Longer term benefits of exercise and escitalopram in the treatment of anxiety in patients with coronary heart disease: Six month follow-up of the UNWIND randomized clinical trial.

BACKGROUND: Anxiety is a common comorbidity in patients with coronary heart disease (CHD) and is associated with worse prognosis. However, effective treatment for anxiety in CHD patients is uncertain. The UNWIND randomized clinical trial showed that 12-week treatment of escitalopram was better than exercise training or placebo in reducing anxiety in anxious CHD patients. The longer-term benefits of treatment for anxiety are not known. METHODS: Patients were randomized to 12 weeks of Escitalopram (up to 20 mg), Exercise (3 times/wk), or placebo pill. At the conclusion of treatment, participants were followed for 6-months to determine the persistence of benefit on the primary anxiety endpoint assessed by the Hospital Anxiety and Depression Scale-Anxiety scale (HADS-A) and to assess the effects of treatment on major adverse cardiac events over a follow-up period of up to 6 years. RESULTS: Of the 128 participants initially randomized, 120 (94%) were available for follow-up. Participants randomized to the Escitalopram condition exhibited lower HADS-A scores (3.9 [3.1, 4.7]) compared to those randomized to Exercise (5.5 [4.6, 6.3]) (P = .007) and Placebo (5.3 [4.1, 6.5]) (P = .053). Over a median follow-up of 3.2 years (IQR: 2.3, 4.5), there were 29 adverse events but no significant between-group differences. CONCLUSION: In the UNWIND trial, 12 weeks of escitalopram treatment was effective in reducing anxiety. These beneficial effects were sustained for 6 months posttreatment. Although moderate or vigorous physical activity has a number of health benefits, exercise was not an effective treatment for anxiety in patients with CHD.

Microvascular Endothelial Function and Neurocognition Among Adults With Major Depressive Disorder.

BACKGROUND: Cardiovascular risk factors (CVRFs) and endothelial dysfunction have been associated independently with poorer neurocognition in middle-aged adults, particularly on tests of frontal lobe function. However, to our knowledge, no studies have examined markers of microvascular dysfunction on neurocognition or the potential interaction between macro- and microvascular biomarkers on neurocognition in middle-aged and older adults with major depressive disorder (MDD). METHODS: Participants included 202 adults with MDD who were not receiving mental health treatment. Microvascular endothelial function was assessed using a noninvasive marker of forearm reactive hyperemia velocity while macrovascular endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery. CVRFs were assessed using the Framingham Stroke Risk Profile and fasting lipid levels. A standardized neurocognitive assessment battery was used to assess three cognitive domains: executive function, working memory, and verbal memory. RESULTS: Greater microvascular dysfunction was associated with poorer neurocognition across all three domains. Microvascular function continued to predict verbal memory performance after accounting for background factors and CVRFs. Macro- and microvascular function interacted to predict working memory performance (F = 4.511, 178, p = 0.035), with a similar nonsignificant association for executive function (F = 2.731, 178, p = 0.095), with moderate associations observed between microvascular function and neurocognition in the presence of preserved FMD (r61 = 0.40, p = 0.001), but not when FMD was impaired (r63 = -0.05, p = 0.675). CONCLUSION: Greater microvascular dysfunction is associated with poorer neurocognition among middle-aged and older adults. This association was strongest in participants with preserved macrovascular function.

Depression, social support, and clinical outcomes following lung transplantation: a single-center cohort study.

