Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Clinic of Neurology and Neurophysiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Transl Psychiatry. 2021 May 21;11(1):308. doi: 10.1038/s41398-021-01423-6.
Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p < 0.001). These results remained significant in a sub-analysis in which all controls were compared with patients suffering from depression matched 1:1 by age and sex (632.26 pg/ml vs. 245.56 pg/ml, p < 0.001). Levels of S100B did not differ significantly between patients and controls (1.06 ng/ml vs. 1.17 ng/ml, p = 0.385). GFAP levels correlated positively with albumin quotients (p < 0.050), S100B levels correlated positively with white blood cell counts (p = 0.001), total protein concentrations (p < 0.001), and albumin quotients (p = 0.001) in the CSF. The significance of the study is limited by its retrospective and open design, methodological aspects, and the control group with idiopathic intracranial hypertension. In conclusion, higher GFAP levels in patients with depression may be indicative of altered microglia activity, especially in astrocytes, in patients with unipolar depression. In addition, correlation analyses support the idea that S100B levels could be related to the integrity of the blood-brain/CSF barrier. Further multimodal and longitudinal studies are necessary to validate these findings and clarify the underlying biological processes.
涉及小胶质细胞活性改变的炎症过程可能在单相抑郁障碍的病理生理学中起重要作用。胶质纤维酸性蛋白(GFAP)和钙结合蛋白 S100B 被认为是小胶质细胞标志物。迄今为止,它们的作用已在单相抑郁症患者的血清和组织材料中进行了研究,但尚未在脑脊液(CSF)中进行研究。因此,本研究旨在检查单相抑郁症患者 CSF 中的 GFAP 和 S100B 水平,以更好地了解它们在情感障碍中的作用。在这项回顾性研究中,调查了 102 例单相抑郁症患者和 39 例特发性颅内高压的心理健康对照者。使用商业上可用的 ELISA 试剂盒测量 GFAP 和 S100B 水平。在常规临床护理期间收集 CSF 常规参数。使用年龄(和性别)校正的 ANOVA 比较 GFAP 和 S100B 的平均值。通过使用独立样本 t 检验分析匹配亚组。此外,在患者组内进行了 GFAP/S100B 水平与 CSF 常规参数之间的相关性分析。单相抑郁症患者的 GFAP 水平明显高于对照组(733.22 pg/ml 与 245.56 pg/ml,p < 0.001)。在对所有对照者与年龄和性别 1:1 匹配的抑郁患者进行亚分析时,这些结果仍然具有统计学意义(632.26 pg/ml 与 245.56 pg/ml,p < 0.001)。患者与对照组之间 S100B 水平无显着差异(1.06 ng/ml 与 1.17 ng/ml,p = 0.385)。GFAP 水平与白蛋白比值呈正相关(p < 0.050),S100B 水平与白细胞计数呈正相关(p = 0.001)、总蛋白浓度(p < 0.001)和 CSF 中的白蛋白比值(p = 0.001)。该研究的意义受到其回顾性和开放性设计、方法学方面以及特发性颅内高压对照组的限制。总之,单相抑郁症患者 GFAP 水平升高可能表明小胶质细胞活性发生改变,尤其是在星形胶质细胞中。此外,相关性分析支持 S100B 水平可能与血脑/CSF 屏障完整性有关的观点。需要进一步的多模态和纵向研究来验证这些发现并阐明潜在的生物学过程。