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1.  Aerobic Exercise and Strength Training Effects on Cardiovascular Sympathetic Function in Healthy Adults: A Randomized Controlled Trial 
Psychosomatic medicine  2013;75(4):375-381.
Exercise has widely documented cardioprotective effects, but the mechanisms underlying these effects are not entirely known. Previously, we demonstrated that aerobic but not strength training lowered resting heart rate and increased cardiac vagal regulation, changes that were reversed by sedentary deconditioning. Here, we focus on the sympathetic nervous system and test whether aerobic training lowers levels of cardiovascular sympathetic activity in rest and that deconditioning would reverse this effect.
We conducted a randomized controlled trial contrasting the effects of aerobic (A) versus strength (S) training on indices of cardiac (preejection period, or PEP) and vascular (low-frequency blood pressure variability, or LF BPV) sympathetic regulation in 149 young, healthy, and sedentary adults. Participants were studied before and after conditioning, as well as after 4 weeks of sedentary deconditioning.
As previously reported, aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. Contrary to prediction, there was no differential effect of training on either PEP (A: mean [SD] −0.83 [7.8] milliseconds versus S: 1.47 [6.69] milliseconds) or LF BPV (A: mean [SD] −0.09 [0.93] ln mm Hg2 versus S: 0.06 [0.79] ln mm Hg 2) (both p values > .05).
These findings, from a large randomized controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on resting state cardiovascular indices of PEP and LF BPV. These results indicate that in healthy, young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in resting sympathetic activity.
Trial Registration identifier: NCT00358137.
PMCID: PMC4518731  PMID: 23630307
sympathetic nervous system; preejection period; low-frequency blood pressure variability; aerobic exercise; randomized controlled trial
2.  Personality Traits and Leptin 
Psychosomatic medicine  2013;75(5):505-509.
Personality traits related to high Neuroticism and low Conscientiousness are consistently associated with obesity. Hormones implicated in appetite and metabolism, such as leptin, may also be related to personality and may contribute to the association between these traits and obesity. The present research examined the association between leptin and Five Factor Model personality traits.
A total of 5,214 participants (58% female; Mean age = 44.42 years, SD = 15.93, range 18 to 94) from the SardiNIA project completed the Revised NEO Personality Inventory, a comprehensive measure of personality traits, and their blood samples were assayed for leptin.
As expected, lower Conscientiousness was associated with higher circulating levels of leptin (r=−.05, p<.001), even after controlling for body mass index, waist circumference, or inflammatory markers (r=−.05, p<.001). Neuroticism, in contrast, was unrelated to leptin (r=.01, p=.31).
Individuals who are impulsive and lack discipline (low Conscientiousness) may develop leptin resistance, which could be one factor that contributes to obesity, whereas the relation between a proneness to anxiety and depression (high Neuroticism) and obesity may be mediated through other physiological and/or behavioral pathways.
PMCID: PMC4511923  PMID: 23697464
Leptin; Personality traits; Appetite; Conscientiousness; Neuroticism; Obesity; Impulsivity; Self-discipline; Inflammation; Depression
3.  Early Adverse Life Events and Resting State Neural Networks in Patients with Chronic Abdominal Pain: Evidence for Sex Differences 
Psychosomatic medicine  2014;76(6):404-412.
Early adverse life (EAL) events and sex have been identified as vulnerability factors for the development of several stress-sensitive disorders, including irritable bowel syndrome (IBS). We aimed to identify disease and sex-based differences in resting state (RS) connectivity associated with EALs in individuals with IBS.
A history of EALs before age 18 was assessed using the early trauma inventory. RS functional magnetic resonance imaging was used to identify patterns of intrinsic brain oscillations in the form of RS networks in 168 people (58 IBS, 28 females; and 110 healthy controls, 72 females). Partial Least Squares, a multivariate analysis technique was used to identify disease and sex differences and possible correlations between EALs and functional connectivity in six identified RS networks.
Associations between EALs and RS networks were observed. While a history of EALs was associated with altered connectivity in the salience/executive control network to a similar extent in male and female IBS patients (Bootstrap ratio [BSR]=3.28-5.61; p=.046), male IBS patients demonstrated additional EAL-related alterations in the cerebellar network (BSR=3.92-6.79; p=.022).
This cross sectional study identified correlations between RS networks and EALs in individuals with IBS. These results suggest that exposure to EALs before age 18 can shape adult RS in both male and female patients in the salience/executive control network, a brain network that has been implicated in the pathophysiology of central pain amplification.
PMCID: PMC4113723  PMID: 25003944
early adverse traumatic life events; irritable bowel syndrome (IBS); resting state networks; salience/executive control network; cerebellar network; sex differences
4.  Persistent Depressive Symptoms and Pain after Cardiac Surgery 
Psychosomatic medicine  2014;76(6):437-444.
Our objectives were to describe trajectories of depressive symptoms and pain at hospital discharge and six weeks later and to examine the relationship of persistent depressive symptoms to pain.
Before and six weeks after hospital discharge, 251 cardiac surgery patients (aged 67.3 ± 9.5 years; 73% male) completed the Beck Depression Inventory (BDI) and the Brief Pain Inventory (BPI). Patients were categorized into two groups based on the presence or absence of persistent depressive symptoms (BDI>10 at both times). Between-group differences in pain interference (BPI-INT) and pain severity (BPI-SEV) were evaluated using repeated measures analysis of variance. Linear regressions were performed to determine if changes in depressive symptoms were related to BPI-INT and BPI-SEV, controlling for demographic and clinical data.
Persistent (16.3%) or worsening depressive symptoms (15.3%) from hospital discharge to six weeks were observed; many experienced at least some persistent pain (BPI-INT - 67.8%; BPI-SEV - 47.8%). From discharge to six weeks, patients with persistent depressive symptoms sustained higher levels of BPI-INT (p<.001) and BPI-SEV (P<.003). In multivariate analysis, only changes in depressive symptoms, not clinical and demographic variables, were related to BPI-INT (p<.001) and BPI-SEV (p=.001).
Persistent depressive symptoms are independently associated with continued pain up to six weeks after hospital discharge. Successful treatment of ongoing pain should include screening for depressive symptoms and initiation of appropriate treatment.
PMCID: PMC4139703  PMID: 24979578
cardiac surgery; depressive symptoms; pain
5.  Associations of chronic stress burden, perceived stress, and traumatic stress with cardiovascular disease prevalence and risk factors in the HCHS/SOL Sociocultural Ancillary Study 
Psychosomatic medicine  2014;76(6):468-475.
The current study examined multiple stress indicators (chronic, perceived, traumatic) in relation to prevalent coronary heart disease (CHD), stroke, and major cardiovascular disease (CVD) risk factors (i.e., diabetes, dyslipidemia, hypertension, current smoking) in the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (2010–2011).
Participants were 5313 men and women, 18–74 years old, representing diverse Hispanic/Latino ethnic backgrounds, who underwent a comprehensive baseline clinical exam and sociocultural exam with measures of stress.
Chronic stress burden was related to a higher prevalence of CHD after adjusting for sociodemographic, behavioral and biological risk factors [OR (95% CI) = 1.22, (1.10–1.36)] and related to stroke prevalence in the model adjusted for demographic and behavioral factors [OR (95% CI) = 1.26, (1.03–1.55∂)]. Chronic stress was also related to a higher prevalence of diabetes [OR=1.20, (1.11–1.31)] and hypertension [OR=1.10 (1.02–1.19)] in individuals free from CVD (N=4926). Perceived stress [OR=1.03 (1.01–1.05)] and traumatic stress [OR=1.15 (1.05–1.26)] were associated with a higher prevalence of smoking. Participants who reported a greater number of lifetime traumatic events also unexpectedly showed a lower prevalence of diabetes [OR=.89 (.83–.97)] and hypertension [OR=.88 (.82–.93)]. Effects were largely consistent across age and sex groups.
The study underscores the utility of examining multiple indicators of stress in relation to health, since the direction and consistency of associations may vary across distinct stress conceptualizations. In addition, the study suggests that chronic stress is related to higher CVD risk and prevalence in Hispanics/Latinos, the largest U.S. ethnic minority group.
PMCID: PMC4349387  PMID: 24979579
Cardiovascular Disease; Coronary Heart Disease; Hispanic; Latino; Stress
Psychosomatic medicine  2014;76(6):430-436.
Depression has been associated with vascular dysfunction, which may be of particular relevance in pregnancy. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and L-arginine play a critical role in vascular function. The objective of this study was to investigate differences in ADMA, SDMA, and L-arginine among pregnant women with major depression compared to pregnant women without depression.
A case-control study was conducted in 21 depressed pregnant women and 42 matched controls. Maternal plasma ADMA, SDMA, and L-arginine were quantified, as well as C-reactive protein (CRP), urine excretion of ADMA, SDMA, L-arginine, and Arginase I.
Plasma L-arginine and ADMA levels were significantly lower in the first trimester in women with depression (37.0±9.2 and 0.298±0.06μmol/L, mean± standard deviation [SD], respectively) compared to matched controls (42.1±11.4 and 0.336±0.08μmol/L, p=0.004 and p=0.002 respectively) and across pregnancy (p<0.001 both). Depressed pregnant women had higher levels of plasma CRP (7.5±3.7 vs. 5.1±4.0 μg/mL, p=0.027), but no differences urine excretion of ADMA, SDMA, or L-arginine, or plasma levels of Arginase I (p values > 0.10).
Pregnant women with depression evidence lower plasma levels of L-arginine and ADMA. These differences are not explained by urinary excretion or Arginase I levels. The mechanism responsible for the observed differences in depressed pregnant women requires further research.
PMCID: PMC4482344  PMID: 24979576
pregnancy; depression; arginine; ADMA; SDMA; CRP
7.  Reaction Time in Adolescence, Cumulative Allostatic Load, and Symptoms of Anxiety and Depression in Adulthood: The West of Scotland Twenty-07 Study 
Psychosomatic Medicine  2015;77(5):493-505.
Supplemental digital content is available in the text.
To examine the relation between reaction time in adolescence and subsequent symptoms of anxiety and depression and investigate the mediating role of sociodemographic measures, health behaviors, and allostatic load.
Participants were 705 members of the West of Scotland Twenty-07 Study. Choice reaction time was measured at age 16. At age 36 years, anxiety and depression were assessed with the 12-item General Health Questionnaire (GHQ) and the Hospital Anxiety and Depression Scale (HADS), and measurements were made of blood pressure, pulse rate, waist-to-hip ratio, and total and high-density lipoprotein cholesterol, C-reactive protein, albumin, and glycosolated hemoglobin from which allostatic load was calculated.
