Bipolar disorder (BD) is a severe chronic disorder that represents one of the main causes of disability among young people. To date, no reliable biomarkers are available to inform the diagnosis of BD or clinical response to pharmacological treatment. Studies focused on coding and noncoding transcripts may provide information complementary to genome-wide association studies, allowing to correlate the dynamic evolution of different types of RNAs based on specific cell types and developmental stage with disease development or clinical course.
Ref. | Sample | RNA Source | RNA Type | Method | Targets | Main Findings |
---|---|---|---|---|---|---|
[28][25] | 15 patients with BD and 17 with MDD during a depression episode and at remission | Whole blood | miRNA | qPCR | miR-499, miR-798 and miR-1908 | Lower levels of all miRNAs in the depressive state compared with remission exclusively in patients with BD |
[27][24] | 58 patients with BD I (19 manic and 39 euthymic) and 51 HCs | Whole blood | miRNA | qPCR | miR-26b-5p, miR-9-5p, miR-29a-3p, miR-106a-5p, miR-106b-5p, miR-107, miR-125a-3p and miR-125b-5p | Levels of miR-29a-3p, miR-106b-5p, miR-107 and miR-125a-3p were significantly higher in patients with BD compared with HCs. Levels of miR-106a-5p and miR-107 were significantly higher in manic patients compared to euthymic patients |
[25][22] | 69 patients with BD (15 depressed, 27 manic and 27 euthymic) and 41 HCs | Plasma exosomes | miRNA | qPCR | Genome wide | Levels of miR-484, miR-652-3p and miR-142-3p were lower, while levels of miR-185-5p were higher in patients with BD compared with HCs. No alterations among different states of BD |
[20][17] | Discovery cohort: 7 patients with BD, 7 with MDD and 6 HCs; validation cohort: 27 patients with BD and 32 with MDD | Plasma | miRNA | Microarray, qPCR | Genome wide | Higher levels of miR-19b-3p in patients with BD compared with patients with MDD |
[33][30] | 54 patients with BD I, 45 with BD II and 42 HCs | PBMC | mRNA | qPCR | COMT, DNMT, GAD67, MECP2, PDYN and SERT | Lower PDYN expression in patients with BD II but not BD I compared with HCs. Higher levels of genes involved in methylation, such as DNMT3b and MECP2, in patients with BD II compared with HCs |
[34][31] | 169 patients with BD and 211 HCs | Whole blood | mRNA | qPCR | NOTCH4 | Higher NOTCH4 levels in patients with BD compared with HC |
[18][32] | 50 patients with BD I and 50 HCs | Whole blood | mRNA, lncRNA | qPCR | SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1 | Levels of VDR, SNHG6, CYP27B1, MALAT1 and Linc00346 were higher in patients compared with HCs |
[24][21] | 20 patients with BD I and 21 HCs | Plasma EV | miRNA | Microarray | Genome wide | 33 nominally significant microRNAs altered in patients with BD |
[17][33] | Discovery cohort: 4 patients with BD and 4 HCs; validation cohort: 16 patients with BD and 16 controls | Whole blood | mRNA, circRNA | NGS and qPCR | Genome wide | 50 circRNAs and 244 mRNAs showed nominally significant higher levels, while 44 circRNAs and 294 mRNAs lower levels in patients with BD compared with HCs |
[16] | Discovery cohort: 18 patients with BD, 44 with MDD, and 31 HCs; validation cohort: 26 patients with BD, 84 with MDD and 74 HCs | Plasma | mRNA, miRNA | NGS and qPCR | Genome wide | Higher levels of hsa-let-7e-5p and hsa-miR-125a-5p in patients with either BD or MDD compared with HCs |
[19][34] | Discovery cohort: 4 patients with BD and 4 HCs; validation cohort: 130 patients with BD and 116 HCs | Whole blood | mRNA, lncRNA | NGS and qPCR | Genome wide | Higher levels of the NR_028138.1 lncRNA in patients with BD compared with HCs |
[21][18] | Discovery cohort: 3 patients with BD II and 3 HCs; validation cohort: 99 patients with BD II and 115 HCs | Serum | miRNA | NGS and qPCR | Genome wide | Levels of miR-7-5p, miR-23b-3p, miR-142-3p, miR-221-5p and miR-370-3p were higher in patients with BD II compared with HCs |
