Unit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund University, Sweden; Department of Gastroenterology and Nutrition, Department of Clinical Sciences Skåne University Hospital, Malmö, Sweden.
Department of Clinical Sciences Malmö, Clinical and Molecular Osteoporosis Research Unit, Lund University, Malmö, Sweden; Department of Geriatrics, Skåne University Hospital, Malmö, Sweden.
J Affect Disord. 2024 Jul 1;356:80-87. doi: 10.1016/j.jad.2024.04.007. Epub 2024 Apr 2.
Systemic low-grade inflammation may be a pathophysiological mechanism in a subtype of depression. In this study we investigate a novel candidate mechanism of inflammatory depression - Selective Glomerular Hypofiltration Syndromes (SGHS) - which are characterized by a reduced estimated glomerular filtration rate (eGFR) based on cystatin C (cysC) relative to eGFR based on creatinine (crea). SGHS have been associated with increased blood levels of pro-inflammatory markers, but have never been investigated in a sample of depressed individuals.
The prevalence of SGHS was compared between 313 patients with difficult-to-treat depression and 73 controls. Since there is no single established eGFR/eGFR-ratio cut-off to define SGHS, several cut-offs were investigated in relation to a depression diagnosis, inflammation, and symptom severity. Plasma inflammatory markers tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6, IL-8, and IL-10 were available from 276 depressed patients. We examined mediation effects of IL-6 on the relationship between SGHS and depression.
Depressed patients were more likely to have SGHS compared to controls defining SGHS as either eGFR/eGFR-ratio < 0.9 (33.2 % vs 20.5 %, p = 0.035) or < 0.8 (15.7 % vs 5.5 %, p = 0.023). Lower eGFR/eGFR-ratio was associated with higher levels of inflammatory markers in depressed patients. IL-6 partly mediated the relationship between SGHS and depression.
This is the first study to demonstrate a link between SGHS and inflammatory depression. If replicated in independent and longitudinal cohorts, this may prove to be a relevant pathophysiological mechanism in some cases of depression that could be targeted in future intervention and prevention studies.
全身性低度炎症可能是一种抑郁症亚型的病理生理机制。在这项研究中，我们研究了一种炎症性抑郁症的新候选机制——选择性肾小球低滤过综合征（SGHS），其特征是基于半胱氨酸蛋白酶抑制剂 C（cysC）的估计肾小球滤过率（eGFR）相对于基于肌酐（crea）的 eGFR 降低。SGHS 与促炎标志物的血液水平升高有关，但从未在抑郁症患者样本中进行过研究。
在 313 名治疗困难的抑郁症患者和 73 名对照者中比较了 SGHS 的患病率。由于没有单一的 eGFR/eGFR 比值截断值来定义 SGHS，因此研究了几个截断值与抑郁症诊断、炎症和症状严重程度的关系。来自 276 名抑郁症患者的血浆炎症标志物肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素（IL）-6、IL-8 和 IL-10 可用。我们研究了 IL-6 在 SGHS 与抑郁症之间的关系中的中介效应。
与对照组相比，抑郁症患者更有可能出现 SGHS，定义 SGHS 为 eGFR/eGFR 比值<0.9（33.2%比 20.5%，p=0.035）或<0.8（15.7%比 5.5%，p=0.023）。较低的 eGFR/eGFR 比值与抑郁症患者的炎症标志物水平升高有关。IL-6 部分介导了 SGHS 与抑郁症之间的关系。
这是第一项证明 SGHS 与炎症性抑郁症之间存在联系的研究。如果在独立的和纵向的队列中得到复制，这可能证明在某些情况下是一种与抑郁症相关的病理生理机制，这可能成为未来干预和预防研究的目标。