In unadjusted models, longer choice reaction time at age 16 years was positively associated with symptoms of anxiety and depression at age 36 years: for a standard deviation increment in choice reaction time, regression coefficients (95% confidence intervals) for logged GHQ score, and square-root–transformed HADS anxiety and depression scores were 0.048 (0.016–0.080), 0.064 (0.009–0.118), and 0.097 (0.032–0.163) respectively. Adjustment for sex, parental social class, GHQ score at age 16 years, health behaviors at age 36 years and allostatic load had little attenuating effect on the association between reaction time and GHQ score, but weakened those between reaction time and the HADS subscales. Part of the effect of reaction time on depression was mediated through allostatic load; this mediating role was of borderline significance after adjustment.
Adolescents with slower processing speed may be at increased risk for anxiety and depression. Cumulative allostatic load may partially mediate the relation between processing speed and depression.
PMCID: PMC4459883  PMID: 25984823
reaction time; anxiety; depression; allostatic load; GHQ = General Health Questionnaire; HADS = Hospital Anxiety and Depression Scale; HbA1c = glycosolated hemoglobin; HDL = high-density lipoprotein; SD = standard deviation
8.  Marital Dissolution and Blood Pressure Reactivity: Evidence for the Specificity of Emotional Intrusion-Hyperarousal and Task-Rated Emotional Difficulty 
Psychosomatic medicine  2009;71(5):532-540.
To assess blood pressure (BP) reactivity as recently separated adults completed a laboratory task asking to mentally reflect on their relationship experiences. Marital separations and the experience of divorce are associated with increased risk for early mortality and poor health outcomes. Few studies, however, have investigated the potential psychophysiological mechanisms that may account for these broad-based associations.
Seventy recently separated or divorced community-dwelling adults (26 men) completed self-report measures of divorce-related psychological adjustment. During a laboratory visit, quasi-continuous BP was assessed across four task periods, including a divorce-specific mental activation task (DMAT). A task-rated emotional difficulty (TRED) index was computed based on participants’ immediate appraisals of the task demands.
After accounting for relevant health-related covariates and depressed mood, participants who reported higher degrees of divorce-related emotional intrusion and physical hyperarousal demonstrated significantly elevated resting BP at entry into the study. When assessing change from a within-person control task to the DMAT, a three-way interaction indicated that men reporting high TRED scores evidenced significant increases in BP, whereas men reporting low TRED scores evidenced significant decreases in BP. Women evidenced no significant changes in BP across study periods.
Results suggest that divorce-related emotional intrusion-hyperarousal and real-time ratings of emotional difficulty (when people think about their separation experience) may play a specific role in BP reactivity, especially for men. These data shed new light on the potential mechanisms that may link marital dissolution and poor health.
PMCID: PMC4467544  PMID: 19414618
divorce; blood pressure reactivity; autonomic psychophysiology; social connectedness and health; emotion intrusion; multilevel modeling
9.  The impact of pre-morbid and post-morbid depression onset on mortality and cardiac morbidity among coronary heart disease patients: A meta-analysis 
Psychosomatic medicine  2012;74(8):786-801.
Depression is associated with increased cardiac morbidity and mortality in the general population and in coronary heart disease (CHD) patients. Recent evidence suggests that patients with new-onset depression post-CHD diagnosis have worse outcomes than those who had previous or recurrent depression. This meta-analysis investigated timing of depression onset in established CHD and CHD-free cohorts to determine what timeframe is associated with greater mortality and cardiac morbidity.
Methodology/Principal Findings
The MEDLINE, EMBASE, and PsycINFO databases were searched systematically to identify articles examining depression timeframe which specified an endpoint of all-cause mortality, cardiac mortality, re-hospitalization, or major adverse cardiac events (MACEs). A meta-analysis was conducted to estimate effect sizes by timeframe of depression.
Twenty-two prospective cohort studies were identified. Nine studies investigated pre-morbid depression in CHD-free cohorts in relation to cardiac death. Thirteen studies in CHD-patient samples examined new-onset depression in comparison to previous or recurrent depression. The pooled effect size (risk ratio) was 0.76 (95% CI 0.48–1.19) for history of depression only, 1.79 (95% CI 1.45–2.21) for pre-morbid depression onset, 2.11 (95% CI 1.66–2.68) for post-morbid or new depression onset, and 1.59 (95% CI 1.08–2.34) for recurrent depression
Both pre-morbid and post-morbid depression onsets are potentially hazardous, and the question of timing may be irrelevant with respect to adverse cardiac outcomes. However, the combination of pre-morbid depression with the absence of depression at the time of a cardiac event (i.e., historical depression only) is not associated with such outcomes, and deserves further investigation.
PMCID: PMC4461377  PMID: 23001393 CAMSID: cams4484
coronary heart disease; depression; timing of onset; mortality; morbidity; outcome; meta-analysis
10.  Prediction of daily food intake as a function of measurement modality and restriction status 
Psychosomatic medicine  2015;77(5):583-590.
Eating research relies on several kinds of indices (e.g., stable, momentary, neural) to accurately reflect food-related reactivity (e.g., disinhibition) and regulation (e.g., restraint) outside the laboratory. However, the degree to which the most commonly used indices predict real-world food consumption, and whether they do so differentially, is largely unknown. Additionally, the predictive validity of these indices might vary depending on whether or not an individual is actively restricting intake.
