Interleukin 17 Selectively Predicts Better Outcomes with Bupropion-SSRI Combination: Novel T Cell Biomarker for Antidepressant Medication Selection

Overview

Journal Brain Behav Immun

Publisher Elsevier

Specialties Allergy & Immunology
Neurology
Psychiatry

Date 2017 Jul 13

PMID 28698115

Citations 34

Authors

Manish K Jha

Abu Minhajuddin

Bharathi S Gadad

Tracy L Greer

Taryn L Mayes

Madhukar H Trivedi

Affiliations

Soon will be listed here.

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.

Citing Articles

Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.

Mogavero M, Salemi M, Lanza G, Rinaldi A, Marchese G, Ravo M iScience. 2024; 27(4):109568.

PMID: 38617564 PMC: 11015462. DOI: 10.1016/j.isci.2024.109568.

Th17 Cells, Glucocorticoid Resistance, and Depression.

Khantakova J, Mutovina A, Ayriyants K, Bondar N Cells. 2023; 12(23).

PMID: 38067176 PMC: 10706111. DOI: 10.3390/cells12232749.

Microbiota Alters and Its Correlation with Molecular Regulation Underlying Depression in PCOS Patients.

Yu L, Chen X, Bai X, Fang J, Sui M Mol Neurobiol. 2023; 61(12):9977-9992.

PMID: 37995075 DOI: 10.1007/s12035-023-03744-7.

Clues from planarians about interleukin-17A and stress that result from light avoidance: IL-17A antagonists reduce defensive responding in flatworms.

Milton M, Inan S, Rawls S Cytokine. 2023; 170:156345.

PMID: 37625214 PMC: 10530327. DOI: 10.1016/j.cyto.2023.156345.

Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin.

Corrigan M, ORourke A, Moran B, Fletcher J, Harkin A Neuronal Signal. 2023; 7(2):NS20220054.

PMID: 37457896 PMC: 10345431. DOI: 10.1042/NS20220054.

References

Felger J . The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications. Curr Top Behav Neurosci. 2016; 31:199-219. DOI: 10.1007/7854_2016_13. View

Trivedi M, Rush A, Wisniewski S, Nierenberg A, Warden D, Ritz L . Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006; 163(1):28-40. DOI: 10.1176/appi.ajp.163.1.28. View

Miller A, Raison C . The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2015; 16(1):22-34. PMC: 5542678. DOI: 10.1038/nri.2015.5. View

Fava M, Rush A, Thase M, Clayton A, Stahl S, Pradko J . 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Prim Care Companion J Clin Psychiatry. 2005; 7(3):106-13. PMC: 1163271. DOI: 10.4088/pcc.v07n0305. View

Rush A, Trivedi M, Wisniewski S, Stewart J, Nierenberg A, Thase M . Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006; 354(12):1231-42. DOI: 10.1056/NEJMoa052963. View

Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M . Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007; 13(10):1173-5. PMC: 5114125. DOI: 10.1038/nm1651. View

Uher R, Tansey K, Dew T, Maier W, Mors O, Hauser J . An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014; 171(12):1278-86. DOI: 10.1176/appi.ajp.2014.14010094. View

Felger J, Li Z, Haroon E, Woolwine B, Jung M, Hu X . Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry. 2015; 21(10):1358-65. PMC: 4862934. DOI: 10.1038/mp.2015.168. View

Raison C, Rutherford R, Woolwine B, Shuo C, Schettler P, Drake D . A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2012; 70(1):31-41. PMC: 4015348. DOI: 10.1001/2013.jamapsychiatry.4. View

10.

Liu A, Lee M, McManus B, Choy J . Induction of endothelial nitric oxide synthase expression by IL-17 in human vascular endothelial cells: implications for vascular remodeling in transplant vasculopathy. J Immunol. 2012; 188(3):1544-50. DOI: 10.4049/jimmunol.1102527. View

11.

Martino M, Rocchi G, Escelsior A, Fornaro M . Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance. Curr Neuropharmacol. 2012; 10(2):97-123. PMC: 3386509. DOI: 10.2174/157015912800604542. View

12.

Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare A . Inflammation and clinical response to treatment in depression: A meta-analysis. Eur Neuropsychopharmacol. 2015; 25(10):1532-43. DOI: 10.1016/j.euroneuro.2015.06.007. View

13.

Jin W, Dong C . IL-17 cytokines in immunity and inflammation. Emerg Microbes Infect. 2015; 2(9):e60. PMC: 3820987. DOI: 10.1038/emi.2013.58. View

14.

Rush A, Trivedi M, Wisniewski S, Nierenberg A, Stewart J, Warden D . Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11):1905-17. DOI: 10.1176/ajp.2006.163.11.1905. View

15.

Waisman A, Hauptmann J, Regen T . The role of IL-17 in CNS diseases. Acta Neuropathol. 2015; 129(5):625-37. DOI: 10.1007/s00401-015-1402-7. View

16.

Toups M, Trivedi M . Biomarkers and the future of treatment for depression. Cerebrum. 2013; 2012:6. PMC: 3574808. View

17.

Warner-Schmidt J, Vanover K, Chen E, Marshall J, Greengard P . Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011; 108(22):9262-7. PMC: 3107316. DOI: 10.1073/pnas.1104836108. View

18.

Huppert J, Closhen D, Croxford A, White R, Kulig P, Pietrowski E . Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J. 2009; 24(4):1023-34. DOI: 10.1096/fj.09-141978. View

19.

Himmerich H, Schonherr J, Fulda S, Sheldrick A, Bauer K, Sack U . Impact of antipsychotics on cytokine production in-vitro. J Psychiatr Res. 2011; 45(10):1358-65. DOI: 10.1016/j.jpsychires.2011.04.009. View

20.

Ebbinghaus M, Gajda M, Boettger M, Schaible H, Brauer R . The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses. Ann Rheum Dis. 2011; 71(2):253-61. DOI: 10.1136/ard.2011.150318. View