Inflammation triples depression risk for older adults with insomnia

UCLA researchers say poor sleepers may benefit from treatments targeted for inflammation-related depression
An older woman lays awake in bed.
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Chronic inflammation, already tied to heart disease and cancer, may also worsen the emotional toll of poor sleep. A new UCLA Health study found that older adults with insomnia who experience inflammatory exposure face triple the risk of developing depressive symptoms compared to sound sleepers.

The study, published in the journal JAMA Psychiatry, is the first to examine the mechanistic link between inflammation, insomnia and risk of depressive mood among older adults.

As humans age, we experience increasing risk of chronic inflammation as our cells and immune system break down. This can be further exacerbated by illness, stress, unhealthy habits, pain and various other factors that can elevate inflammation. Additionally, more than 1 in 10 adults over 60 years old in the U.S. experience major depression each year, which can exacerbate other health problems such as cognitive decline, disability and overall mortality, according to previous research.

Inflammation and insomnia have each been linked to depression risk, whether causally or biologically, but no study to date has examined whether older adults with insomnia are more vulnerable to depressive symptoms when experiencing elevated inflammation. 

The UCLA study led by psychiatrist Dr. Michael Irwin sought to determine whether there was a mechanistic link between insomnia, inflammation and depression among older adults. 

The randomized clinical control trial enrolled 160 adults ages 60 and over in Los Angeles of whom 53 had insomnia and 107 were healthy sleepers. The healthy and insomnia patients were randomly divided into two treatment groups: exposure to inflammatory challenge vs. placebo. Irwin and colleagues assessed for depressive mood in both groups after inflammatory exposure using the Profiles of Mood States depression subscale. Participants were also evaluated for depressive symptom severity and inflammatory cytokines in blood samples. 

Inflammatory challenge induced increases in inflammation and depressive symptoms.  Further, in older adults who were exposed to inflammatory challenge, a three-fold greater increase in depressive mood and symptoms in those with insomnia as compared to healthy sleepers. Participants with insomnia were also depressed for far longer after inflammation was induced, showing depressed mood for six hours or longer compared to transient increases in healthy sleepers. 

“Insomnia not only robs older adults of rest but also primes their immune system to make them uniquely vulnerable to depression when faced with inflammation,” said Irwin, who also directs UCLA Health’s Cousins Center for Psychoneuroimmunology and is a member of the UCLA Health Jonsson Comprehensive Cancer Center. “Treatments targeted at this inflammation-related depression may prevent depression and benefit these patients to improve their overall quality of life.”

Irwin said further research is needed to determine if these findings are generalizable to younger populations with insomnia. Additionally, further research is needed to validate these results among non-white populations which have a disproportionate risk of insomnia and depression compared to white populations.

Article: Inflammatory Exposure and Depression in Older Adults With Insomnia A Randomized Clinical Control Trial; Michael B. Irwin, MD, et al.; Published online July 16, 2025 JAMA Psychiatry
doi:10.1001/jamapsychiatry.2025.1327

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