We assessed food reactivity and food craving regulation in 46 healthy participants (30 female, age 18–30) using standard measurements in three modalities: (1) self-reported (stable) traits using surveys that are popular in the eating literature, and (2) momentary craving ratings and (3) neural activation using aggregated fMRI data gathered during a food reactivity-and-regulation task. We then used these data to predict variance in real-world consumption of craved energy-dense “target” foods across two weeks among normal-weight participants randomly assigned to restrict or monitor their target food intake.
The predictive validity of 4 of the 6 indices varied significantly by restriction status. When participants were not restricting intake, momentary (B = 0.21, SE = 0.05) and neural (B = 0.08, SE = 0.04) reactivity positively predicted consumption, and stable (B = −0.22, SE = 0.05) and momentary (B = −0.24, SE = 0.05) regulation negatively predicted consumption. When restricting, stable (B = 0.36, SE = 0.12) and neural (B = 0.51, SE = 0.12) regulation positively predicted consumption.
Commonly used indices of regulation and reactivity differentially relate to an ecologically-valid eating measurement depending on the presence of restriction goals, and thus have strong implications for predicting real-world behaviors.
PMCID: PMC4459907  PMID: 25984820
eating; food consumption; prediction; restriction; fMRI
11.  Personality Facets and All-Cause Mortality Among Medicare Patients Aged 66 to 102: A Follow-on Study of Weiss and Costa (2005) 
Psychosomatic medicine  2014;76(5):370-378.
To investigate associations between the personality factors and survival during 8 years follow-up.
Domains of personality and selected facet scores were assessed in 597 Medicare recipients (aged 66 to 102 years) who were followed up for approximately 8 years. Personality domains and factors were assessed using the Revised NEO Personality Inventory (NEO-PI-R). Using proportional hazards regression, the present study builds on a previous analysis of the NEO-PI-R domains and selected facet scores, which revealed that the Neuroticism facet Impulsiveness, Agreeableness facet Straightforwardness, and Conscientiousness facet Self-Discipline were related to longer life during 4 years of follow-up. In the present study, we extended the follow-up period by an additional 4 years, examining all 30 facets, and using accelerated failure time (AFT) modeling as an additional analytic approach. Unlike proportional hazards regression, AFT permits inferences about the median survival length conferred by predictors. Each facet was tested in a model that included health-related covariates and NEO-PI-R factor scores for dimensions that did not include that facet.
Over the 8-year mortality surveillance period, Impulsiveness was not significant, but Straightforwardness and Self-Discipline remained significant predictors of longevity. When dichotomized, being high versus average or low on Self-Discipline was associated with an approximately 34% increase in median lifespan. Longer mortality surveillance also revealed that each standard deviation of Altruism, Compliance, Tender-Mindedness, and Openness to Fantasy was associated with an estimated 9–11% increase in median survival time.
After extending the follow-up period from 4 to 8 years, Self-Discipline remained a powerful predictor of survival. Facets associated with imagination, generosity, and higher quality interpersonal interactions become increasingly important when the follow-up period was extended to 8 years.
PMCID: PMC4096682  PMID: 24933014
mortality; facets; elderly; openness; agreeableness; conscientiousness; NEO-FFI
12.  Acculturative stress and inflammation among Chinese immigrant women 
Psychosomatic medicine  2014;76(5):320-326.
Among Chinese immigrant populations, increasing duration of US residence is associated with elevated risk for various chronic diseases. Although lifestyle changes following migration have been extensively studied in immigrant populations, less understood is the psychosocial impact of acculturative stress upon biological markers of health. Thus, the purpose of the present study is to examine associations between acculturative stress and inflammatory markers in a Chinese immigrant population.
Study participants (n=407 foreign-born Chinese American women) completed questionnaires assessing levels of stress, including acculturative stress and positive and negative life events in the past year. Participant height and weight were measured using standard protocols and blood samples were drawn for assessment of circulating serum levels of C-reactive protein (CRP) and soluble tumor necrosis factor receptor 2 (sTNFR2).
Higher levels of acculturative stress were significantly associated with higher levels of CRP (B=0.07, 95% CI=0.01-0.13, p=0.031) and sTNFR2 (B=0.02, 95% CI=0.004-0.03, p=0.012), adjusting for age and body mass index (BMI). The latter association was no longer statistically significant when overall acculturation (i.e., identification with American culture) was included in the model. Life events were not associated with CRP or sTNFR2.
This study shows that acculturative stress is associated with inflammation markers in a Chinese immigrant population. These findings suggest that immigrant health trajectories may be adversely influenced by psychological distress associated with the demands of acculturation. Replication in other immigrant samples is needed to fully establish the biological correlates and clinical consequences of acculturation stress.
PMCID: PMC4164056  PMID: 24846001
migration; acculturation; stress; Asian; inflammation
13.  Depressive Symptom Clusters as Predictors of 6-Year Increases in Insulin Resistance: Data from the Pittsburgh Healthy Heart Project 
Psychosomatic medicine  2014;76(5):363-369.
To examine longitudinal bidirectional associations between two depressive symptom clusters – the cognitive-affective and somatic-vegetative clusters – and insulin resistance, a marker of pre-diabetes.
Participants were 269 adults aged 50–70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study. At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose. We examined baseline BDI-II total, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance computed from fasting insulin and glucose. We also examined baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores.
