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1.  Socioeconomic Status, Daily Affective and Social Experiences, and Inflammation during Adolescence 
Psychosomatic medicine  2015;77(3):256-266.
To assess the relation between socioeconomic status (SES) and inflammation during adolescence and determine whether daily affective and social experiences across a 15-day period mediate this relation.
Adolescents (n = 316) completed daily diary reports of positive affect, negative affect, and negative social interactions for 15 days and provided whole blood spot samples for the assessment of C-reactive protein (CRP). Parents provided information on SES, including the highest level of education they and their spouses completed and household income.
Lower parent education was associated with higher levels of adolescent CRP, controlling for age, gender, ethnicity, and body mass index (β = −.12; p = .031). Mean daily positive affect, negative affect, and negative social interactions were examined as potential mediators of this association. In these models, parent education was no longer associated with adolescent CRP (β = −.09; p = .12), and only positive affect was related to CRP (β = −.12; p = .025). Bootstrapping confirmed the mediating role of positive affect (indirect effect = −.015, 95% CI = [−.038, −.002]).
Adolescents with less educated parents tended to have higher levels of CRP, which may be explained by their lower levels of positive affect. Findings suggest that a lack of positive affect may be a pathway by which SES confers early risk for poor health in adulthood. It is possible that adolescents who display positive affect during daily life in circumstances of relatively adverse socioeconomic circumstances may have better health outcomes related to lower inflammatory factors.
PMCID: PMC4397124  PMID: 25829237
social status; CRP; positive affect; adolescents
2.  Depressive symptoms, antidepressant medication use and new onset of diabetes in participants of the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study 
Psychosomatic medicine  2015;77(3):303-310.
To assess in participants in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study (DPP/DPPOS) whether diagnosis of diabetes predicted: elevated depressive symptoms (DS) or antidepressant medicine (ADM) use after diagnosis; diabetes status or duration had significant effect on DS or ADM use; and associations between A1C, fasting plasma glucose (FPG), normalization of FPG and DS or ADM use post diagnosis.
DPP participants in 3 treatment arms [intensive lifestyle (ILS), metformin (MET), placebo (PLC)] were assessed semiannually or annually for diabetes, glucose control, ADM use, and DS. DS was measured using Beck Depression Inventory (BDI) questionnaire. Among the total 3234 enrolled participants, 1285 developed diabetes whose levels of depression were measured before and after their diabetes diagnosis.
Neither DS nor ADM use increased significantly following diabetes diagnosis. After diabetes diagnosis, higher FPG was associated with greater ADM use in the ILS arm independent of potential confounders; a 10 mg/dl higher in FPG is associated with 8.8% more odds of ADM use. Higher FPG, and higher A1C were associated with higher BDI scores in all three arms. On average, a participant with 10 mg/dl higher rise in FPG had a 0.07 increase in BDI score. Similarly, 1% higher A1c was associated with a 0.21 point increase in BDI score. On contrary, normalization of FPG was associated with lower BDI scores. In participants with FPG that had normalized, there was a decrease of 0.30 points in the BDI score compared to those whose FPG had not normalized.
Contrary to clinical attributions, the diagnosis of diabetes did not show an immediate impact on BDI scores or ADM use. However, higher glucose levels after diagnosis were associated with small but significant higher BDI score and more ADM use.
PMCID: PMC4397126  PMID: 25775165
diagnosis of diabetes; depressive symptoms; antidepressant medication; pre-diabetes; type 2 diabetes mellitus; prevention
3.  Effects of Long Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates 
Psychosomatic medicine  2015;77(3):267-278.
Major depressive disorder and coronary heart disease (CHD) often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on CHD risk remain unclear. We determined the effects of a SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA.
42 adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase, and assigned to SSRI (sertraline HCl 20 mg/kg, po, once/day) or Placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months CAA extent was measured using histomorphometry.
Before and during treatment depressed monkeys had lower BW, body mass index (BMI), and plasma high density lipoprotein cholesterol, and higher heart rates during the pretreatment (p<0.01) but not the treatment phase (p=0.17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, BMI, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (Depressed, Nondepressed) × 2 (Placebo, Sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than nondepressed monkeys (p<0.036), and in sertraline than placebo-treated monkeys (p=0.040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than in untreated depressed monkeys, and 6.5 times higher than in non-depressed monkeys, on average.
Depressed animals develop more CAA, and that longterm treatment with sertraline promotes CAA.
PMCID: PMC4397139  PMID: 25829239
Selective serotonin reuptake inhibitor; coronary artery atherosclerosis; depression; nonhuman primates; females; CHD
4.  Divorce and Health: Current Trends and Future Directions 
Psychosomatic medicine  2015;77(3):227-236.
Social relationships play a vital role in health and wellbeing, and it follows that loss experiences can be highly stressful for some people. This paper reviews what is known about the association between marital separation, divorce and health outcomes.
Key findings in the area of divorce and health are discussed, and the review outlines a series of specific questions for future research. In particular, the paper integrates research in social epidemiology with research in social psychophysiology. The former approach provides a broad-based estimate of the association between marital status and health outcomes, whereas the latter approach studies mechanisms of action and individual differences associated with increased risk for poor outcomes.
The experience of separation or divorce confers risk for poor health outcomes, including a 23% higher mortality rate. However, most people cope well and are resilient after their marriage or long-term relationship ends. Despite the fact that resilience is the most common response, a small percentage of people (approximately 10–15%) struggle quite substantially, and it appears that the overall elevated adverse health risks are driven by the poor functioning of this group. Several candidate mechanisms and novel (ambulatory) assessment techniques are discussed that may elucidate the poor outcomes among people who adapt poorly to separation.
To increase knowledge on the association between divorce and health, three primary areas require more research: (a) genetic and third variable explanations for divorce-related health outcomes; (b) better studies of objective social behavior following separation; and, (c) increased attention to interventions targeting high risk adults.
PMCID: PMC4397145  PMID: 25829240
Divorce; marital separation; relationships; stress; health; resilience
5.  Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality 
Psychosomatic medicine  2015;77(3):215-226.
Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes.
We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses.
Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects.
Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes.
PMCID: PMC4397577  PMID: 25829236
cardiovascular recovery; exercise; cardiovascular challenge; cardiovascular disease; mortality; longitudinal
6.  Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice 
Psychosomatic medicine  2010;72(4):376-382.
To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE−/− mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis.
A total of 43, 12-week-old, apoE−/− mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations.
There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05).
These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.
PMCID: PMC4784697  PMID: 20368478
oxytocin; atherosclerosis; inflammation; interleukin-6; visceral adipose tissue
7.  Associations of fatigue from mid to late life with physical performance and strength in early old age: Results from a British prospective cohort study 
Psychosomatic medicine  2015;77(7):823-832.
To examine associations of fatigue in mid and later life with physical performance and strength in early old age.
Data on approximately 1800 men and women from the UK Medical Research Council National Survey of Health and Development with data on fatigue at ages 43 and 60-64 years were used. Fatigue was defined as perceived tiredness and was assessed prospectively at ages 43 and 60-64. At both ages, participants were categorized as having no, occasional or frequent fatigue. Physical performance and strength were measured at age 60-64 using four objective measures: grip strength, standing balance, chair rising, and timed get-up-and-go (TUG) tests.
There were associations between reports of frequent fatigue at both ages and poorer grip strength, chair rise and TUG performance at 60-64 years. Furthermore, individuals reporting frequent fatigue at both ages had weaker grip strength (β -4.09 kg, 95% CI -6.71, -1.48), and slower chair rise (β -4.65 rep./min, 95% CI -6.65, -2.64) and TUG (β -4.22 cm/s, 95% CI -12.16, -2.28) speeds when compared to those who reported no fatigue at both time points. These associations were robust and were maintained after adjustment for a range of covariates including physical activity and health status.
Reports of frequent fatigue were associated with poorer physical performance in early old age, especially if sustained from mid to later life. These findings indicate that it is not just fatigue but fatigue sustained across adulthood that has implications for later life functioning.
PMCID: PMC4568292  PMID: 26176776
Aging; Life course; Fatigue; Physical performance; Strength
8.  Childhood Club Participation and All-cause Mortality in Adulthood: A 65-year Follow-up Study of a Population-representative Sample in Scotland 
Psychosomatic medicine  2015;77(7):712-720.
Social participation in middle- and older-age is associated with lower mortality risk across many prospective cohort studies. However there is a paucity of evidence on social participation in youth in relation to mortality, which could help inform an understanding of the origin of the association, and give credence to causality. The present study investigates the relation of early life club membership—a proxy measure of social participation—with mortality risk in older age in a nationally representative sample.
We linked historical data collected on the 6-Day Sample of the Scottish Mental Survey 1947 during the period 1947-1963 with vital status records up to April 2014. Analyses were based on 1059 traced participants (446 deceased).
Club membership at age 18 years was associated with lower mortality risk by age 78 years (hazard ratio=0.54, 95% CI 0.44 to 0.68, p<.001). Club membership remained a significant predictor in models that included early life health, socioeconomic status (SES), measured intelligence, and teachers’ ratings of dependability in personality.
In a study which circumvented the problem of reverse causality, a proxy indicator of social participation in youth was related to lower mortality risk. The association may be mediated by several behavioural and neurobiological factors, which prospective ageing cohort studies could address.
PMCID: PMC4568296  PMID: 26176775
Club membership; Intelligence; Mortality risk; Personality; Social participation; Socioeconomic status
9.  Educational Attainment and the Heritability of Self-Reported Hypertension Among Male Vietnam-Era Twins 
Psychosomatic medicine  2008;70(7):781-786.
To investigate the potential for gene × environment interaction in hypertension by examining the extent to which educational attainment modifies the heritability of hypertension in male twins. Prior twin and family studies have established that hypertension runs in families and is heritable. In addition, epidemiological research indicates that the prevalence of hypertension differs by socioeconomic factors, such as educational attainment.
Twin structural equation modeling was used to examine educational attainment as a moderator of heritability of hypertension. Participants were 4301 monozygotic and 3414 dizygotic male Vietnam-era twins who provided data on both education (in years) and self-report of physician diagnosis of hypertension or medication usage.
Heritability was 17 points lower among co-twins concordant for educational attainment of ≤14 years (0.46, 95% CI = 0.32–0.57) relative to co-twins concordant for >14 years of education (0.63, 95% CI = 0.54–0.71). The significant moderation of the heritability (p = .04) was confirmed in twin models examining educational attainment as a continuous moderator of hypertension.
These results demonstrate that the expression of genetic vulnerability to hypertension can vary as a function of environmental factors, including education level, and that nongenetic pathways may differentially contribute to risk among those with fewer years of education.
PMCID: PMC4767498  PMID: 18725432
hypertension; twins; education
10.  Inequalities in Lung Cancer Care of Elderly Patients with Schizophrenia: An Observational Cohort Study 
Psychosomatic medicine  2014;76(3):215-220.
Cancer mortality is higher in individuals with schizophrenia, a finding that may be due, in part, to inequalities in care. We evaluated gaps in lung cancer diagnosis, treatment, and survival among elderly individuals with schizophrenia.
The Surveillance, Epidemiology, and End Results (SEER) database linked to Medicare records was used to identify primary non-small cell lung cancer (NSCLC) patients ≥66 years of age. Lung cancer stage, diagnostic evaluation, and rates of stage-appropriate treatment were compared among patients with and without schizophrenia using unadjusted and multiple regression analyses. Survival was compared among groups using Kaplan-Meier methods.
Of the 96,702 NSCLC patients in SEER, 1,303 (1.3%) had schizophrenia. In comparison to the general population, patients with schizophrenia were less likely to present with late-stage disease after controlling for age, sex, marital status, race/ethnicity, income, histology, and comorbidities (odds ratio [OR]: 0.82; 95% confidence interval [CI]: 0.73-0.93) and were less likely to undergo appropriate evaluation (p<0.050 for all comparisons). Adjusting for similar factors, patients with schizophrenia were also less likely to receive stage-appropriate treatment (OR: 0.50, 95% CI: 0.43-0.58). Survival was decreased among patients with schizophrenia (mean survival 22.3 vs. 26.3 months, p=0.002), however no differences were observed after controlling for treatment received (p=0.4).
Elderly patients with schizophrenia present with earlier stages of lung cancer, but are less likely to undergo diagnostic evaluation or to receive stage appropriate treatment, resulting in poorer outcomes. Efforts to increase treatment rates for elderly patients with schizophrenia may lead to improved survival in this group.
PMCID: PMC4747031  PMID: 24677164
Schizophrenia; elderly; non-small cell lung cancer; health care disparities; cigarette smoking; health outcomes
11.  Leukocyte beta-adrenergic receptor sensitivity and depression severity in patients with heart failure 
Psychosomatic medicine  2014;76(9):726-731.
