Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds

Michele Fornaro, Giulio Rocchi, Andrea Escelsior, Paola Contini, Matteo Martino

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 (60 mg/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.

Original languageEnglish
Pages (from-to)300-307
Number of pages8
JournalJournal of Affective Disorders
Volume145
Issue number3
DOIs
Publication statusPublished - Mar 5 2013
Externally publishedYes

Fingerprint

Interleukin-10
Interleukin-1
Cytokines
Major Depressive Disorder
Interleukin-12
Therapeutics
Depression
Duloxetine Hydrochloride
Depressive Disorder
Interleukin-4
Sample Size
Antidepressive Agents
Interleukin-2
Serotonin
Norepinephrine
Biomarkers
Pharmaceutical Preparations

Keywords

  • Cytokines
  • Depression
  • Duloxetine
  • Th1
  • Th2

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds. / Fornaro, Michele; Rocchi, Giulio; Escelsior, Andrea; Contini, Paola; Martino, Matteo.

In: Journal of Affective Disorders, Vol. 145, No. 3, 05.03.2013, p. 300-307.

Research output: Contribution to journalArticle

Fornaro, Michele ; Rocchi, Giulio ; Escelsior, Andrea ; Contini, Paola ; Martino, Matteo. / Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds. In: Journal of Affective Disorders. 2013 ; Vol. 145, No. 3. pp. 300-307.
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AU - Fornaro, Michele

AU - Rocchi, Giulio

AU - Escelsior, Andrea

AU - Contini, Paola

AU - Martino, Matteo

PY - 2013/3/5

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N2 - 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 (60 mg/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.

AB - 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 (60 mg/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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