Depressive symptoms are common among lung transplant candidates and have been associated with poorer clinical outcomes in some studies. Previous studies have been plagued by methodologic problems, including small sample sizes, few clinical events, and uncontrolled confounders, particularly perioperative complications. In addition, few studies have examined social support as a potential protective factor. We therefore examined the association between pretransplant depressive symptoms, social support, and mortality in a large sample of lung transplant recipients. As a secondary aim, we also examined the associations between psychosocial factors, perioperative outcomes [indexed by hospital length of stay (LOS)], and mortality. We hypothesized that depression would be associated with longer LOS and that the association between depression, social support, and mortality would be moderated by LOS. Participants included lung transplant recipients, transplanted at Duke University Medical Center from January 2009 to December 2014. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI-II) and social support using the Perceived Social Support Scale (PSSS). Medical risk factors included forced vital capacity (FVC), partial pressure of carbon dioxide (PCO2 ), donor age, acute rejection, and transplant type. Functional status was assessed using six-minute walk distance (6MWD). We also controlled for demographic factors, including age, gender, and native disease. Transplant hospitalization LOS was examined as a marker of perioperative clinical outcomes. Participants included 273 lung recipients (174 restrictive, 67 obstructive, 26 cystic fibrosis, and six "other"). Pretransplant depressive symptoms were common, with 56 participants (21%) exhibiting clinically elevated levels (BDI-II ≥ 14). Greater depressive symptoms were associated with longer LOS [adjusted b = 0.20 (2 days per 7-point higher BDI-II score), P < 0.01]. LOS moderated the associations between depressive symptoms (P = 0.019), social support (P < 0.001), and mortality, such that greater depressive symptoms and lower social support were associated with greater mortality only among individuals with longer LOS. For individuals with LOS ≥ 1 month, clinically elevated depressive symptoms (BDI-II ≥ 14) were associated with a threefold increased risk of mortality (HR = 2.97). Greater pretransplant depressive symptoms and lower social support may be associated with greater mortality among a subset of individuals with worse perioperative outcomes.

Depressive symptoms and early mortality following lung transplantation: A pilot study.

BACKGROUND: Impaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pretransplant depression, quality of life (QoL), and post-transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short-term mortality in a consecutive series of lung transplant recipients. METHODS: Depression (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR=1.6]) and again approximately 2 weeks following transplantation (median=0.5 months [IQR=0.5]), in a series of 66 patients transplanted between March 2013 and April 2014. The association between psychiatric diagnoses from participants' comprehensive pretransplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality. RESULTS: During a median follow-up of 2.8 years (range 0.4-3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR=2.17 [1.01, 4.67], P=.048), and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pretransplant depression, history of depression, nor QoL was associated with mortality. CONCLUSIONS: Greater post-transplant depressive symptoms are independently associated with mortality among lung transplant recipients.

Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial.

BACKGROUND: Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. METHODS: The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70%-85% VO2peak), escitalopram (5-20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. CONCLUSIONS: The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients.

Effects of Exercise and Sertraline on Measures of Coronary Heart Disease Risk in Patients With Major Depression: Results From the SMILE-II Randomized Clinical Trial.

OBJECTIVE: To assess the effects of supervised and home-based aerobic exercise training, and antidepressant pharmacotherapy (sertraline) on coronary heart disease (CHD) risk factors in a sample of participants with major depressive disorder (MDD). METHODS: The Standard Medical Intervention versus Long-term Exercise (SMILE)-II study randomized 202 adults (153 women, 49 men) diagnosed as having MDD to one of four interventions, each of 4-month duration: supervised exercise, home-based exercise, antidepressant medication (sertraline, 50-200 mg daily), or placebo pill. Patients underwent a structured clinical interview for depression and completed the Hamilton Depression Rating Scale. CHD risk factors included brachial artery flow-mediated dilation, carotid intima-media thickness, serum lipids, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk. RESULTS: Compared with placebo, active treatment of depression (supervised exercise, home-based exercise, sertraline therapy) was associated with an improvement in CHD risk factors (improved flow-mediated dilation [p = .032], reduced progression of intima-media thickness [p = .037], and a reduction in 10-year ASCVD [p = .049]). The active treatments did not differ from each other in their effects on the CHD risk outcomes. CONCLUSIONS: Both exercise and antidepressant medication improved CHD risk factors and lowered ASCVD risk in patients with MDD. Because MDD is associated with increased risk for CHD events, treatment of depression with exercise or sertraline may reduce the risk of developing CHD in patients with MDD. TRIAL REGISTRATION: Clinical Trials Government Identifier: NCT-00331305.