Clinical outcomes are worse for patients with heart failure (HF) and elevated depression symptoms. Depression related sympatho-immune dysregulation may be one mechanism leading to poorer HF prognosis. Sympathetically mediated adrenergic activity is known to regulate immune activity via β-adrenergic receptors (β-ARs). However, studies show conflicting relationships between leukocyte β-AR sensitivity and depression symptoms. The aim of this study was to determine in patients with HF the relationship of leukocyte β-AR sensitivity with two diverse measures of depression, self-report questionnaire versus clinical diagnostic interview.
Patients with HF (N=73, mean age = 56.3, S.D. = 13.0) completed the Beck Depression Inventory −1A (BDI) and a modified Structured Clinical Interview for the DSM-IV (SCID). Leukocyte β-AR sensitivity was determined from isoproterenol stimulated cyclic AMP levels; plasma norepinephrine and epinephrine were also assessed.
Patients with major depression determined by SCID had significantly higher β-AR sensitivity than non-depressed (F(6, 72) = 9.27, p = .003, η2 = .12). Meanwhile, the BDI revealed a more complex relationship. Minimal, mild, and moderate-to-severe depression symptom groups had significant differences in β-AR sensitivity (F(7, 72) = 7.03, p = .002, η2 = .18), with mild symptoms appearing to correspond with reduced β-AR sensitivity and moderate-to-severe symptoms with higher β-AR sensitivity.
By deconstructing depression measurements a greater depth of information may be garnered to potentially reveal subtypes of depression symptoms and their relation to β-AR sensitivity in HF.
PMCID: PMC4744799  PMID: 25373889
Beta-adrenergic; heart failure; depression
12.  The Association of Depression, Cognitive Impairment without Dementia and Dementia with Risk of Ischemic Stroke: A Cohort Study 
Psychosomatic medicine  2015;77(2):200-208.
To determine if depression, cognitive impairment without dementia (CIND), and/or dementia are each independently associated with risk of ischemic stroke and to identify characteristics that could modify these associations.
This retrospective-cohort study examined a population-based sample of 7,031 Americans > 50 years old participating in the Health and Retirement Study (HRS) (1998-2008) who consented to have their interviews linked to their Medicare claims. The 8-item Center for Epidemiologic Studies Depression Scale and/or International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) depression diagnoses were used to identify baseline depression. The Modified Telephone Interview for Cognitive Status and/or ICD-9-CM dementia diagnoses were used to identify baseline CIND or dementia. Hospitalizations for ischemic stroke were identified via ICD-9-CM diagnoses.
After adjusting for demographics, medical comorbidities, and health-risk behaviors, CIND alone (Odds Ratio [OR]: 1.37, 95%CI: 1.11, 1.69) and co-occurring depression and CIND (OR: 1.65, 95%CI: 1.24, 2.18) were independently associated with increased odds of ischemic stroke. Depression alone was not associated with odds of ischemic stroke (OR: 1.11, 95%CI: 0.88, 1.40) in unadjusted analyses. Neither dementia alone (OR: 1.09, 95%CI: 0.82, 1.45) nor co-occurring depression and dementia (OR: 1.25, 95%CI: 0.89, 1.76) were associated with odds of ischemic stroke after adjusting for demographics.
CIND as well as co-occurring depression and CIND are independently associated with increased risk of ischemic stroke. Individuals with co-occurring depression and CIND represent a high-risk group that may benefit from targeted interventions to prevent stroke.
PMCID: PMC4333011  PMID: 25647752
depression; cognitive impairment; dementia; ischemic stroke
13.  Zen and the Art of Multiple Comparisons 
Psychosomatic medicine  2015;77(2):114-125.
The need for appropriate multiple comparisons correction when performing statistical inference is not a new problem. However, it has come to the forefront in many new modern data-intensive disciplines. For example, researchers in areas such as imaging and genetics are routinely required to simultaneously perform thousands of statistical tests. Ignoring this multiplicity can cause severe problems with false positives, thereby introducing non-reproducible results into the literature. This article serves as an introduction to hypothesis testing and multiple comparisons for practical research applications, with a particular focus on its use in the analysis of functional magnetic resonance imagining (fMRI) data. We will discuss hypothesis testing and a variety of principled techniques for correcting for multiple tests. We also illustrate potential pitfalls and problems that can occur if the multiple comparisons issue is not dealt with properly. We conclude by discussing effect size estimation, an issue often linked with the multiple comparisons problem.
PMCID: PMC4333023  PMID: 25647751
multiple comparisons; family-wise error rate; false detection rate; fMRI; effect size estimation
14.  Placebo Improvement in Pharmacologic Treatment of Menopausal Hot Flashes: Time Course, Duration, and Predictors 
Psychosomatic medicine  2015;77(2):167-175.
