# Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $552,663

## Abstract

Depression, one of the most common diseases in older adults, carries significant risk for morbidity and
mortality. Because of the burgeoning population of older adults, the enormous burden of late-life depression,
and the limited efficacy of current antidepressants in older adults, biologically plausible models that translate
into depression prevention efforts are needed. Insomnia predicts depression recurrence, and is a modifiable
target for depression prevention. Yet, it is not known how insomnia gets converted into biological- and affective
risk for depression, which is critical for identification of molecular targets for pharmacologic interventions, and
for refinement of insomnia treatments that target affective responding to improve efficacy. 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), we hypothesize that older adults with insomnia will show heightened inflammatory- and
affective responding to inflammatory challenge as compared to those without insomnia. We aim 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. If the hypotheses are confirmed, older adults with two “hits”, insomnia and inflammation, would
represent a high risk group to be prioritized for monitoring and for depression prevention efforts using
treatments that target insomnia or inflammation. Moreover, this study will inform the development of
mechanism-based treatments that target affect responses in addition to sleep behaviors, and which might also
be coupled with efforts to reduce inflammation to optimize efficacy of depression prevention.

## Key facts

- **NIH application ID:** 9925164
- **Project number:** 5R01AG051944-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Michael R Irwin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $552,663
- **Award type:** 5
- **Project period:** 2016-09-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925164

## Citation

> US National Institutes of Health, RePORTER application 9925164, Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms (5R01AG051944-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9925164. Licensed CC0.

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