Efficacy of Adjunctive Exercise for the Behavioral Treatment of Major Depression

描述(由申请人提供)：严重抑郁障碍(MDD)是发达国家导致残疾的主要原因[85]，并与生产力下降、增加 卫生保健利用率和死亡率[86]。有几种经验支持的治疗方法，如抗抑郁药物和认知行为疗法，用于治疗MDD；然而，研究表明，多达34%的人对这些治疗没有反应[5]。此外，大规模的STAR-D试验显示，对于对初始干预无效的患者，联合或连续使用抗抑郁药物和CBT的疗效有限[7]，并呼吁开发替代疗法[8]。在过去的研究中，运动干预代表了一种与强烈效果大小相关的替代策略。例如，一项关于运动计划与非运动条件治疗MDD的荟萃分析回顾发现，总体组间效应大小表明运动干预在改善情绪方面具有显著优势[10]。此外，运动已被证明可以增强认知功能，特别是注意力和记忆力[40，41]。这种增强，以及锻炼对情绪的好处，可能是由于脑源性神经营养因子(BDNF)的增加。由于抑郁症与低水平的脑源性神经营养因子有关，而抗抑郁药物似乎增加了脑源性神经营养因子，因此脑源性神经营养因子可能是运动发挥作用的一个中介[32，33]。当前的应用程序旨在调查 有氧运动与行为激活联合治疗对MDD的影响综合运动疗法已被证明对治疗焦虑症是有效的[21]，但与经验支持的BA抑郁症治疗相结合的模式还有待研究。BA提供了一种与运动相结合的有前景的形式，因为它侧重于适应性动作和活动安排[24]。目前的研究将招募32名MDD患者参加总共9个疗程(BA+运动(BA+EX)或BA+伸展控制条件(BA+CNTL)的9个疗程(BA 60分钟、EX或CNTL 30分钟)的积极治疗阶段。将收集有关身体健康、注意力、记忆力和脑源性神经营养因子水平的数据。此外，关于抑郁情绪和功能水平的自我报告和临床医生评级项目将在每周会议上进行评估。数据分析将主要调查联合干预的可行性和可接受性，并提供治疗效果的初步估计。我们还将检查辅助运动干预的神经心理学(即记忆和注意力)和神经生理学(即BDNF)的相关性，作为未来机制研究的前奏。本申请的最终目标是培养申请者在临床试验研究中的技能，重点是锻炼对情绪的干预 精神错乱。除了相关的课程、培训和指导，这项拟议的研究研究将有助于申请人成为这一专业领域的有知识的研究人员的目标，并计划未来扩大对有需要的少数族裔个人的干预

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is the leading cause of disability in the developed world [85] and is associated with lost productivity, increased health care utilization, and mortality [86]. Several empirically supported treatments, such as antidepressant medication and cognitive behavioral therapy, exist for the treatment of MDD; however, studies have shown that as many as 34% of individuals do not respond to these treatments [5]. Moreover, the large-scale STAR-D trial has shown limited efficacy for combined or sequential treatment with antidepressants and CBT for patients failing to respond to initial interventions [7], with calls for the development of alternative treatments [8]. Exercise interventions represent an alternative strategy associated with strong effect sizes in past studies. For example, a meta-analytic review of exercise programs as compared to non-active conditions for the treatment of MDD found a large overall between-group effect size indicating a significant advantage of exercise interventions for mood benefits [10]. Additionally, exercise has been shown to enhance cognitive functioning, especially attention and memory [40, 41]. This enhancement, as well as the mood benefits derived from exercise, may be due to increases in brain-derived neurotrophic factor (BDNF). Since depression is associated with low levels of BDNF, and antidepressant medication appears to increase BDNF, BDNF may be a mediator through which exercise exerts its effects [32, 33]. The current application aims to investigate the effect of a combined aerobic exercise and behavioral activation treatment (BA) for MDD. Combined exercise treatments have been shown to be efficacious for the treatment of anxiety [21], but a combined model with the empirically-supported depression treatment of BA has yet to be investigated. BA provides a promising format for combination with exercise due to its focus on adaptive action and activity scheduling [24]. The current study will recruit 32 MDD patients for an active treatment phase of 9 total sessions (60 minutes of BA, 30 minutes of EX or CNTL) of either BA plus exercise (BA+EX) or BA plus a stretching control condition (BA+CNTL). Data regarding physical fitness, attention, memory, and BDNF levels will be collected. Additionally, self-report and clinician-rated items regarding depressed mood and level of functioning will be assessed at each weekly session. Data analysis will primarily investigate the feasibility and acceptability of the combined intervention as well as provide preliminary estimates of the efficacy of the treatment. We will also examine the neuropsychological (i.e., memory and attention) and neurophysiological (i.e., BDNF) correlates of the adjunctive exercise intervention as a prelude to future studies of mechanism. The ultimate goal of this application is to develop the applicant's skills in clinical trials research, with a focus on exercise interventions for mood disorders. This proposed research study in addition to relevant coursework, training, and mentorship will aid in the applicant's goal of becoming a knowledgeable researcher in this area of expertise, with plans for future expansion of this intervention for minority individuals in need