This study characterized the time course, duration of improvement and clinical predictors of placebo response in treatment of menopausal hot flashes.
Data were pooled from two trials conducted in the MsFLASH network, providing a combined placebo group (N=247) and a combined active treatment group (N=297). Participants recorded hot flash frequency in diaries twice daily during treatment (week 0-8) and subsequent follow-up (week 9-11). The primary outcome variable was clinically significant improvement, defined as >=50% decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement.
Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at week 8. Of placebo responders who were improved at both weeks 4 and 8, 77% remained clinically improved at week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (OR 5.61, 95% CI: 2.41-13.07, p<0.001); current smokers (OR 2.30, 95% CI: 1.05-5.06, p=0.038); and hot flash severity in screening (OR 1.45, 95% CI: 1.00-2.10, p=0.047).
Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that non-specific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.
PMCID: PMC4333078  PMID: 25647753
placebo response; placebo improvement; hot flash treatment; menopause
15.  Early Life Adversity and Adult Biological Risk Profiles 
Psychosomatic medicine  2015;77(2):176-185.
To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship.
We analyzed data on 1,180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States (MIDUS) study. ELA assessments were based on childhood socioeconomic disadvantage (i.e. on welfare, perceived low income, less-educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including: education, social relationships, and health behaviors.
Childhood socioeconomic adversity was associated with increased AL (B=0.094, SE=0.041) and physical abuse (B=0.263, SE=0.091), with non-significant associations for parental divorce and death. Adult education mediated the relationship between socioeconomic ELA and cumulative allostatic load to the point of non-significance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism.
The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable adjusted analysis.
PMCID: PMC4396808  PMID: 25650548
early life adversity; biological risk factor; allostatic load; life course
16.  Dietary antioxidant intake and its association with cognitive function in an ethnically diverse sample of US adults 
Psychosomatic medicine  2015;77(1):68-82.
Dietary antioxidants can inhibit reactions accompanying neurodegeneration, and thus prevent cognitive impairment. We describe associations of dietary antioxidants with cognitive function in a large biracial population, while testing moderation by sex, race and age and mediation by depressive symptoms.
This was a cross-sectional analysis of 1,274 adults (541 men and 733 women) aged 30–64y at baseline (Mean±SD: 47.5±9.3) in the Healthy Aging in Neighborhoods of Diversity Across the Lifespan Study (HANDLS), Baltimore city, MD. Cognitive performance in the domains of memory, language/verbal, attention, spatial, psychomotor speed, executive function, and global mental status were assessed. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) scale was used to measure depressive symptoms. Dietary intake was assessed with two 24-hr recalls, estimating daily consumption of total carotenoids, vitamins A, C and E, per 1,000 kcal.
Among key findings, one standard deviation (SD~2.02 mg/1,000kcal) higher vitamin E was associated with a higher score on verbal memory, immediate recall, (β=+0.64±0.19, p=0.001) and better language/verbal fluency performance (β=+0.53±0.16, p=0.001), particularly among the younger age group. Women with higher vitamin E intake (β=+0.68±0.21, p=0.001) had better performance on a psychomotor speed test. The vitamin E-verbal memory association was partially mediated by depressive symptoms (proportion mediated=13–16%).
In sum, future cohort studies and dietary interventions should focus on associations of dietary vitamin E with cognitive decline, specifically for domains of verbal memory, verbal fluency and psychomotor speed.
PMCID: PMC4597309  PMID: 25478706
Antioxidants; cognitive function; depressive symptoms; midlife
17.  Ethnic Differences in Resting Heart Rate Variability: A Systematic Review and Meta-Analysis 
Psychosomatic medicine  2015;77(1):16-25.
Ethnic disparities in cardiovascular morbidity and mortality are widely documented in the literature. Recently, research has shown that decreased parasympathetic (PNS) cardiac modulation is associated with the established and emerging risk factors for cardiovascular disease (CVD) and stroke. In consideration of the disproportionate CVD risk and disease profile of African Americans (AAs), it is plausible that decreased cardiac PNS functioning may partially explain these disparities. In the present systematic review and meta-analysis, we assess the available evidence for a reliable ethnic difference in tonic vagally-mediated heart rate variability (HRV), an indicator of PNS cardiac modulation.
A systematic literature search was conducted yielding studies comparing tonic HRV in AAs and European Americans (EAs). Adjusted standardized effect sizes, (Hedges g), were calculated using a mixed effects model with restricted maximum likelihood estimation for 17 studies containing appropriate measures of vagally-mediated HRV.
