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1.  [No title available] 
PMCID: PMC3946309  PMID: 24434950
2.  [No title available] 
PMCID: PMC3955875  PMID: 24470132
3.  [No title available] 
PMCID: PMC3971435  PMID: 24470133
4.  Gene Behavior Interaction of Depressive Symptoms and the Apolipoprotein E ε4 Allele on Cognitive Decline 
Psychosomatic medicine  2014;76(2):101-108.
Objective
Depressive symptoms and the APOE ε4 allele are independent risk factors for cognitive decline. However, it is not clear whether the presence of both depressive symptoms and the APOE ε4 allele increases cognitive decline.
Methods
A prospective study of a population-based sample of 4,150 (70% African American and 63% women) participants, aged 65 years and older, who were interviewed at 3-year intervals. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression scale, with each item coded as presence or absence of a symptom. The APOE genotype was ascertained by DNA samples collected during follow-up. Cognitive function was assessed at the initial and follow-up interviews (average follow-up of 9.2 years), using a standardized global cognitive score.
Results
There were 1405 (34%) participants with one or more copies of the APOE ε4 allele. In participants with no depressive symptoms, cognitive function decreased by 0.0412-unit per year among those with no copies and 0.0704-unit per year among those with one or more copies of the APOE ε4 allele. For each additional symptom of depression, cognitive decline increased by 0.0021-unit per year among those with no copies and 0.0051-unit per year among those with one or more copies of the APOE ε4 allele. The three-way interaction of depressive symptoms, APOE ε4 allele, and time was significant (p=0.021).
Conclusions
The association of depressive symptoms on cognitive decline was increased among participants with one or more copies of the APOE ε4 allele compared to those without the allele.
doi:10.1097/PSY.0000000000000029
PMCID: PMC4142223  PMID: 24434953
APOE Gene; Depressive Symptoms; Cognitive Decline; Gene Behavior Interaction
5.  The Association between Major Depressive Disorder in Childhood and Risk Factors for Cardiovascular Disease in Adolescence 
Psychosomatic medicine  2014;76(2):122-127.
Objective
Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops, or how early in life this association can be detected.
Methods
In an ongoing study of pediatric depression, we compared CVD risk factors, including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD, across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (MDD; N=210), never-depressed siblings of probands (N=195), and controls with no history of any major psychiatric disorder (N=161).
Results
When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking ([odds ratio [OR] 12.54, 95% confidence interval [CI] = 4.36–36.12) and were less physically active than controls (OR .59, CI = .43–.81) and siblings (OR .70, CI = .52–.94), and had a higher rate of obesity than did controls (OR 3.67, CI = 1.42–9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs 1.62–4.36; CIs = 1.03–15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD.
Conclusions
Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD.
doi:10.1097/PSY.0000000000000028
PMCID: PMC4186704  PMID: 24470130
Depression; cardiovascular disease; risk factors; adolescence
6.  [No title available] 
PMCID: PMC4290164  PMID: 24336428
7.  Depressive Symptom Clusters as Predictors of Incident Coronary Artery Disease Events: A 15-Year Prospective Study of Older Adults 
Psychosomatic medicine  2013;76(1):38-43.
Objective
Because it is not known whether particular clusters of depressive symptoms are more cardiotoxic than others, we compared the utility of four clusters in predicting incident coronary artery disease (CAD) events over 15 years in large cohort of older primary care patients.
Methods
Participants were 2,537 primary care patients aged ≥ 60 years who were screened for depression between 1991–1993 and had no existing CAD diagnosis. Depressive symptoms clusters scores (depressed affect, somatic symptoms, interpersonal distress, and positive affect) were computed from responses on the Center for Epidemiologic Studies Depression Scale administered at baseline. CAD events, defined as the occurrence of a nonfatal acute myocardial infarction or CAD death during the follow-up period, were identified using electronic medical record and National Death Index data.
Results
There were 678 CAD events. In separate fully-adjusted Cox proportional hazard models (controlling for demographics and cardiovascular risk factors), the depressed affect (HR = 1.11, 95% CI: 1.04–1.20), somatic (HR = 1.17, 95% CI: 1.08–1.26), and positive affect (HR = 0.88, 95% CI: 0.82–0.95) clusters each predicted CAD events. When the depressive symptom clusters were entered simultaneously into the fully-adjusted model, however, only the somatic cluster remained predictive of CAD events (HR = 1.13, 95% CI: 1.03–1.23).
