Biomedical subjects

Stephen B Manuck

Publications and source records attributed to Stephen B Manuck.

At least 19 recordsLinked to original sources

PubMed2006

Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity.

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

Adult↗

PubMed2006

Stimulated production of interleukin-8 covaries with psychosocial risk factors for inflammatory disease among middle-aged community volunteers.

A growing literature suggests that psychosocial factors, such as chronic stress and depression, are associated with increased vulnerability to inflammatory disease; however, the mechanisms of this effect remain unclear. One possibility is that these psychosocial characteristics are associated with activation of innate inflammatory pathways. Here, we explore relationships between a range of psychosocial risk factors for inflammatory disease and a measure of inflammatory potential, lipopolysaccharide-induced production of the monocyte-derived proinflammatory cytokines/chemokines interleukin (IL)-1beta, IL-6, TNF-alpha, and IL-8 among a community sample of 183 healthy adults aged 30-54 years. After controlling for demographic factors, health behavior practices, blood pressure, and white blood cell count, hierarchical regression analyses revealed a positive relationship between production of IL-8 and symptoms of depression, trait negative affect, and perceived stress. In contrast, there was an inverse relationship between IL-8 production and perceived social support. Relationships between IL-8 and symptoms of depression and perceived stress were attributable primarily to dispositional differences in NA. The relationship between negative affect measures and IL-8 was independent of social support. Although there were significant univariate associations between higher IL-6 production and symptoms of depression and less social support, these relationships did not withstand adjustment for demographic controls. There were no significant associations between IL-1beta or TNF-alpha and any of the psychosocial parameters. Our findings suggest that individuals at greater psychosocial risk for the development of inflammatory diseases, including cardiovascular disease, also show greater stimulated production of the proinflammatory chemokine, IL-8. Further exploration of this potential psychophysiological pathway is warranted.

Adult↗

PubMed2006

Human choline transporter gene variation is associated with corticolimbic reactivity and autonomic-cholinergic function.

BACKGROUND: Our previous work has shown genetic variation in the human choline transporter gene (CHT1) to be associated with depressive symptoms and autonomic cardiac (cholinergic) dysregulation. Here, functional magnetic resonance imaging (fMRI) was used to examine the relation between a single nucleotide polymorphism (SNP) in CHT1 on regional brain reactivity relevant to autonomic (cholinergic) function. METHODS: Thirty-two participants of European ancestry (18 men, 14 women; age: 33-54 years) completed an fMRI protocol using corticolimbic reactivity and prefrontal inhibitory control paradigms. Resting cholinergic function, as measured by heart rate variability (HRV), was quantified from electrocardiogram. Subjects were genotyped for a CHT1 G/T SNP. RESULTS: GG homozygotes had greater right (R) dorsal amygdala (p < .008), bilateral anterior cingulate (p < .009), and R caudate reactivity (p < .015) than T-allele carriers. Heart rate variability was related to R frontal cortex (Brodmann Areas 6, 9, and 46), R hippocampal formation, bilateral caudate, and bilateral anterior cingulate reactivity (p's < .007). CONCLUSIONS: CHT1 variation is related to differences in a distributed corticolimbic circuitry mediating behavioral and physiologic arousal. These relations may contribute to a biological mechanism by which genetic variation in cholinergic neurotransmission affects cognition, mood, and autonomic cardiac function.

Adult↗

PubMed2006

Dispositional impulsivity in normal and abnormal samples.

