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Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine

BACKGROUND: Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to deter...

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Autores principales: Zhou, Yanling, Wang, Chengyu, Lan, Xiaofeng, Li, Hanqiu, Chao, Ziyuan, Ning, Yuping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444441/
https://www.ncbi.nlm.nih.gov/pubmed/34526064
http://dx.doi.org/10.1186/s12974-021-02245-5
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author Zhou, Yanling
Wang, Chengyu
Lan, Xiaofeng
Li, Hanqiu
Chao, Ziyuan
Ning, Yuping
author_facet Zhou, Yanling
Wang, Chengyu
Lan, Xiaofeng
Li, Hanqiu
Chao, Ziyuan
Ning, Yuping
author_sort Zhou, Yanling
collection PubMed
description BACKGROUND: Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in TRD patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect. METHODS: Sixty-six patients with TRD received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined. RESULTS: TRD patients with pain had a higher antidepressant response rate (χ(2) = 4.062, P = 0.044) and remission rate (χ(2) = 4.062, P = 0.044) than patients without pain. Before ketamine treatment, GM-CSF and IL-6 levels were higher in the pain group than in the non-pain and HC groups. In the pain group, levels of TNF-α and IL-6 at day 13 and GM-CSF, fractalkine, IFN-γ, IL-10, MIP-3α, IL-12P70, IL-17α, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, MIP-1β, and TNF-α at day 26 were lower than those at baseline; in the non-pain group, TNF-α levels at day 13 and day 26 were lower than those at baseline. In the pain group, the changes of IL-6 were associated with improvement in pain intensity (β = 0.333, P = 0.001) and depressive symptoms (β = 0.478, P = 0.005) at day 13. Path analysis showed the direct (β = 2.995, P = 0.028) and indirect (β = 0.867, P = 0.042) effects of changes of IL-6 on improvement in depressive symptoms both were statistically significant. CONCLUSION: This study suggested that an elevated inflammatory response plays a critical role in individual differences in TRD patients with or without pain. Ketamine showed great antidepressant and analgesic effects in TRD patients with pain, which may be related to its effects on modulating inflammation. TRIAL REGISTRATION: ChiCTR, ChiCTR-OOC-17012239. Registered on 26 May 2017 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02245-5.
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spelling pubmed-84444412021-09-16 Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine Zhou, Yanling Wang, Chengyu Lan, Xiaofeng Li, Hanqiu Chao, Ziyuan Ning, Yuping J Neuroinflammation Research BACKGROUND: Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in TRD patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect. METHODS: Sixty-six patients with TRD received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined. RESULTS: TRD patients with pain had a higher antidepressant response rate (χ(2) = 4.062, P = 0.044) and remission rate (χ(2) = 4.062, P = 0.044) than patients without pain. Before ketamine treatment, GM-CSF and IL-6 levels were higher in the pain group than in the non-pain and HC groups. In the pain group, levels of TNF-α and IL-6 at day 13 and GM-CSF, fractalkine, IFN-γ, IL-10, MIP-3α, IL-12P70, IL-17α, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, MIP-1β, and TNF-α at day 26 were lower than those at baseline; in the non-pain group, TNF-α levels at day 13 and day 26 were lower than those at baseline. In the pain group, the changes of IL-6 were associated with improvement in pain intensity (β = 0.333, P = 0.001) and depressive symptoms (β = 0.478, P = 0.005) at day 13. Path analysis showed the direct (β = 2.995, P = 0.028) and indirect (β = 0.867, P = 0.042) effects of changes of IL-6 on improvement in depressive symptoms both were statistically significant. CONCLUSION: This study suggested that an elevated inflammatory response plays a critical role in individual differences in TRD patients with or without pain. Ketamine showed great antidepressant and analgesic effects in TRD patients with pain, which may be related to its effects on modulating inflammation. TRIAL REGISTRATION: ChiCTR, ChiCTR-OOC-17012239. Registered on 26 May 2017 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02245-5. BioMed Central 2021-09-15 /pmc/articles/PMC8444441/ /pubmed/34526064 http://dx.doi.org/10.1186/s12974-021-02245-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhou, Yanling
Wang, Chengyu
Lan, Xiaofeng
Li, Hanqiu
Chao, Ziyuan
Ning, Yuping
Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title_full Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title_fullStr Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title_full_unstemmed Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title_short Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
title_sort plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444441/
https://www.ncbi.nlm.nih.gov/pubmed/34526064
http://dx.doi.org/10.1186/s12974-021-02245-5
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