Conclusions
Our findings suggest that the longitudinal relationship between overall depressive symptom severity and incident CAD events may be driven primarily by the somatic cluster.
doi:10.1097/PSY.0000000000000023
PMCID: PMC3891500  PMID: 24367122
Coronary artery disease; depression; depressive symptoms clusters; elderly; primary care; prospective study
8.  Psychological Trauma and Functional Somatic Syndromes: A Systematic Review and Meta-Analysis 
Psychosomatic medicine  2013;76(1):2-11.
Objective
This meta-analysis systematically examined the association of reported psychological trauma and posttraumatic stress disorder (PTSD) with functional somatic syndromes including fibromyalgia, chronic widespread pain, chronic fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome. Our goals were to determine the overall effect size of the association and to examine moderators of the relationship.
Methods
Literature searches identified 71 studies with a control or comparison group and examined the association of the syndromes with traumatic events including abuse of a psychological, emotional, sexual, or physical nature sustained during childhood or adulthood, combat exposure, or PTSD. A random effects model was used to estimate the pooled odds ratio and 95% CI. Planned subgroup analyses and meta-regression examined potential moderators.
Results
Individuals who reported exposure to trauma were 2.7 (95% CI = 2.27 – 3.10) times more likely to have a functional somatic syndrome. This association was robust against both publication bias and the generally low quality of the literature. The magnitude of the association with PTSD was significantly larger than with sexual or physical abuse. Chronic fatigue syndrome had a larger association with reported trauma than either irritable bowel syndrome or fibromyalgia. Studies using non-validated questionnaires or self-report of trauma reported larger associations than those using validated questionnaires.
Conclusions
Findings highlight limitations of the existing literature and emphasize the importance of conducting prospective studies, further examining the potential similarities and differences of these conditions, and pursuing hypothesis-driven studies of the mechanisms underlying the link between trauma, PTSD, and functional somatic syndromes.
doi:10.1097/PSY.0000000000000010
PMCID: PMC3894419  PMID: 24336429
functional somatic syndromes; trauma; PTSD; meta-analysis
9.  Effect of Collaborative Care for Depression on Risk of Cardiovascular Events: Data from the IMPACT Randomized Controlled Trial 
Psychosomatic medicine  2013;76(1):29-37.
Objective
Although depression is a risk and prognostic factor for cardiovascular disease (CVD), depression trials involving cardiac patients have not observed the anticipated cardiovascular benefits. To test our hypothesis that depression treatment delivered before clinical CVD onset reduces risk of CVD events, we conducted an 8-year follow-up study of the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) randomized controlled trial.
Methods
Participants were 235 primary care patients aged ≥60 years with major depression or dysthymia who were randomized to a 12-month collaborative care program involving antidepressants and psychotherapy (85 without and 35 with baseline CVD) or usual care (83 without and 32 with baseline CVD). Hard CVD events (fatal/nonfatal) were identified using electronic medical record and Medicare/Medicaid data.
Results
119 patients (51%) had a hard CVD event. As hypothesized, the Treatment x Baseline CVD interaction was significant (p = .021). IMPACT patients without baseline CVD had a 48% lower risk of an event than Usual Care patients (28% vs. 47%, HR = 0.52, 95% CI: 0.31–0.86). The number needed to treat to prevent one event over five years was 6.1. The likelihood of an event did not differ between IMPACT and Usual Care patients with baseline CVD (86% vs. 81%, HR = 1.19, 95% CI: 0.70–2.03).
Conclusions
Collaborative depression care delivered before CVD onset halved the excess risk of hard CVD events among older, depressed patients. Our findings raise the possibility that the IMPACT intervention could be used as a CVD primary prevention strategy.
Trial Registration
clinicaltrials.gov Identifier: NCT01561105 (http://clinicaltrials.gov/ct2/show/NCT01561105)
doi:10.1097/PSY.0000000000000022
PMCID: PMC3899245  PMID: 24367124
depression; coronary disease; cerebrovascular disorders; follow-up studies; prevention
10.  RSA Reactivity in Current and Remitted Major Depressive Disorder 
Psychosomatic medicine  2013;76(1):66-73.
Objective
Low resting respiratory sinus arrhythmia (RSA) levels and blunted RSA reactivity are thought to index impaired emotion regulation capacity. Major Depressive Disorder (MDD) has been associated with abberant RSA reactivity and recovery to a speech stressor task relative to healthy controls. Whether impaired RSA functioning reflects aspects of the depressed mood state or a stable vulnerability marker for depression is unknown.
Methods
We compared resting RSA and RSA reactivity between individuals with MDD (n=49), remitted depression (RMD, n=24), and healthy controls (n=45). ECG data were collected during a resting baseline, a paced-breathing baseline, and two reactivity tasks (speech stressor, cold exposure).
