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Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia

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Abstract

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imbalance in the pathophysiological mechanism of schizophrenia. This study aimed to explore the little-known area regarding the composite score of peripheral cytokines, the IRS/CIRS, and its correlation with white matter integrity and the specific microstructures most affected in schizophrenia. First-episode patients with schizophrenia (FEPS, n = 94) and age- and sex-matched healthy controls (HCs, n = 50) were enrolled in this study. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The whole brain white matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging (DTI) using a 3-T Prisma MRI scanner. The IRS/CIRS in FEPS was significantly higher than that in HCs (p = 1.5 × 10−5) and Cohen’s d effect size was d = 0.74. FEPS had a significantly lower whole-brain white matter average FA (p = 0.032), which was negatively associated with IRS/CIRS (p = 0.029, adjusting for age, sex, years of education, BMI, and total intracranial volume), but not in the HCs (p > 0.05). Among the white matter microstructures, only the cortico-spinal tract was significantly correlated with IRS/CIRS in FEPS (r =  − 0.543, p = 0.0009). Therefore, elevated IRS/CIRS may affect the white matter in FEPS.

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Data Availability

The datasets generated during the current study will be made available from the corresponding author on reasonable request once the dataset has been fully exploited by the authors.

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Acknowledgements

We would like to thank all of the study participants and staff.

Funding

This work was supported by the capital health research and development of special (2022–1-2131); the National Natural Science Foundation of China grants 82171507, 81761128021, and 81771452; the National Institute of Health grant R01MH112180; the Estonian Research Council-European Union Regional Developmental Fund Mobilitas Plus Program No. MOBTT77 and the Estonian Research Council personal research funding team grant project No. PRG878; the National Natural Science Foundation of China (82001415); and the Capital’s Funds for Health Improvement and Research (CFH2020-2–2134).

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Authors and Affiliations

  1. Beijing Huilongguan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China

    Mengzhuang Gou, Wei Li, Jinghui Tong, Yanfang Zhou, Ting Xie, Ting Yu, Wei Feng, Yanli Li, Song Chen, Baopeng Tian, Shuping Tan, Zhiren Wang, Shujuan Pan, Ping Zhang, Junchao Huang & Yunlong Tan

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Xingguang Luo & Chiang-Shan R. Li

  3. Department of Physiology, Faculty of Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia

    Li Tian

  4. Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA

    L. Elliot Hong

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  1. Mengzhuang Gou
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Contributions

Li Tian, Yunlong Tan, and L. Elliot Hong designed the project and obtained the funding for this study. Mengzhuang Gou, Wei Li, Jinghui Tong, Yanfang Zhou, Ting Xie, Ting Yu, Wei Feng, Yanli Li, Song Chen, Shujuan Pan, Ping Zhang, and Junchao Huang were responsible for recruiting patients, performing clinical ratings, neuroimaging, and collecting samples. Mengzhuang Gou analyzed all the data and wrote the paper. Yunlong Tan and Li Tian are responsible for the integrity of data and the accuracy of data analysis. Baopeng Tian, Zhiren Wang, Shuping Tan, Xingguang Luo, Chiang-Shan R. Li, and L. Elliot Hong were invited in evolving the ideas and editing the manuscript. All authors have contributed to and have approved the final manuscript.

Corresponding authors

Correspondence to Li Tian or Yunlong Tan.

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All study-related procedures were performed only after the participants enrolled in this study provided written informed consent. The study protocol was approved by the Ethics Committee of Beijing Huilongguan Hospital.

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Conflict of Interest

LEH has received or plans to receive research funding or consulting fees on research projects from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Luye Pharma, Sound Pharma, IGC Pharma, Takeda, and Regeneron. None was involved in the design, analysis, or outcomes of the study. All other authors declare no competing commercial and financial interests.

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Gou, M., Li, W., Tong, J. et al. Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia. Mol Neurobiol 61, 2754–2763 (2024). https://doi.org/10.1007/s12035-023-03694-0

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