Regression analyses, adjusted for demographic factors and baseline HOMA score, revealed that the baseline BDI-II somatic-vegetative score (β = .14, p = .025), but not the cognitive-affective (β = .001, p = .98) or total (β = .10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index (BMI) was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (all ps >.56).
Among adults aged 50–70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing BMI.
PMCID: PMC4065635  PMID: 24846000
depression; symptom clusters; insulin resistance; homeostatic model of assessment (HOMA); type 2 diabetes; prospective study
14.  Daily Marital Interaction Quality and Carotid Artery Intima Medial Thickness in Healthy Middle Aged Adults 
Psychosomatic medicine  2014;76(5):347-354.
To examine the association between marital interaction quality during daily life and subclinical cardiovascular disease (CVD). Studies have shown that marital status and quality of marriage are associated with cardiovascular health. However, little is known about the role of marital interaction quality during daily life in contributing to these effects.
The sample consisted of 281 healthy, employed middle-aged adults who were married or living with a partner in a marital-like relationship (mean age = 42.0 years, 88% white, 52% men). Marital interaction quality was assessed using hourly real-time Ecological Momentary Assessments (EMAs) for 4 days, with participants rating their current or recent partner interactions on positive and negative characteristics (e.g., agreeableness and conflict). Carotid artery intima medial thickness (IMT) was assessed using ultrasound imaging.
Adjusting for demographics, positive marital interaction was inversely associated with IMT, [b = −.02 F(1, 275) = 9.18, p = .002], and negative marital interaction was positively associated with IMT, [b = .02 F(1, 275) = 10.29, p = .001]. These associations were not accounted for by behavioral and biological cardiovascular disease (CVD) risk factors and were consistent across age, sex, race, and education. The associations were also independent of marital interaction frequency, nonmarital social interaction quality, and personality factors. Global reports of marital quality, in contrast, were not associated with IMT.
Marital quality as measured during real-time interactions between partners was associated with subclinical cardiovascular disease in healthy middle-aged adults. This study supports the utility of real-time social interaction assessment for characterizing links between social relationships and cardiovascular health.
PMCID: PMC4274937  PMID: 24915293
marital quality; marital interaction; ecological momentary assessment; intima-media thickness; cardiovascular disease
15.  Hostility and Physiological Responses to Acute Stress in People With Type 2 Diabetes 
Psychosomatic Medicine  2015;77(4):458-466.
Hostility is associated with cardiovascular mortality and morbidity, and one of the mechanisms may involve heightened reactivity to mental stress. However, little research has been conducted in populations at high risk for cardiovascular disease. The aim of the present study was to assess the relationship between hostility and acute stress responsivity in individuals with Type 2 diabetes.
A total of 140 individuals (median age [standard deviation] 63.71 [7.00] years) with Type 2 diabetes took part in laboratory-based experimental stress testing. Systolic blood pressure, diastolic blood pressure, heart rate, plasma interleukin-6 (IL-6), and salivary cortisol were assessed at baseline, during two stress tasks, and 45 and 75 minutes later. Cynical hostility was assessed using the Cook Medley Cynical Hostility Scale.
Participants with greater hostility scores had heightened increases in IL-6 induced by the acute stress tasks (B = 0.082, p = .002), independent of age, sex, body mass index, smoking, household income, time of testing, medication, and baseline IL-6. Hostility was inversely associated with cortisol output poststress (B = −0.017, p = .002), independent of covariates. No associations between hostility and blood pressure or heart rate responses were observed.
Hostile individuals with Type 2 diabetes may be susceptible to stress-induced increases in inflammation. Further research is needed to understand if such changes increase the risk of cardiovascular disease in this population.
PMCID: PMC4431675  PMID: 25886832
Type 2 diabetes mellitus; hostility; interleukin-6; salivary cortisol; psychological stress; AUC = area under the curve; BMI = body mass index; CAD = coronary artery disease; CI = confidence intervals; CVD = cardiovascular disease; DBP = diastolic blood pressure; HbA1c = glycated hemoglobin; HR = heart rate; IL-6 = interleukin-6; SBP = systolic blood pressure; T2DM = Type 2 diabetes mellitus
16.  Allostatic Load and Health in the Older Population of England: A Crossed-Lagged Analysis 
Psychosomatic Medicine  2014;76(7):490-496.
Supplemental digital content is available in the text.
Allostatic load, a composite measure of accumulated physical wear and tear, has been proposed as an early sign of physiological dysregulation predictive of health problems, functional limitation, and disability. However, much previous research has been cross sectional and few studies consider repeated measures. We investigate the directionality of associations between allostatic load, self-rated health, and a measure of physical function (walking speed).
The sample included men and women 60 and older who participated in Wave 2 (2004) and Wave 4 (2008) of the English Longitudinal Study of Ageing (n = 6132 in Wave 2). Allostatic load was measured with nine biomarkers using a multisystem summary approach. Self-rated health was measured using a global 5 point summary indicator. Time to walk 8 ft was used as a measure of function. We fitted and tested autoregressive cross-lagged models between the allostatic load measure, self-rated health, and walking speed in Waves 2 and 4. Models were adjusted for age, sex, educational level, and smoking status at Wave 2 and for time-varying indicators of marital status, wealth, physical activity, and social support.
Allostatic load predicted slower walking speed (standardized estimate = −0.08, 95% confidence interval [CI] = −0.10 to −0.05). Better self-rated health predicted faster walking speed (standardized estimate = 0.11, 95% CI = 0.08-0.13) as well as lower allostatic load (standardized estimate = −0.15, 95% CI = −0.22 to −0.09), whereas paths from allostatic load and walking speed to self-rated health were weaker (standardized estimates = −0.05 [95% CI = −0.07 to −0.02] and 0.06 [95% CI = 0.04–0.08]).
Allostatic load can be a useful risk indicator of subsequent poor health or function.
PMCID: PMC4418773  PMID: 25153937
allostatic load; self-rated health; walking speed; cross-lagged; older age; CI = confidence interval; ELSA = English Longitudinal Study of Ageing; AIC = Akaike Information Criteria
17.  The effects of environmental enrichment on depressive- and anxiety-relevant behaviors in socially isolated prairie voles 
Psychosomatic medicine  2014;76(4):277-284.
Social isolation is associated with depression, anxiety and negative health outcomes. Environmental enrichment, including environmental and cognitive stimulation with inanimate objects and opportunities for physical exercise, may be an effective strategy to include in treatment paradigms for affective disorders as a function of social isolation. In a rodent model – the socially monogamous prairie vole – we investigated the hypothesis that depression- and anxiety-related behaviors following social isolation would be prevented and remediated with environmental enrichment.
Experiment 1 investigated the preventive effects of environmental enrichment on negative affective behaviors when administered concurrently with social isolation. Experiment 2 investigated the remediating effects of enrichment on negative affective behaviors when administered following a period of isolation. Behaviors were measured in 3 operational tests: open field; forced swim test; and elevated plus maze.
In isolated prairie voles, enrichment prevented depression- (immobility in FST, group × housing interaction, P=0.049) and anxiety-relevant behaviors (exploration in open field, group × housing interaction, P=0.036; exploration in elevated plus maze, group × housing interaction, P=0.049). Delayed enrichment also remediated these behaviors in isolated animals (immobility in forced swim test, main effect of housing, P=0.001; exploration in open field, main effect of housing, P=0.047; exploration in elevated plus maze, main effect of housing, P=0.001), and was slightly more effective than physical exercise alone in remediating anxiety-relevant behaviors.
These findings provide insight into the beneficial effects of an enriched environment on depression- and anxiety-relevant behaviors using a translational rodent model of social isolation.
PMCID: PMC4020982  PMID: 24804886
anxiety; depression; environmental enrichment; exercise; microtus; social behavior
18.  Association of the Physiological Stress Response with Depressive Symptoms in Breast Cancer Patients 
Psychosomatic medicine  2014;76(4):252-256.
Literature on the relationship of depressive symptoms and stress hormones after cancer diagnosis has been mixed, with some studies showing a relationship and other studies showing none. Time since diagnosis may explain these contradictory findings. This study examined the relationship of depressive symptoms to stress hormones in breast cancer patients using 12 month longitudinal data.
Patients with Stage II or III breast cancer (N=227) were assessed every 4 months from diagnosis/surgery to 12 months. They completed the Centers for Epidemiological Studies Depression scale (CES-D) Iowa Short Form and the Perceived Stress Scale (PSS) and blood samples were obtained to measure stress hormones (i.e., cortisol, adrenocorticotropin hormone (ACTH), norepinephrine, and epinephrine).
Depressive symptoms were negatively related to cortisol levels (β=−0.023, p=0.002) but were positively related to rate of change in cortisol (β=0.003, p=0.003). Neither ACTH, epinephrine nor norepinephrine covaried with depressive symptoms (all ps>.05). When the CES-D and PSS were both used to predict cortisol, only the CES-D was significantly related (β= −.025, p=.017).
Depressive symptoms were negatively related to cortisol but this relationship changed from the time of diagnosis/surgery through 12 months. Cortisol may initially provide a buffering effect against depression during the stress of initial diagnosis and treatment but this relationship appears to change over time.
PMCID: PMC4056449  PMID: 24804879
Cancer; depression; stress; cortisol
19.  Heart rate variability characteristics in a large group of active-duty Marines and relationship to posttraumatic stress 
Psychosomatic medicine  2014;76(4):292-301.
Heart rate variability (HRV), thought to reflect autonomic nervous system function, is lowered in conditions such as posttraumatic stress disorder (PTSD). The potential confounding effects of traumatic brain injury (TBI) and depression in the relationship between HRV and PTSD have not been elucidated in a large cohort of military service members. Here we describe HRV associations with stress disorder symptoms in a large study of Marines, while accounting for well-known covariates of HRV and PTSD including TBI and depression.
Four battalions of male active-duty Marines (N=2430) were assessed 1-2 months prior to a combat deployment. HRV was measured during 5 minutes of rest. Depression and PTSD were assessed using the Beck Depression Inventory and Clinician Administered PTSD scale respectively.
After accounting for covariates including TBI, a regression indicated that lower levels of high frequency (HF) HRV were associated with a diagnosis of PTSD (beta = -.20, p=.035). Depression and PTSD severity were correlated (r= .49, p <.001), however participants with PTSD but relatively low depression scores exhibited reduced HF compared to controls (p=.012). Marines with deployment experience (n=1254) had lower HRV than those with no experience (p = .033).
