Transcriptomics in interferon-α-treated patients identifies inflammation-, neuroplasticity- and oxidative stress-related signatures as predictors and correlates of depression
Open accessAbstract
Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI). Whole-blood transcriptomic analyses were conducted to investigate the following: (1) baseline gene expression differences associated with future development of IFN-α-induced depression, before IFN-α, and (2) longitudinal gene expression changes from baseline to weeks 4 or 24 of IFN-α treatment, separately in those who did and did not develop depression. Transcriptomics data were analyzed using Partek Genomics Suite (1.4-fold, FDR adjusted p⩽0.05) and Ingenuity Pathway Analysis Software. Twenty patients (34%) developed IFN-α-induced depression. At baseline, 73 genes were differentially expressed in patients who later developed depression compared with those who did not. After 4 weeks of IFN-α treatment, 592 genes were modulated in the whole sample, representing primarily IFN-α-responsive genes. Substantially more genes were modulated only in patients who developed depression (n=506, compared with n=70 in patients who did not), with enrichment in inflammation-, neuroplasticity- and oxidative stress-related pathways. A similar picture was observed at week 24. Our data indicate that patients who develop IFN-α-induced depression have an increased biological sensitivity to IFN-α, as shown by larger gene expression changes, and specific signatures both as predictors and as correlates.
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Patients who develop depression during interferon-alpha treatment present a hyperactive immune response that is evident by measuring mRNA but not plasma cytokines.
“patients who develop depression during this immune challenge present a hyperactive immune response that is evident by measuring mRNA but not plasma cytokines (Hepgul et al., 2016).”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Hepgul et al., 2016
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- Authors
- Hepgul, N., Cattaneo, A., Agarwal, K., Baraldi, S., Borsini, A., Bufalino, C., Forton, D. M., Mondelli, V., Nikkheslat, N., Lopizzo, N., Riva, M. A., Russell, A., Hotopf, M., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- King's College Hospital (GB)
- St George's Hospital (GB)
- University of Brescia (IT)
- University of Milan (IT)
- Corresponding author
- Pariante, Carmine M
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2016-04-12
- Volume
- 41
- Issue
- 10
- Pages
- 2502-2511
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4983179
- OpenAlex
- W2338312264
- Cited by
- 62
- References
- 54
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 1
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- South London and Maudsley NHS Foundation Trust (MR/L014815/1, MR/J002739/1)
- National Institute for Health and Care Research (CL-2008-17-005, MR/J002739/1, MR/L014815/1, NF-SI-0515-10102)
- Academy of Medical Sciences (AMS-SGCL5-Mondelli)
- King's College London
- Medical Research Council (MR/L014815/1, MR/N029488/1, MR/J002739/1)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- chronic hepatitis C, depression vulnerability, gene expression signatures, inflammation, neuroplasticity, oxidative stress, whole blood transcriptomics, depression biomarkers
- MeSH terms
- Adult, Analysis of Variance, Antiviral Agents, Depression, Female, Hepatitis C, Humans, Keratins, Male, Middle Aged, Psychiatric Status Rating Scales, Surveys and Questionnaires, Cohort Studies, Signal Transduction, Gene Expression, Interferon-alpha, Oxidative Stress, Computational Biology, Gene Expression Profiling
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