Transcriptomic predictors of inflammation-induced depressed mood
Open accessAbstract
Inflammation plays a significant role in the pathophysiology of depression. However, not all individuals exposed to inflammatory challenge develop depression, and identifying those at risk is necessary to develop targeted monitoring, prevention, and treatment strategies. Within a randomized double-blind placebo-controlled study (n = 115), we examined whether leukocyte transcriptome profiles predicted inflammation-induced depressed mood in volunteers who received low-dose intravenous endotoxin (n = 58; aged 18-50). At baseline, transcription factor (TF) activities were assessed using genome-wide transcriptional profiling of peripheral blood mononuclear cells and promoter-based bioinformatic analyses. Then, participants were administered endotoxin. Self-reported depressed mood was assessed using the Profile of Mood States. Based on extant studies linking transcriptional profiles to depressive disorder, we examined whether post-endotoxin depressed mood is predicted by baseline activity of TFs related to immune activation, sympathetic activation, and glucocorticoid insensitivity: respectively, nuclear factor kappa B (NF-kB), cAMP response element-binding protein (CREB), and glucocorticoid receptor (GR). Twenty-one participants (36%) experienced an increase in depressed mood from baseline to 2 h post endotoxin, when depressive response peaks. Bioinformatics analyses controlling for age, sex, ethnicity, body mass index, and physical sickness response revealed that post-endotoxin depressed mood was predicted by increased baseline activity of TFs related to inflammation (NF-kB) and beta-adrenergic signaling (CREB) and by decreased activity of GR-related TFs (P's < 0.001). Inflammation-induced depressed mood is predicted by peripheral transcriptome profiles related to immune activation, sympathetic activation, and glucocorticoid insensitivity. With further replication, these stress-related molecular profiles could be used for a novel genomic approach for identifying individuals at high-risk for the inflammatory subtype of depression.
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Inflammation-induced depressed mood can be predicted by elevated blood mononuclear cell transcription factor activity related to immune activation (NFκB), sympathetic activation, and glucocorticoid insensitivity.
“Inflammation-induced depressed mood can be predicted by elevated blood mononuclear cell transcription factor activity related to immune activation (NFκB), sympathetic activation, and glucocorticoid (GC) insensitivity [62].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [62]
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- Authors
- Cho, J. H.-J., Irwin, M. R., Eisenberger, N. I., Lamkin, D. M., & Cole, S. W.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Neuropsychopharmacology
- Published
- 2019-01-14
- Volume
- 44
- Issue
- 5
- Pages
- 923-929
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6462041
- OpenAlex
- W2909111591
- Cited by
- 54
- References
- 59
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 3 · 2019: 4
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (5R01MH091352)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (K23AG049085)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- depressive mood, endotoxin challenge, leukocyte transcriptome, transcription factor activity, NF-kB, CREB, glucocorticoid receptor, glucocorticoid resistance, beta-adrenergic signaling, immune activation, peripheral blood mononuclear cells, risk prediction
- MeSH terms
- Adolescent, Adult, Depression, Double-Blind Method, Endotoxins, Female, Humans, Inflammation, Leukocytes, Mononuclear, Male, Middle Aged, Receptors, Glucocorticoid, NF-kappa B, Computational Biology, CREB-Binding Protein, Young Adult, Transcriptome
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