Correction to: Low Life Course Socioeconomic Status (SES) Is Associated with Negative NEO PI-R Personality Patterns.

After the publication of the original article, the Editor was notified by Duke University that they have determined the authorship to be incomplete. Consequently, Dr Edward Suarez has been added as a co-author to represent his contribution to the conception and design of the work and acquisition of the data.

The Effects of Tryptophan Enhancement and Depletion on Plasma Catecholamine Levels in Healthy Individuals.

OBJECTIVE: Central nervous system (CNS) serotonin (5-HT) exerts both excitatory and inhibitory effects on the sympathetic nervous system (SNS) in animals. In this study, we examine the effects of tryptophan enhancement and depletion on plasma catecholamine levels in humans. METHODS: The total sample consisted of 164 healthy men and women who were tested for 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and 85 to a tryptophan depletion condition. Both protocols consisted of a "sham day," followed by an "active day." Blood samples for assessment of plasma norepinephrine and epinephrine levels were collected before and after tryptophan enhancement/depletion. Data were analyzed using general linear models. Separate analyses were conducted for each study arm and for each measure. RESULTS: In the depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and norepinephrine (F(5,335) = 2.79, p = .018) showed small increases on active versus "sham" depletion days. There were also significant day by time interactions for epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked increase in epinephrine (Premean = 23.92 (12.23) versus Postmean = 81.57 (62.36)) and decrease in norepinephrine (Premean = 257.2 (106.11) versus Postmean = 177.04 (87.15)), whereas levels of both catecholamines were stable on the "sham day." CONCLUSIONS: CNS 5-HT exerts both inhibitory and excitatory effects on SNS activity in humans, potentially due to stimulation of CNS 5-HT receptors that have shown to have inhibitory (5-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS effects in animal models.

Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene.

Chronic psychosocial stress adversely affects health and is associated with the development of disease [Williams, 2008]. Systematic epidemiological and genetic studies are needed to uncover genetic variants that interact with stress to modify metabolic responses across the life cycle that are the proximal contributors to the development of cardiovascular disease and precipitation of acute clinical events. Among the central challenges in the field are to perform and replicate gene-by-environment (G × E) studies. The challenge of measurement of individual experience of psychosocial stress is magnified in this context. Although many research datasets exist that contain genotyping and disease-related data, measures of psychosocial stress are often either absent or vary substantially across studies. In this paper, we provide an algorithm to create a synthetic measure of chronic psychosocial stress across multiple datasets, applying a consistent criterion that uses proxy indicators of stress components. We validated the computed scores of chronic psychosocial stress by observing moderately strong and significant correlations with the self-rated chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho = 0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of the self-rated and computed measures. Finally, we demonstrate the utility of this computed chronic psychosocial stress variable by providing three additional replications of our previous finding of gene-by-stress interaction with central obesity traits [Singh et al., 2015].

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

BACKGROUND: Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits. PURPOSE: The purpose of this study is to determine whether central nervous system serotonin influences the association between hostility and fasting glucose in African American women. METHODS: The study consisted of 119 healthy volunteers (36 African American women, 27 White women, 21 White males, and 35 African American males, mean age 34 ± 8.5 years). Serotonin related compounds were measured in cerebrospinal fluid. Hostility was measured by the Cook-Medley Hostility Scale. RESULTS: Hostility was associated with fasting glucose and central nervous system serotonin related compounds in African American women only. Controlling for the serotonin related compounds significantly reduced the association of hostility to glucose. CONCLUSIONS: The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

Recovery expectations and long-term prognosis of patients with coronary heart disease.

BACKGROUND: Expectations of patients regarding their prospects for recovery have been shown to predict subsequent physical and social functioning. Evidence regarding the impact of expectations on clinical outcomes is limited. METHODS: At the inpatient service of a tertiary care hospital, we evaluated beliefs of patients undergoing coronary angiography about their prognosis as predictors of long-term survival and 1-year functional status. Baseline assessments, including a measure of expectations for recovery, were obtained during hospitalization with mortality follow-up for approximately 15 years. Patients with significant obstructive coronary artery disease were interviewed while in the hospital and enrolled in follow-up. Functional status was assessed at baseline and 1 year later with questionnaires reflecting physical capabilities. Analyses controlled for age, sex, disease severity, comorbidities, treatments, demographics, depressive symptoms, social support, and functional status. There were 1637 total deaths, 885 from cardiovascular causes, in the 2818 patients in these analyses. The outcomes were total mortality, cardiovascular mortality, and 1-year functional status. RESULTS: Expectations were positively associated with survival after controlling for background and clinical disease indicators. For a difference equivalent to an interquartile range of expectations, the hazard ratio (HR) for total mortality was 0.76 (95% confidence interval [CI], 0.71-0.82) and 0.76 (95% CI, 0.69-0.83) for cardiovascular mortality. The HRs were 0.83 (95% CI, 0.76-0.91) and 0.79 (95% CI, 0.70-0.89) with further adjustments for demographic and psychosocial covariates. Similar associations (P < .001) were observed for functional status. CONCLUSION: Recovery expectations at baseline were positively associated with long-term survival and functioning in patients with coronary artery disease.

Low life course socioeconomic status (SES) is associated with negative NEO PI-R personality patterns.

BACKGROUND: Low socioeconomic status (SES) is associated with poor health. One potential pathway accounting for this relationship may be an association between low SES and personality characteristics that affect health. METHODS: Associations among parent's education, current SES (education and income), and personality were examined among 233 African Americans and Caucasian, male and female community volunteers. RESULTS: Using multivariate analysis of variance (MANOVA) to model neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness simultaneously, participant's education, household income, and father's and mother's education each had significant main effects on personality. When examining the life course--the combination of both current and childhood SES--distinctive patterns emerged for each domain, depending upon whether mother's or father's education was used to index childhood SES. When using mother's education as a childhood SES index, a high life course SES (high participant's SES/high mother's education) was associated with high extraversion and openness. Using father's education as a childhood SES index, a low life course SES (low participant's SES/low father's education) was associated with disproportionately high neuroticism and low conscientiousness. These effects did not differ by race or sex. CONCLUSION: The implications of these findings for the role of personality in the SES-health relationship are discussed.

Central nervous system serotonin and clustering of hostility, psychosocial, metabolic, and cardiovascular endophenotypes in men.

OBJECTIVE: To use measures of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and genotype of a functional polymorphism of the monoamine oxidase A gene promoter (MAOA-uVNTR) to study the role of central nervous system (CNS) serotonin in clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes. METHODS: In 86 healthy male volunteers, we evaluated CSF levels of the primary serotonin metabolite 5HIAA and MAOA-uVNTR genotype for association with a panel of 29 variables assessing hostility, other psychosocial, metabolic, and cardiovascular endophenotypes. RESULTS: The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those of men with less active alleles for 15 of the 29 endophenotypes. MAOA-uVNTR genotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, body mass index, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles. CONCLUSIONS: These findings indicate that, in men, indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, whereas decreased CNS serotonin function is associated with a less favorable profile.

Prospective study of externalizing and internalizing subtypes of posttraumatic stress disorder and their relationship to mortality among Vietnam veterans.

Posttraumatic stress disorder (PTSD) can be a complex disorder, and some studies have found that samples of individuals with PTSD contain subtypes that may relate to health outcomes. The goals were to replicate previously identified PTSD subtypes and examine how subtype membership relates to mortality. Data from the Vietnam Experience Study and a clinical sample of Vietnam veterans were combined (n = 5248) to address these research questions. Consistent with previous studies, 3 PTSD subtypes emerged: externalizers (n = 317), internalizers (n = 579), and low pathology (n = 280). Posttraumatic stress disorder diagnosis was associated with increased risk of all-cause and behavioral-cause (eg, homicide, suicide) mortality. Both externalizing and internalizing subtypes had higher mortality and were more likely to die from cardiovascular causes than those without PTSD. Externalizers were more likely to die from substance-related causes than those without PTSD. The value of considering possible PTSD subtypes is significant in that it may contribute to identifying more specific targets for treatment and rehabilitation in veterans with PTSD.

Hostility and fasting glucose in African American women.

OBJECTIVE: To examine whether the relationship of hostility (HOST) to fasting glucose indices is moderated by sex and race. HOST has been associated with abnormalities in glucose metabolism. Prior studies suggested that this association may be more prevalent in women and in African American (AA) individuals. METHODS: A total of 565 healthy AA and white (W) men and women (mean age = 33 +/- 6 years) were assessed. HOST was measured by the 27-item version of the Cook Medley HOST Scale. The moderating effects of sex and race were evaluated for the associations of HOST to fasting glucose, insulin, and insulin sensitivity (HOMA-IR). RESULTS: Analysis showed a moderating effect of sex and race on the association of HOST to fasting glucose (p = .03), but not for insulin (p = .12). Analysis of HOMA-IR revealed a trend (p = .06) for the interaction. Stratified analyses by race and sex revealed a positive association between HOST and fasting glucose only in AA women, which remained significant after controlling for age and body mass index. CONCLUSION: A relationship between HOST and fasting glucose was evident in AA women only, a group that has twice the risk of developing Type 2 diabetes compared with W women. Further studies are needed to elucidate the mechanisms by which HOST may affect glucose metabolism in AA women.

Evaluation of lifetime trauma exposure and physical health in women with posttraumatic stress disorder or major depressive disorder.

The current study examines lifetime trauma exposure rates in 148 women with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), or neither diagnosis and whether this is related to measures of PTSD, depression, hostility, health symptoms, and health care utilization. Findings indicate that multiple trauma exposures were prevalent in this sample, with 96% of those with PTSD and 79% of those with MDD reporting three or more trauma exposures compared to 46% in the comparison group. Controlling for diagnostic status, regression analysis for PTSD symptom severity reveals that the trauma exposure adult physical assault category was significantly associated with more severe PTSD and depressive symptoms, whereas the childhood violence category was most associated with increased hostility. PTSD and MDD groups reported greater past year health conditions and health care utilization.

Childhood socioeconomic status and serotonin transporter gene polymorphism enhance cardiovascular reactivity to mental stress.

OBJECTIVE: To test the hypothesis that low socioeconomic status (SES) and the 5HTTLPR L allele are associated with increased cardiovascular reactivity (CVR) to stress in a larger sample and that SES and 5HTTLPR genotypes interact to enhance CVR to stress. CVR to mental stress has been proposed as one mechanism linking stress to the pathogenesis of cardiovascular disease. The more transcriptionally efficient long (L) allele of a polymorphism of the serotonin transporter gene promoter (5HTTLPR) has been found associated with increased risk of myocardial infarction. We found the long allele associated with larger CVR to mental stress in a preliminary study of 54 normal volunteers. METHODS: Subjects included 165 normal community volunteers stratified for race, gender, and SES, who underwent mental stress testing. RESULTS: Childhood SES as indexed by Father's Education Level was associated with larger systolic blood pressure (SBP) (p < .05) and diastolic blood pressure (DBP) (p = .01) responses to mental stress. The L allele was associated with larger SBP (p = .04), DBP (p < .0001), and heart rate (p = .04) responses to mental stress compared with the short (S) allele. Subjects with the SS genotype and high Father's Education exhibited smaller SBP (5.2 mm Hg) and DBP (2.9 mm Hg) responses than subjects with LL genotype and low Father's Education (SBP = 13.3 mm Hg, p = .002; DBP = 9.7 mm Hg, p < .0001). CONCLUSIONS: Both the 5HTTLPR long allele and low SES, particularly during childhood, are associated with increased CVR to mental stress, which could account, at least in part, for the increased cardiovascular disease risk associated with these characteristics. If confirmed in further research, these characteristics could be used to identify persons who might benefit from preventive interventions.

Hostility, drinking pattern and mortality.

AIMS: This study examined the association of hostility to drinking pattern and whether this association mediated the relation of hostility to mortality. PARTICIPANTS AND DESIGN: Subjects were 3326 current drinkers from the Vietnam Experience Study cohort who were followed for vital status. SETTING: United States. MEASUREMENTS: Hostility was measured by an abbreviated version of the Cook-Medley Hostility Scale (ACM). The alcohol variables were total monthly intake of alcohol, drinking frequency, drinks per drinking day and drinking > or = 5 drinks on at least one occasion in the past month (i.e. heavy episodic drinking). FINDINGS: Regression analyses showed associations between the ACM and total monthly intake of alcohol (P < 0.0001), drinks per drinking day (P < 0.0001) and heavy episodic drinking (P < 0.0001), but not with frequency of drinking days. Hostility, drinks per drinking day, heavy episodic drinking and total monthly alcohol intake were also associated with all-cause mortality (all Ps < 0.0001). Further analyses showed that drinking pattern, particularly drinks per drinking day, may account partially for the relation of hostility to mortality. CONCLUSIONS: High hostility is associated with elevated mortality and a deleterious drinking pattern characterized by relatively high intake per drinking occasion. Drinking pattern could help explain the relationships between hostility and health.

Sleep quality varies as a function of 5-HTTLPR genotype and stress.

OBJECTIVE: To test the hypothesis that allelic variation in 5HTT gene-linked polymorphic region (5-HTTLPR) genotype was associated with sleep quality (Pittsburgh Sleep Quality Index, PSQI) as a main effect and as moderated by the chronic stress of caregiving. Serotonin (5HT) is involved in sleep regulation and the 5HT transporter (5HTT) regulates 5HT function. A common 44-base pair deletion (s allele) polymorphism in the 5-HTTLPR is associated with reduced 5HTT transcription efficiency and 5HT uptake in vitro. METHODS: Subjects were 142 adult primary caregivers for a spouse or parent with dementia and 146 noncaregiver controls. Subjects underwent genotyping and completed the PSQI. RESULTS: Variation in 5-HTTLPR genotype was not related to sleep quality as a main effect (p > .36). However, there was a caregiver X 5-HTTLPR interaction (p < .009), such that the s allele was associated with poorer sleep quality in caregivers as compared with controls. CONCLUSIONS: Findings suggest that the s allele may moderate sleep disturbance in response to chronic stress.

Depressive symptoms, race, and glucose concentrations: the role of cortisol as mediator.

OBJECTIVE: This study examined the associations of depressive symptoms with glucose concentrations and morning cortisol levels in 665 African-American and 4,216 Caucasian Vietnam-era veterans. RESEARCH DESIGN AND METHODS: Glucose level was measured as a three-level variable (diabetes, impaired glucose, and normal). Depressive symptoms were measured by the Obvious Depression Scale (OBD) from the Minnesota Multiphasic Personality Inventory. RESULTS: Regression models showed significant race x OBD interactions in relation to glucose concentration (P < 0.0001) and cortisol (P < 0.0001). The OBD was positively associated with glucose concentration and cortisol in both racial groups. However, the magnitude of those associations was larger for African Americans. Further analyses suggested that cortisol partially mediated the race difference in the relation of depressive symptoms to glucose concentrations. CONCLUSIONS: These results suggest that enhanced hypothalamic pituitary adrenal activity plays an important role in the relation of depressive symptoms to dysregulated glucose metabolism and may partially explain the differential effects of depressive symptoms on glucose levels in African-American and Caucasian male subjects.

Associations of a regulatory polymorphism of monoamine oxidase-A gene promoter (MAOA-uVNTR) with symptoms of depression and sleep quality.

OBJECTIVE: To examine the relationships among the variable number of tandem repeats in the monoamine oxidase-A linked polymorphic region allelic variation (MAOA-uVNTR) and the symptoms of depression and sleep quality. The monoamine oxidase-A (MAOA) gene, which plays a vital role in degradation of neurotransmitters such as serotonin, norepinephrine, and dopamine, contains a polymorphism in its promoter region (MAOA-uVNTR) that affects transcriptional efficiency. MAOA-uVNTR genotype has been associated with both psychological and physical measures. METHODS: The sample consisted of 74 males enrolled in a case/control study of caregivers for relatives with dementia. Age- and race-adjusted linear regression models were used to examine the association between low versus high MAOA-uVNTR activity alleles, symptoms of depression (Center for Epidemiological Studies of Depression), and sleep quality ratings (Pittsburgh Sleep Quality Index). RESULTS: MAOA-uVNTR alleles associated with less transcriptional activity were related to increased symptoms of depression (p < .04; Cohen's d = 0.52) and poorer sleep quality (p < .04; Cohen's d = 0.31). CONCLUSIONS: Individuals with less active MAOA-uVNTR alleles may be at increased risk for depressive symptoms and poor sleep.

Facets of openness predict mortality in patients with cardiac disease.

OBJECTIVE: To examine the NEO Personality Inventory (NEO PI) Openness to Experience (O) domain and its facets as predictors of cardiac deaths and all-cause mortality. METHODS: The NEO PI was administered to a sample of 977 coronary catheterization patients with significant coronary artery disease. Over an average 15-year follow-up period, 266 cardiac deaths and 463 total deaths occurred. The relationships of O scores to mortality were examined with Cox proportional hazard models. Each model included age, left ventricular ejection fraction, severity of congestive heart failure, and number of diseased vessels as covariates. RESULTS: The O domain score was not associated with all-cause mortality and only approached significance for decreased cardiac deaths (p = .055). However, a higher score for Openness to Feelings was associated with a decreased risk of cardiac death (p < .01) and all-cause mortality (p < .01). High Openness to Actions was also associated with decreased cardiac mortality (p < .01) and all-cause mortality (p = .03) risk. Higher Openness to Aesthetics and Ideas were only associated with decreased cardiac death risk (both p values <.04). In contrast, Openness to Fantasy and Values were not associated with longevity. Previous evidence suggested that educational achievement may account for the effects of Openness to Experience on mortality; however, controlling for educational achievement did not change the results. CONCLUSION: These findings suggest that greater emotional awareness and high curiosity, as indicated by the NEO PI Feelings and Actions facets, are associated with increased patient longevity independently of other risk factors and educational achievement.

Prospective associations between sedentary lifestyle and BMI in midlife.

OBJECTIVE: A strong positive cross-sectional relationship between BMI and a sedentary lifestyle has been consistently observed in numerous studies. However, it has been questioned whether high BMI is a determinant or a consequence of a sedentary lifestyle. RESEARCH METHODS AND PROCEDURES: Using data from four follow-ups of the University of North Carolina Alumni Heart Study, we examined the prospective associations between BMI and sedentary lifestyle in a cohort of 4595 middle-aged men and women who had responded to questionnaires at the ages of 41 (standard deviation 2.3), 44 (2.3), 46 (2.0), and 54 (2.0). RESULTS: BMI was consistently related to increased risk of becoming sedentary in both men and women. The odds ratios of becoming sedentary as predicted by BMI were 1.04 (95% confidence limits, 1.00, 1.07) per 1 kg/m(2) from ages 41 to 44, 1.10 (1.07, 1.14) from ages 44 to 46, and 1.12 (1.08, 1.17) from ages 46 to 54. Controlling for concurrent changes in BMI marginally attenuated the effects. Sedentary lifestyle did not predict changes in BMI, except when concurrent changes in physical activity were taken into account (p < 0.001). The findings were not confounded by preceding changes in BMI or physical activity, age, smoking habits, or sex. DISCUSSION: Our findings suggest that a high BMI is a determinant of a sedentary lifestyle but did not provide unambiguous evidence for an effect of sedentary lifestyle on weight gain.

Neighborhood characteristics moderate effects of caregiving on glucose functioning.

OBJECTIVE: Adverse neighborhood environments and caregiving for a relative with dementia are both stressors that have been associated with poor health. The present study examined the extent to which three self-report measures of neighborhood characteristics interact with caregiving status (caregiver versus noncaregiver) to modify an important stress related health outcome: plasma glucose. METHODS: The study sample consisted of 147 community recruited caregivers and 147 participants who did not have caregiving responsibilities. We hypothesized that negative neighborhood characteristics would magnify effects of caregiving on plasma glucose levels. Regression analyses were conducted to examine the interaction of three neighborhood characteristic measures with caregiving status in predicting fasting plasma glucose (FPG) and glycosylated hemoglobin concentration (HbA1c), with control for age, race, gender, relation to care recipient (spouse or relative), body mass index, income, and education. RESULTS: Of the three neighborhood measures, the one reflecting crime concerns significantly moderated the effect of caregiving on FPG (p < .002) and HbA1c (p < .001). For participants with better neighborhood characteristics, caregivers and noncaregivers were similar with respect to indicators of glucose metabolism; however, for participants with worse neighborhood characteristics, caregivers had higher levels of FPG and HbA1c, as compared with noncaregivers. CONCLUSIONS: Poor health outcomes, such as impaired glucose control, may be found among caregivers who fear neighborhood crime.

Hostility, age, and mortality in a sample of cardiac patients.

This study examined hostility as a predictor of survival in a sample of 1,328 patients who had documented coronary artery disease. After controlling for disease severity, there was a significant interaction between age and hostility. Hostility was significantly associated with poorer survival but only in younger (<61.2 years) patients.