Exercise as Treatment for Anxiety: Systematic Review and Analysis.

BACKGROUND: Exercise has been shown to reduce symptoms of anxiety, but few studies have studied exercise in individuals preselected because of their high anxiety. PURPOSE: The objective of this study is to review and critically evaluate studies of exercise training in adults with either high levels of anxiety or an anxiety disorder. METHODS: We conducted a systematic review of randomized clinical trials (RCTs) in which anxious adults were randomized to an exercise or nonexercise control condition. Data were extracted concerning anxiety outcomes and study design. Existing meta-analyses were also reviewed. RESULTS: Evidence from 12 RCTs suggested benefits of exercise, for select groups, similar to established treatments and greater than placebo. However, most studies had significant methodological limitations, including small sample sizes, concurrent therapies, and inadequate assessment of adherence and fitness levels. CONCLUSIONS: Exercise may be a useful treatment for anxiety, but lack of data from rigorous, methodologically sound RCTs precludes any definitive conclusions about its effectiveness.

Stress and coping in caregivers of patients awaiting solid organ transplantation.

Caregivers for patients undergoing solid organ transplantation play an essential role in the process of transplantation. However, little is known about stress and coping among these caregivers. Six hundred and twenty-one primary caregivers of potential candidates for lung (n = 317), liver (n = 147), heart (n = 115), and/or kidney (n = 42) transplantation completed a psychometric test battery at the time of the candidate's initial pre-transplant psychosocial evaluation. Caregivers were generally well adjusted, with only 17% exhibiting clinical symptoms of depression (Beck Depression Inventory-II score >13) and 13% reporting clinical levels of anxiety (State Trait Anxiety Inventory score >48). Greater caregiver burden and negative coping styles were associated with higher levels of depression. Greater objective burden and avoidant coping were associated with higher levels of anxiety. Caregivers evidenced a high degree of socially desirable (i.e., defensive) responding, which may reflect a deliberate effort to minimize fears or worries so as to not jeopardize patients' listing status.

Is Exercise a Viable Treatment for Depression?

Depression is a common disorder that is associated with compromised quality of life, increased health care costs, and greater risk for a variety of medical conditions, particularly coronary heart disease. This review examines methods for assessing depression and discusses current treatment approaches. Traditional treatments include psychotherapy and antidepressant medications, but such treatments are not effective for all patients and alternative approaches have recently received increased attention, especially the use of aerobic exercise. This review examines evidence that exercise is effective in improving depressive symptoms among patients with major depression and offers practical suggestions for helping patients initiate and maintain exercise in their daily lives.

Exercise and Escitalopram in the Treatment of Anxiety in Patients with Coronary Heart Disease: One Year Follow-Up of the UNWIND Randomized Clinical Trial.

Anxiety is common among patients with coronary heart disease (CHD) and is associated with a worse prognosis. UNWIND was a 12-week randomized clinical trial comparing exercise and escitalopram to placebo on measures of anxiety, depression, and CHD biomarkers. Primary results of the trial reported that treatment with escitalopram, but not exercise, was associated with significant reductions in anxiety and depression. At 1-year follow-up, participants completed the Hospital Anxiety-Depression Scale-Anxiety (HADS-A) along with the HADS-Depression (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Godin Leisure Time Exercise survey to assess physical activity. Results showed that those patients randomized to escitalopram had lower scores on the HADS-A compared to those randomized to exercise (P = 0.006) and had less depression compared to exercise on the HADS-D (P = 0.004) and BDI-II (P = 0.004). Participants randomized to exercise reported higher levels of physical activity at 1-year compared to those randomized to Placebo (P = 0.039). However, despite reporting being more physically active, those randomized to exercise did not have less anxiety or depression compared to placebo controls. Escitalopram appears to be a safe and effective treatment for anxiety; exercise has many health benefits, but does not appear to be effective in treating anxiety.

