Experimental Model of Depression in Aging: Anxiety, Inflammation, and Reward Mechanisms
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Neural Indices of Monetary Reward Sensitivity during Effort-Based Decision Making
研究概览
简要总结
The purpose of this study is to use an experimental inflammatory challenge to examine whether older adults with symptoms of anxiety experience loss of pleasure or loss of motivation when they are exposed to inflammation. Loss of pleasure or loss of motivation will be evaluated using self-report questionnaires, computer tasks, and during a brain scan.
详细描述
Participants will undergo phone screening, two in-person visits, and telephone follow-up. The first visit will last 4 hours and the second visit will last 10.5 hours. Phone screening and follow-up will take no longer than 30 minutes.
Phone Screening and Visit #1:
Following phone screening to determine potential eligibility, participants will have an in-person evaluation. Following informed consent in the first session, participants will undergo semi-structured clinical interviews and complete questionnaires to assess medical- and medication histories; current- and past history of psychiatric disorders, and evaluation of behavioral symptoms of anxiety and depression. They will also complete computer tasks that assess motivation and sensitivity to reward. As part of one of these tasks, they will be asked to provide a picture of a loved one, which they will later view during a fMRI scan.
Visit #2 and telephone follow-up:
The second session will be about two weeks later. It will begin at 7:30AM and will involve placement of two intravenous catheters (one in each arm), evaluation of heart rate and blood pressure, administration of endotoxin vs. placebo, repeated blood sampling along with questionnaires about mood and symptoms for approximately 10.5 hours. Two hours post-injection participants will complete a 1-hour brain scan that includes tasks to assess motivation and sensitivity to reward. Study staff will escort the participant to a nearby facility to complete the brain scan. 24 hrs and 2-weeks following this session, study staff will call the subject and ask about physical and mood symptoms, using the same set of items used during the experimental protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinded infusion
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants will be required to be in good general health (as evaluated during the phone and in-person baseline session)
- •Participants will be aged 60 to 80 years.
- •Half the participants (n=40) will be those with clinically significant anxiety as defined by a score of 5 or greater on the GAD-7;
- •Half the participants (n=40) will be those with low anxiety as defined by a GAD-7 score of <5.
排除标准
- •Presence of chronic mental or physical illness (except for anxiety)
- •History of allergies, autoimmune, liver, or other severe chronic diseases
- •Current and regular use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, aspirin, immune modifying drugs, opioid analgesics, statins, antihypertensive drugs, anti-arrhythmic drugs, and antidepressant medications (none in the last 6 months)
- •Nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks
- •Previous history of fainting during blood draws.
- •Claustrophobia
- •Metal in the body
- •Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders;
- •Presence of comorbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders;
- •Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk;
- •Presence of chronic infection, which may elevate pro-inflammatory cytokines;
- •Presence of an acute infectious illness in the two weeks prior to an experimental session.
- •Current Axis I psychiatric disorders other than anxiety as determined by the Research Version of the Structured Clinical Interview
- •Lifetime history of suicide attempt or inpatient psychiatric admission.
- •Sleep Disorders: Current history of sleep apnea or nocturnal myoclonus;
- •Phase-shift disorder
- •Current and/or past regular use of hormone-containing medications including steroids;
- •Current and/or past regular use of non-steroid anti-inflammatory drugs;
- •Current and/or past regular use of immune modifying drugs that target specific immune responses such as cytokine antagonists;
- •Current and/or past regular use of analgesics such as opioids;
- •Current and/or past regular use of cardiovascular medications, including antihypertensive, anti-arrhythmic, antianginal, and anticoagulant drugs;
- •Current smoking
- •Current excessive caffeine use (>600 mg/day) because of the known effects on pro-inflammatory cytokine levels;
- •Evidence of recreational drug use from urine test.
- •Body mass index > 35 because of the effects of obesity on proinflammatory cytokine activity
- •Any clinically significant abnormality on screening laboratory tests
- •Clinically significant abnormalities in electrocardiogram
研究组 & 干预措施
Endotoxin
Endotoxin 0.8 ng/kg body weight
干预措施: Endotoxin (Biological)
Placebo
same volume of 0.9% saline
干预措施: Placebo (Biological)
结局指标
主要结局
Neural Indices of Monetary Reward Sensitivity during Effort-Based Decision Making
时间窗: approximately 2 hours post-injection for 14 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess sensitivity for monetary reward, as operationalized by VS and VMPFC activity during receipt of monetary reward (vs. fixation) and during choice of low vs. high reward trials during the EEfRT.
Neural Indices of Reward Motivation - Anticipatory Reward Response
时间窗: approximately 2 hours post-injection for 7 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of monetary reward cue trials vs no-reward cue trials during the Monetary Incentive Delay Task.
Neural Indices of Reward Sensitivity for Non-Monetary Reward
时间窗: approximately 2 hours post-injection for 10 minutes
Sensitivity for non-monetary reward as assessed by VS and VMPFC activity when viewing positive non-social vs neutral images, and when viewing positive social vs. neutral images, in a positive picture viewing task.
Neural Indices of Reward Motivation - Effort-Based Decision Making
时间窗: approximately 2 hours post-injection for 14 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess effort-based motivational processing, as assessed by VS, ventromedial prefrontal cortex (vmPFC), and pre-supplementary motor area (pre-SMA) activity with choice phase as event onset during an adapted version of the Effort Expenditure for Rewards Task (EEfRT).
次要结局
- Social Incentive Delay Task - Neural Indices of Social Reward Motivation(approximately 2 hours post-injection for 7 minutes)
- Social Incentive Delay Task - Neural Indices of Social Reward Sensitivity(approximately 2 hours post-injection for 7 minutes)
- Behavioral Indices of Reward Motivation - Effort-Based Decision Making(Pre-injection and approximately 2 hours post-injection)
- Resting state functional connectivity(2 hours post-injection for 7 minutes)
- Behavioral Indices of Reward Sensitivity and Learning - Probabilistic Reward Task(Pre-injection and approximately 2 hours post-injection)
- Behavioral Indices of Reward motivation - close other social reward(2 hours post-injection)
- Monetary Incentive Delay Task -Neural Indices of Monetary Reward Sensitivity(approximately 2 hours post-injection for 7 minutes)
- Social Incentive Delay Task - Neural Indices of Reward Sensitivity for Close Social Reward(approximately 2 hours post-injection for 7 minutes)
- Depressed Mood Subscale of the Profile of Mood States (POMS)(10 hours)
- Social Incentive Delay Task - Neural Indices of Reward Motivation for Close Social Reward(approximately 2 hours post-injection for 7 minutes)
- Motivation for social and non-social reward (interest in activities scale).(10 hours)
研究者
Chloe Boyle, PhD
Adjunct Assistant Professor
University of California, Los Angeles