Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination

Novel T cell biomarker for antidepressant medication selection

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n = 166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p = 0.037) but not for side-effects (p = 0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size = 0.78, p = 0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

Original languageEnglish (US)
JournalBrain, Behavior, and Immunity
DOIs
StateAccepted/In press - 2017

Fingerprint

Bupropion
Interleukin-17
Antidepressive Agents
Biomarkers
T-Lymphocytes
Th17 Cells
Citalopram
Dopamine
Th2 Cells
Th1 Cells
Therapeutics
Blood-Brain Barrier
Placebos
Cytokines

Keywords

  • Antidepressant
  • Bupropion
  • Dopamine
  • Inflammation
  • Interleukin 17
  • Moderator
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

@article{b845094627004ee2b919249f6e68422f,
title = "Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection",
abstract = "Background: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n = 166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p = 0.037) but not for side-effects (p = 0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size = 0.78, p = 0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.",
keywords = "Antidepressant, Bupropion, Dopamine, Inflammation, Interleukin 17, Moderator, T cells",
author = "Jha, {Manish K.} and Abu Minhajuddin and Gadad, {Bharathi S.} and Greer, {Tracy L.} and Mayes, {Taryn L.} and Trivedi, {Madhukar H.}",
year = "2017",
doi = "10.1016/j.bbi.2017.07.005",
language = "English (US)",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination

T2 - Novel T cell biomarker for antidepressant medication selection

AU - Jha, Manish K.

AU - Minhajuddin, Abu

AU - Gadad, Bharathi S.

AU - Greer, Tracy L.

AU - Mayes, Taryn L.

AU - Trivedi, Madhukar H.

PY - 2017

Y1 - 2017

N2 - Background: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n = 166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p = 0.037) but not for side-effects (p = 0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size = 0.78, p = 0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

AB - Background: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n = 166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p = 0.037) but not for side-effects (p = 0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size = 0.78, p = 0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

KW - Antidepressant

KW - Bupropion

KW - Dopamine

KW - Inflammation

KW - Interleukin 17

KW - Moderator

KW - T cells

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U2 - 10.1016/j.bbi.2017.07.005

DO - 10.1016/j.bbi.2017.07.005

M3 - Article

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -