Older adults with insomnia experienced significantly higher levels of depressed mood after inflammatory exposure than those without insomnia, according to a randomized clinical trial involving 160 nondepressed participants aged 60 years or older.
The trial tested whether low-dose endotoxin, which safely mimics infection-related inflammation, would increase depressive symptoms more strongly in people with insomnia. Of the 160 participants, 53 met DSM-5 criteria for insomnia disorder, and 107 did not. Seventy-nine were randomized to receive endotoxin (0.8 ng/kg intravenously), while 81 received placebo.
Depressed mood was assessed using the Profiles of Mood States depression subscale (POMS-D), including self- and observer-rated versions. Clinical measures of depression severity included the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Depression (HAM-D). Blood samples were collected regularly to measure inflammatory cytokines, including interleukin 6 and tumor necrosis factor α .
Participants with insomnia showed a significantly greater increase in depressed mood following endotoxin exposure than controls. The condition-by-group interaction for POMS-D was statistically significant. Observer-rated mood changes showed a similar pattern.
In the insomnia group, the mean difference in area under the curve (MD-AUC) for self-rated POMS-D was 8.23, compared to −1.65 in the control group. For observer-rated POMS-D, insomnia participants had an MD-AUC of 0.35, compared to 0.05 in controls.
Endotoxin induced increases in interleukin 6 and tumor necrosis factor α levels in both groups, with no significant differences between them. Among participants with insomnia, the inflammatory response was significantly associated with increased POMS-D scores. No association was found in the control group.
Depressive symptoms measured by MADRS and HAM-D also rose more in the insomnia group. The MD-AUC for MADRS was 7.59, and for HAM-D, 4.38, both reaching clinically meaningful thresholds. In contrast, symptom increases in the control group did not meet criteria for clinical significance.
All participants completed the study, and no adverse events were reported. Follow-up assessments conducted 1 day and 7 days after the intervention confirmed that depression scores had returned to baseline.
“Older adults with insomnia showed an exaggerated vulnerability to depressive mood and symptoms in response to inflammatory challenge,” noted Michael R. Irwin, MD, of the Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, and colleagues.
The study found that older adults with insomnia exhibited greater increases in depressive symptoms in response to experimental inflammatory exposure compared with those without insomnia. The researchers suggested that insomnia may be associated with heightened depressive responses to inflammation and noted the potential relevance for monitoring during periods of inflammatory challenge.
Full disclosures can be found in the published study.
Source: JAMA Psychiatry