Results
A group by time quadratic effect emerged (F=4.36(2,109), p=.015) for RSA across phases of the speech stressor (baseline, instruction, preparation, speech, recovery). Follow-up analyses revealed that those with MDD uniquely exhibited blunted RSA reactivity, whereas RMD and controls both exhibited normal task-related vagal withdrawal and post-task recovery. The group by time interaction remained after covariation for age, sex, waist circumference, physical activity, and respiration, but not sleep quality.
Conclusions
These results provide new evidence that abberant RSA reactivity marks features that track the depressed state, such as poor sleep, rather than a stable trait evident among asymtomatic persons.
doi:10.1097/PSY.0000000000000019
PMCID: PMC3906687  PMID: 24367127
Major Depression; Remitted Depression; RSA; reactivity; stress
11.  Effects of acute stress on cardiac endocannabinoids, lipogenesis, and inflammation in rats 
Psychosomatic medicine  2013;76(1):20-28.
Objective
Trauma exposure can precipitate acute/post-traumatic stress responses (AS/PTSD) and disabling cardiovascular disorders (CVD). Identifying acute stress-related physiologic changes that may increase CVD risk could inform development of early CVD-prevention strategies. The endocannabinoid system (ECS) regulates hypothalamic-pituitary-adrenal (HPA) axis response and stress-related cardiovascular function. We examine stress-related endocannabinoid system (ECS) activity and its association with cardiovascular biochemistry/function following acute stress.
Methods
Rodents (n=8-16/group) were exposed to predator odor or saline; elevated plus maze (EPM), blood pressure (BP), serum and cardiac tissue ECS markers, and lipid metabolism were assessed at 24h and 2wks post-exposure.
Results
At 24h the predator odor group demonstrated anxiety-like behavior and had (a) elevated serum markers of cardiac failure/damage (brain natriuretic peptide [BNP]: 275.1 vs. 234.6, p=0.007; troponin-I: 1.50 vs. 0.78, p=0.076), lipogenesis (triacylglycerols [TAG]: 123.5 vs. 85.93, p=0.018), and inflammation (stearoyl delta-9 desaturase activity [SCD-16]: 0.21 vs. 0.07, p<0.001); (b) significant decrease in cardiac endocannabinoid (2-arachidonoyl-sn-glycerol, 2-AG: 29.90 vs. 65.95, p<0.001) and fatty acid ethanolamides (FAE: oleoylethanolamide, OEA: 114.3 vs. 125.4, p=0.047; palmitoylethanolamide, PEA: 72.96 vs. 82.87, p=0.008); and (c) increased cardiac inflammation (IL-1β/IL-6 ratio: 19.79 vs.13.57, p=0.038; TNF-α/IL-6 ratio: 1.73 vs. 1.03, p=0.019) and oxidative stress (thiobarbituric acid reactive substances [TBARS]: 7.81 vs. 7.05, p=0.022), that were associated with cardiac steatosis (higher TAG: 1.09 vs. 0.72, p<0.001). Cardiac lipogenesis persisted, and elevated BP emerged two weeks after exposure.
Conclusions
Acute psychological stress elicits ECS-related cardiac responses associated with persistent, potentially-pathological changes in rat cardiovascular biochemistry/function.
doi:10.1097/PSY.0000000000000025
PMCID: PMC3988664  PMID: 24367128
Acute stress; cardiovascular status; endocannabinoids; lipogenesis; inflammation; triacylglycerols
12.  Perceived Stress and Change in Cognitive Function Among Adults Aged 65 and Older 
Psychosomatic medicine  2013;76(1):80-85.
Objective
Exposure to acute and chronic stress can affect learning and memory but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample.
Methods
Participants included 6,207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging project. Two to five in-home assessments were completed over an average of 6.8 years of follow up, and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a 6-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment.
Results
Mixed effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B=-0.0379, SE=0.0025, p<.001) and a faster rate of cognitive decline (stress × time interaction: B=-0.0015, SE=0.0004, p<.001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age or education.
Conclusion
Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults aged 65 and above.
doi:10.1097/PSY.0000000000000016
PMCID: PMC4185366  PMID: 24367123
aging; cognitive function; longitudinal; risk factors; stress
13.  Somatoform Pain: A developmental theory and translational research review 
Psychosomatic medicine  2012;74(7):717-727.
