Aging and Reward System Response to Inflammation and Anxiety Study

Experimental Model of Depression in Aging: Anxiety, Inflammation, and Reward Mechanisms

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.

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.

Inclusion Criteria:

• 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.
• 3/4 the participants (n=30) will be those with clinically significant anxiety as defined by a score of 5 or greater on the GAD-7;
• 1/4 the participants (n=10) will be those with low anxiety as defined by a GAD-7 score of <5.

Exclusion Criteria:

• 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