Coping effectively with heart failure (COPE-HF): design and rationale of a telephone-based coping skills intervention.

BACKGROUND: Coping Effectively with Heart Failure (COPE-HF) is an ongoing randomized clinical trial funded by the National Institutes of Health to evaluate if a coping skills training (CST) intervention will result in improved health status and quality of life as well as reduced mortality and hospitalizations compared with a heart failure education (HFE) intervention. METHODS AND RESULTS: Two hundred heart failure (HF) patients recruited from the Duke University Medical Center and the University of North Carolina Hospital system will be randomized to a CST intervention (16 weekly 30-minute telephone counseling sessions including motivational interviewing and individually tailored cognitive behavioral therapy) or to an HFE intervention (16 weekly 30-minute telephone sessions including education and symptom monitoring). Primary outcomes will include postintervention effects on HF biomarkers (B-type natriuretic peptide, ejection fraction) and quality of life, as well as long-term clinical outcomes (hospitalizations and death). Secondary analyses will include an evaluation of treatment effects across subpopulations, and potential mechanisms by which CST may improve clinical outcomes. CONCLUSIONS: COPE-HF is a proof-of-concept study that should provide important insights into the health benefits of a CST intervention designed to enhance HF self-management, improve health behaviors, and reduce psychologic distress.

Exercise and pharmacotherapy in patients with major depression: one-year follow-up of the SMILE study.

OBJECTIVE: To examine a 1-year follow-up of a 4-month, controlled clinical trial of exercise and antidepressant medication in patients with major depressive disorder (MDD). METHODS: In the original study, 202 sedentary adults with MDD were randomized to: a) supervised exercise; b) home-based exercise; c) sertraline; or d) placebo pill. We examined two outcomes measured at 1-year follow-up (i.e., 16 months post randomization): 1) continuous Hamilton Depression Rating Scale score; and 2) MDD status (depressed; partial remission; full remission) in 172 available participants (85% of the original cohort). Regression analyses were performed to examine the effects of treatment group assignment, as well as follow-up antidepressant medication use and self-reported exercise (Godin Leisure-Time Exercise Questionnaire), on the two outcomes. RESULTS: In the original study, patients receiving exercise achieved similar benefits compared with those receiving sertraline. At the time of the 1-year follow-up, rates of MDD remission increased from 46% at post treatment to 66% for participants available for follow-up. Neither initial treatment group assignment nor antidepressant medication use during the follow-up period were significant predictors of MDD remission at 1 year. However, regular exercise during the follow-up period predicted both Hamilton Depression Rating Scale scores and MDD diagnosis at 1 year. This relationship was curvilinear, with the association concentrated between 0 minute and 180 minutes of weekly exercise. CONCLUSION: The effects of aerobic exercise on MDD remission seem to be similar to sertraline after 4 months of treatment; exercise during the follow-up period seems to extend the short-term benefits of exercise and may augment the benefits of antidepressant use. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00331305.

Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease: The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease (UNWIND) Randomized Clinical Trial.

Importance: Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain. Objective: To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers. Design, Setting, and Participants: This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment. Interventions: Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent. Main Outcomes and Measures: The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines. Results: The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, -4.0; 95% CI, -4.7 to -3.2; escitalopram, -5.7; 95% CI, -6.4 to -5.0) compared with those randomized to placebo (-3.5; 95% CI, -4.5 to -2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (-1.67; 95% CI, -2.68 to -0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, -0.2 to 0.3; escitalopram z score = -0.24; 95% CI, -0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P = .01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P = .04). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups. Conclusions and Relevance: Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD. Trial Registration: ClinicalTrials.gov Identifier: NCT02516332.

Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials.

OBJECTIVES: To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale, randomized, controlled trials (RCTs). METHODS: We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance between January 1966 and July 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation; mean age > or =18 years of age; duration of treatment >1 month; incorporated aerobic exercise components; supervised exercise training; the presence of a nonaerobic-exercise control group; and sufficient information to derive effect size data. RESULTS: Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = 0.158; 95% confidence interval [CI]; 0.055-0.260; p = .003), executive function (g = 0.123; 95% CI, 0.021-0.225; p = .018), and memory (g = 0.128; 95% CI, 0.015-0.241; p = .026). CONCLUSIONS: Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods.

Cerebrovascular risk factors and cerebral hyperintensities among middle-aged and older adults with major depression.

OBJECTIVES: To examine the association between cerebral hyperintensities and cerebrovascular risk factors (CVRF) among middle-aged and older adults with major depressive disorder (MDD). METHODS: Thirty patients (aged 55-77 years) with MDD and no history of stroke participated in a magnetic resonance imaging assessment to assess for the presence of cerebral hyperintensities and underwent a physical examination to assess stroke risk as indexed by the Framingham Stroke Risk Profile (FSRP). In addition, intima medial thickness (IMT) was measured in the left and right carotid arteries. RESULTS: Higher FSRP levels were associated with total greater cerebral hyperintensities (r = 0.64), as well as greater subependymal hyperintensities (r = 0.47), confluent periventricular changes (r = 0.46), and tended to be associated with subcortical gray matter hyperintensities (r = 0.34). A quadratic relationship was observed between IMT and total cerebral hyperintensities (b = 4.84), and higher IMT levels were associated with greater subependymal hyperintensities (r = 0.40). CONCLUSIONS: Higher levels of CVRF are associated with graded increases in cerebral hyperintensities among middle-aged and older adults with MDD.

The modifying effects of social support on psychological outcomes in patients with heart failure.

OBJECTIVE: We examined the modifying effects of social support on depressive symptoms and health-related quality of life (QoL) in patients receiving coping skills training (CST). METHOD: We considered the modifying effects of social support in the Coping Effectively with Heart Failure clinical trial, which randomized 179 heart failure (HF) patients to either 4 months of CST or usual care enhanced by HF education (HFE). CST involved training in specific coping techniques, whereas HFE involved education about HF self-management. Social support was assessed by the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Social Support Inventory, QoL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), and depression was assessed with the Beck Depression Inventory-II (BDI-II). RESULTS: Linear regression models revealed a significant Intervention Group × Baseline Social Support interaction for change in KCCQ total scores (p = .006) and BDI-II scores (p < .001). Participants with low social support assigned to the CST intervention showed large improvements in KCCQ scores (M = 11.2, 95% CI [5.7, 16.8]), whereas low-social-support patients assigned to the HFE controls showed no significant change (M = -0.8, 95% CI [-7.2, 5.6]). Similarly, BDI-II scores in participants with low social support in the CST group showed large reductions (M = -8.7, 95% CI [-11.3, -6.1]) compared with low-social-support HFE participants (M = -3.0, 95% CI [-6.0, -0.1]). CONCLUSIONS: HF patients with low social support benefit substantially from telephone-based CST interventions. Targeting HF patients with low social support for behavioral interventions could prove to be a cost-effective strategy for improving QoL and reducing depression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Exercise fails to improve neurocognition in depressed middle-aged and older adults.

