Cardiorespiratory fitness and response to exercise treatment in depression.
ABSTRACT: Background:Exercise improves cardiorespiratory fitness (CRF) and reduces depressive symptoms in people with depression. It is unclear if changes in CRF are a predictor of the antidepressant effect of exercise in people with depression. Aims:To investigate whether an increase in CRF is a predictor of depression severity reduction after 12 weeks of exercise (trial registration: DRKS study ID, DRKS00008745). Method:The present study includes participants who took part in vigorous (n = 33), moderate (n = 38) and light (n = 39) intensity exercise and had CRF information (as predicted maximal oxygen uptake, V?O2max) collected before and after the intervention. Depression severity was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). V?O2max (L/min) was assessed with the Åstrand-Rhyming submaximal cycle ergometry test. The main analysis was conducted pooling all exercise intensity groups together. Results:All exercise intensities improved V?O2max in people with depression. Regardless of frequency and intensity of exercise, an increase in post-treatment V?O2max was significantly associated with reduced depression severity at follow-up (B = -3.52, 95% CI -6.08 to -0.96); adjusting for intensity of exercise, age and body mass index made the association stronger (B = -3.89, 95% CI -6.53 to -1.26). Similarly, increased V?O2max was associated with higher odds (odds ratio = 3.73, 95% CI 1.22-11.43) of exercise treatment response (?50% reduction in MADRS score) at follow-up. Conclusions:Our data suggest that improvements in V?O2max predict a greater reduction in depression severity among individuals who were clinically depressed. This finding indicates that improvements in V?O2max may be a marker for the underpinning biological pathways for the antidepressant effect of exercise. Declaration of interest:None.
Project description:The aim of this study is to evaluate the effect of a high-intensity functional exercise program on depressive symptoms among older care facility residents with dementia.Residents (n?=?186) with a diagnosis of dementia, age???65?years, Mini-Mental State Examination score???10, and dependence in activities of daily living were included. Participants were randomized to a high-intensity functional exercise program or a non-exercise control activity conducted 45?min every other weekday for 4?months. The 15-item Geriatric Depression Scale (GDS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were administered by blinded assessors at baseline, 4, and 7?months.No difference between the exercise and control activity was found in GDS or MADRS score at 4 or 7?months. Among participants with GDS scores???5, reductions in GDS score were observed in the exercise and control groups at 4?months (-1.58, P?=?0.001 and -1.54, P?=?0.004) and 7?months (-1.25, P?=?0.01 and -1.45, P?=?0.007). Among participants with MADRS scores???7, a reduction in MADRS score was observed at 4?months in the control group (-2.80, P?=?0.009) and at 7?months in the exercise and control groups (-3.17, P?=?0.003 and -3.34, P?=?0.002).A 4-month high-intensity functional exercise program has no superior effect on depressive symptoms relative to a control activity among older people with dementia living in residential care facilities. Exercise and non-exercise group activities may reduce high levels of depressive symptoms.
Project description:In order to assess the effect of gray matter volumes and cortical thickness on antidepressant treatment response in late-life depression, the authors examined the relationship between brain regions identified a priori and Montgomery-Åsberg Depression Rating Scale (MADRS) scores over the course of an antidepressant treatment trial.In a nonrandomized prospective trial, 168 patients who were at least 60 years of age and met DSM-IV criteria for major depression underwent MRI and were enrolled in a 12-week treatment study. Exclusion criteria included cognitive impairment or severe medical disorders. The volumes or cortical thicknesses of regions of interest that differed between the depressed group and a comparison group (N=50) were determined. These regions of interest were used in analyses of the depressed group to predict antidepressant treatment outcome. Mixed-model analyses adjusting for age, education, age at depression onset, race, baseline MADRS score, scanner, and interaction with time examined predictors of MADRS scores over time.Smaller hippocampal volumes predicted a slower response to treatment. With the inclusion of white matter hyper-intensity severity and neuropsychological factor scores, the best model included hippocampal volume and cognitive processing speed to predict rate of response over time. A secondary analysis showed that hippocampal volume and frontal pole thickness differed between patients who achieved remission and those who did not.These data expand our understanding of the prediction of treatment course in late-life depression. The authors propose that the primary variables of hippocampal volume and cognitive processing speed, subsuming other contributing variables (episodic memory, executive function, language processing) predict antidepressant response.
