Preexisting mild sleep disturbance as a vulnerability factor for inflammation-induced depressed mood: a human experimental study
Open accessAbstract
Sleep disturbance and depression are common, particularly in females, and sleep disturbance is a well-known risk factor for depression. Systemic inflammation has been suggested as a potential mechanism of this association. This study examined whether preexisting sleep disturbance acted as a vulnerability factor for depressed mood induced by an inflammatory challenge in healthy females vs males. In a randomized double-blind placebo-controlled design, volunteers aged 18–50 (N=111; 67 females) were assigned to placebo or low-dose endotoxin. Before substance administration, sleep disturbance was assessed using the Pittsburgh Sleep Quality Index and dichotomized using median split (⩾3 vs <3). Self-reported depressed mood (profile of mood states) and circulating proinflammatory cytokines (interleukin-6, tumor necrosis factor-α) were repeatedly assessed over 6 h. Among females, moderation of depressed mood by sleep disturbance was significant even after adjustment for covariates (X2=12.73, df=6, P<0.05). There was a robust time-by-condition interaction in females with sleep disturbance (X2=26.22, df=6, P<0.001), but not in females without sleep disturbance (X2=8.65, df=6, P=0.19). Although cytokines increased equally in all females, the correlations between cytokines and depressed mood were significantly stronger in females with sleep disturbance. Among males, no moderating effect of sleep disturbance was observed. Inflammation-induced depressed mood was considerably more severe among females reporting mild sleep disturbance compared with those reporting no sleep disturbance, suggesting that even mild sleep disturbance may increase vulnerability for inflammation-induced depression in females. Furthermore, sleep disturbance appears to increase the vulnerability to depression by augmenting affective sensitivity to cytokines rather than by enhancing cytokine responses to inflammatory challenge in females.
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Inflammation may act as a vulnerability factor, so that later sleep disturbance triggers increased depressive symptoms.
“which suggests that inflammation might also serve as a vulnerability factor, in which subsequent exposure to sleep disturbance triggers increase in depressive symptoms (Cho et al, 2016).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Cho et al, 2016
Sleep disturbance (poor sleep quality) is associated with exaggerated increase of depressive symptoms following inflammatory challenge mainly in females.
“sleep disturbance (ie, poor sleep quality) is associated with exaggerated increase of depressive symptoms following inflammatory challenge mainly in females (Cho et al, 2016).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Cho et al, 2016
In healthy females and males, preexisting sleep disturbance led to exaggerated increase in depressed mood response to inflammatory challenge (endotoxin) compared with no sleep disturbance.
“we found that the presence of preexisting sleep disturbance led to exaggerated increase in depressed mood response to inflammatory challenge as compared those who reported no sleep disturbance (Figure 9).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Cho et al, 2016
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- Authors
- Cho, H. J., Eisenberger, N. I., Olmstead, R., Breen, E. C., & Irwin, M. R.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Cho, H J
- Venue
- Translational Psychiatry
- Published
- 2016-03-08
- Volume
- 6
- Issue
- 3
- Pages
- e750-e750
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4872448
- OpenAlex
- W2293103284
- Cited by
- 64
- References
- 40
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 6
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Brain and Behavior Research Foundation
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (UL1TR000124, KL2TR000122)
- National Institute on Aging (R01AG026364, R01AG034588, K23AG049085, P30AG028748)
- National Heart, Lung, and Blood Institute (R01HL095799)
- National Institute of Mental Health (R01MH091352)
- National Institute on Drug Abuse (R01DA032922)
- National Cancer Institute (R01CA160245, R01CA119159)
- NIH Clinical Center
- National Center for Advancing Translational Sciences (Grant UL1TR000124, UCLA CTSI Grant UL1TR000124)
- Clinical and Translational Science Institute, University of California, Los Angeles (UL1TR000124, KL2TR000122)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- sleep disorders, depression, systemic inflammation, endotoxin challenge, interleukin-6, TNF-α, inflammatory cytokines, sex differences, vulnerability factors
- MeSH terms
- Adolescent, Adult, Depressive Disorder, Double-Blind Method, Female, Humans, Inflammation, Male, Middle Aged, Risk Factors, Severity of Illness Index, Sleep Wake Disorders, Sex Distribution, Young Adult
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