Qunjun Liang , Bo Peng , Shengli Chen , Hongyue Wei , Shiwei Lin , Xiaoshan Lin , Ying Li , Yingli Zhang , Zhifeng Zhou , Ziyun Xu , Gangqiang Hou , Yingwei Qiu
{"title":"Inflammation and psychomotor retardation in depression: The moderating role of glymphatic system","authors":"Qunjun Liang , Bo Peng , Shengli Chen , Hongyue Wei , Shiwei Lin , Xiaoshan Lin , Ying Li , Yingli Zhang , Zhifeng Zhou , Ziyun Xu , Gangqiang Hou , Yingwei Qiu","doi":"10.1016/j.bbi.2025.03.024","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Psychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.</div></div><div><h3>Methods</h3><div>A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.</div></div><div><h3>Results</h3><div>GS function in patients was impaired compared with that in HCs (<em>t</em> = –2.635, <em>p</em> = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (<em>F</em> = 6.725, <em>p</em> = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (<em>F</em> = 13.86, <em>p</em> = 0.047) and FC (<em>F</em> = 13.765, <em>p</em> < 0.001) in the motor circuit.</div></div><div><h3>Conclusion</h3><div>A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 387-395"},"PeriodicalIF":8.8000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0889159125001096","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Psychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.
Methods
A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.
Results
GS function in patients was impaired compared with that in HCs (t = –2.635, p = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (F = 6.725, p = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (F = 13.86, p = 0.047) and FC (F = 13.765, p < 0.001) in the motor circuit.
Conclusion
A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.