Sleep and Healthy Aging Research on Depression for Younger Women

Compelling evidence indicates inflammation plays a role in depression, but potential mechanisms linking inflammation to depression, such as dysregulated reward processing, are poorly understood. This study comprehensively evaluates effects of inflammation on reward across dimensions (e.g., anticipating versus receiving a reward) and types (e.g., money vs. smiling faces) in younger and older women. Characterizing how inflammation shapes the dynamic and multidimensional reward system, and how this may differ by age, may give insight into risk factors for depression and help identify critical points for intervention.

This study will use an inflammatory challenge (i.e., endotoxin) to assess effects of inflammation on the behavioral response to social and non-social rewards, using tasks that assess reward motivation, sensitivity, and learning. Both elevated inflammation and reward dysregulation are associated with depression and have been shown to predict depression onset; understanding how inflammation alters the reward system in the laboratory setting may provide insight into risk factors and help identify potential areas for intervention. In this placebo-controlled, randomized, double-blind study of low dose endotoxin in 40 adult premenopausal women (25-44 y), the investigators will examine effects of endotoxin on reward responsiveness across dimensions (i.e., motivation, sensitivity, learning) and reward types (e.g., social and non-social). The investigators hypothesize that as compared to placebo, endotoxin will 1) decrease non-social reward responses across reward dimensions; 2) decrease "general" social reward responses across reward dimensions; 3) increase "close" social reward responses across reward dimensions; 4) decrease resting eye blink rate (EBR); EBR will be correlated with learning and motivation for non-social reward. The second component of the study is to examine whether effects of endotoxin on reward differ as a function of age; in particular it is hypothesized that effects will be more robust in younger compared to older women. In order to test for age differences, this study will use data from 40 older women (65+ y) participating in a parallel ongoing randomized controlled trial (ClinicalTrials.gov Identifier: NCT03256760). Thus, the investigation aims to: 1) Evaluate effects of inflammation on non-social reward as a function of age; 2) Evaluate effects of inflammation on general and close social reward as a function of age; 3) Examine changes in dopaminergic activity as a mechanism linking effects of inflammation on non-social reward processing as a function of age.

Eligibility Criteria:
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 biologically female and premenopausal (as evaluated by self report).
* Participants will 25-44 years of age.

Exclusion Criteria:

* Presence of chronic mental or physical illness
* 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.
* 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
* Lifetime history of suicide attempt or inpatient psychiatric admission.
* 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
* 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.
* 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