This cross-sectional analysis of a large cohort supports associations between PTSD and reduced HRV when accounting for TBI and depression symptoms. Future post-deployment assessments will be used to determine whether pre-deployment HRV can predict vulnerability and resilience to the serious psychological and physiological consequences of combat exposure.
PMCID: PMC4062545  PMID: 24804881
sympathetic nervous system; PTSD; vagal tone; combat; depression; parasympathetic
20.  A general enhancement of autonomic and cortisol responses during social evaluative threat 
Psychosomatic medicine  2009;71(8):877-885.
The idea that distinct psychosocial factors may underlie specific patterns of neuroendocrine stress responses has been a topic of recurrent debate. We examined a recent contribution to this debate, the Social Self Preservation Theory, which predicts that stressors involving social evaluative threat (SET) characteristically activate the hypothalamic-pituitary-adrenal (HPA) axis.
Sixty-one healthy university students (31 females) performed a challenging speech task in one of three conditions that aimed to impose increasing levels of SET: performing the task alone (no social evaluation), with 1 evaluating observer, or with 4 evaluating observers. Indices of sympathetic (pre-ejection period) and parasympathetic (heart rate variability) cardiac drive were obtained by impedance- and electrocardiography. Salivary cortisol was used to index HPA activity. Questionnaires assessed affective responses.
Affective responses (shame/embarrassment, anxiety, negative affect, and self-esteem), cortisol, heart rate, sympathetic, and parasympathetic activation all differentiated evaluative from non-evaluative task conditions (p<.001). The largest effect-sizes were observed for cardiac autonomic responses. Physiological reactivity increased in parallel with increasing audience size (p<.001). A rise in cortisol was predicted by sympathetic activation during the task (p<.001), but not by affective responses.
It would appear that SET determines the magnitude, rather than the pattern, of physiological activation. This potential to broadly perturb multiple physiological systems may help explain why social stress has been associated with a range of health outcomes. We propose a threshold-activation model as a physiological explanation for why engaging stressors, such as those involving social evaluation or uncontrollability, may appear to selectively induce cortisol release.
PMCID: PMC4414334  PMID: 19779143
social evaluation; autonomic reactivity; HPA-axis; response specificity; shame; self-esteem; psychological stress
21.  Optimism and Recovery After Acute Coronary Syndrome: A Clinical Cohort Study 
Psychosomatic Medicine  2015;77(3):311-318.
Optimism is associated with reduced cardiovascular mortality, but its impact on recovery after acute coronary syndrome (ACS) is poorly understood. We hypothesized that greater optimism would lead to more effective physical and emotional adaptation after ACS and would buffer the impact of persistent depressive symptoms on clinical outcomes.
This prospective observational clinical study took place in an urban general hospital and involved 369 patients admitted with a documented ACS. Optimism was assessed with a standardized questionnaire. The main outcomes were physical health status, depressive symptoms, smoking, physical activity, and fruit and vegetable consumption measured 12 months after ACS, and composite major adverse cardiac events (cardiovascular death, readmission with reinfarction or unstable angina, and coronary artery bypass graft surgery) assessed over an average of 45.7 months.
We found that optimism predicted better physical health status 12 months after ACS independently of baseline physical health, age, sex, ethnicity, social deprivation, and clinical risk factors (B = 0.65, 95% confidence interval [CI] = 0.10–1.20). Greater optimism also predicted reduced risk of depressive symptoms (odds ratio = 0.82, 95% CI = 0.74–0.90), more smoking cessation, and more fruit and vegetable consumption at 12 months. Persistent depressive symptoms 12 months after ACS predicted major adverse cardiac events over subsequent years (odds ratio = 2.56, 95% CI = 1.16–5.67), but only among individuals low in optimism (optimism × depression interaction; p = .014).
Optimism predicts better physical and emotional health after ACS. Measuring optimism may help identify individuals at risk. Pessimistic outlooks can be modified, potentially leading to improved recovery after major cardiac events.
PMCID: PMC4396437  PMID: 25738438
myocardial infarction; optimism; depression; recovery; ACS = acute coronary syndrome; CI = confidence interval; GRACE = Global Registry of Acute Coronary Events; BDI = Beck Depression Inventory; CHD = coronary heart disease; SES = socioeconomic status; SF-12 = 12-Item Short Form Health Survey
22.  Personality traits and circadian blood pressure patterns: A seven year prospective study 
Psychosomatic medicine  2014;76(3):237-243.
A nighttime dip in blood pressure is associated with decreased risk of cardiovascular morbidity and mortality. We examined whether personality traits predict nighttime dipping blood pressure.
A community-based sample of 2,848 adults from Sardinia (Italy) completed the Revised NEO Personality Inventory and 7.34-years later (SD=0.87) were examined with 24-hour ambulatory blood pressure monitoring. The primary analyses examined the associations of personality traits with continuous and categorical measures of mean arterial, systolic and diastolic blood pressure nighttime dipping.
Agreeableness and conscientiousness were associated with more nocturnal blood pressure dipping (β = .05, p=.025 and β = .07, p<.001, respectively) and lower systolic blood pressure at night (β = -.045, p=.018 and β = -.032; p=.072, respectively). Non-dippers were particularly more impulsive (p=.009), less trusting (p=.004), and less self-disciplined (p=.001), but there was no significant association between nocturnal dipping blood pressure and trait anxiety (p=.78) or depression (p=.59). The associations were stronger when comparing extreme dippers (nighttime drop ≥ 20%) to reverse dippers (nighttime increase in blood pressure). Indeed, scoring 1 SD higher on conscientiousness was associated with about 40% reduced risk of reverse dipping (OR = 1.43, CI = 1.08-1.91).
We found evidence that reduced nighttime blood pressure dipping is associated with antagonism and impulsivity related traits but not with measures of emotional vulnerability. The strongest associations were found with conscientiousness, a trait that may have broad impact on cardiovascular health.
PMCID: PMC4008636  PMID: 24608035
Ambulatory Blood Pressure Monitoring; Circadian Rhythm; Dipping; Impulsivity; Conscientiousness; Trust; Personality; Systolic blood pressure; Cardiovascular
23.  Sex Differences in Mental Stress-Induced Myocardial Ischemia in Young Survivors of an Acute Myocardial Infarction 
Psychosomatic medicine  2014;76(3):171-180.
Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than men.
We studied 98 post-MI patients (49 women and 49 men) aged 38-60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent [99mTc]sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions.
Women aged 50 or younger, but not older women, showed a more adverse psychosocial profile than age-matched men, but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease (CAD). Compared with age-matched men, women aged 50 or younger exhibited a higher SDS with mental stress (3.1 vs. 1.5, p=0.029) and had twice the rate of MSIMI (SDS ≥3), 52% vs. 25%, while ischemia with physical stress did not differ (36% vs 25%). In older patients there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and lifestyle factors, CAD severity and depression.
MSIMI post-MI is more common in women aged 50 or younger compared to age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.
PMCID: PMC4008686  PMID: 24608039
cardiovascular diseases; stress; ischemia; gender
24.  Vitamin D Supplementation for Depressive Symptoms: A Systematic Review and Meta-analysis of Randomized Controlled Trials 
Psychosomatic medicine  2014;76(3):190-196.
To review the effects of vitamin D supplementation on depression or depressive symptoms in randomized controlled trials. Although low vitamin D levels have been observationally associated with depression and depressive symptoms, the effect of vitamin D supplementation as an antidepressant remains uncertain.
MEDLINE, CINAHL, Allied and Complimentary Medicine Database, PsycINFO, Scopus, and The Cochrane Library, and references of included reports (through May 2013) were searched. Two independent reviewers identified randomized trials that compared the effect of vitamin D supplementation on depression or depressive symptoms to a control condition. Two additional reviewers independently reviewed and extracted relevant data; disagreements were reconciled by consensus. The Cochrane Risk of Bias Tool was used to assess study quality. Seven trials (3191 participants) were included.
Vitamin D supplementation had no overall effect on depressive symptoms (standardized mean difference [SMD], −0.14; 95% CI, −0.33 to 0.05; P = 0.16), although considerable heterogeneity was observed. Subgroup analysis showed that vitamin D supplementation for participants with clinically significant depressive symptoms or depressive disorder had a moderate, statistically significant effect (2 studies: SMD, −0.60; 95% CI, −1.19 to −0.01; P = 0.046), but a small, nonsignificant effect for those without clinically significant depression (5 studies: SMD, −0.04; CI, −0.20 to 0.12; P = 0.61). Most trials had unclear or high risk of bias. Studies varied in the amount, frequency, duration, and mode of delivery of vitamin D supplementation.
Vitamin D supplementation may be effective for reducing depressive symptoms in patients with clinically significant depression; however, further high quality research is needed.
PMCID: PMC4008710  PMID: 24632894
vitamin D; depression; depressive symptoms; randomized controlled trials; meta-analysis; systematic review
25.  Childhood Adversity and Inflammation in Breast Cancer Survivors 
Psychosomatic medicine  2014;76(3):208-214.
Elevated inflammation predicts behavioral symptoms, disease progression, and mortality in patients with breast cancer and breast cancer survivors, although predictors of inflammation remain largely unknown. Adverse experiences in childhood have been associated with higher rates of psychological and physical illness, and elevated inflammatory activity in studies of healthy adults. However, little research has examined the association between childhood adversity and inflammation in the context of cancer, where inflammation is particularly relevant for health.
The current study examined the association between three types of childhood adversity—abuse, neglect, and a chaotic home environment—and inflammatory markers (interleukin [IL]-6 and C-reactive protein), in breast cancer survivors who had completed primary cancer treatment 1 year earlier (n = 152).
The combined measure of childhood adversity was associated with elevations in plasma levels of IL-6 (B = 0.009, p = .027, η2 = 0.027, after controlling for age, body mass index, ethnicity, alcohol use, and cancer treatment (surgery, radiation, and/or chemotherapy). Examination of individual types of adversity demonstrated a positive association between abuse and IL-6 (B = 0.043, p = .030, η2 = 0.026), chaotic home environment and IL-6 (B = 0.031, p = .005, η2 = 0.043), and chaotic home environment and soluble tumor necrosis factor receptor type II (B = 0.012, p = .009, η2 = 0.037), after controlling for relevant confounds.
Childhood adversity was associated with elevated markers of inflammation in breast cancer survivors, with potential negative implications for health and well-being. In particular, chaotic home environment showed unique links with inflammatory outcomes.
PMCID: PMC4357419  PMID: 24632893
early life stress; maltreatment; inflammation; immune dysregulation; cytokines; carcinoma

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