Project description:Background:Adjuvant therapy may cause multiple sideeffects on long term health, including reduced cardiorespiratory fitness (CRF) in patients with breast cancer (1, 2). However, there is currently limited knowledge regarding the effect of different types of adjuvant cancer treatment on CRF in other cancer populations. The primary objective of the present study was to assess whether previously known correlates (age, diagnosis, initial CRF, physical activity level), type of adjuvant treatment and cancer-related fatigue were associated with changes in V?O2max in patients with breast, prostate or colorectal cancer. Methods:Prospective study with two time points of assessment, 85 patients scheduled for adjuvant cancer treatment were included. Cardiorespiratory fitness was assessed by V?O2max during a maximal incremental exercise test on a treadmill before start of adjuvant therapy and again six months later. Physical activity level was recorded with a physical activity monitor (Sense Wear™ Mini) at baseline as average minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Physical fatigue at baseline was reported using the Multidimensional Fatigue Inventory-20 questionaire. Results:In multivariate linear regression analysis, 30?min higher daily MVPA at baseline was associated with a 5% higher V?O2max at six months follow up when adjusted for adjuvant treatment (P?=?0.010). Patients receiving adjuvant chemotherapy had a mean decline in V?O2max of 10% (-?19, -?1; 95% confidence interval) compared to patients receiving adjuvant endocrine treatment (P?=?0.028). Adjuvant radiotherapy, fatigue, age and diagnosis were not significantly associated with changes in V?O2max . Conclusion:The results of the present study indicate that adjuvant chemotherapy is associated with a subsequent reduction in V?O2max in patients with cancer whereas MVPA before start of adjuvant treatment is positively associated with a higher V?O2max after end of adjuvant treatment.
Project description:Exercise can relieve both depressive and anxiety disorders and it is therefore of importance to establish movement patterns of mildly to moderately affected sufferers to estimate the treatment potential. The aim is to describe the physical activity patterns of people affected by mild to moderate depressive and/or anxiety symptoms using objective measures of physical activity.The design of the study was cross-sectional using data from 165 people aged 18-65 years, with mild to moderate depressive and/or anxiety disorder symptoms (scoring ≥ 10 on the PHQ-9). Diagnoses were made using Mini International Neuropsychiatric Interview (MINI) and symptom severity was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). The participants wore accelerometers for a week to evaluate physical activity patterns.No statistically significant differences were detected between different diagnoses, though depressed participants tended to be less active and more sedentary. Only one-fifth of the sample followed public health guidelines regarding physical activity. Each one point increase in MADRS was associated with a 2.4 minute reduction in light physical activity, independent of moderate-to-vigorous physical activity and sedentary time. MADRS was positively associated with number of sedentary bouts.The physical activity pattern of people with depressive and/or anxiety disorders was characterized by large amounts of sedentary time and low fulfillment of physical activity guidelines. There is therefore a large treatment potential for this group by increasing exercise. The results suggest that instead of focusing exclusively on high intensity exercise for treating depressive and anxiety disorders, health care providers might encourage patients to reduce sedentary time by increasing light physical activity and decreasing the number of sedentary bouts, though further studies are needed that can determine directionality.
Project description:Obesity in adolescence increases the risk for early adult cardiovascular disease. We recently showed that 6 months of diet, exercise, and metformin resulted in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity. The purpose of the present study was to determine whether changes in cardiorespiratory fitness (CRF) after 6 months of structured diet and exercise (DE) or DE plus metformin are related to the previously observed changes in adiposity, markers of inflammation, and intrahepatic fat.Sixteen obese pubertal adolescents between the ages of 10 and 17 were randomized into a structured lifestyle program consisting of DE or DE plus metformin. Subjects performed aerobic and resistance exercise 3 d·wk?¹, 30 min per session. Cycle ergometer maximal oxygen consumption (V?O2max), body composition, blood markers (glucose, insulin, homeostatic model assessment-insulin resistance, interleukin-6, hsCRP), and intrahepatic fat were measured at baseline and 6 months.In the cohort, as whole-body weight decreased by 4.0% (P = 0.009), body mass index decreased by 4.9% (P = 0.003), percent body fat decreased by 8.8% (P < 0.001), and V?O2max improved in 10 of 16 subjects. The addition of metformin provided no further effect on body composition, CRF, or inflammatory factors. More favorable changes in adiposity, adiponectin, and a trend toward blood glucose and interleukin-6 concentrations (P = 0.07) were observed in subjects who increased V?O2max at 6 months (n = 10) compared with no change in these variables in those who did not improve V?O2max.Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents. Improvements in V?O2max seem to be associated with more favorable metabolic outcomes.
Project description:Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Åsberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus (r = 0.66; p = 0.01), but not the right hippocampus (r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high (r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom (df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants.
Project description:Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
Project description:Metabolic syndrome (MetS) is the co-occurrence of obesity and metabolic derangements. Prior research implicates MetS in prolongation of the course of depression in older adults, but its effect on antidepressant response is unknown in this population. The objective was to determine whether MetS and related metabolic dyscrasias are associated with decreased rate of remission from depression in older adults treated pharmacologically for depression.Secondary analysis of a randomized controlled trial.Three academic medical centers in North America.Adults aged 60 and older (mean age 69.1) with major depressive disorder (MDD) (N = 435).Open-label, protocolized treatment with extended-release venlafaxine for 12 or more weeks.Time to remission from depression, with remission defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 10 or less at last two visits.Two hundred twenty-two participants (51%) met criteria for MetS at baseline; MetS was associated with greater severity (MADRS score) and chronicity of depression at baseline. Remission was achieved in 182 participants (42%). In the unadjusted analysis, MetS was associated with prolonged time to remission (hazard ratio for remission = 0.71, 95% confidence interval = 0.52-0.95), but this relationship was not significant in the adjusted model; greater number of MetS components and lower high-density lipoprotein cholesterol had similar effects. Only diastolic blood pressure (DBP) was a significant predictor of time to remission before and after adjustment, with higher DBP predicting longer time to remission. Insulin sensitivity did not predict time to remission.The presence of MetS in older adults with depression was associated with greater symptom severity and chronicity of depression, which appears to have accounted for the poorer antidepressant response observed in those with MetS. Additionally, our preliminary finding of an association between higher DBP and poorer antidepressant response bears further examination and replication.
Project description:Patients with major depressive disorder (MDD) have an augmented risk of cardiovascular morbidity and mortality. Although a link between depression and autonomic dysfunction as well as reduced cardio-respiratory fitness (CRF) is well documented, the underlying cause is a matter of debate. Therefore, we studied the interplay between autonomic function, body composition and severity of the disease to disentangle possible physiological factors influencing the assumed lack of CRF in MDD patients. We investigated seventeen patients suffering from MDD and seventeen control subjects matched with respect to age, sex, body-mass-index, and smoking habits. A resting baseline assessment and a cardiopulmonary exercise test including a prolonged recovery period were performed to study autonomic function (i.e., heart rate responses and heart rate variability) during rest, exercise and recovery as well as CRF. Most investigated autonomic indices were significantly different at rest, during exercise as well as during recovery indicating altered autonomic modulation. Nevertheless, none of our participants was classified as chronotropically incompetent. As expected, a reduced CRF (i.e., peak oxygen uptake and peak power output, p < 0.01) was observed in patients compared to controls. In addition, a correlation of baseline heart rate and of heart rate during recovery with the ventilatory threshold 1 (p < 0.05) was found in patients only, indicating a relation to the lack of CRF. Furthermore, we observed a positive correlation of the severity of the disease with the weekly sitting time (p < 0.01) as well as a negative correlation with the activity time in the intensity domain walking (p < 0.001) and with the total score of the International Physical Activity Questionnaire (p < 0.01) for patients. This study shows that patients with MDD have altered autonomic function not only during resting conditions but also during exercise as well as recovery from exercise. Intervention studies are needed to evaluate how the described autonomic alterations can be influenced by increasing CRF due to appropriate exercise training programs.
Project description:Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53?±?8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA?+?SFC (ALA?+?SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac-]p), oxygen consumption rate ([Formula: see text]), and carbon dioxide production rate ([Formula: see text]) were measured with depression severity by the Montgomery-Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac-]p, [Formula: see text] and [Formula: see text] during the test were attenuated only in ALA?+?SFC ([before vs. after] × workload; all, P?<?0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P?<?0.05) with decreased MADRS-score (P?=?0.001). Thus, ALA?+?SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.