Somatoform pain is a highly prevalent, debilitating condition and a tremendous public health problem. Effective treatments for somatoform pain are urgently needed. The etiology of this condition is, however, still unknown. On the basis of a review of recent basic and clinical research, we propose one potential mechanisms of symptom formation in somatoform pain and a developmental theory of its pathogenesis. The emerging evidence from animal and human studies in developmental neurobiology, cognitive-affective neuroscience, psychoneuroimmunology, genetics, epigenetics, and clinical and treatment studies of somatoform pain all point to the existence of a shared physical and social pain neural system. Research findings also show that non-optimal early experiences interact with genetic predispositions to influence the development of this shared system and ability to regulate it in an effective way. Interpersonal affect regulation between infant and caregiver is crucial for the optimal development of these brain circuits. The aberrant development of this shared neural system during infancy, childhood and adolescence, therefore, may ultimately lead to an increased sensitivity to physical and social pain and to problems with their regulation in adulthood. The authors critically review translational research findings that support this theory and discuss its clinical and research implications. Specifically, the proposed theory and reviewed research suggest that psychotherapeutic and/or pharmacologic interventions that foster the development of affect regulation capacities in an interpersonal context will also serve to more effectively modulate aberrantly activated neural pain circuits and thus be of particular benefit in the treatment of somatoform pain.
doi:10.1097/PSY.0b013e3182688e8b
PMCID: PMC4272574  PMID: 22929064
Somatoform Pain; Pain Disorder; Somatization; Developmental Neuroscience; Interpersonal Affect Regulation; Translational Research
14.  Depressed Mood and Flow-Mediated Dilation: A Systematic Review and Meta-Analysis 
Psychosomatic medicine  2011;73(5):360-369.
Objective
This systematic and quantitative review evaluates the literature on associations between depressed mood and flow-mediated dilation (FMD), a measure of endothelial function, in adults.
Methods
Published English-language articles (through December 2010) were identified from literature searches, assessed for data extraction, and evaluated for quality.
Results
The literature includes cross-sectional (n = 9) and retrospective examinations (n = 3) of how FMD correlates with clinical or subclinical depression in healthy adults and cardiovascular patients (total N across 12 studies = 1491). FMD was assessed using a variety of methodologies. Samples were predominately older white and Asian subjects with higher socioeconomic status. In eight of the 12 articles selected for this review, at least one significant inverse association was noted between depressed mood and FMD, with primarily moderate effect sizes. The overall meta-analysis (random-effects model) revealed a combined effect size of correlation coefficient r = 0.19 (95% confidence interval = 0.08–0.29, p = .001). Significant combined effects were found for subgroups of studies that a) received better quality ratings (r = 0.29), b) examined patients with cardiovascular disease or with cardiovascular disease risk factors/comorbidity (r = 0.29), c) used maximum vasodilation to quantify FMD (r = 0.27), and d) assessed samples that had a mean age of 55 years and older (r = 0.15).
Conclusions
Diverse studies support the inverse correlation between depressed mood and endothelial function, as measured by FMD. This literature would be strengthened by prospective studies, increased methodological consistency in FMD testing, and broader sampling (e.g., African Americans, younger age, lower socioeconomic status).
doi:10.1097/PSY.0b013e31821db79a
PMCID: PMC4266566  PMID: 21636660
review; meta-analysis; depression; mood; flow-mediated dilation; vasodilation
15.  Racial Differences in the Impact of Social Support on Nocturnal Blood Pressure 
Psychosomatic medicine  2009;71(5):524-531.
Objective
To investigate whether black and white adults benefit similarly from perceived social support in relation to blood pressure (BP) dipping during sleep.
Methods
The Interpersonal Support Evaluation List (ISEL, 12-item version), which measures the perceived availability of several types of functional social support, was examined for interactive effects with race on dipping of mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) derived from 24-hour ambulatory blood pressure monitoring (ABPM). The sample consisted of 156 young to middle-aged adults (61 blacks, 95 whites; mean age = 35.7 years).
Results
Mean ISEL scores did not differ between racial groups. Controlling for age, body mass index (BMI), resting BP, and socioeconomic status (SES), the interaction of social support by race yielded associations with nighttime dipping in MAP and DBP (p < .001) as well as SBP (p < .01). As ISEL scores increased among white participants, the extent of dipping increased in MAP, SBP, and DBP (p < .01), explaining 10%, 10%, and 8% of the variance, respectively. Conversely, black participants exhibited associations between increasing ISEL scores and decreasing levels of dipping in MAP, SBP, and DBP (p < .05), accounting for 9%, 8%, and 8% of the variance, respectively.
