Effects of Exercise Training on Older Patients With Major Depression

Background: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. Objective: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. Methods: One hundred fifty-six men and women with MDD (age, ≥50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. Results: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. Conclusions: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD

Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial

BACKGROUND: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient’s treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition. METHODS/DESIGN: Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30–60 mg/d); or (3) escitalopram (10–20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes. DISCUSSION: The PReDICT study’s evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007

Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders

Background: Substantial research progress can be achieved if available clinical datasets can be mapped to the National Institute of Mental Health Research-Domain-Criteria (RDoC) constructs. This mapping would allow investigators to both explore more narrowly defined clinical phenotypes and the relationship of these phenotypes to biological markers and clinical outcomes approximating RDoC criteria.Methods: Using expert review and consensus, we defined four major depression phenotypes based on specific RDoC constructs. Having matched these constructs to individual items from the Hamilton Depression Rating Scale and Quick Inventory of Depressive Symptomatology, we identified subjects meeting criteria for each of these phenotypes from two large clinical trials of patients treated for major depression. In a post hoc analysis, we evaluated the overall treatment response based on the phenotypes: Core Depression (CD), Anxiety (ANX), and Neurovegetative Symptoms of Melancholia (NVSM) and Atypical Depression (NVSAD).Results: The phenotypes were prevalent (range 10.5-52.4%, 50% reduction range 51.9-82.9%) and tracked with overall treatment response. Although the CD phenotype was associated with lower rates of remission in both cohorts, this was mainly driven by baseline symptom severity. However, when controlling for baseline severity, patients with the ANX phenotype had a significantly lower rate of remission.Limitations: The lack of replication between the studies of the phenotypes' treatment prediction value reflects important variability across studies that may limit generalizability.Conclusion: Further work evaluating biological markers associated with these phenotypes is needed for further RDoC concept development

Visioning the Future: Scenarios Modeling of the Florida Coastal Everglades

In this paper, we provide screening-level analysis of plausible Everglades ecosystem response by 2060 to sea level rise (0.50 m) interacting with macroclimate change (1.5 °C warming, 7% increase in evapotranspiration, and rainfall that either increases or decreases by 10%). We used these climate scenarios as input to the Ecological Landscape Model to simulate changes to seven interactive hydro-ecological metrics. Mangrove forest and other marine influences migrated up to 15 km inland in both scenarios, delineated by the saltwater front. Freshwater habitat area decreased by 25–30% under our two climate change scenarios and was largely replaced by mangroves and, in the increased rainfall scenario, open water as well. Significant mangroves drowned along northern Florida Bay in both climate change scenarios due to sea level rise. Increased rainfall of 10% provided significant benefits to the spatial and temporal salinity regime within the marine-influenced zone, providing a more gradual and natural adjustment for at-risk flora and fauna. However, increased rainfall also increased the risk of open water, due to water depths that inhibited mangrove establishment and reduced peat accumulation rates. We infer that ecological effects related to sea level rise may occur in the extreme front-edge of saltwater intrusion, that topography will control the incursion of this zone as sea level rises, and that differences in freshwater availability will have ecologically significant effects on ecosystem resilience through the temporal and spatial pattern of salinity changes