{"title":"CD4+ T-cell subsets are associated with chronic stress effects in newly diagnosed anxiety disorders","authors":"Bindong Dai, Tao Li, Jinya Cao, Xiaohui Zhao, Yinan Jiang, Lili Shi, Jing Wei","doi":"10.1016/j.ynstr.2024.100661","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><p>Prior research has indicated a connection between CD4<sup>+</sup> T cells and the development of anxiety, but the specific CD4<sup>+</sup> T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4<sup>+</sup> T cell subsets and anxiety, as well as to explore whether CD4<sup>+</sup> T cell subsets mediate the effect of chronic psychological stress on anxiety.</p></div><div><h3>Methods</h3><p>56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4<sup>+</sup> T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4<sup>+</sup> T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed.</p></div><div><h3>Results</h3><p>We discovered fifteen notably distinct CD4<sup>+</sup> T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27<sup>+</sup>CD45RA<sup>−</sup> Th cells, CD27<sup>+</sup>CD28<sup>+</sup> Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4<sup>+</sup> T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27<sup>+</sup>CD28<sup>+</sup> Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031).</p></div><div><h3>Conclusions</h3><p>Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4<sup>+</sup> T-cell subsets. Specifically, the memory subset of CD27<sup>+</sup>CD45RA<sup>−</sup> Th cells and the naïve subset of CD27<sup>+</sup>CD28<sup>+</sup> Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27<sup>+</sup>CD28<sup>+</sup> Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100661"},"PeriodicalIF":4.3000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000572/pdfft?md5=65c245f59de5070bfa5773fd652c699b&pid=1-s2.0-S2352289524000572-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Stress","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352289524000572","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Aim
Prior research has indicated a connection between CD4+ T cells and the development of anxiety, but the specific CD4+ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4+ T cell subsets and anxiety, as well as to explore whether CD4+ T cell subsets mediate the effect of chronic psychological stress on anxiety.
Methods
56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4+ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4+ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed.
Results
We discovered fifteen notably distinct CD4+ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27+CD45RA− Th cells, CD27+CD28+ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4+ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27+CD28+ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031).
Conclusions
Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4+ T-cell subsets. Specifically, the memory subset of CD27+CD45RA− Th cells and the naïve subset of CD27+CD28+ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27+CD28+ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.