[32][29] | 51 patients with BD and 116 HCs | White blood | mRNA | qPCR | COMT, GCAT, NRG1, PSAT1, SHMT2, SLC1A4 and SRR | A logistic ridge regression model including age, gender and mRNA expression levels of the 7 NMDAR genes showed an AUC of 0.92 in differentiating patients with BD from HCs |
[29][26] | 20 patients with BD, 20 with MDD and 20 HCs | Whole blood | miRNA | Microarray and qPCR | Genome wide | 5 miRNAs showed higher levels specifically in patients with BD compared with HCs (hsa-miR-140-3p, hsa-miR-30d-5p, hsa-miR-330-5p, hsa-miR-378a-5p and hsa-miR-21-3p), while hsa-miR-330-3p and hsa-miR-345-5p showed higher levels in both BD and MDD |
[30][27] | 19 patients with BD, 20 with SZ and 20 HCs | PBMC | circRNA | NGS and qPCR | Genome wide | Levels of 30 circRNAs were specifically altered in patients with BD compared with HCs |
[35] | 50 patients with BD and 50 HCs | PBMC | lncRNA | qPCR | 3 lncRNAs related to oxidative stress (lincRNA-p21, lincRNA-ROR and lincRNA-PINT) | Levels of all lncRNAs were lower in patients with BD, and specifically in male patients with BD, compared with HCs |
[36] | 50 patients with BD and 50 HCs | PBMC | lncRNA | qPCR | 5 lncRNAs related to oxidative stress (H19, LUCAT1, RMST, MEG3 and MT1DP) | Levels of LUCAT1, RMST and MEG3 were lower in patients with BD, specifically in male patients with BD, compared with HCs |
[37] | 63 patients with BD, 42 with MDD and 55 HCs | PBMC | miRNA | qPCR | miR-499-5p | Higher levels of miR-499-5p in patients with BD (regardless of disease phase) compared with HCs |
[22][19] | Serum: 41 patients with BD, 43 with MDD and 93 HCs; fibroblasts: 12 patients with BD, 23 with MDD and 15 HCs | Serum and fibroblasts | mRNA | qPCR | IGFBP2 | Lower IGFBP2 levels exclusively in patients with BD compared with HCs |
[38] | 37 rapid cycling patients with BD in different affective states and 40 HCs | PBMC | mRNA | qPCR | 19 candidate genes | Lower levels of POLG and OGG1 in patients with BD compared with HCs; higher levels of NDUFV2 in patients in a depressed state compared with those in an euthymic state. A gene expression score including all genes showed an AUC of 0.73 in separating patients from HCs |
[39] | 50 patients with BD and 50 HCs | PBMC | lncRNA | qPCR | DISC1 and DISC2 | Lower levels of DISC1 and higher levels of DISC2 in patients with BD compared with HCs (AUC: 0.76 and 0.68, respectively) |
[40] | 50 patients with BD and 50 HCs | PBMC | lncRNA | qPCR | 6 apoptosis-related lncRNAs (CCAT2, TUG1, PANDA, NEAT1, FAS-AS1 and OIP5-AS1) | Levels of CCAT2, TUG1 and PANDA were higher and levels of OIP5-AS1 were lower in patients with BD patients compared with HCs. CCAT2 and TUG1 expression levels were only different in male subgroups |
[23][20] | 11 drug-free manic psychotic patients with BD and 9 HCs | Plasma | miRNA | Nanostring and qPCR | Genome wide | Higher levels of hsa-miR-25-3p and hsa-miR-144-3p, and lower levels of hsa-miR-6721-5p in patients with BD compared with HCs |
[41] | 66 patients with BD and 66 HCs | Plasma | miRNA | qPCR | 15 miRNAs | A model including levels of miR-15b-5p, miR-155-5p, miR-134-5p and miR-652-3p showing a 83.3% sensitivity and 78.8% specificity |
[42] | 56 patients with BD I and 52 HCs | Whole blood | miRNA | qPCR | hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p and hsa-miR-4725 | Higher levels of hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p and lower levels of hsa-miR-145-5p in patients with BD compared with HCs |
[43] | 50 patients with BD and 50 HCs | Whole blood | lncRNA | qPCR | Five NF-κB-associated lncRNAs (ANRIL, CEBPA-DT, H19, NKILA and HNF1A-AS1) | Lower levels of ANRIL, CEBPA-DT and HNF1-AS1 and higher levels of NKILA in patients with BD compared with HC. HFN1A-AS1 showed the best diagnostic parameters (AUC: 0.86). |