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Interaction effect of the serum interleukin-6 level and anxiety on the 12-week pharmacotherapeutic responses of patients with depressive disorders

Research output: Contribution to journalArticlepeer-review

Wonsuk Choi, Hee-Ju Kang, Ju-Wan Kim, Hee Kyung Kim, Ho-Cheol Kang, Ju-Yeon Lee, Sung-Wan Kim, Robert Stewart, Jae-Min Kim

Original languageEnglish
Pages (from-to)166-171
Number of pages6
JournalJournal of affective disorders
Accepted/In press9 Apr 2022
Published1 Jul 2022

Bibliographical note

Funding Information: The study was funded by a grant of National Research Foundation of Korea Grant [ NRF-2019M3C7A1031345 and NRF-2020R1A2C2003472 ] to Jae-Min Kim. Robert Stewart is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London , and from the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust . Robert Stewart is also a National Institute for Health Research (NIHR) Senior Investigator. Publisher Copyright: © 2022 Elsevier B.V.


  • 20220420_IL6 and Dep outcomes_final combined

    20220420_IL6_and_Dep_outcomes_final_combined.docx, 174 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:11 May 2022

    Version:Accepted author manuscript

    Licence:CC BY-NC-ND

King's Authors


Background: Despite the pathogenic role played by interleukin-6 (IL-6) signaling in depression, the association between baseline peripheral IL-6 signaling and the antidepressant treatment responses noted in clinical studies remains controversial. We investigated the effects of the baseline serum IL-6 (sIL-6) level and anxiety symptoms on the 12-week remission rate of depressed outpatients who received stepwise antidepressant treatments. Methods: At baseline, sIL-6 levels were measured, and anxiety symptoms were evaluated using the Hospital Anxiety Depression Scale-Anxiety subscale (HADS-A), in 1094 patients. All received stepwise antidepressant treatment. Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7, was assessed. Results: The individual and interaction effects of the sIL-6 level (as a binary [low vs. high, based on the median value of 1.65 pg/mL] or continuous variable) and the HADS-A score (as a binary [<12 vs. ≥12] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. Patients with both low sIL-6 levels (<1.65 pg/mL) and HADS-A scores <12 had the highest 12-week remission rate; a significant interaction effect was also apparent. This effect was significant even when the data were analyzed as continuous variables. Conclusions: Our study suggests that the sIL-6 level can serve as a biomarker predicting the outcome of antidepressant treatment according to the severity of anxiety symptoms.

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