抑郁症患者的社交抑制与白细胞介素6诱导转录因子STAT3激活谱的改变有关

IF 3.7 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health Pub Date : 2025-03-01 DOI:10.1016/j.bbih.2025.100968

Katharina von Knebel , Julia Staab , Anke Gregus , Linus Remling , Oliver Wirths , Carsten Spitzer , Christoph Herrmann-Lingen , Holger M. Reichardt , Thomas Meyer

{"title":"抑郁症患者的社交抑制与白细胞介素6诱导转录因子STAT3激活谱的改变有关","authors":"Katharina von Knebel , Julia Staab , Anke Gregus , Linus Remling , Oliver Wirths , Carsten Spitzer , Christoph Herrmann-Lingen , Holger M. Reichardt , Thomas Meyer","doi":"10.1016/j.bbih.2025.100968","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Numerous studies have described the role of STAT3 (signal transducer and activator of transcription 3) in infections, but little is known on whether this transcription factor is linked to negative affectivity (NA) and social inhibition (SI), leading to social withdrawal as a typical symptom of various infections.</div></div><div><h3>Methods</h3><div>In this study, we isolated peripheral blood mononuclear cells (PBMCs) from 63 consecutive depressed patients (mean age 41.4 ± 16.1 years; 40 females) before and after psychotherapeutic intervention and measured STAT3 tyrosine phosphorylation (pSTAT3) with and without <em>in vitro</em> interleukin-6 (IL-6) stimulation of these cells using flow cytometry. In addition, all study participants were assessed for NA and SI using the German version of the Type D Scale-14 (DS-14) questionnaire with a cut-off level of ≥10 for each subscale.</div></div><div><h3>Results</h3><div>While NA was unrelated to STAT3 activity, PBMCs from SI-positive patients had an increased baseline STAT3 activation level, which made the cells less sensitive to <em>in vitro</em> IL-6 stimulation (11.5% vs. 9.1%, p = 0.036). The stimulatory capacity, defined as the difference in pSTAT3 levels from IL-6-stimulated to unstimulated cells during hospitalization, was significantly lower in PBMCs from SI-positive than from SI-negative patients (−1.7% vs. 6.6%, p = 0.007). The sensitivity of PBMCs to IL-6 stimulation was negatively correlated with the SI score (r = −0.295, p = 0.019). Of note, the altered sensitivity to STAT3 phosphorylation remained stable, when adjusted for clinically relevant confounders in multivariate analysis (Exp(β) = 0.891, 95%-confidence interval = 0.804–0.988, p = 0.029).</div></div><div><h3>Conclusion</h3><div>These findings point towards a possible relationship between STAT3 signaling and social inhibition in depressed patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100968"},"PeriodicalIF":3.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Social inhibition in depressed patients is associated with an altered activation profile of the interleukin-6-inducible transcription factor STAT3\",\"authors\":\"Katharina von Knebel , Julia Staab , Anke Gregus , Linus Remling , Oliver Wirths , Carsten Spitzer , Christoph Herrmann-Lingen , Holger M. Reichardt , Thomas Meyer\",\"doi\":\"10.1016/j.bbih.2025.100968\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Numerous studies have described the role of STAT3 (signal transducer and activator of transcription 3) in infections, but little is known on whether this transcription factor is linked to negative affectivity (NA) and social inhibition (SI), leading to social withdrawal as a typical symptom of various infections.</div></div><div><h3>Methods</h3><div>In this study, we isolated peripheral blood mononuclear cells (PBMCs) from 63 consecutive depressed patients (mean age 41.4 ± 16.1 years; 40 females) before and after psychotherapeutic intervention and measured STAT3 tyrosine phosphorylation (pSTAT3) with and without <em>in vitro</em> interleukin-6 (IL-6) stimulation of these cells using flow cytometry. In addition, all study participants were assessed for NA and SI using the German version of the Type D Scale-14 (DS-14) questionnaire with a cut-off level of ≥10 for each subscale.</div></div><div><h3>Results</h3><div>While NA was unrelated to STAT3 activity, PBMCs from SI-positive patients had an increased baseline STAT3 activation level, which made the cells less sensitive to <em>in vitro</em> IL-6 stimulation (11.5% vs. 9.1%, p = 0.036). The stimulatory capacity, defined as the difference in pSTAT3 levels from IL-6-stimulated to unstimulated cells during hospitalization, was significantly lower in PBMCs from SI-positive than from SI-negative patients (−1.7% vs. 6.6%, p = 0.007). The sensitivity of PBMCs to IL-6 stimulation was negatively correlated with the SI score (r = −0.295, p = 0.019). Of note, the altered sensitivity to STAT3 phosphorylation remained stable, when adjusted for clinically relevant confounders in multivariate analysis (Exp(β) = 0.891, 95%-confidence interval = 0.804–0.988, p = 0.029).</div></div><div><h3>Conclusion</h3><div>These findings point towards a possible relationship between STAT3 signaling and social inhibition in depressed patients.</div></div>\",\"PeriodicalId\":72454,\"journal\":{\"name\":\"Brain, behavior, & immunity - health\",\"volume\":\"44 \",\"pages\":\"Article 100968\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, behavior, & immunity - health\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666354625000262\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, behavior, & immunity - health","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666354625000262","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

