OLDER adults with insomnia are significantly more vulnerable to increased depressive symptoms following inflammatory exposure than those without insomnia, with effects persisting longer and highlighting the need for targeted depression prevention in this population.
Insomnia and inflammation are common among older adults and are both recognised risk factors for late-life depression. While previous research has established that inflammation can provoke depressive symptoms, it remains unclear whether individuals with insomnia exhibit heightened sensitivity to such inflammatory challenges. Understanding this relationship is clinically important as it may inform more personalised monitoring and intervention strategies in older adults vulnerable to depression.
This assessor-blinded, parallel-condition randomised clinical trial recruited 160 nondepressed adults aged 60 years or older from a community sample in Los Angeles between 2017 and 2022. Participants were stratified by insomnia disorder status (53 with insomnia, 107 controls) and randomised to receive either an inflammatory challenge—intravenous endotoxin—or placebo. The primary outcome was depressed mood measured using the Profiles of Mood States depression subscale (POMS-D), with secondary outcomes including depressive symptom severity and inflammatory cytokine levels. Of the participants, 79 (26 insomnia, 53 controls) received endotoxin, and 81 (27 insomnia, 54 controls) received placebo. Analysis indicated that endotoxin induced a significantly greater increase in depressive mood among those with insomnia compared to controls (condition × group interaction: F10,1478 = 4.7; P < .001), with observer-rated depressive symptoms similarly heightened (F3,450 = 5.5; P = .001). Despite similar cytokine elevations in both groups, only the insomnia group showed a strong correlation between inflammatory response and depressive symptom increases (β = 0.33; 95% CI, 0.26–0.41; P < .001). These data demonstrate that insomnia magnifies vulnerability to inflammation-linked mood disturbances.
These findings affirm that older adults with insomnia have a heightened risk of depressive symptoms when exposed to systemic inflammation, a scenario common in infections, chronic illness, or other inflammatory states.Future research should explore integrated therapeutic approaches that target these intersecting risk pathways and assess long-term effects on mental health outcomes in diverse older populations.
Reference
Irwin MR, et al. Inflammatory exposure and depression in older adults with insomnia: a randomized clinical Trial. JAMA Psychiatry. 2025;DOI:10.1001/jamapsychiatry.2025.1327.
