Introduction
Major psychiatric disorders
Biomarker potential of EVs in brain disorders
Methods
Results
RNA cargo
Animal studies
Human studies
Schizophrenia
Bipolar disorder
Major depressive disorder
Protein cargo
Schizophrenia
Bipolar disorder
Major depressive disorder
Metabolite cargo
Author/Year | Disease | Sample size | Exosome source | Potential biomarker | Remarks |
---|---|---|---|---|---|
Du et al. 2019 [29] | SCZ | 149 cases, 146 controls | Serum | A set of 11 miRNA (miR-206 was one of the top ones that was validated by qRT-PCR) | Blood EV miRNAs may be potentially considered as a diagnostic biomarker for SCZ |
Khadimallah et al. 2021 [34] | EPP (SCZ) | 138 cases, 134 controls | Plasma | miR-137 and COX6A2 | Changes in miR-137/COX6A2 plasma EV levels could be used as a proxy marker for dysfunction of PVI cortical microcircuit |
Tsoporis et al. 2022 [33] | SCZ | 11 cases 10 controls | Plasma | miR-203a-3p, DJ-1 protein | miR-203a-3p and DJ-1 protein could be promising targets for the treatment of oxidative stress-related SCZ |
Tan et al. 2021 [35] | SCZ | 5 cases, 5 controls | Plasma | Four differentially expressed EV circRNAs validated by qRT-PCR (has_circ: chr3_196488683_196483770_ − 4913, has_circ: chr5_69175537_69174877_ + 660, has_circ: chr5_143057747_143054439_ + 3308, has_circ: chr6_130956499_130926605_ − 29,894) | miR-34a, miR-34c, and miR-449a, three of the targets for the four identified circRNAs, are thought to play a role in the pathogenesis of SCZ |
Banigan et al. 2013 [27] | SCZ and BD | 8 SCZ cases, 6 BD cases, 6 controls | PFC | miR-497 and miR-29c | Levels of miR-497 and miR-29c were significantly higher in SCZ and BD, respectively, than in controls |
Amoah et al. 2020 [9] | SCZ and BD | 29 SCZ cases, 26 BD cases, 25 controls | Orbito-frontal cortex | miR-223 | Antipsychotics exert cell-specific regulation over miRNA-233 abundance |
Choi et al. 2017 [28] | BD | 4 cases, 6 controls | BA24 | miR-149 | Significantly higher levels of miR-149 in patients; miRNAs in EVs could be possible biomarkers for BD pathogenesis |
Ceylan et al. 2020 [37] | BD | 69 cases, 41 controls | Plasma | miR-484, miR-652–3p, miR-142–3p, miR-185–5p | Downregulated miR-484, miR-652–3p, and miR-142–3p; upregulated miR-185–5p |
Wei et al. 2020 [31] | MDD | 33 cases, 46 controls | Serum | hsa-miR-139-5p | miR-139-5p is a negative regulator of neural stem cell proliferation and neuronal differentiation |
Liang et al. 2020 [38] | MDD | 30 cases, 30 controls | Serum | miR-139-5p | Patients with MDD had higher blood levels of EVs miR-139-5p, which might be a biomarker for MDD |
Li et al. 2021 [30] | TRD (MDD) | 4 cases, 4 controls | Plasma | has-miR-335 and has-miR-1292 | These miRNAs are associated with synaptic function and TRD |
Hung et al. 2021 [39] | MDD | 52 cases, 31 controls | Serum | let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155 | EV negative regulatory miRNAs are useful criteria for antidepressant therapy |
Lee et al. 2020 [46] | SCZ | 60 cases, 60 controls | Plasma (NDEVs and ADEVs) | ADEV-Aβ42 | Higher levels of ADEV-Aβ42 in cases than in controls; EV levels of Aβ and tau may be a stronger indicator of intracellular pathology than peripheral levels |
Goetzl et al. 2021 [48] | FP (SCZ) | 10 cases, 10 controls | Plasma (NDEVs and ADEVs) | ATP synthase, MFN2, CYPD, humanin, MOTS-c, myosin VI, SNPH (mitochondrial proteins) | Lower ATP synthase activity in ADEVs of patients; lower levels of MFN2, CYPD, humanin, and MOTS-c in ADEVs and NDEVs of patients; higher levels of myosin VI in NDEVs than in ADEVs in patients and controls; higher levels of SNPH in NDEVs of patients |
Ranganathan et al. 2022 [5] | SCZ | 24 cases, 12 controls | Plasma | GFAP, α-II-SPECTRIN | GFAP concentration was significantly higher and α-II-Spectrin concentration was significantly lower in patients than in controls |
BD | 55 cases | Plasma (NDEVs) | TNFR/NF-κB | Biomarker potential of NDEVs in psychiatry; brain insulin signaling is a pathophysiological mechanism involved in BD | |
Rhee et al. 2020 [71] | BD and MDD | 42 BD cases, 30 MDD cases, 36 controls | Serum (bacteria-derived EVs) | Prevotella 2 and Ruminococcaceae UCG-002 genera (serum microbiome composition) | Patients with MDD had significantly higher prevalence of the Prevotella 2 and Ruminococcaceae UCG-002 genera than either patients with BD or controls |
Kuwano et al. 2018 [50] | MDD | 34 cases, 34 controls | Plasma (NDEVs) | IL34 | Higher IL34/CD81 was recommended as a diagnostic biomarker for MDD |
Jiang et al. 2021 [52] | MDD | 10 cases, 10 controls | Plasma | SERPINF1, miR-186-5p | EVs SERPINF1 may be a valid biomarker for MDD progression; miR-186-5p may be a possible therapeutic target |
Nasca et al. 2021 [40] | MDD | 64 cases, 29 controls | Serum (brain-enriched EVs) | L1CAM + EVs, IRS-1 | The mean number of L1CAM + EVs and the mean concentration of IRS-1 in L1CAM + EVs were higher in the MDD group than in the controls |
Gelle et al. 2021 [51] | MDD | 42 cases, 40 controls | Serum | BDNF, pro-BDNF | EVs may be involved in modulation of BDNF |
Wallensten et al. 2021 [54] | SED (MDD) | 31 SED cases, 31 MDD cases, 61 controls | Plasma (ADEVs & platelet-derived EVs) | GFAP, AQP4, CD154 | Concentrations of EVs co-expressing AQP4 and GFAP and of CD154-positive EVs were significantly higher in patients with MDD than in controls; BBB leakage of ADEVs may be increased in patients with MDD |
Wang et al. 2021 [64] | MDD | 6 cases, 6 controls | Plasma | SIG-1R | SIG-1R was significantly enriched in EVs from patients; in depression, EVs may have an antidepressant-like effect, suggesting a potential strategy for MDD treatment |
Goetzl et al. 2021 [47] | MDD | 20 cases, 10 controls | Plasma (NDEVs) | 12 neuron functional mitochondrial proteins | 11 proteins were significantly lower and one was higher in NDEVs of patients compared with controls; numerous processes involved in neuronal mitochondria are likely to be altered in MDD |
Du et al. 2021 [55] | SCZ | 385 cases, 332 controls | Serum | 25 EV-derived metabolites with good to excellent performance | L-arginine is connected to NOS1, DPEP2, ALAS1, and GAD1; taurine is connected to GAD1 |
Du et al. 2022 [56] | BD | 32 cases, 40 controls | Serum | A set of 15 metabolites as the optimal set for differentiating patients with BD from controls | The importance of blood EVs metabolites as a powerful potential biomarker for BD diagnosis |