Serina A. Neumann

Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers

Objective: Recent evidence suggests that higher peripheral levels of interleukin 6 (IL-6) are associated with poorer cognitive function and predict future cognitive decline among the elderly. The current investigation extends the study of relationships between plasma IL-6 and cognitive performance to healthy middle-aged adults and to an examination of more specific cognitive domains. Methods: Five hundred relatively healthy community volunteers aged 30 to 54 had blood drawn for the determination of plasma IL-6 levels and completed a battery of neuropsychological tests evaluating memory and executive function. Results: After controlling for age, gender, race, and education, hierarchical regression analyses revealed an inverse relationship between circulating levels of IL-6 and performance on clusters of tests assessing auditory recognition memory, attention/working memory, and executive function. In contrast, there was no association between IL-6 and performance on tests of general memory. Secondary analyses demonstrated that relationships between IL-6 and auditory recognition and working memory and executive function were independent of a number of health factors, including body mass index, smoking, and hypertension. Conclusions: These findings contribute to a growing body of evidence linking chronic inflammation to poorer cognitive functioning and extend these findings to a midlife community sample, raising the possibility that IL-6 may represent a biomarker for risk of future cognitive decline. IL = interleukin; CNS = central nervous system; BMI = body mass index; WMS = Wechsler Memory Scale; BP = blood pressure.

Similar patterns of cardiovascular response during emotional activation as a function of affective valence and arousal and gender

OBJECTIVE Laboratory studies of emotion-induced cardiovascular responses have been conducted predominantly with a specific affects approach rather than a dimensional approach. The purpose of this study was to apply the principles of the Circumplex Model of Affect (i.e., valence and arousal) to investigate cardiovascular reactivity during emotional activation in men and women. METHODS Forty-two healthy university students (mean age = 19.45, 52% women, 58% Caucasian) engaged in personally relevant recall tasks that varied as a function of valence and arousal. Self-reported valence and arousal, systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate (HR), preejection period (PEP), stroke index (SI), cardiac index (CI), and total peripheral resistance (TPR) were measured during baseline and task periods. RESULTS Cardiovascular responses were found to be largely comparable across the recall tasks and were characterized by significant increases in blood pressure, HR, and TPR, and decreases in SI (Ps < .001). In addition, SBP during negative valence tasks was significantly higher than during positive valence tasks (P < .03), and PEP lengthened more during low as compared to high arousal tasks (P < .03). CONCLUSIONS These results highlight the similarity of hemodynamic adjustments during the verbal expression of emotion across gender and the dimensions of valence and arousal. The overall response pattern suggests alpha-adrenergically mediated sympathetic activation and vagal withdrawal.

Stimulated production of proinflammatory cytokines covaries inversely with heart rate variability.

Objective: To examine whether high-frequency heart rate variability, an indirect measure of parasympathetic (vagal) control over variations in heart rate, is associated with immune reactivity to an in vitro inflammatory challenge. Convergent evidence from the animal literature shows that the autonomic nervous system plays a key role in regulating the magnitude of immune responses to inflammatory stimuli. Signaling by the parasympathetic system inhibits the production of proinflammatory cytokines by activated monocytes/macrophages and thus decreases local and systemic inflammation. As yet, no direct human evidence links parasympathetic activity to inflammatory competence. Methods: We examined the relationship of variations in heart rate, recorded during paced respiration, to lipopolysaccharide-induced production of the inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 among a community sample of 183 healthy adults (mean age = 45 years; 59% male; 92% White, 7% African-American). Results: Consistent with animal findings, higher derived estimates of vagal activity measured during paced respiration were associated with lower production of the proinflammatory cytokines TNF-α and IL-6 (r = −.18 to −.30), but were not related to production of the anti-inflammatory cytokine IL-10. These associations persisted after controlling for demographic and health characteristics, including age, gender, race, years of education, smoking, hypertension, and white blood cell count. Conclusions: These data provide initial human evidence that vagal activity is inversely related to inflammatory competence, raising the possibility that vagal regulation of immune reactivity may represent a pathway linking psychosocial factors to risk for inflammatory disease. ANS = autonomic nervous system; HRV = heart rate variability; HF = high frequency; LF = low frequency; rMSSD = root mean square of successive differences; IL = interleukin; TNF = tumor necrosis factor; LPS = lipopolysaccharide; WBC = white blood count; BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure.

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 (ps < .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.

Alexithymia and Cardiovascular Risk in Older Adults: Psychosocial, Psychophysiological, and Biomedical Correlates

Psychosocial correlates of alexithymia were examined in 102 healthy, older adults (ages 53-83; 76% male). Alexithymic ( n = 26) and non-alexithymic ( n = 30) groups, defined by top ( S 70) and bottom ( h 54) quartiles of the distribution of Toronto Alexithymia Scale (26-item) scores, were compared with respect to psychosocial, psychophysiological, and biomedical risk factors for cardiovascular disease. Both categorical ratings and continuous scores of alexithymia were associated with significantly greater levels of trait anxiety, anger-in, neuroticism, hostility, perceived stress, depression, and lower levels of social support. Compared to non-alexithymics, alexithymics displayed significantly greater blood pressure responses to anger provocation and tended to have a greater percent body fat. The groups did not differ in resting cardiovascular parameters, heart rate reactivity, fasting glucose and lipoprotein lipids, body mass index, waist-to-hip ratio, social desirability, or trait anger. These findings suggest several psychosocial and psychophysiological pathways by which alexithymia may confer risk for cardiovascular disease among older adults.

