Sleep and Healthy Aging Research for Depression (SHARE-D) Study

This study will use an inflammatory challenge (i.e., endotoxin) to probe acute inflammatory-
and depression responses (primary outcome) in older adults as a function of insomnia. Older
adults with insomnia show chronic inflammation; sleep disturbance also activates inflammatory
signaling; chronic inflammation primes acute inflammatory responses; chronic inflammation, as
well as acute inflammatory reactivity, predict depression over the following year; and
finally, endotoxin induces acute inflammation along with depressive symptoms, with
preliminary evidence that "two-hits" (i.e., sleep disturbance and inflammatory challenge) are
associated with exaggerated increases in depression, especially in women. In this
placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults
(60-80 y; stratified by sex) with insomnia (n=80) vs. comparisons without insomnia (n=80),
the investigators hypothesize that older adults with insomnia will show heightened
inflammatory- and affective responding to inflammatory challenge as compared to those without
insomnia. The investigation aims to: 1) examine differences in depressive symptoms and
measures of negative affect responding as a function of insomnia and inflammatory challenge;
2) examine differences in measures of positive affect responding as a function of insomnia
and inflammatory challenge; and 3) examine differences in experimentally-induced inflammation
in relation to depressive symptoms and measures of negative- and positive affect responding
as a function of insomnia.

- 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.

- Half the participants (N=80) will be those with insomnia disorder as assessed by
the Structured Clinical Interview for Diagnosis, Diagnostic Statistical Manual 5
and the Duke Structured Interview for Sleep Disorders, and will be required to
fulfill a minimal severity of mild insomnia with a Insomnia Severity Index score
greater than 10, as well as evidence of poor sleep efficiency (<85%).

- The other half will be those without insomnia identified as not having insomnia
by any of these assessments.

- Exclusion Criteria: Following a structured telephone interview, prospective
participants with the following conditions will not advance to the in-person baseline
session:

- Presence of chronic mental or physical illness (except for insomnia)

- 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); and nightshift work or time zone shifts
(> 3hrs) within the previous 6 weeks, or previous history of fainting during
blood draws.

- 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 proinflammatory cytokines;

- Presence of an acute infectious illness in the two weeks prior to an experimental
session.

- Current Axis I psychiatric disorders as determined by the Research Version of the
Structured Clinical Interview including a current major depressive disorder and
substance dependence (a prior history of depression is not an exclusion
criterion, which will be considered for a pre-planned sensitivity analysis and
will be used as a pre-classification variable in the generation of the two
groups, and in the randomization schedule);

- Lifetime history of suicide attempt or inpatient psychiatric admission. Sleep
Disorders:

- Current history of sleep apnea or nocturnal myoclonus;

- Phase-shift disorder, which will be identified by the Structured Clinical
Interview and the Duke Structured Interview for Sleep Disorders ; Medication and
Substance Use:

- 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, antiarrhythmic, antianginal, and anticoagulant drugs;

- Use of antidepressant medications or other psychotropic medications; (16) current
smoking or excessive caffeine use (>600 mg/day) because of the known effects on
proinflammatory cytokine levels;

- Evidence of recreational drug use from urine test. Health Factors:

- Body mass index > 35 because of the effects of obesity on proinflammatory
cytokine activity and also on risk for sleep disordered breathing;

- Any clinically significant abnormality on screening laboratory tests

- Clinically significant abnormalities in electrocardiogram