PDF(Pubmed)
Abstract：
Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of \"MCCA+jICA\" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the \"MCCA+jICA\" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from \"MCCA+jICA\" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.
摘要：
重度抑郁症(MDD)是一种全球流行的精神疾病,然而，其病因仍然很大程度上难以捉摸。科学界最近的兴趣集中在铁稳态破坏与MDD之间的相关性上。先前的研究表明，MDD患者的外周血和大脑中的铁水平异常；然而，这些发现并不一致。这项研究涉及95名年龄在18-35岁的MDD患者和66名性别和年龄匹配的健康对照（HCs），他们接受了3D-T1和定量磁化率图（QSM）序列扫描以评估灰质体积（GMV）和脑铁浓度，分别。使用酶联免疫吸附测定（ELISA）在49个MDD个体和41个HC的子集中测量了血浆铁蛋白（pF）水平，同时收集其血液数据。我们假设MDD患者的大脑形态变化与大脑和周围铁水平的异常调节有关。多模态典型相关分析加联合独立成分分析（MCCAjICA）算法主要用于研究脑铁浓度与GMV之间的协变模式。“MCCAjICA”结果显示，MDD患者双侧苍白球和尾状核的QSM值低于HCs。而在双侧丘脑和壳核，MDD患者的QSM值高于HC.这些脑区的GMV值与QSM呈显著正相关。与HC相比，MDD患者的双侧壳核的GMV值增加。与HCs相比，MDD患者中一小部分丘脑的GMV值降低。此外，基底神经节结构中基于感兴趣区域(ROI)的比较结果与"MCCA+jICA"分析结果一致.ELISA结果表明，MDD患者的pF水平高于HC。相关分析表明，pF的增加与左丘脑中的铁含量呈正相关。最后,从“MCCA+jICA”分析获得的协变模式作为分类特征,在支持向量机(SVM)模型中有效区分了MDD患者和HCs.我们的发现表明，MDD患者外周铁蛋白升高可能会破坏大脑中铁的正常代谢，导致脑铁水平和GMV的异常变化。