Heart Rate Variability Is Associated With Polymorphic Variation in the Choline Transporter Gene

Objective: The objective of this study was to determine whether interindividual variation in parasympathetic (cholinergic) and sympathetic (adrenergic) regulation of heart rate (as estimated by frequency components of heart rate variability [HRV]) may be accounted for, in part, by genetic variation in the choline transporter, a component of acetylcholine neurotransmission. Methods: Resting HRV estimates of high- (HF) and low-frequency (LF) power and LF/HF ratio were determined from electrocardiogram recordings collected continuously over 5 minutes in 413 white individuals of European ancestry (49% men; aged 30–54 years [mean, 44 years]). Subjects were genotyped for a single nucleotide polymorphism (SNP) located in the 3′ untranslated region of the choline transporter gene (CHT1). Frequencies of the alternate CHT1 alleles, labeled G and T, were 76% and 24%. Results: Compared with GG homozygotes, participants having any T allele had greater HF power (p <.02), lower LF power (p <.02), and lower LF/HF ratios (p <.005). Relative to men, women had lower LF power (p <.001) and lower LF/HF ratios (p <.005). Conclusions: These findings show that polymorphic variation in the CHT1 gene is associated significantly with interindividual variability in HRV indices related to parasympathetic (cholinergic) activity. ACh = acetylcholine; CHT1 = choline transporter gene; UTR = untranslated region; HRV = heart rate variability; HF = high frequency; LF = low frequency; nu = normalized units; ln = natural log; BMI = body mass index.

Normative variation in self-reported sleep quality and sleep debt is associated with stimulated pro-inflammatory cytokine production.

Activation of innate inflammatory pathways, marked by increased production of pro-inflammatory cytokines, has been proposed as a potential mechanism linking poor sleep and inflammatory disease risk. In the present study, we examined associations of self-reported sleep quality and duration, and a calculated measure of sleep debt with the production of pro-inflammatory cytokines, interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)-alpha among a community sample of 156 healthy adults. Bivariate correlations revealed an inverse association between sleep quality and production of all the three pro-inflammatory cytokines that was retained for IL-1beta after controlling for demographic and health characteristics. Hierarchical linear regressions also revealed that higher sleep debt scores predicted greater production of IL-1beta and IL-6 after adjusting for covariates. Secondary analyses showed an interaction between sleep debt and body mass index (BMI) in the prediction IL-1beta, suggesting that the impact of sleep debt on cytokine production is greater among participants with lower BMI scores. Further exploration of this potential psychophysiological pathway linking sleep difficulty and inflammatory disease susceptibility is warranted.

Role-played interpersonal interaction: Ecological validity and cardiovascular reactivity

Conflictual role-play scenarios have been used to model brief interpersonal interaction and to elicit cardiovascular reactivity in the laboratory. Here we discuss data suggesting that role-played interactions constitute an ecologically valid laboratory task that may improve laboratory-to-field generalization of cardiovascular response. Specifically, our research indicates that young adults perceive the stress associated with role-play scenarios as similar to that encountered in everyday life. Furthermore, these stress appraisals moderate cardiovascular response to role-play in men. We also find that a social stressor (i.e. speech task) is perceived as significantly more similar to a real-life stressor as compared to other standard laboratory tasks. We propose that particular constellations of cognitive, affective, and behavioral responses to laboratory-based social stressors, such as role-played interaction, may elicit different patterns of hemodynamic response. Further understanding of interrelations among cognitive, affective, behavioral, and physiological response patterns may assist in the study of cardiovascular reactivity as a potential mechanism linking personality factors and the development of cardiovascular disease.

Silent Myocardial Ischemia and Cardiovascular Responses to Anger Provocation in Older Adults

To determine if older, asymptomatic individuals with no prior history of coronary heart disease with exercise-induced silent myocardial ischemia (SI) during graded exercise treadmill testing exhibit exaggerated cardiovascular reactivity to anger provocation, we compared 42 SI participants and 95 controls. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) changes from baseline to three tasks & #x2014;anger recall, speech role-play, and mental arithmetic with harassment & #x2014;were assessed. Compared to controls, SI displayed greater HR responses for the speech role-play task only. The SI group was significantly older, had higher levels of fasting glucose and triglycerides, and had lower HDL-cholesterol. In multiple regression analyses, after controlling for these differences, SI was significantly associated with greater HR responses to the speech role-play. In sum, the SI group had significantly exaggerated HR responses to the speech role-play task, whereas SBP and DBP reactivity were comparable between groups. This suggests minimally enhanced cardiovascular reactivity among older SI patients that may nonetheless increase risk for cardiac events.

Postural effects on hemodynamic response to interpersonal interaction

Laboratory studies of stress-induced cardiovascular reactivity have been conducted predominantly with participants in a seated posture. This procedure may contribute to limited laboratory-field generalization of cardiovascular response. The present study examined hemodynamic adjustments underlying pressor responses, in addition to heart rate and systolic time intervals, during seated and standing role-played, interpersonal interaction in 60 young adults. Irrespective of gender or race, blood pressure responses to the seated and standing interactions were comparable. However, seated interactions yielded a significantly greater increase in heart rate, shortened preejection period and decreased stroke index as compared to standing. Alternatively, interacting while standing yielded a significantly increased left ventricular ejection time and total peripheral resistance in comparison to sitting. These results suggest that hemodynamic adjustments during stressful interpersonal interaction vary as a function of posture, with somewhat greater cardiac influences apparent while seated and a more pronounced vascular response while standing.