Conclusion
As perceived social support increased, white adults received cardiovascular benefits as suggested by enhanced nocturnal dipping of BP, but black adults accrued risks as evidenced by blunted declines in BP during sleep.
doi:10.1097/PSY.0b013e31819e3a93
PMCID: PMC4266568  PMID: 19321852
social support; nocturnal dipping; ambulatory blood pressure; racial differences
16.  Relationship Between Obesity and Depression: Characteristics and Treatment Outcomes with Antidepressant Medication 
Psychosomatic medicine  2013;75(9):863-872.
Objective
Obesity and Major Depressive Disorder (MDD) often co-occur. However, differences between obese and normal-weight depressed patients and the moderating effect of obesity on antidepressant treatment outcome have not been well studied.
Methods
662 subjects in the COmbining Medications to Enhance Depression Outcomes (COMED) were randomized to treatment with escitalopram plus placebo, bupropion plus escitalopram, or venlafaxine plus mirtazapine for a 12 week primary treatment phase and 16 week follow-up. Body Mass Index (BMI) was calculated at baseline. Subjects were divided into BMI classes according to World Health Organization criteria: 1) normal (and low) weight (NW), 2) overweight (OW), 3) obese I (OB1) and 4) obese II+ (OB2). Clinical characteristics were compared using Chi-squared or Kruskall-Wallis testing. Outcomes were assessed using a repeated effects model, unadjusted and adjusted for baseline variables differing across BMI classes.
Results
31.4% of the subjects were normal weight; 46.2% were obese. Higher BMI was associated with greater medical illness (p<0.001), social phobia (p=0.003) and bulimia (p=0.026). Lower BMI was associated with higher rates of Post Traumatic Stress Disorder (p=0.002) and drug abuse. Treatment outcomes, including remission, did not differ across classes. However, lower BMI was associated with more frequent (p=0.024, unadjusted, 0.053 adjusted) and more severe (p=0.008 unadjusted, 0.053 adjusted) side effects.
Conclusions
We found a high rate of obesity compared to the general population and significant differences in presentation and comorbidity, but not medication use and antidepressant outcomes, in subjects across BMI classes. Lower BMI classes had higher rates of comorbidities associated with poor outcome, which may have obscured outcome differences.
Trial Registration
clinicaltrials.gov Identifier: NCT 00270647
doi:10.1097/PSY.0000000000000000
PMCID: PMC3905462  PMID: 24163386
Depression; Obesity; Treatment Resistance
17.  Lifetime Trauma Exposure and Prospective Cardiovascular Events and All-cause Mortality: Findings from the Heart and Soul Study 
Psychosomatic medicine  2013;75(9):849-855.
Objective
Little is known about the effect of cumulative psychological trauma on health outcomes in patients with cardiovascular disease. The objective of this study was to prospectively examine the association between lifetime trauma exposure and recurrent cardiovascular events or all-cause mortality in patients with existing cardiovascular disease.
Method
1,021 men and women with cardiovascular disease were recruited in 2000–2002 and followed annually. Trauma history and psychiatric comorbidities were assessed at baseline using the Computerized Diagnostic Interview Schedule for DSM-IV. Health behaviors were assessed using standardized questionnaires. Outcome data was collected annually, and all medical records were reviewed by two independent, blinded physician adjudicators. We used Cox proportional hazards models to evaluate the association between lifetime trauma exposure and the composite outcome of cardiovascular events and all-cause mortality.
Results
During an average of 7.5 years follow-up, there were 503 cardiovascular events and deaths. Compared with the 251 participants in the lowest trauma exposure quartile, the 256 participants in the highest exposure quartile had a 38% greater risk of adverse outcomes (HR 1.38, 95% CI 1.06–1.81), adjusted for age, sex, race, income, education, depression, posttraumatic stress disorder, generalized anxiety disorder, smoking, physical inactivity, and illicit drug abuse.
Conclusions
Cumulative exposure to psychological trauma was associated with an increased risk of recurrent cardiovascular events and mortality, independent of psychiatric comorbidities and health behaviors. These data add to a growing literature showing enduring effects of repeated trauma exposure on health that are independent of trauma-related psychiatric disorders such as depression and posttraumatic stress disorder.
doi:10.1097/PSY.0b013e3182a88846
PMCID: PMC4014357  PMID: 24149074
Cardiovascular disease; psychological trauma; myocardial infarction; depression; post-traumatic stress disorder; cardiovascular mortality
18.  The Effects of a Telehealth Coping Skills Intervention on Outcomes in Chronic Obstructive Pulmonary Disease: Primary Results from the INSPIRE-II Study 
Psychosomatic medicine  2014;76(8):581-592.
Objective
Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life. Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic quality of life and on the combined medical endpoint of COPD-related hospitalizations and all-cause mortality.
