Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
J Affect Disord. 2023 Oct 1;338:341-348. doi: 10.1016/j.jad.2023.06.028. Epub 2023 Jun 17.
Unipolar depression has been associated with increased levels of glial dysfunction and neurodegeneration biomarkers, such as Glial Fibrillary Acidic Protein (GFAP) and Neurofilament light chain (NfL). However, previous studies were conducted on patients taking psychotropic medication and did not monitor longitudinal associations between disease status and GFAP/NfL.
Treatment-naïve patients with unipolar depression (n = 110) and healthy controls (n = 33) were included. GFAP/NfL serum levels were analyzed by Single Molecule Array at baseline and 3-month follow-up. The primary endpoint was GFAP/NfL levels in patients with depression compared with healthy controls. The secondary endpoint was the associations between GFAP/NfL with depression severity and cognitive function.
The patients' mean HAM-D17 score was 18.9 (SD 3.9) at baseline and improved by 7.9 (SD 6.8) points during follow-up. GFAP/NfL was quantified in all individuals. At baseline, the adjusted GFAP levels were -16.8 % (95 % CI: -28.8 to -1.9, p = 0.03) lower among patients with depression compared to healthy controls, while NfL levels were comparable between the groups (p = 0.57). In patients with depression, mean NfL levels increased from baseline to follow-up (0.68 pg/ml, p = 0.03), while GFAP levels were unchanged (p = 0.24). We did not find consistent associations between NfL/GFAP with depression scores or cognitive function.
This largest study of serum NfL/GFAP levels in patients with depression did not support previous findings of elevated GFAP/NfL in patients with depression or positive associations with depression severity. Although limited by a small control group, our study may support the presence of glial dysfunction but not damage to neurons in depression.
单相抑郁症与神经胶质功能障碍和神经退行性生物标志物水平升高有关，例如胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）。然而，之前的研究是在服用精神药物的患者中进行的，并未监测疾病状态与 GFAP/NfL 之间的纵向关联。
纳入了 110 例未经治疗的单相抑郁症患者和 33 名健康对照者。在基线和 3 个月随访时通过单分子阵列分析 GFAP/NfL 血清水平。主要终点是比较抑郁症患者与健康对照组的 GFAP/NfL 水平。次要终点是 GFAP/NfL 与抑郁严重程度和认知功能的相关性。
患者的 HAM-D17 评分在基线时为 18.9（标准差 3.9），随访期间改善了 7.9（标准差 6.8）点。对所有个体进行了 GFAP/NfL 的定量分析。在基线时，与健康对照组相比，抑郁症患者的调整后的 GFAP 水平低了-16.8%（95%置信区间：-28.8 至-1.9，p=0.03），而两组的 NfL 水平无差异（p=0.57）。在抑郁症患者中，NfL 水平从基线到随访期间呈上升趋势（0.68pg/ml，p=0.03），而 GFAP 水平不变（p=0.24）。我们未发现 NfL/GFAP 与抑郁评分或认知功能之间存在一致的相关性。
这是最大规模的关于抑郁症患者血清 NfL/GFAP 水平的研究，并未支持抑郁症患者 GFAP/NfL 升高或与抑郁严重程度呈正相关的先前发现。尽管控制组较小，但我们的研究可能支持抑郁症中存在神经胶质功能障碍而不是神经元损伤。
