Physical exercise training as preceding treatment to cognitive behavioral therapy in mild to moderate major depressive disorder: A randomized controlled trial.

BACKGROUND: Many patients with major depressive disorder (MDD) remain untreated or do not respond to cognitive behavioral therapy (CBT). Physical exercise shows antidepressive effects and may serve as an effective augmentation treatment. However, research on combining exercise with CBT is sparse in MDD and underlying mechanisms of exercise are not well understood to date. METHODS: 120 outpatients with MDD were randomized to either a high intensity exercise group (HEX), a low intensity exercise group (LEX), or a waiting list control group (WL). After 12 weeks of exercise training or waiting period, all patients received a manualized CBT. RESULTS: Seventy-five patients with MDD completed both the exercise program/ waiting period and the CBT. While physical fitness improved in HEX after the exercise program, it did not change in LEX and WL. Depressive symptoms improved in all three groups from baseline to post-CBT and the group by time interaction was not significant. Regression analyses revealed that the amount of fitness improvement during exercise predicted the subsequent CBT response. LIMITATIONS: The dropout rate was relatively high, preparatory CBT sessions during exercise / waiting period may have influenced depressive symptoms, and no patients with severe MDD were included. CONCLUSIONS: High intense physical exercise did not lead to a general enhancement of CBT outcome, but higher increases in physical fitness seem to improve symptom change during CBT. Our results suggest that the implementation of more individually tailored exercise programs could be a promising approach for future research and clinical practice.

Serum brain-derived neurotrophic factor (BDNF) at rest and after acute aerobic exercise in major depressive disorder.

Physiological mechanisms of an anti-depressive effect of physical exercise in major depressive disorder (MDD) seem to involve alterations in brain-derived neurotrophic factor (BDNF) level. However, previous studies which investigated this effect in a single bout of exercise, did not control for confounding peripheral factors that contribute to BDNF-alterations. Therefore, the underlying cause of exercise-induced BDNF-changes remains unclear. The current study aims to investigate serum BDNF (sBDNF)-changes due to a single-bout of graded aerobic exercise in a group of 30 outpatients with MDD, suggesting a more precise analysis method by taking plasma volume shift and number of platelets into account. Results show that exercise-induced increases in sBDNF remain significant (p < .001) when adjusting for plasma volume shift and controlling for number of platelets. The interaction of sBDNF change and number of platelets was also significant (p = .001) indicating larger sBDNF-increase in participants with smaller number of platelets. Thus, findings of this study suggest an involvement of peripheral as well as additional - possibly brain-derived - mechanisms explaining exercise-related BDNF release in MDD. For future studies in the field of exercise-related BDNF research, the importance of controlling for peripheral parameters is emphasized.

Neurobiological mechanisms of exercise and psychotherapy in depression: The SPeED study-Rationale, design, and methodological issues.

BACKGROUND/AIMS: Even though cognitive behavioral therapy has become a relatively effective treatment for major depressive disorder and cognitive behavioral therapy-related changes of dysfunctional neural activations were shown in recent studies, remission rates still remain at an insufficient level. Therefore, the implementation of effective augmentation strategies is needed. In recent meta-analyses, exercise therapy (especially endurance exercise) was reported to be an effective intervention in major depressive disorder. Despite these findings, underlying mechanisms of the antidepressant effect of exercise especially in combination with cognitive behavioral therapy have rarely been studied to date and an investigation of its neural underpinnings is lacking. A better understanding of the psychological and neural mechanisms of exercise and cognitive behavioral therapy would be important for developing optimal treatment strategies in depression. The SPeED study (Sport/Exercise Therapy and Psychotherapy-evaluating treatment Effects in Depressive patients) is a randomized controlled trial to investigate underlying physiological, neurobiological, and psychological mechanisms of the augmentation of cognitive behavioral therapy with endurance exercise. It is investigated if a preceding endurance exercise program will enhance the effect of a subsequent cognitive behavioral therapy. METHODS: This study will include 105 patients diagnosed with a mild or moderate depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). The participants are randomized into one of three groups: a high-intensive or a low-intensive endurance exercise group or a waiting list control group. After the exercise program/waiting period, all patients receive an outpatient cognitive behavioral therapy treatment according to a standardized therapy manual. At four measurement points, major depressive disorder symptoms (Beck Depression Inventory, Hamilton Rating Scale for Depression), (neuro)biological measures (neural activations during working memory, monetary incentive delay task, and emotion regulation, as well as cortisol levels and brain-derived neurotrophic factor), neuropsychological test performance, and questionnaires (psychological needs, self-efficacy, and quality of life) are assessed. RESULTS: In this article, we report the design of the SPeED study and refer to important methodological issues such as including both high- and low-intensity endurance exercise groups to allow the investigation of dose-response effects and physiological components of the therapy effects. CONCLUSION: The main aims of this research project are to study effects of endurance exercise and cognitive behavioral therapy on depressive symptoms and to investigate underlying physiological and neurobiological mechanisms of these effects. Results may provide important implications for the development of effective treatment strategies in major depressive disorder, specifically concerning the augmentation of cognitive behavioral therapy by endurance exercise.