Methods
We conducted a dual-site, randomized clinical trial with assessments at baseline and after 16 weeks of treatment. The study population comprised 326 outpatients with COPD aged 38 to 81 years, randomized to Coping Skills training (CST) or to COPD Education (COPD-ED). Patients completed a battery of quality of life (QoL) instruments, pulmonary function tests, and functional measures and were followed for up to 4.4 years to assess medical outcomes.
Results
The CST group exhibited greater improvements in psychological QoL compared to controls (P = .001), including less depression (Cohen’s d=0.22 [95%CI 0.08, 0.36]) and anxiety (d=0.17 [95%CI 0.02, 0.33]), and better overall mental health (d=0.17 [95%CI 0.03, 0.32]), emotional role functioning (d= 0.29 [95%CI 0.10, 0.48]), vitality (d= 0.27 [95%CI 0.11, 0.42]), and social functioning (d= 0.21 [95%CI 0.03, 0.38]). A significant baseline psychological QoL by Treatment group interaction revealed that CST with lower QoL at baseline achieved even greater improvements in psychological QoL compared to COPE-ED. CST participants also exhibited greater improvements in Somatic QoL (P = .042), including greater improvements in pulmonary QoL (d= 0.13 [95%CI 0.01, 0.24]), less fatigue (d= 0.34 [95%CI 0.18, 0.50]), and less shortness of breath (d= 0.11 [95%CI −0.01, 0.23]) and greater improvement in distance walked on the 6 Minute Walk Test (d= 0.09 [95%CI 0.01, 0.16]). However, there was no significant difference in risk of time to COPD-related hospitalization or all-cause mortality between CST (34 events) and COPD-ED (32 events) (P= 0.430).
Conclusions
A telehealth coping skills training intervention produced clinically meaningful improvements in quality of life and functional capacity, but no overall improvement in risk of COPD-related hospitalization and all-cause mortality.
Trial Registration
clinicaltrials.gov Identifier NCT00736268
doi:10.1097/PSY.0000000000000101
PMCID: PMC4197099  PMID: 25251888
COPD; stress; depression; coping skills; disease-management
19.  TREATING ANXIETY IN THE PRESENCE OF MEDICAL COMORBIDITY: CALMLY MOVING FORWARD 
Psychosomatic medicine  2013;75(8):710-712.
doi:10.1097/PSY.0000000000000011
PMCID: PMC3929342  PMID: 24096773
20.  Testosterone in Newly Diagnosed, Antipsychotic-Naïve Men with Nonaffective Psychosis: A Test of the Accelerated Aging Hypothesis 
Psychosomatic medicine  2011;73(8):643-647.
Objective
Schizophrenia has been associated with age-related abnormalities, including abnormal glucose tolerance, increased pulse pressure, increased inflammation, abnormal stem cell signalling and shorter telomere length. These metabolic abnormalities as well as other findings suggest schizophrenia and related disorders might be associated with accelerated aging. Testosterone activity has a progressive decline with increasing age.
Methods
We tested the hypothesis that circulating biologically active testosterone is lower in newly diagnosed, antipsychotic-naïve male patients with nonaffective psychosis than in matched control subjects.
Results
Patients (n=33) were matched to control subjects (n=33) for age, gender, body mass index, socioeconomic status of the family of origin, and smoking. The free androgen index (FAI), a measure of biologically active testosterone, was significantly lower in the psychosis group [mean 57.7%, SD=26.1] than in control subjects [71.6%, 27.0; p=0.04], with an effect size of 0.53. Multivariate analysis also supported the findings. In the psychosis group, FAI had a significant negative correlation with the conceptual disorganization item (r=-0.35, p=0.049), but not with reality distortion (r=-0.21; p=0.24), negative symptoms (r=0.004; p=0.98) or depression (r=-0.014; p=0.94).
Conclusion
Lower testosterone is consistent with accelerated aging in nonaffective psychosis, but further testing of this hypothesis is needed.
doi:10.1097/PSY.0b013e318230343f
PMCID: PMC4185195  PMID: 21949421
Schizophrenia; sex hormone; androgen; senescence; aging; first episode
21.  Effects of Medical Comorbidity on Anxiety Treatment Outcomes in Primary Care 
Psychosomatic medicine  2013;75(8):713-720.
Objective
To evaluate the effects of medical comorbidity on anxiety treatment outcomes.