Impulsive behaviors, which can include aggression, substance use and suicide, are common and core features of the DSM Axis II Cluster B personality disorders. The construct of dispositional impulsivity is multidimensional and a number of self-report measures have been created to represent features of this trait (e.g., novelty seeking, behavioral disinhibition, nonplanning). Because these questionnaires are rarely administered together in the same sample, little is known about how they are related to one another. The current study was conducted to examine the structure of dimensional impulsive personality traits in a large normative sample (n=351). Analyses revealed that dispositional impulsivity was represented by three moderately correlated latent factors labeled thrill seeking, nonplanning and disinhibited behavior. Confirmatory factor analyses were also used to examine the extent to which the internal structure of these impulsive personality traits was similar in a sample defined as abnormal (i.e., DSM-III-R Cluster B PD diagnoses; n=70). Results revealed that the structure of these traits was consistent across the two samples in a model that constrained factor loadings and structural covariances (NFI=0.89; CFI=95; RMSEA=0.04). In addition, correlational relationships between the impulsivity factor scores and behavioral and sociodemographic factors (e.g., socioeconomic status, substance use) were consistent across the two samples. These results help to establish a common framework for understanding the multidimensional nature of impulsivity. Results from these analyses also lend support to a large body of work that demonstrates that normal and abnormal personality features are related.

Aggression↗

PubMed2006

Community socioeconomic status is associated with carotid artery atherosclerosis in untreated, hypertensive men.

BACKGROUND: Individuals of low socioeconomic status (SES) are at increased risk for cardiovascular disease relative to persons of more advantaged social position. Recent evidence suggests that community SES (variation in the material and social resources of communities) also predicts incident cardiovascular disease, and may do so independently of individual level SES. In this study we examined whether community SES is similarly associated with preclinical vascular disease, as measured by carotid artery ultrasonography. METHODS: Subjects were 230 untreated hypertensive men without history of coronary heart disease, residing in and around Pittsburgh, PA (80% white, 20% African-American; mean age, 56 years). Community SES was defined by levels of income, economic disadvantage (eg, poverty, unemployment), housing costs, and educational attainment in the US Census tract of residence for each subject. A composite community SES score was calculated for each subject as the average of all extracted census measures. Individual SES was estimated from subjects' years of education and current annual income. RESULTS: Regression analyses accounting for traditional risk factors showed community disadvantage to be associated with greater intima-medial thickness (b = 0.02, P < .05) and plaque occurrence (odds ratio [OR] = 1.51, P < .01). The latter association persisted on multivariable adjustment for both risk factors and individual markers of social position (SES) (OR = 1.68, P < .01). CONCLUSIONS: Irrespective of one's own income or educational attainment, untreated hypertensive men living in poorer communities are more likely to exhibit preclinical atherosclerosis than residents of more affluent areas.

Adult↗

PubMed2006

Neural basis of individual differences in impulsivity: contributions of corticolimbic circuits for behavioral arousal and control.

The objective of the current study was to analyze the neural correlates of behavioral arousal and inhibitory control as they relate to individual differences in impulsivity via well-established functional MRI amygdala reactivity and prefrontal inhibitory control paradigms in healthy adult subjects. Impulsivity correlated positively with activity of the bilateral ventral amygdala, parahippocampal gyrus, dorsal anterior cingulate gyrus (BA 32), and bilateral caudate. Conversely, impulsivity correlated negatively with activity of the dorsal amygdala and ventral prefrontal cortex (BA 47). Together, these findings suggest that dispositional impulsivity is influenced by the functional interplay of corticolimbic behavioral arousal and control circuits.

Adult↗

PubMed2006

Apolipoprotein E polymorphism and preclinical carotid artery disease in untreated hypertensive men.

METHODS: The apolipoprotein E (apoE) polymorphism was evaluated alone, and in interaction with smoking status, in predicting carotid intima-medial thickness and plaque among 182 untreated, hypertensive, white men (mean age 56+/-8.9 years). RESULTS: After covariate adjustment (age, education, smoking, body mass index, systolic and diastolic blood pressure, glucose, total : high-density lipoprotein), apoE genotype (no [epsilon]4 versus any [epsilon]4) predicted mean ([beta]=-0.139, P=0.023) and maximum ([beta]=-0.138, P=0.028) intima-medial thickness, as well as plaque ([beta]=-0.744; P=0.072). Tests of a genotype-x-smoking interaction were non-significant. CONCLUSIONS: Mean intima-medial thickness was greater in men with the 3/3 than [epsilon]4 genotypes (2/4 3/4 4/4), suggesting genetic risk for carotid atherosclerosis may be conferred by the [epsilon]3, rather than the [epsilon]4, allele.

