The Mitochondrial Stress, Brain Imaging, and Epigenetics Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Average TSST-induced Elevation in Cortisol
研究概览
简要总结
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. These defects induce mitochondrial allostatic load (MAL). The 2-day protocol, plus home-based data collection, will provide a comprehensive assessment of the multi-systemic dysregulation associated with MAL or mitochondrial dysfunction, and the link to physical and mental health-related symptoms.
Aim 1: Determine the influence of MAL on systemic AL biomarkers.
Aim 2: Establish the influence of MAL on stress reactivity profiles.
Aim 3. Examine the association between MAL and psychological functioning.
详细描述
Age-related physical and cognitive decline, as well as the risk of neurological diseases, are increased by the effects of psychosocial stress. Psychosocial stress triggers neuroendocrine, metabolic, cardiovascular, and inflammatory changes in the body. These changes vary in nature and magnitude between individuals, and are associated with long-term disease risk. However, the biological determinants of the stress response are not well understood.
This project aims to translate the preclinical findings (how mitochondria regulate the different organ systems and major stress response axes are activated during psychological stress) by studying a population of individuals with varying degree of mitochondrial dysfunction, and to test potential neural mechanism, and why some individuals respond more strongly than others to the same stressor.
Each participant will be studied over two consecutive days. Participants will be housed on campus to standardize study conditions. On Day 1, participants will donate blood and saliva, undergo a neuropsychological assessment, and complete questionnaires to assess psychosocial functioning and psychiatric symptoms. After lunch, the investigator will monitor dynamic changes in mental health-related biological outcomes (positive and negative affect, circulating levels of the inflammatory cytokine IL-6, and salivary cortisol) in response to a standardized laboratory challenge. On Day 2, participants will undergo a medical evaluation to assess clinical symptoms and undergo a whole brain neuroimaging session where both resting and stress elicited activity will be measured. A variant of the same stressor as on Day 1 will be used in the neuroimaging session. Participants will then be debriefed, concluding the individuals participation in the study. Participants also complete a home-based saliva and stool collection to examine diurnal variation in salivary hormones, and to examine microbiome composition. This translational project will generate a unique combination of complimentary molecular, cellular, and neuroimaging data that will advance our understanding of the links between mitochondria, the brain, and mental health-related outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- •Men and women patients between 18 and 55 years of age
- •Willing to provide saliva samples and have venous catheter installed for blood collection during the hospital visit
- •Willing to provide informed consent and capacity to consent
- •Use of effective method of birth control for women of childbearing capacity
- •English Speaking
排除标准
- •Individuals with cognitive deficit incapable of providing informed consent will not be included
- •Symptoms of flu or other seasonal infection four weeks preceding hospital visit
- •Raynaud's syndrome (Raynaud phenomenon)
- •Involvement in any therapeutic trials listed on clinicaltrials.gov, including exercise
- •Metal inside or outside the body or claustrophobia prohibitive to MRI testing
- •Diagnosed with mitochondrial disease m.3243A>G, or large scale mtDNA deletion (for healthy controls)
结局指标
主要结局
Average TSST-induced Elevation in Cortisol
时间窗: Day 1 post challenge (approximately 2 hours)
This is designed to measure cortisol reactivity to the trier social stress test (TSST), quantified from salivary cortisol (LC-MS) over an 8-timepoints timecourse. The elevation will be measured as the area under the curve (AUC) for the cortisol time course.
Average Allostatic Load Index
时间窗: Blood collected on Day 1
Groups will be compared on a quantitative allostatic load (AL) index integrating baseline fasting measures of neuroendocrine, immune and metabolic systems, urinary catecholamines, hematological measures, and hair/diurnal cortisol levels. 32 different biomarkers were analyzed for this outcome. The full range of the allostatic load index score is 0 to 32. A lower score is considered better, and a higher score is considered worse.
次要结局
- Average TSST-induced Elevation in Heart Rate(Baseline and 2 hours post challenge on Day 1)
- Correlation Between Anxiety and Mitochondrial Respiration(Day 1)
- Average Neuropsychological Function(Day 2 neuropsychological session)
研究者
Martin Picard
Associate Professor of Behavioral Medicine (in Psychiatry and Neurology)
Columbia University