Methods
Data were analyzed from 1,004 primary care patients enrolled in a trial of a collaborative care intervention for anxiety. Linear mixed models accounting for baseline characteristics were used to evaluate effects of overall medical comorbidity [2 or more chronic medical conditions (CMCs) vs. fewer than 2 CMCs] and specific CMCs (migraine, asthma, and gastrointestinal disease) on anxiety treatment outcomes at 6, 12, and 18 months.
Results
At baseline, patients with two or more CMCs (n = 582; 58.0%) reported more severe anxiety symptoms [10.5 (95% CI = 10.1 to 10.9) vs. 9.5 (95% CI = 9.0 to 10.0); p = .003) and anxiety-related disability [17.6 (95% CI = 17.0 to 18.2) vs. 16.0 (95% CI = 15.3 to 16.7); p = .001). However, their clinical improvement was comparable to those with one or zero CMCs (predicted Δ in anxiety symptoms = −3.9 vs. −4.1 at 6 months, −4.6 vs. − 4.4 at 12 months, −4.9 vs. −5.0 at 18 months; predicted Δ in anxiety-related disability = −6.4 vs. −6.9 at 6 months, −6.9 vs. −7.3 at 12 months, −7.3 vs. −7.5 at 18 months). The only specific CMC with a detrimental effect was migraine, which was associated less improvement in anxiety symptoms at 18 months (predicted Δ = −4.1 vs. −5.3).
Conclusions
Effectiveness of the anxiety intervention was not significantly affected by presence of multiple CMCs; however, migraine sufferers displayed less improvement at long-term follow up.
Clinical Trials Registration
www.clinicaltrials.gov Identifier: NCT00347269
doi:10.1097/PSY.0b013e31829def54
PMCID: PMC3797868  PMID: 23886736
anxiety; medical illness; asthma; migraine; primary care; randomized controlled trial
22.  The association of depressive symptoms and pulmonary function in healthy adults 
Psychosomatic medicine  2013;75(8):737-743.
Objective
Chronic lung disease is exacerbated by comorbid psychiatric issues and treatment of depression may improve disease symptoms. We sought to add to the literature as to whether depression is associated with pulmonary function in healthy adults.
Methods
In 2,551 healthy adults from New York State, USA, we studied the association of depression via the Center for Epidemiologic Studies Depression scale (CES-D) score and forced expiratory volume (FEV1) and forced vital capacity (FVC) using general linear models and a cross sectional design.
Results
We identified statistically significant inverse trends in FEV1, FVC, FEV1% and FVC% by CES-D category especially in ever smokers and men. When adjusted for covariates, the difference in FEV1 and FEV1% for smokers with >18.5 lifetime pack years from CES-D score 0-3 to ≥16 (depressed) is approximately 0.25 L and 5.0%; adjusted P for trend are <0.001 and 0.019, respectively. In men, we also observed statistically significant inverse trends in pulmonary function with increasing CES-D.
Conclusions
We identified an inverse association of depressive symptoms and pulmonary function in healthy adults especially in men and individuals with a heavy smoking history. Further studies of these associations are essential for the development and tailoring of interventions for the prevention and treatment of chronic lung disease.
doi:10.1097/PSY.0b013e3182a15672
PMCID: PMC3797871  PMID: 23960159
pulmonary disease; chronic lung disease; depression; respiratory function tests
23.  Randomized Controlled Trial of Mindfulness-based Stress Reduction for Prehypertension 
Psychosomatic medicine  2013;75(8):10.1097/PSY.0b013e3182a3e4e5.
Objective
Mindfulness-based stress reduction (MBSR) is an increasingly popular practice demonstrated to alleviate stress and treat certain health conditions. MBSR may reduce elevated blood pressure (BP). Treatment guidelines recommend lifestyle modifications for BP in the prehypertensive range (SBP 120–139 or DBP 80–89), followed by antihypertensives if BP reaches hypertensive levels. MBSR has not been thoroughly evaluated as a treatment for prehypertension. A randomized clinical trial of MBSR for high BP was conducted to determine whether BP reductions associated with MBSR exceed those observed for an active control condition consisting of progressive muscle relaxation training (PMR).
Methods
56 men (43%) and women (57%) averaging 50.3 (SD = 6.5) years of age (91% Caucasian) with unmedicated BP in the prehypertensive range were randomized to 8 weeks of MBSR or PMR delivered in a group format. Treatment sessions were administered by 1 treatment provider and lasted approximately 2.5 hours each week. Clinic BP was the primary outcome measure. Ambulatory BP was a secondary outcome measure.