Adult↗

PubMed2005

The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers.

CONTEXT: The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism. OBJECTIVE: The objective of this study was to test the hypothesis that low central serotonergic activity is associated with the metabolic syndrome. DESIGN, SETTING, PARTICIPANTS: This was a cross-sectional study of 345 healthy community volunteers, aged 30-55 yr, not taking medications for hypertension, lipid disorders, or diabetes. OUTCOME MEASURES: Central serotonergic responsivity was assessed with the iv citalopram challenge test. The serum prolactin area under the curve (AUC) over 150 min was calculated, and all analyses were adjusted for age, sex, plasma citalopram concentration, and baseline prolactin. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Insulin resistance was estimated by homeostasis model assessment. RESULTS: Compared with other individuals, persons meeting either NCEP or IDF criteria for the metabolic syndrome had lower mean prolactin responses (P < 0.05 for both). Using logistic regression, a decrease in prolactin AUC of 1 sd (-13.6 ng/ml.h) more than doubled the odds of having the metabolic syndrome (NCEP criteria: odds ratio, 2.38; 95% confidence interval, 1.14-4.97; P = 0.02; IDF criteria: odds ratio, 2.80; 95% confidence interval, 1.48-5.30; P = 0.002). Finally, the prolactin AUC was negatively associated with insulin resistance (beta = -0.03, P = 0.02). CONCLUSIONS: Corroborating previous evidence, the metabolic syndrome was associated with diminished brain serotonergic activity as reflected in a comparative blunting of the prolactin response to a selective serotonergic challenge. This association may have implications for the etiology, prevention, and treatment of the metabolic syndrome.

Adult↗

PubMed2005

Trait positive affect and antibody response to hepatitis B vaccination.

Recent evidence suggests that dispositional positive affect may be associated with decreased vulnerability to upper respiratory infections. To explore a potential pathway of this relationship, we examined whether trait positive affect is related to an in vivo immune response relevant for host resistance to infection. Eighty-four healthy, graduate students who tested negative for prior expose to the hepatitis B virus were administered the standard hepatitis B vaccination series. Five months after the first dose, a blood sample was collected for the measurement of specific antibody response to the vaccine and subjects completed a battery of psychosocial questionnaires. Higher scores on a measure of dispositional positive affect were associated with a greater antibody response to hepatitis B vaccination. This relationship occurred after controlling for demographics and body mass and was largely independent of concomitant levels of dispositional negative affect, optimism, and extraversion. In the presence of dispositional positive affect, there was no independent effect of trait negative affect on antibody response. Physical activity played a protective role for individuals low in positive affect, being related to higher antibody responses. These data provide initial evidence that individual differences in dispositional positive affect may be of health significance, being related to an in vivo immune response relevant for protection against infection.

Adult↗

PubMed2005

White-coat hypertension and autonomic nervous system dysregulation.

BACKGROUND: White-coat hypertension, defined as high blood pressure (BP) on clinical assessment but normal BP elsewhere or on ambulatory measurement, is a common but poorly understood phenomenon. The current study asks whether individuals with white-coat hypertension have abnormal autonomic-cardiac regulation, similar to that observed in sustained or persistent hypertension. METHODS: Participants were men (ages 40 to 70 years; 63% white, 37% African American) not receiving any cardiovascular medications who were classified as persistent hypertensive (n = 40), white-coat hypertensive (n = 40), or normotensive (n = 40) on the basis of clinic and daytime ambulatory BP, using a threshold criterion for hypertension of 140/90 mmHg. Persistent and white-coat hypertensive subjects were matched on ethnicity and clinic BP, and white-coat hypertensive subjects and normotensive subjects were matched on race and daytime ambulatory BP. Frequency domain analysis of resting beat-to-beat heart rate variability (HRV) was used to estimate parasympathetic and sympathetic control of the heart. RESULTS: Relative to normotensive subjects, both persistent and white-coat hypertensive subjects had lower high-frequency (HF) (P < .03) and low-frequency (LF) power (P < .051) and thus less parasympathetic activity. In addition, white-coat and persistent hypertensive subjects had significantly greater LF/HF ratios, indicating greater sympathetic-to-parasympathetic activity, as compared with normotensive subjects (P < .03). CONCLUSIONS: These findings suggest similarities between persistent and white-coat hypertensive subjects reflecting attenuated parasympathetic control of the heart. In addition, the association between white-coat hypertension and autonomic dysregulation, particularly diminished parasympathetic tone, may serve as a mechanism for increased risk for cardiovascular events in affected individuals.

