The Mechanisms Underlying the Antidepressant Effects of Physical Activity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Patient Health Questionnaire-9 score
研究概览
简要总结
It is well established that any level of physical activity can help prevent and treat depression, with more strenuous activity having a greater effect. Understanding the mechanisms driving this antidepressant effect is important because it could allow exercise programmes to be made more effective, accessible, and targeted. Such knowledge could contribute to social prescribing, increasingly a priority for mental healthcare. Importantly, physical activity is highly scalable, low cost, well suited to early intervention, and has beneficial impacts on physical health co-morbidities. This trial may provide initial indications of whether there are sub-groups of depressed individuals who are particularly likely to benefit from physical activity, lead to strategies to personalise physical activity prescription based on motivational factors, and pave the way for augmentative approaches, for example combining physical activity with psychological interventions.
To date the mechanisms driving the antidepressant effects of physical activity in humans are poorly understood. Building on links between depressive symptoms, reward processing and dopamine, plus evidence from animal studies that physical activity is anti-inflammatory and boosts both dopamine and reward processing, the overarching aim of this trial is to understand the mechanisms underlying the effects of physical activity in depression, focusing on the concept of motivation.
The key objective is to conduct a randomised controlled trial (RCT) in N=250 depressed participants comparing aerobic exercise to a stretching/relaxation control condition, examining a range of mechanistic factors. The proposed trial will examine the impact of physical activity at multiple, linked potential levels of explanation: (1) immune-metabolic markers; (2) dopamine synthesis capacity; (3) activation in the brain's reward and effort processing circuitry;(4) effort-based decision making incorporating computational analysis; and (5) symptom networks based on fine-grained, daily measurements.
详细描述
The primary objective is to conduct a randomised controlled trial (RCT) in N=250 depressed participants comparing aerobic exercise to a stretching/relaxation control condition, examining effects on a range of potential clinical and mechanistic factors: depressive symptoms; immune-metabolic function; activation in the brain's reward and effort processing circuitry using functional magnetic resonance imaging (fMRI); cognitive tasks, focusing on reward processing; and a subset (approximately one-third) of participants will complete L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA) positron emission tomography (PET).
The secondary objectives are to assess: (1) the degree to which changes in the mechanistic factors are related to changes in interest-activity symptoms of depression resulting from aerobic exercise; (2) whether baseline mechanistic or clinical factors are associated with symptomatic improvement measured by symptom questionnaires following the exercise intervention; (3) whether aerobic exercise-induced changes in the brain circuits underlying cognitive control overlap with those implicated in motivation.
The trial will use an RCT design, with depressed participants randomised to eight weeks of either 45 minutes aerobic exercise of moderate-to-vigorous intensity activity (experimental group: three times per week, N=125) or 45 minutes of non-aerobic stretching/guided relaxation (control group: three times per week, N=125). The target sample size following expected attrition is N~105 per arm. Participants will complete the trial in staggered cohorts, with no more than six participants per class.
Blood and saliva samples will be taken before the intervention at baseline (between weeks -1 and 0), mid-intervention (week 3 and week 4), and post-intervention (week 9 to week 14) visits, to assess changes in immune-metabolic markers. Blood and saliva samples will also be collected at baseline and post-intervention from approximately 30 healthy controls.
Functional neuroimaging during effort-based decision-making and cognitive control will be taken at baseline and post-intervention. The same functional neuroimaging measures will also be collected at baseline and post-intervention from approximately 30 healthy controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
The control arm is stretching and relaxation. Prior research indicates that participants have similar efficacy expectations regarding mild stretching and aerobic exercise, which will help to improve masking. Due to the nature of the interventions, it is not possible for the participants to be masked as to the intervention they are undergoing, but all study information will be agnostic about which intervention we expect to be more effective, and all analysis will be performed by blinded staff. The trial will assess expectations and preferences about the intervention conditions, allowing for sensitivity analyses.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •will include:
- •PHQ9≥12 (moderate depression).
- •Current physical activity level below 30 min moderate physical activity, once per week.
- •Fluency in English.
- •Willingness to undergo the interventions.
- •Willing and able to provide written informed consent.
排除标准
- •will include:
- •Medical contraindications to either intervention.
- •Neurological illness.
- •Past or current diagnosis of psychosis, bipolar disorder, or substance/alcohol use disorder, unless restricted to a depressive episode.
- •Unable to complete self-administered cognitive or questionnaire assessments.
- •Symptoms or cognitive impairment that would limit capacity to consent.
- •Regular use of anti-inflammatory medication (more than once per week).
研究组 & 干预措施
Aerobic exercise
Participants will be randomised to eight weeks of 45 min aerobic exercise of moderate-to-vigorous activity (experimental group: three times per week, N=125).
干预措施: Aerobic exercise (Other)
Stretching and relaxation
Participants will be randomised to eight weeks of 45 min aerobic exercise of stretching and relaxation (control group: three times per week, N=125).
干预措施: Stretching and relaxation (Other)
结局指标
主要结局
Patient Health Questionnaire-9 score
时间窗: Post-intervention (week 9 to week 14)
Depression symptoms will be measured using the Patient Health Questionnaire-9 (PHQ-9). Minimum score is 0, maximum score is 27. Higher scores mean a worse outcome.
次要结局
- Physical activity(Baseline assessment period (between weeks -1 and 0) to post-intervention (week 9 to week 14), and follow-up (weeks 21 and 33))
- Aerobic capacity: CPET(Baseline (between weeks -1 and 0) and post-intervention (week 9 to week 14))
- Ecological Momentary Assessment(Baseline assessment period (between weeks -1 and 0) to post-intervention (week 9 to week 14))
- Inflammatory response (cytokines)(Baseline (between weeks -1 and 0), mid-intervention (week 3 or week 4), and post-intervention (week 9 to week 14))
- Inflammatory response (genetic markers)(Baseline (between weeks -1 and 0), mid-intervention (week 3 or week 4), and post-intervention (week 9 to week 14))
- Inflammatory response (flow cytometry immunophenotype)(Baseline (between weeks -1 and 0), mid-intervention (week 3 or week 4), and post-intervention (week 9 to week 14))
- Neuroendocrine system(Baseline (between weeks -1 and 0), mid-intervention (week 3 or week 4), and post-intervention (week 9 to week 14))
- Metabolic function(Baseline (between weeks -1 and 0), mid-intervention (week 3 or week 4), and post-intervention (week 9 to week 14))
- Dopamine synthesis capacity(Baseline (between weeks -1 and 0) and post-intervention (week 4-9 to week 14))
- Functional magnetic resonance imaging (fMRI) during cognitive tasks(Baseline (between weeks -1 and 0) and post-intervention (week 9 to week 14))
- Online cognitive tasks(During every other week of the intervention (weeks -1/0, week 1, week 3, week 5, week 7, week 9 to week 14))
- Depression symptoms(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6))
- Anxiety (GAD7 score)(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Anxiety (STAI score)(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Anhedonia (SHAPS score)(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Anhedonia (DARS score)(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Apathy(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Fatigue(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Cognitive impairment(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Self-efficacy(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Self-esteem(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))
- Sleep quality(During every other week of the intervention (weeks -1/0, week 2, week 4, week 6, week 9 to week 14))