for age, and estimated IQ. Results indicated that performance on learning and memory tasks was significantly poorer in adults having any APOE epsilon 4 allele, relative to adults with APOE epsilon 2 and epsilon 3 genotypes (P <.01). Attention span did not differ by genotype. These findings, the first in a sample of middle-aged adults, suggest that the APOE polymorphism is a marker for age-related decline in memory (detectable prior to overt, clinical manifestations of memory loss), and/or a marker for individual differences in memory ability across the life span. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:707-711, 2000.

Adult↗
PubMed2000

A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.

This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.

Adult↗
PubMed2000

White-coat hypertension and carotid artery atherosclerosis: a matching study.

BACKGROUND: Blood pressure (BP) measurements obtained in the clinic have long served as the basis for determining risk of hypertensive vascular disease, yet many patients with high BP in the physician's office are normotensive elsewhere. It remains unclear whether such patients with "white coat" hypertension elude the risk of atherosclerosis. METHODS: Community residents 40 to 70 years of age and not receiving any cardiovascular medications were recruited to participate in a study of cardiovascular risk factors. On the basis of clinic and daytime ambulatory BP and a threshold criterion of 140/90 mm Hg, subjects were classified as having persistent hypertension, white-coat hypertension, or persistent normotension. One-to-one matching was conducted in male participants on the basis of race and BP. Subjects with persistent hypertension and white-coat hypertension were matched on clinic BP, and those with white-coat hypertension and normotension were matched on daytime ambulatory BP. RESULTS: The 3 matched groups of men (n=40 in each group) were similar in age, smoking status, and fasting glucose and lipid levels. Compared with the normotensive subjects, subjects with either persistent or white-coat hypertension had greater mean body mass index, waist-hip ratio, and fasting insulin concentration. On the basis of standardized duplex ultrasound examination of the carotid arteries, mean maximal intimal-medial thickness and plaque index in subjects with white-coat hypertension were greater than among normotensive subjects and equal to that of the subjects with persistent hypertension. CONCLUSION: When compared with unmedicated individuals with comparable elevations in clinic BP, individuals with white-coat hypertension appear not to be protected from the atherosclerotic sequelae of hypertension.

Adult↗
PubMed2000

Effects of lovastatin on cognitive function and psychological well-being.

PURPOSE: Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function, mood, and behavior, but few clinical trials have studied these effects. SUBJECTS AND METHODS: In this double-blind investigation, 209 generally healthy adults with a serum low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Assessments of neuropsychological performance, depression, hostility, and quality of life were conducted at baseline and at the end of the treatment period. Summary effect sizes were estimated as z scores on a standard deviation (SD) scale. RESULTS: Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains, consistent with the effects of practice on test performance (all P <0.04), whereas those treated with lovastatin improved only on tests of memory recall (P = 0.03). Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small, but statistically significant, differences for tests of attention (z score = 0.18; 95% confidence interval (CI), 0.06 to 0.31; P = 0.005) and psychomotor speed (z score = 0.17; 95% CI, 0.05 to 0.28; P = 0. 004) that were consistent with greater improvement in the placebo group. Psychological well-being, as measured several ways, was not affected by lovastatin. CONCLUSION: Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function. Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed, the clinical importance of which is uncertain.

Adult↗
PubMed2000

Behaviorally-evoked plasma catecholamine response and 24-hour excretion of urinary catecholamines among cardiac and vascular reactors.

Individuals differ in the cardiac and vascular processes that underlie blood pressure elevations evoked by environmental stimuli; such differences may reflect variability in sympathoadrenal response. We separated 108 healthy, young-adult males into those with predominant elevations in either cardiac output or peripheral resistance when exposed to psychological challenges. We then asked if they differed on other measures of cardiovascular response, concomitant plasma catecholamine reactions or 24-h urinary excretion of catecholamines. Cardiac reactors, relative to vascular reactors, showed reduced cardiac pre-ejection period, a smaller reduction in stroke volume, and elevated plasma epinephrine response and 24-h urinary epinephrine excretion. Vascular reactors, relative to cardiac reactors, responded to mental stress with more elevated diastolic blood pressure, a rise in peripheral resistance and pulse wave velocity, and a greater reduction in stroke volume. Vascular reactors, however, did not show plasma norepinephrine response or 24-h urinary norepinephrine excretion that was greater than cardiac reactors. The results provide partial support for the hypothesis that variability in sympathoadrenal activity contributes to individual differences in cardiac and vascular reactivity, and extend prior observations by demonstrating covariation of behaviorally-elicited cardiac reactivity with the 24-h excretion of epinephrine.

Adolescent↗
PubMed1999

Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene.

BACKGROUND: Central nervous system (CNS) serotonergic activity correlates inversely with human aggressive behavior, and individual differences in aggressive disposition are at least partially heritable. This study was conducted to evaluate the possible association between measures of antagonistic behavior and an intronic polymorphism of the gene coding for tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. METHODS: Locally recruited men and women (n = 251) were genotyped for the A218C polymorphism located in intron 7 of the TPH gene. All subjects were administered standard interview and questionnaire indices of aggression and anger-related traits of personality; in a portion of subjects, CNS serotonergic activity was assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). RESULTS: Persons having any TPH U allele scored significantly higher on measures of aggression and tendency to experience unprovoked anger and were more likely to report expressing their anger outwardly than individuals homozygous for the alternate L allele. In men, but not women, peak prolactin response to fenfluramine was also attenuated among subjects having any U allele, relative to LL homozygotes. CONCLUSIONS: Individual differences in aggressive disposition are associated with an intronic polymorphism of the TPH gene in a nonpatient sample of community-derived volunteers.

Aggression↗
PubMed1999

Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism.

A deletion/insertion polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) was reported to be associated with dimensional measures of neuroticism, although subsequent replication attempts have failed. These replication attempts, however, have been dissimilar to the initial study in sample size, distribution of allelic frequency and/or assessment of neuroticism. The current study was conducted in a further attempt to replicate the initial finding using: (a) a sample that was more comparable to each of the individual samples in the initial report; and (b) identical psychometric methodology to assess neuroticism. Two hundred and twenty-five Caucasian adults were genotyped for the 5-HTTLPR polymorphism and completed the NEO Personality Inventory. Results did not replicate the association between the 5-HTTLPR polymorphism and neuroticism; individuals with the short form of this variant did not report higher NEO Neuroticism. Indeed, men with the short form reported lower Anxiety, a finding that is directionally opposite to the initial results. These findings, combined with other failures to replicate, indicate that the reproducibility of the association between the 5-HTTLPR polymorphism and neuroticism must be regarded as questionable. The contradictory findings suggest the need for a replication attempt in a large, normative sample that is stratified by ethnicity and sex.

Adult↗
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↗