PURPOSE: Although cross-sectional studies have demonstrated an association between higher levels of aerobic fitness and improved neurocognitive function, there have been relatively few interventional studies investigating this relationship, and results have been inconsistent. We assessed the effects of aerobic exercise on neurocognitive function in a randomized controlled trial of patients with major depressive disorder (MDD). METHODS: Two-hundred and two sedentary men (n = 49) and women (n = 153), aged 40 yr and over and who met diagnostic criteria for MDD, were randomly assigned to the following: a) supervised exercise, b) home-based exercise, c) sertraline, or d) placebo pill. Before and after 4 months of treatment, participants completed measures of: Executive Function (Trail Making Test B-A difference score, Stroop Color-Word, Ruff 2 & 7 Test, Digit Symbol), Verbal Memory (Logical Memory, Verbal Paired Associates), and Verbal Fluency/Working Memory (Animal Naming, Controlled Oral Word Association Test, Digit Span). Multivariate analyses of covariance were performed to test the effects of treatment on posttreatment neuropsychological test scores, with baseline neuropsychological test scores, age, education, and change in depression scores entered as covariates. RESULTS: The performance of exercise participants was no better than participants receiving placebo across all neuropsychological tests. Exercise participants performed better than participants receiving sertraline on tests of executive function but not on tests of verbal memory or verbal fluency/working memory. CONCLUSIONS: We found little evidence to support the benefits of an aerobic exercise intervention on neurocognitive performance in patients with MDD.

Coping and quality of life in patients awaiting lung transplantation.

OBJECTIVE: Patients with end-stage lung disease (ESLD) experience significant decrements in quality of life (QOL). Although coping strategies are related to QOL in patients with ESLD, the extent to which specific native lung disease moderates this relationship is unknown. METHODS: We investigated the relationship between coping, native lung disease, and QOL among 187 patients awaiting lung transplantation, including 139 patients with chronic obstructive pulmonary disease (COPD) and 48 with cystic fibrosis (CF). Participants completed a psychosocial battery assessing psychological QOL, physical QOL, and coping strategies. RESULTS: For both COPD and CF patients, higher levels of Active Coping (P< .0001) and lower levels of Disengagement (P< .0001) were associated with better psychological QOL. For physical QOL, we observed a Native Disease x Coping interaction (P=.01) such that Active Coping was associated with better physical QOL in patients with COPD but not in patients with CF. CONCLUSIONS: The relationship between coping and QOL may vary as a function of native lung disease. Patients' native disease may need to be considered in order to develop effective interventions to help patients cope successfully with ESLD.

Cerebrovascular risk factors, vascular disease, and neuropsychological outcomes in adults with major depression.

OBJECTIVE: To investigate the relationship of cerebrovascular risk factors (CVRFs), endothelial function, carotid artery intima medial thickness (IMT), and neuropsychological performance in a sample of 198 middle-aged and older individuals with major depressive disorder (MDD). Neuropsychological deficits are common among adults with MDD, particularly among those with CVRFs and potentially persons with subclinical vascular disease. METHODS: CVRFs were indexed by the Framingham Stroke Risk Profile (FSRP) and serum cholesterol levels obtained by medical history and physical examination. Patients completed a neuropsychological test battery including measures of executive functioning, working memory, and verbal recall. Vascular function was indexed by carotid artery IMT and brachial artery flow mediated dilation (FMD). Hierarchical multiple regression analyses were used to investigate the association between CVRFs, vascular disease, and neurocognitive performance. RESULTS: Greater FSRP scores were associated with poorer executive functioning (b = -0.86; p = .041) and working memory (b = -0.90; p = .024). Lower high-density lipoprotein levels also were associated with poorer executive functioning (b = 1.03; p = .035). Higher IMT (b = -0.83; p = .028) and lower FMD (b = 1.29; p = .032) were associated with poorer executive functioning after controlling for CVRFs. Lower FMD was also associated with poorer working memory (b = 1.58; p = .015). CONCLUSIONS: Greater CVRFs were associated with poorer neuropsychological performance. Vascular dysfunction also was associated with neuropsychological decrements independent of traditional CVRFs.

Exercise and pharmacotherapy in the treatment of major depressive disorder.

OBJECTIVE: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. METHODS: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50-200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). RESULTS: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). CONCLUSIONS: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors.