Table 3.
Depressive disorder (DSM-5 or similar) effects on circulation extracellular vesicles.
| Study Year | Sample | Severity of Depression | Extracellular Vesicles | Major Findings |
|---|---|---|---|---|
| 2020 [111] |
Subjects with MDD (drug-free; 28 ± 1.7 years; n = 33) or Schizophrenia (drug-free; 29 ± 1; n = 36) and HC (29 ± 1; n = 46) | HAMD and MADRS | Blood collection: overnight fasting Isolation and detection: serum; SEC + centrifugation/concentration Characterization: qRT-PCR, miRNA-seq, bioinformatics |
38 blood exosomal miRNAs differently expressed in MDD and HC, 24 were upregulated and 14 downregulated (from 351 miRNAs for differential analysis); axon guidance and development, dendrite, Wnt signaling pathway, neuron-to-neuron synapse and PI3K-Akt signaling pathway were closely related to MDD; ↑ hsa-miR-139-5p top differentially expressed between MDD and HC (specific for MDD, not Schizophrenia); hsa-miR-139-5p and a cluster of 15 miRNAs or 10 miRNAs with excellent performance to differentiate between MDD and schizophrenia (MDD-specific) |
| 2020 [113] |
Subjects with MDD in a current major depressive episode (43 ± 2 years; n = 64) and age and sex-matched HC (38 ± 2 years; n = 29) | HDRS-21 | Blood collection: 6 h fasting, 6 h no PE Isolation and detection: plasma; precipitation + ultracentrifugation; WB expression array (CD63, CD81, ALIX, FLOT1, ICAM1, EpCam, ANXA5, and TSG101) Characterization: ExoCET (AChE activity), FC, ELISA |
Unchanged EXOs between MDD and HC; ↑ L1CAM+ EXOs in MDD; ↑ IRS-1 in L1CAM+ EXOs in MDD (no sex or psychotropic medication differences); no between-group difference in pSer-IRS-1 in L1CAM+ EXOs (only sex differences in MDD group); IRS-1 in L1CAM+ EXOs correlated with systemic IR for HC but not MDD; no relationship between IRS-1 in L1CAM+ EXOs and depression severity in MDD; the highest IRS-1 in L1CAM+ EXOs correlated with depressed mood, feelings of guilt, suicidality and anhedonia (MDD) |
| 2020 [112] |
Subjects with MDD (34 ± 11; n = 30) or BD subjects (46 ± 10; n = 42) and HC (43 ± 6; n = 36) | HAMD and YMRS | Blood collection: no specifications Isolation and detection: serum; centrifugation + filtration (0.22 μm) Characterization: PCR, bioinformatics |
EVs Prevotella 2 and Ruminococcaceae UCG-002 genera significantly more prevalent in MDD than BD or HC; apoptosis function differed between groups |
| 2018 [114] |
MDD Subjects in acute episode of MDD (drug-free, 31 ± 7; n = 34) and sex and age-matched HC (n = 34) | BDI-II | Blood collection: no specifications Isolation and detection: plasma; sandwich ELISA detection (CD81) Characterization: sandwich ELISA |
Neuron-related blood biomarkers moderately to strongly positively correlated with CD81; ↑ IL-34/CD81 in MDD (compared to control); SYP/CD81 and TNFR1/CD81 positively correlated with depression scores |
Notes: “Microparticles” and “microvesicles” terminology was used by most authors to define EVs < 1 μm. Therefore, we used the generic nomenclature extracellular vesicles (EVs). We specifically used the terminology exosomes (EXOs) when EVs were characterized based on appropriate markers. The markers and nomenclature used for different circulatory cell-derived EVs are illustrated in Figure 1. AChE, acetylcholinesterase, BD, bipolar disorder, BDI-II, Beck depression inventory-second edition, ELISA, enzyme-linked immunosorbent assay, FC, flow cytometry, HAMD, Hamilton rating scale for depression, HC, healthy controls, HDRS-21, Hamilton Depression Rating Scale, IL-34, interleukin-34, IRS-1, insulin receptor substract-1, L1CAM, L1 cell adhesion molecule, MADRS, Montgomery–Asberg depression rating scale, MDD, major depressive disorder, PCR, polymerase chain reaction, qRT-PCR, quantitative reverse transcription polymerase chain reaction, SEC, size exclusion chromatography, SYP, synaptophysin, TNFR1, tumor necrosis factor receptor 1, WB, Western blot, YMRS, 11-item Young Mania Rating Scale and ↑, increase.