Meta-analysis results suggest that AAs have greater HRV than EAs (Hedges g = .93, 95% C.I. [.25, 1.62]) even after consideration of several covariates including health status, medication use, and subgroup stratification by gender and age.
These findings suggest that decreased vagally-mediated HRV is not likely to account for the persistent health disparities experienced by AAs with respect to cardiovascular disease risk and burden. These disparities underscore the need for continued research addressing socio-ethnic cardiovascular differences and the biobehavioral mechanisms involved
PMCID: PMC4293235  PMID: 25551201
ethnic differences; health disparities; heart rate variability; meta-analysis
18.  Psychosocial Stress as a Risk Factor for Sepsis: A Population-Based Cohort Study 
Psychosomatic medicine  2015;77(1):93-100.
To characterize the relationship between stress and future risk of sepsis. We also evaluated the role of depression in this relationship.
We used population-based data on 30,183 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, characterizing stress using the Perceived Stress Scale (PSS) and depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). We identified incident sepsis events as hospitalizations for a serious infection with the presence of ≥2 SIRS criteria. We assessed associations between PSS and incidence of sepsis over one- and ten-years of follow-up, adjusting for demographics and chronic medical conditions and assessing the role of health behaviors and CES-D in these relationships.
During 2003–2012, 1,500 participants experienced an episode of sepsis. Mean PSS and CES-D scores were 3.2±2.9 and 1.2±2.1. PSS was associated with increased one-year adjusted incidence of sepsis (HR 1.21 per PSS standard deviation; 95% CI: 1.06–1.38); multivariable adjustment for health behaviors and CES-D did not change this association (1.20; 1.20; 1.03–1.39). PSS was also associated with increased 10-year adjusted incidence of sepsis (HR 1.07 per PSS standard deviation; 95% CI: 1.02–1.13). Multivariable adjustment showed that health behaviors did not affect this long-term association whereas addition of CES-D reduced the association between PSS and sepsis during 10-year follow-up (HR 1.04; 0.98–1.11).
Increased stress was associated higher one-year adjusted incidence of sepsis, even after accounting for depressive symptoms. The association between stress and ten-year adjusted incidence of sepsis was also significant, but this association was reduced when adjusting for depressive symptoms. Reduction of stress may limit short-term sepsis risk.
PMCID: PMC4293326  PMID: 25469683
sepsis; infection; stress; epidemiology; depression
19.  Effects of Feedback on the Perception of Inspiratory Resistance in Children with Persistent Asthma: A Signal Detection Approach 
Psychosomatic medicine  2013;75(8):729-736.
Accurate discrimination of asthma episodes increases the likelihood they will be managed effectively. The purpose of the study was to examine the effect of feedback in a signal detection task on perception of increased airflow obstruction in children with persistent asthma.
The effect of feedback training on the perception of resistive loads was evaluated in 155 children with persistent asthma between 8 and 15 years of age. Each child participated in four experimental sessions that occurred about once every 2 weeks, an initial session followed by three training sessions. During the initial session, the threshold resistance to breathing was determined for each child. Subsequently, each child was randomly assigned to one of two resistive load training conditions in a signal detection paradigm: training with immediate performance feedback or training with no performance feedback.
The threshold resistance to breathing, determined in the initial session, was equivalent between groups. Children in the feedback condition discriminated more accurately between both the presence and absence of increases in the resistance to breathing (206 ± 48 vs. 180 ± 39 correct responses, p < .001), and differences over time between groups increased reliably as a function of training (139 ± 34 vs. 120 ± 29 correct responses, p < .001). Response times and confidence ratings were equivalent between groups, and no differences in breathing patterns were observed between groups.
Feedback training results in improved perception of respiratory sensations in children with asthma, a finding with implications for strategies of asthma self-management.
PMCID: PMC4668923  PMID: 24077770
asthma; children; discrimination (psychology); resistive loads; respiration; signal detection
20.  Work Stress, Caregiving and Allostatic Load: Prospective results from Whitehall II cohort study 
Psychosomatic medicine  2015;77(5):539-547.
Studies investigating health effects of work and family stress usually consider these factors in isolation. The present study investigated prospective interactive effects of job strain and informal caregiving on allostatic load (AL), a multisystem indicator of physiological dysregulation.
