Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

Gaojia Zhang; Ling Li; Yan Kong; Dandan Xu; Yu Bao; Zhiting Zhang; Zhixiang Liao; Jiao Jiao; Dandan Fan; Xiaojing Long; Ji Dai; Chunming Xie; Zhiqiang Meng; Zhijun Zhang

doi:10.1016/j.gendis.2023.02.049

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

Genes Dis. 2023 Apr 10;11(2):1009-1021. doi: 10.1016/j.gendis.2023.02.049. eCollection 2024 Mar.

Authors

Gaojia Zhang¹, Ling Li¹, Yan Kong², Dandan Xu¹, Yu Bao³, Zhiting Zhang⁴, Zhixiang Liao⁵, Jiao Jiao¹, Dandan Fan¹, Xiaojing Long⁵, Ji Dai^{4

6}, Chunming Xie¹, Zhiqiang Meng^{3

4

6}, Zhijun Zhang^{1

7}

Affiliations

¹ Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
² Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
³ Shenzhen Key Laboratory of Drug Addiction, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, Guangdong 518000, China.
⁴ CAS Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
⁵ Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
⁶ Shenzhen-Hong Kong Institute of Brain Sciences-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong 518000, China.
⁷ Brain Cognition and Brain Disease Institute, Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.

Abstract

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder (MDD). Vitamin D-binding protein (VDBP) is altered in plasma and postmortem dorsolateral prefrontal cortex (DLPFC) tissues of MDD patients. Thereby, the role of VDBP as a potential biomarker of MDD diagnosis was further assessed. Total extracellular vesicles (EVs) and brain cell-derived EVs (BCDEVs) were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls (HCs) in discovery (20 MDD patients and 20 HCs) and validation cohorts (88 MDD patients and 38 HCs). VDBP level in the cerebrospinal fluid (CSF) from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide (LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles (MDEVs). VDBP was significantly decreased in MDD plasma MDEVs compared to HCs, and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs. VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice. A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques. VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice. The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

Keywords: Biomarker; Cerebrospinal fluid; Major depressive disorder; Microglia derived extracellular vesicles; Vitamin-D binding protein.