Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds
Abstract
Background Correlational studies investigating neurohormonal-cytokine modulation by antidepressants suggest, among others, variations in cytokines balances as state markers of different biological subtypes of major depressive disorder (MDD) and response predictors to specific treatments. Objective of the study was to investigate cytokines modulation by duloxetine, a relatively newer SNRI with "clean" dual serotonin/norepinephrine mechanism.Methods 30 MDD patients and 32 healthy controls were assessed using Hamilton Depression Scale (HAM-D) and monitored for levels of IL-1β, IL-2, IL-4, IL-10, IL-12, IFN-γ and TNF-α, at baseline, week 6 and week 12 of duloxetine treatment (60mg/day) and at baseline, respectively.Results Early responders (ER: defined at week 6 by reduction >50% of baseline HAM-D score) and early non-responders (ENR) showed opposite trends in cytokine levels during duloxetine treatment: ENR were characterized by baseline Th2 shift compared to controls (lower IL-1β, IFN-γ and TNF-α) with increase in Th1 cytokines levels during treatment (increase of IL-1β, IL-12, IFN-γ, IL-1β/IL-10 and TNF-α/IL-10, decrease of IL-10), achieving clinical response at week 12; ER were characterized by baseline Th2-to-Th1 relative switch compared to ENR (higher IL-1β, IL-1β/IL-10 and TNF-α/IL-10) with reduction in Th1 cytokines levels during treatment (decrease of TNF-α and TNF-α/IL-10), achieving clinical response at week 6.Limitations Small sample size.Conclusions In accordance to early clinical response, duloxetine treatment could divide depressed patients into at least 2 subgroups characterized by clinical and laboratory differentiated behavior, suggesting different neurobiological background within depressive syndrome differentially sensitive to different drug components: pro-serotonergic effect and increase in Th1 cytokines in ENR vs. pro-noradrenergic effect and decrease in Th1 cytokines in ER.
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- Authors
- Fornaro, M., Rocchi, G., Escelsior, A., Contini, P., & Martino, M.
- Affiliations
- University of Catania (IT)
- University of Genoa (IT)
- Ospedale Policlinico San Martino (IT)
- Corresponding author
- Fornaro, Michele
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 145
- Issue
- 3
- Pages
- 300-307
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2110567133
- Cited by
- 59
- References
- 46
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- 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
- duloxetine, major depressive disorder, cytokines, antidepressant response, Th1/Th2 balance, early responders, serotonin-norepinephrine reuptake inhibitors, neuroinflammation, IL-1β, TNF-α, IL-10, interferon-gamma, IL-12, IL-4
- MeSH terms
- Duloxetine Hydrochloride, Adult, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Interferon-gamma, Interleukin-2, Male, Middle Aged, Psychiatric Status Rating Scales, Thiophenes, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-4, Case-Control Studies, Cytokines, Interleukin-10, Treatment Outcome, Interleukin-12, Interleukin-1beta
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