Results
Analyses were based on intent-to-treat. Patients randomized to MBSR exhibited a 4.8 mm Hg reduction in clinic SBP, which was larger than the 0.7 mm Hg reduction observed for PMR, p = .016. Those randomized to MBSR exhibited a 1.9 mm Hg reduction in DBP, compared to a 1.2 mm Hg increase for PMR, p = .008. MBSR did not result in larger decreases in ambulatory BP than PMR.
Conclusions
MBSR resulted in a reduction in clinic SBP and DBP compared to PMR.
doi:10.1097/PSY.0b013e3182a3e4e5
PMCID: PMC3834730  PMID: 24127622
Mindfulness; meditation; prehypertension; blood pressure; clinical trial; MBSR
24.  Racial differences in heart rate variability during sleep in women: The SWAN Sleep Study 
Psychosomatic medicine  2013;75(8):783-790.
Background
Heart rate variability (HRV) differs markedly by race, yet few studies have evaluated these relationships in women. Moreover, none have evaluated HRV during sleep, despite sleep's importance to cardiovascular health.
Methods
We addressed these gaps by examining HRV during sleep in African American, Chinese and white women (mean age 51.2 ± 2.2). Sleep and HRV during sleep (sHRV) were measured concurrently.
Results
Heart rate variability during stage 2 non-rapid eye movement (NREM) and rapid eye movement (REM) sleep differed significantly by race after adjusting for possible confounders. Normalized high frequency HRV was significantly lower in white compared to African American and Chinese participants (white NREM=0.35 ±.01, REM=0.23 ± .01; African American NREM=0.43 ± 0.02, REM=0.29 ± 0.02; Chinese NREM=0.47 ± 0.03, REM=0.33 ± 0.02; p’s<.001). The inverse was seen for low frequency power, with higher values in white compared to African American and Chinese participants (white NREM=0.66 ± .01, REM=0.77 ± .01; African American=NREM 0.58 ± 0.02, REM=0.71 ± 0.02; Chinese=0.53 ± 0.03, REM=0.68 ± 0.02; p’s<.010). Whites also exhibited higher low-to-high frequency HRV ratios during sleep compared to African American and Chinese women (white NREM=2.42 ± 1.07, REM=5.05 ± 1.07; African American NREM=1.69 ± 1.09, REM=3.51 ± 1.09; Chinese NREM=.35 ± 1.07, REM=2.88 ± 1.13; p’s<.001).
Conclusions
Race was robustly related to HRV during sleep. Compared to African American and Chinese women, whites exhibited decreased vagally-mediated control of the heart during sleep. Rresearch is needed to evaluate whether sHRV, including race differences, is prospectively associated with cardiovascular disease.
doi:10.1097/PSY.0b013e3182a7ec5c
PMCID: PMC3902648  PMID: 24077772
heart rate variability; sleep; race; cardiovasular disease; autonomic tone; women
25.  Anger Management Style Moderates Effects of Attention Strategy During Acute Pain Induction on Physiological Responses to Subsequent Mental Stress and Recovery: A Comparison of Chronic Pain Patients and Healthy Nonpatients 
Psychosomatic medicine  2009;71(4):454-462.
Objectives:
To examine whether high trait anger-out chronic low back (CLBP) patients would show exceptionally large symptom-specific lower paraspinal (LP) responses, compared with healthy nonpatients, during pain induction, a subsequent mental stressor, and recovery when they were urged to suppress awareness of pain and suffering.
Methods:
CLBP patients (n = 93) and nonpatients (n = 105) were assigned randomly to one of four attention strategy conditions for use during pain induction: sensory-focus, distraction, suppression, or control. All participants underwent a cold pressor, and then performed mental arithmetic. They completed the anger-out (AOS) and anger-in (AIS) subscales of the Anger Expression Inventory.
Results:
General Linear Model procedures were used to test Attention Strategy Condition X Patient/Nonpatient Status × AOS (or AIS) × Period interactions for physiological indices. Significant interactions were found such that: a) high trait anger-out patients in the Suppression condition seemed to show the greatest LP reactivity during the mental arithmetic followed by the slowest recovery compared with other conditions; b) high trait anger-out patients and nonpatients in the Suppression condition seemed to show the slowest systolic blood pressure recoveries compared with other conditions.
Conclusions:
Results extend previous work by suggesting that an anger-out style moderates effects of how attention is allocated during pain on responses to and recovery from a subsequent mental stressor. Results provide further evidence that trait anger-out and trait anger-in among CLBP patients are associated with increased LP muscle tension during and after pain and mental stress.
doi:10.1097/PSY.0b013e318199d97f
PMCID: PMC4180112  PMID: 19251875
attention strategies; acute pain; trait anger-out; symptom-specific reactivity; chronic pain patients

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