大量研究已经描述了STAT3（信号换能器和转录激活因子3）在感染中的作用，但对于该转录因子是否与负情感（NA）和社会抑制（SI）相关，导致社会退缩作为各种感染的典型症状知之甚少。方法在本研究中，我们从63例连续抑郁患者(平均年龄41.4±16.1岁；40名女性)在心理治疗干预前后，并使用流式细胞术测量在体外白细胞介素-6 （IL-6）刺激和不刺激这些细胞的STAT3酪氨酸磷酸化（pSTAT3）。此外，所有研究参与者使用德文版D型量表-14 （DS-14）问卷进行NA和SI评估，每个子量表的截止水平≥10。结果虽然NA与STAT3活性无关，但si阳性患者的pbmc具有较高的基线STAT3激活水平，这使得细胞对体外IL-6刺激的敏感性降低（11.5%比9.1%,p = 0.036）。刺激能力（定义为住院期间il -6刺激细胞与未刺激细胞之间pSTAT3水平的差异）在si阳性患者的pbmc中显著低于si阴性患者（- 1.7% vs. 6.6%, p = 0.007）。PBMCs对IL-6刺激的敏感性与SI评分呈负相关（r = - 0.295, p = 0.019）。值得注意的是，在多变量分析中调整临床相关混杂因素后，对STAT3磷酸化的敏感性改变保持稳定（Exp(β) = 0.891, 95%可信区间= 0.804-0.988,p = 0.029）。结论这些发现提示STAT3信号通路与抑郁症患者社交抑制之间可能存在关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Social inhibition in depressed patients is associated with an altered activation profile of the interleukin-6-inducible transcription factor STAT3

Objective

Numerous studies have described the role of STAT3 (signal transducer and activator of transcription 3) in infections, but little is known on whether this transcription factor is linked to negative affectivity (NA) and social inhibition (SI), leading to social withdrawal as a typical symptom of various infections.

Methods

In this study, we isolated peripheral blood mononuclear cells (PBMCs) from 63 consecutive depressed patients (mean age 41.4 ± 16.1 years; 40 females) before and after psychotherapeutic intervention and measured STAT3 tyrosine phosphorylation (pSTAT3) with and without in vitro interleukin-6 (IL-6) stimulation of these cells using flow cytometry. In addition, all study participants were assessed for NA and SI using the German version of the Type D Scale-14 (DS-14) questionnaire with a cut-off level of ≥10 for each subscale.

Results

While NA was unrelated to STAT3 activity, PBMCs from SI-positive patients had an increased baseline STAT3 activation level, which made the cells less sensitive to in vitro IL-6 stimulation (11.5% vs. 9.1%, p = 0.036). The stimulatory capacity, defined as the difference in pSTAT3 levels from IL-6-stimulated to unstimulated cells during hospitalization, was significantly lower in PBMCs from SI-positive than from SI-negative patients (−1.7% vs. 6.6%, p = 0.007). The sensitivity of PBMCs to IL-6 stimulation was negatively correlated with the SI score (r = −0.295, p = 0.019). Of note, the altered sensitivity to STAT3 phosphorylation remained stable, when adjusted for clinically relevant confounders in multivariate analysis (Exp(β) = 0.891, 95%-confidence interval = 0.804–0.988, p = 0.029).