Adult↗

PubMed2005

The socio-economic status of communities predicts variation in brain serotonergic responsivity.

BACKGROUND: We reported previously that the socio-economic status (SES) of individuals predicts variation in brain serotonergic responsivity, as assessed by neuropharmacological challenge in an adult community sample, and that this association is qualified by allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic responsivity covaries similarly with the SES of communities, as indexed by US Census data in the same study sample. METHOD: Community SES was defined by levels of income, economic disadvantage, housing costs, and educational attainment of census tracts in which 249 locally recruited study participants (54% male) resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak plasma prolactin (Prl) concentration following acute administration of the serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR genotyping was available on 131 participants. RESULTS: Subjects residing in census tracts of lower SES showed a blunted Prl response to fenfluramine (diminished serotonergic responsivity) relative to individuals living in more affluent neighborhoods. When adjusted for personal income and education, SES at the community level continued to predict fenfluramine-stimulated Prl responses and did so independently of 5-HTTLPR genotype. CONCLUSIONS: Area-level indices of relative social and economic disadvantage covary with individual differences in brain serotonergic responsivity, and this association is, in part, independent of individually defined SES. These findings may be relevant to reported effects of low community SES on the prevalence of psychiatric disorders or behaviors associated with dysregulation of central serotonergic function, such as depression, impulsive aggression, and suicide.

Adult↗

PubMed2005

A convergent-divergent approach to context processing, general intellectual functioning, and the genetic liability to schizophrenia.

Convergent and divergent validity are critically important in developing psychological measures that reveal interpretable deficits in disordered populations. This article reports on 2 studies that evaluated the validity of context processing measures. In Experiment 1, a confirmatory factor analysis of data from 481 healthy adults established the convergent validity of 2 context processing measures and showed that context processing accounted for significant amounts of variance in standard IQ and working memory measures. In Experiment 2, 20 schizophrenia patients, 16 of their healthy siblings, and 28 controls were evaluated using a novel, short context processing measure, the dot pattern expectancy (DPX) task. The DPX was sensitive to specific deficits in schizophrenia patients and their healthy siblings. These findings support the construct validity of context processing measures, suggest context processing is a component of intellectual functioning, and demonstrate that brief context processing measures remain sensitive to psychopathological deficits.

Adult↗

PubMed2004

Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults.

PURPOSE: In our initial study of the potential effects of cholesterol-lowering interventions on cognitive functioning, treatment with lovastatin as compared with placebo caused performance decrements on several neuropsychological tests, whereas scores on other tests were unaffected. The current study was designed to confirm and extend those findings. METHODS: The study comprised 308 hypercholesterolemic adults between 35 and 70 years of age. Employing a randomized double-blind design, we assigned participants to daily treatment with placebo, 10 mg of simvastatin, or 40 mg of simvastatin for 6 months. A neuropsychological test battery was administered to assess cognitive functioning at baseline and at the end of the treatment period. RESULTS: A total of 283 subjects completed the study: 94 subjects on placebo, 96 taking 10 mg of simvastatin, and 93 taking 40 mg of simvastatin. Compared with placebo, decremental effects of simvastatin treatment were found on tests previously observed to be sensitive to statins (P = 0.008; difference in summary z scores = 0.18; 95% confidence interval [CI]: 0.07 to 0.29) and on tests not previously administered (P = 0.04; difference in summary z scores = 0.17; 95% CI: 0.05 to 0.29), but not on tests previously observed to be insensitive to statins (P = 0.84; difference in summary z scores = 0.02; 95% CI: -0.07 to 0.10). For the three tests specifically affected by simvastatin, effects on cognitive performance were small, manifest only as failure to improve during the 6 months of treatment (compared with placebo), and were confounded by baseline differences on one test. CONCLUSION: This study provides partial support for minor decrements in cognitive functioning with statins. Whether such effects have any long-term sequelae or occur with other cholesterol-lowering interventions is not known.

Adult↗

PubMed2004

Serotonergic function in the central nervous system is associated with daily ratings of positive mood.

Serotonin constrains a broad array of animal and human behavior and may also inhibit the expression of mood or affective states among humans. For the most part, this research has focused on the association of central serotonergic function with negative affectivity (i.e., anxiety, depression, hostility), with less attention on the relationship between serotonergic function and positive affect or mood. The current study was conducted to examine the relationship between a measure of central serotonergic activity and daily ratings of positive and negative mood in a nonpatient sample. Two hundred and fifty-four adults, aged 24-60, completed end-of-day ratings of positive and negative mood items over 7 consecutive days. A neuropharmacological challenge was administered to index central serotonergic function, i.e., the maximal prolactin (PRL) response to fenfluramine, a serotonin releasing agent. Hierarchical linear regression analyses indicated that the peak PRL response to fenfluramine was positively associated with positive mood, averaged over 7 days, after controlling for known predictors of the PRL response. This relationship remained significant after controlling for average negative mood, for the presence of a current DSM-III-R diagnosis, and for trait measures of Neuroticism and Extraversion. In contrast, the PRL response to fenfluramine was not associated with average negative mood, although it was inversely correlated with trait negative affectivity (i.e., Neuroticism). These results suggest that deficiencies in serotonergic function may reflect the relative absence of positive mood.

Adult↗

PubMed2004

Exaggerated blood pressure responses during mental stress are prospectively related to enhanced carotid atherosclerosis in middle-aged Finnish men.

BACKGROUND: Hemodynamic reactions to mental stress may contribute to atherosclerosis. We previously observed cross-sectional relationships between blood pressure reactions to a standardized stress battery and carotid intima-media thickness (IMT) in the Kuopio Ischemic Heart Disease (KIHD) study. These are the first prospective results on this relationship. METHODS AND RESULTS: Men from 4 age cohorts (42 to 60 years old at study onset) were challenged with a standardized mental stress battery, and heart rate and blood pressure reactions were assessed. Ultrasound measures of common carotid IMT were collected at this time and 7 years later as noninvasive markers of atherosclerosis. Data were collected from a sample of 756 men at both times. Systolic blood pressure reactions to mental stress at study onset were positively related to mean carotid IMT 7 years later (beta=0.035, P=0.001, by blood pressure quartile, IMT=0.91, 0.93, 0.96, 1.00 mm) and to the progression of IMT (beta=0.020, P=0.006, by blood pressure quartile, DeltaIMT=0.08, 0.09, 0.11, 0.11 mm). Similar significant relations were shown for maximal IMT and plaque height. Diastolic blood pressure responses were less strongly related to carotid IMT than were systolic responses. Heart-rate responses were unrelated. Adjustment for standard risk factors did not substantially reduce the relation between systolic blood pressure reactivity and the progression of mean carotid IMT (standardized beta=0.059, P=0.026), maximal carotid IMT (standardized beta=0.084, P=0.006), or plaque height (standardized beta=0.093, P=0.008). CONCLUSIONS: The degree of systolic blood pressure reactivity to mental challenge is prospectively related to carotid IMT in middle-aged and older men, independent of known risk factors.

Adult↗

PubMed2004

Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences.

RATIONALE: The neuroendocrine response to intravenous citalopram may provide an acute, functional, in vivo measure of the neural serotonin (5-HT) system. OBJECTIVE: To refine the quantification of acute neuroendocrine responses following intravenous citalopram in studies of 5-HT function. METHODS: In 75 adult healthy subjects taking part in four similar protocols, we measured plasma prolactin and cortisol, as well as serial citalopram concentrations following intravenous citalopram (10 mg, 20 mg, 40 mg, 0.33 mg/kg) and placebo. The relationship between the AUC for intravenous citalopram during the first 150 min (AUC(150)) and the magnitude of the neuroendocrine response was determined. The role of pharmacokinetic (PK) parameters, as well as sensitivity to placebo injections, in influencing the neuroendocrine response to citalopram was then evaluated. RESULTS: Citalopram produced a dose-dependent increase in cortisol and prolactin. The maximal increase from baseline correlated significantly but modestly with citalopram's AUC(150) (prolactin r(2)=0.23, P<0.0001; cortisol r(2)=0.3, P<0.0001). Additionally, citalopram's AUC(150) was affected by between-subject differences in both the peripheral and central volume of distribution. However, the neuroendocrine responses to citalopram did not correlate with the responses to placebo. CONCLUSIONS: The parenteral citalopram challenge test is characterized by a modest concentration-response relationship, with concentration influenced by variable PK factors. Accounting for individual differences in drug distribution may improve the power of the citalopram challenge test, when used as an in vivo measure of central 5-HT function.

Adult↗

PubMed2004

Genetics of monoamine metabolites in baboons: overlapping sets of genes influence levels of 5-hydroxyindolacetic acid, 3-hydroxy-4-methoxyphenylglycol, and homovanillic acid.

BACKGROUND: Monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) are associated with several psychiatric disorders. Limited evidence suggests that monoamine levels are heritable, but no information concerning genetic relationships among monoamines is available. Further genetic analysis can help explain phenotypic correlations among monoamine levels and might eventually help identify genes involved in response to therapy or risk of psychopathology. METHODS: Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-hydroxy-4-methoxyphenylglycol (MHPG) were measured in cerebrospinal fluid from 271 baboons (Papio hamadryas). Variance components methods were used to estimate heritabilities, and multivariate analyses were used to estimate genetic correlations (pleiotropy) and environmental correlations between metabolites. RESULTS: Each metabolite exhibited significant heritability in baboons (5-HIAA: h(2) =.30 +/-.17; MHPG: h(2) =.36 +/-.16; HVA: h(2) =.50 +/-.19). Multivariate analyses revealed genetic correlations between 5-HIAA and HVA and between HVA and MHPG. Environmental correlations were found between 5-HIAA and HVA and between 5-HIAA and MHPG. CONCLUSIONS: Overlapping, nonidentical sets of genes influence individual variation in 5-HIAA, MHPG, and HVA levels among baboons. The phenotypic correlation between 5-HIAA and HVA observed in nonhuman primates and humans is likely due to both shared genetic and environmental factors. Genetic analyses of monoamine levels in primates can provide novel information concerning the genetics of variation among humans.

Analysis of Variance↗

PubMed2004

A comparison of d, l-fenfluramine and citalopram challenges in healthy adults.

Dimensional personality characteristics (e.g. impulsivity) and related behaviors and psychiatric disorders are linked to abnormalities of central nervous system (CNS) serotonergic functioning. Although neuroendocrine [e.g. plasma prolactin (PRL)] responses to the serotonin agonist, fenfluramine, have been used widely to index CNS serotonergic responsivity, safety concerns constrain continued use of fenfluramine. Citalopram, which inhibits serotonin reuptake, may serve as an alternative pre-synaptic neuropharmacologic challenge agent, due to its high selectivity and absence of intrinsic activity at serotonin or other receptor families. Twenty-two healthy adults who had been administered a fenfluramine challenge before May 1996 completed a 5-h oral citalopram challenge 3-6 years later. PRL responsivity to citalopram correlated significantly with PRL response to fenfluramine for baseline-corrected maximal and area-under-the-curve (AUC) indices ( r's > or =0.49, P's< or =0.02). The magnitude of the correlations is notable given the length of time between challenges. The results support the use of citalopram as an alternate neuroendocrine challenge to index CNS serotonergic responsivity.

Adult↗