Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

Jingqi He; Yisen Wei; Jinguang Li; Ying Tang; Junyu Liu; Zhangyin He; Risheng Zhou; Xingtao He; Honghong Ren; Yanhui Liao; Lin Gu; Ning Yuan; Xiaogang Chen; Jinsong Tang

doi:10.1186/s12888-023-04952-0

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels

BMC Psychiatry. 2023 Jun 27;23(1):470. doi: 10.1186/s12888-023-04952-0.

Authors

Jingqi He^{1

2}, Yisen Wei^{2

3}, Jinguang Li^{2

4}, Ying Tang², Junyu Liu^{2

5}, Zhangyin He^{1

6}, Risheng Zhou⁷, Xingtao He⁷, Honghong Ren^{2

8}, Yanhui Liao¹, Lin Gu^{9

10}, Ning Yuan¹¹, Xiaogang Chen¹², Jinsong Tang^{13

14}

Affiliations

¹ Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Psychiatry, National Center for Mental Disorders, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Department of Psychiatry, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
⁴ Affiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Xiangya Nursing School of Central South University, Changsha, China.
⁶ School of Mental Health, Wenzhou Medical University, Wenzhou, China.
⁷ The Ninth Hospital of Changsha, Changsha, China.
⁸ Department of Psychiatry, Shandong Provincial Hospital, Shandong University, Jinan, China.
⁹ RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.
¹⁰ Research Center for Advanced Science and Technology (RCAST), University of Tokyo, Tokyo, Japan.
¹¹ Hunan Provincial Brain Hospital (The Second People's Hospital of Hunan Province), Changsha, China. 214723726@qq.com.
¹² Department of Psychiatry, National Center for Mental Disorders, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China. Chenxiaogang@csu.edu.cn.
¹³ Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. tangjinsong@zju.edu.cn.
¹⁴ Zigong Mental Health Center, Zigong, China. tangjinsong@zju.edu.cn.

Abstract

Background: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels.

Methods: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously.

Result: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males.

Conclusion: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Keywords: Cytokines; Inflammation; Interleukin-6; Sex; Treatment-resistant schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Humans
Inflammation
Interleukin-6
Male
Schizophrenia* / drug therapy
Schizophrenia, Treatment-Resistant
Sex Characteristics

Substances

Interleukin-6
IL6 protein, human