Subjects were 7,007 British civil servants from the Whitehall II cohort study. Phase 3 (1991-1994) served as the baseline, Phases 5 (1997-1999) and 7 (2002-2004) as follow-ups. Job strain (high job demands combined with low control) and caregiving (providing care to aged or disabled relatives) were assessed at baseline. AL index (possible range 0-9) was assessed at baseline and both follow-ups based on 9 cardiovascular, metabolic and immune biomarkers. Linear mixed effect models were used to examine the association of job strain and caregiving with AL.
High caregiving burden (above the sample median weekly hours of providing care) predicted higher AL levels, with the effect strongest in those also reporting job strain [b = 0.36, 95% CI: 0.01– 0.71)]; however, the interaction between job strain and caregiving was not significant (p = 0.56). Regardless of job strain, participants with low caregiving burden (below sample median) had lower subsequent AL levels than non-caregivers [b = 0.22, 95% CI: 0.06–0.37].
The study provides some evidence for adverse effects of stress at work combined with family demands on physiological functioning. However, providing care to others may also have health protective effects if it does not involve excessive time commitment.
PMCID: PMC4471110  PMID: 25984826
work stress; job strain; informal caregiving; allostatic load
21.  Associations between Depression and Anxiety Symptoms with Retinal Vessel Caliber in Adolescents and Young Adults 
Psychosomatic medicine  2014;76(9):732-738.
Previous longitudinal studies suggest that depression and anxiety are associated with risk for cardiovascular disease. The aim of the present study was to test whether an association between depression and anxiety symptoms and retinal vessel caliber, an indicator of subclinical cardiovascular risk, is apparent as early as adolescence and young adulthood.
Participants were 865 adolescents and young adults who participated in the Brisbane Longitudinal Twin Study and the Twin Eye Study in Tasmania. Participants completed the Somatic and Psychological Health Report (SPHERE), including assessments of depression/anxiety and somatic symptom subscales, when they were M=16.5 years, and they underwent retinal imaging M=2.5 years later (range=2 years before to 7 years after the depression/anxiety assessment). Retinal vessel caliber was assessed using computer software.
Results: Depression and anxiety symptoms were associated with wider retinal arteriolar caliber in this sample of adolescents and young adults (β=0.09, p=.016), even after adjusting for other cardiovascular risk factors (β=0.08, p=.025). Multiple regression analyses revealed that affective symptoms of depression/anxiety were associated with retinal vessel caliber independently of somatic symptoms.
Depression and anxiety symptoms are associated with measurable signs in the retinal microvasculature in early life, suggesting that pathological microvascular mechanisms may be operative in the association between depression and anxiety with cardiovascular disease starting as early as adolescence.
PMCID: PMC4290848  PMID: 25373892
depression; anxiety; retinal vessel caliber; cardiovascular; adolescence; young adults
22.  Life Satisfaction and Frequency of Doctor Visits 
Psychosomatic medicine  2013;76(1):86-93.
Identifying positive psychological factors that reduce health care use may lead to innovative efforts that help build a more sustainable and high quality health care system. Prospective studies indicate that life satisfaction is associated with good health behaviors, enhanced health, and longer life, but little information is available about the association between life satisfaction and health care use. We tested whether higher life satisfaction was prospectively associated with fewer doctor visits. We also examined potential interactions between life satisfaction and health behaviors.
Participants were 6,379 adults from the Health and Retirement Study, a prospective and nationally representative panel study of American adults over the age of 50. Participants were tracked for four years. We analyzed the data using a generalized linear model with a gamma distribution and log link.
Higher life satisfaction was associated with fewer doctor visits. On a six-point life satisfaction scale, each unit increase in life satisfaction was associated with an 11% decrease in doctor visits—after adjusting for sociodemographic factors (RR = 0.89, 95% CI = 0.86 to 0.93). The most satisfied respondents (N=1,121; 17.58%) made 44% fewer doctor visits than the least satisfied (N=182; 2.85%). The association between higher life satisfaction and reduced doctor visits remained even after adjusting for baseline health and a wide range of sociodemographic, psychosocial, and health-related covariates (RR = 0.96, 95% CI = 0.93 to 0.99).
Higher life satisfaction is associated with fewer doctor visits, which may have important implications for reducing health care costs.
PMCID: PMC4608020  PMID: 24336427
life satisfaction; successful aging; health care utilization; doctor visit; psychological well-being; positive psychology
23.  Omega-3 Supplementation and Loneliness-Related Memory Problems: Secondary Analyses Of A Randomized Controlled Trial 
Psychosomatic medicine  2014;76(8):650-658.
Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems.
Participants (N=138) from a parent randomized controlled trial (RCT) were randomized to the placebo, 1.25 grams/day of omega-3, or 2.50 grams/day of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the RCT.
Controlling for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory post-supplementation, as measured by immediate (b = −0.28, t(117) = −2.62, p = .010) and long-delay (b = −.06, t(116) = −2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25 grams/day and 2.50 grams/day supplementation groups, all p values > .10. The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests, all p values > .32.
These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the utility of exploring novel interventions for treating episodic memory problems among lonely people. identifier: NCT00385723
PMCID: PMC4288961  PMID: 25264972
loneliness; cognition; memory; omega-3; intervention
24.  Childhood Socioeconomic Disadvantage and Pre-diabetes and Diabetes in Later Life: A Study of Biopsychosocial Pathways 
Psychosomatic medicine  2014;76(8):622-628.
We examined the relationship between childhood socioeconomic status (SES) and glucoregulation in later life and used a life-course framework to examine critical periods and underlying pathways.
Data came from the MIDUS (Midlife in the U.S.) national study (n=895). Childhood SES indicators retrospectively reported at MIDUS I were used to create a childhood SES disadvantage index. Adult SES disadvantage and potential pathways were measured at MIDUS I and included waist circumference, depressive symptoms, and physical activity. Glucose and HbA1c, measured approximately 9-10 years later at MIDUS II, were used to create the ordinal outcome measure (no diabetes/prediabetes/diabetes).
Childhood SES disadvantage predicted increased odds of prediabetes and diabetes net of age, gender, race, and smoking (OR=1.11, 95% CI: 1.01-1.22). Childhood SES disadvantage predicted adult SES disadvantage (β=.26, p=.001) and the three key mediators: higher waist circumference (β=.10, p=.002), lower physical activity (β=−.11, p=.001), and marginally higher depressive symptoms (β=.07, p=.072). When childhood and adult SES disadvantage were in the same model, only adult SES predicted glucoregulation (OR=1.07, 95% CI: 1.01-1.13). The SES disadvantage measures were no longer significantly associated with glucoregulation after including waist circumference, physical activity, and depressive symptoms, all of which were significant predictors of glucoregulation.
The consequences of childhood SES disadvantage are complex and include both critical period and pathway effects. The lack of a direct effect of childhood SES on glucoregulation does not negate the importance of early environment but suggests that early-life socioeconomic factors propel unequal life-course trajectories that ultimately influence health.
PMCID: PMC4229367  PMID: 25272201
childhood disadvantage; health disparities; socioeconomic status; diabetes; obesity; depressive symptoms
25.  Social Integration and Mortality in Patients with Coronary Heart Disease: Findings from the Heart and Soul Study 
Psychosomatic medicine  2014;76(8):659-668.
To determine why lower social integration predicts higher mortality in patients with coronary heart disease (CHD).
The association between social integration and mortality was examined prospectively in 1019 outpatients with stable CHD from the Heart and Soul Study. Baseline social integration was assessed with the Berkman Social Network Index (SNI). Cox proportional hazards models were used to determine the extent to which demographic and disease-relevant confounders and potential biological, behavioral, and psychological mediators explained the association between social integration and mortality.
During a mean follow-up period of 6.7 years (SD = 2.3), the age-adjusted annual rate of mortality was 6.3% among socially isolated patients and 4.1% among non-isolated patients (age-adjusted hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.26–2.05; p < .001). After adjustment for demographic and disease-relevant confounders, socially isolated patients had a 50% greater risk of death than non-isolated patients (HR: 1.50, 95% CI: 1.07–2.10). Separate adjustment for potential biological (HR: 1.53, CI: 1.05–2.25) and psychological mediators (HR: 1.52, CI: 1.08–2.14) did not significantly attenuate this association, whereas adjustment for potential behavioral mediators did (HR: 1.30, CI: 0.91–1.86). C-reactive protein and hemoglobin A1c were identified as important biological and omega-3 fatty acids, smoking, and medication adherence as important behavioral potential mediators, with smoking making the largest contribution.
In this sample of outpatients with baseline stable CHD, the association between social integration and mortality was largely explained by health-related behavioral pathways, particularly smoking.
PMCID: PMC4197069  PMID: 25264970
coronary artery disease; epidemiology; social integration; mortality; observational study; survival analysis

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