Cytokine-induced depression during IFN-α treatment: The role of IL-6 and sleep quality
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Depressive symptoms, poor sleep quality, and systemic markers of inflammation (e.g., interleukin (IL)-6) are frequently associated. Interferon-alpha (IFN-alpha) therapy results in Major Depressive Disorder (MDD) in some people, offering the possibility to elucidate the relationship of MDD to sleep and inflammation during treatment. In particular, delineating the temporal relations among these factors could help inform their causal relationships. To this end, a cohort of 95 non-depressed hepatitis C patients was followed prospectively for four consecutive months during IFN-alpha therapy. We found that higher pre-treatment levels of circulating IL-6 predicted incidence of MDD (X(2)(1)=7.7; p<0.05). Time-lagged mixed-effect analyses supported uni-directional associations in which IL-6 predicted next month's PSQI scores (F(47,11.6)=78.4; p<0.0005), and PSQI scores predicted next month's depressive Beck Depression Inventory-II (BDI) scores (F(16,22.6)=3.4; p<0.005). In addition, on any given month of treatment, IL-6 levels predicted BDI symptoms the following month (F(16,97.5)=7.3; p<0.0005), and conversely BDI predicted next month's IL-6 (F(14,7.4)=5.2; p<0.05) - providing evidence for a positive feedback relationship between depressive symptoms and systemic inflammation. These data provide further evidence that high levels of inflammation and poor sleep quality may be risk factors for IFN-alpha induced depression. Furthermore, these findings highlight the complex temporal relationships that exist among sleep, depression, and inflammation, and support the need for further prospective investigations to elucidate the dynamics that underlie depression during IFN-alpha treatment.
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One prospective study of patients receiving interferon-α for hepatitis C indicates that depression may also promote inflammation.
“However, one prospective study of patients receiving the pro-inflammatory cytokine interferonα (IFN-α) for hepatitis C indicates that depression may also promote inflammation.[14]”
From SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: Research Article: Suicidal Ideation and Inflammation (2013) · cites this paper as [14]
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- Authors
- Prather, A. A., Rabinovitz, M., Pollock, B. G., & Lotrich, F. E.
- Affiliations
- University of Pittsburgh (US)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Lotrich, Francis E.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 23
- Issue
- 8
- Pages
- 1109-1116
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2783448
- OpenAlex
- W2071238162
- Cited by
- 139
- References
- 97
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 16 · 2015: 12 · 2014: 16 · 2013: 10 · 2012: 17
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23MH074012)
- 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
- interferon-alpha, interleukin-6, sleep quality, major depressive disorder, systemic inflammation, hepatitis C
- MeSH terms
- Analysis of Variance, Antiviral Agents, Major Depressive Disorder, Hepatitis C, Predictive Value of Tests, Surveys and Questionnaires, Sleep, Time Factors, Interleukin-6, Interferon-alpha, Diagnostic and Statistical Manual of Mental Disorders
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