Depressive disorder and antidepressants from an epigenetic point of view

Table 3 MicroRNA expression studies on depressed suicide victims

miRNAs	Alteration	Subjects and collected tissue	Ref.
miR-218	↓ miR-218 and ↑ DCC in PFC	11 male suicide victims with MDD and 12 male controls. Brain tissue (PFC; BA44)	Torres-Berrío et al[82], 2017
↓ miR-142-5p, miR-137, miR-489, miR-148b, miR-101, miR-324-5p, miR-301a, miR-146a, miR-335, miR-494, miR-20b, miR-376a*, miR-190, miR-155, miR-660, miR-130a, miR-27a, miR-497, miR-10a, miR-20a, miR-142-3p. ↓ by 30% or more: miR-211, miR-511, miR-424, miR-369-3p, miR-597, miR-496, miR-517c, miR-184, miR-34a, miR-34b-5p, miR-24-1*, miR-594, miR-34c-5p, miR-17*, miR-545, miR-565	Globally ↓ miRNAs expression by 17% on average in depressed subjects. miR-148b targets DNMT3B, protein level was upregulated in depressed subjects. miR-34a targets BCL2, protein level was downregulated in depressed subjects	18 suicide victims (2 females and 16 males) with depression and 17 male control subjects. Brain tissue (PFC; BA9)	Smalheiser et al[83], 2012
miR-1202	↓ miR-1202, and ↑ GRM4 mRNA expression in BA44	25 suicide victims (2 females and 23 males) with MDD and 29 control subjects (4 females and 25 males). Brain tissue (PFC; BA44). 32 subjects with MDD (24 females and 10 males) and 18 control subjects (8 females and 10 males). Blood	Lopez et al[84], 2014
miR-30e	↑ miR-30e, ↓ ZDHHC21 protein	16 suicide victims (7 females and 9 males) with MDD and 16 controls (6 females and 10 males). Brain tissue (PFC; BA9)	Gorinski et al[85], 2019
miR-19a-3p	↑ miR-19a-3p (might be involved in the modulation of TNF-α signaling)	12 depressed patients with severe suicidal ideation, 12 control subjects. PBMC	Wang et al[86], 2018
More than 10 miRNAs	↑ miR-17-5p, miR-20b-5p, miR-106a-5p, miR-330-3p, miR-541-3p, miR-582-5p, miR-890, miR-99b-3p, miR-550-5p, miR-1179. ↓ miR-409-5p, let-7g-3p, miR-1197	9 depressed suicide victims (3 females and 6 males) and 11 control subjects (2 females and 9 males). Brain tissue (locus coeruleus)	Roy et al[37], 2017
miR-326	↓ miR-326, ↑ UCN1	5 male suicide victims with MDD and 8 male controls. Edinger-Westphal nucleus	Aschrafi et al[87], 2016
10 miRNAs tested	↑ miR-34c-5p, miR-139-5p, miR-195, miR-320c. ↓ SAT1 and SMOX mRNA	15 male suicide victims with MDD and 16 male control subjects. Brain tissue (BA44)	Lopez et al[88], 2014
miR-204-5p, miR-320b, miR-323a-3p, miR-331-3p	↑ miR-204-5p, miR-320b, miR-323a-3p, miR-331-3p in ACC and lateral habenula. miR-323a-3p influences the expression of ERBB4. Decreased expression in ACC and lateral habenula	39 suicide victims with MDD (13 females and 26 males) and 41 control subjects (10 females and 31 males) for ACC region. 24 suicide victims with MDD (10 females and 14 males), 13 control subjects (5 females and 8 males) for lateral habenula. Brain tissue (ACC and lateral habenula)	Fiori et al[89], 2021
171 miRNA differently expressed	↑ 117 miRNAs. ↓ 54 miRNAs	22 (10 females and 12 males) MDD subjects (10 died by suicide, 12 died from cause other than suicide) and 25 control subjects (10 females and 15 males). Brain tissue (ACC)	Yoshino et al[90], 2020
miR-128-3p	↑ miR-128-3p. ↓ WNT5B, DVL1 and LEF1	20 MDD (10 females and 10 males) subjects and 22 control subjects (9 females and 13 males). Brain tissue (AMG)	Roy et al[91], 2020
miR-16	↓ miR-16	36 MDD (21 females and 15 males) subjects and 30 controls (17 females and 13 males). CSF	Song et al[92], 2015

↓: Decreased expression; ↑: Increased expression; ACC: Dorsal anterior cingulate cortex; AMG: Amygdala; BA44: Brodmann area 44; BA9: Brodmann area 9; BCL2: B-cell lymphoma 2; CSF: Cerebrospinal fluid; DCC: Developmental netrin-1 guidance cue receptor; DNMT3B: Gene coding for DNA methyltransferase 3; DVL1: Dishevelled segment polarity 1; GRM4: Gene coding for metabotropic glutamate receptor 4; LEF1: Lymphoid enhancer binding factor 1; MDD: Major depressive disorder; miR: MicroRNA; mRNA: Messenger RNA; PBMC: Peripheral blood mononuclear cells; PFC: Prefrontal cortex; SAT1: Gene coding for spermidine/spermine N1 -acetyltransferase 1; SMOX: Gene coding for spermine oxidase; TNFα: Tumor necrosis factor; UCN1: Urocortin; WNT5B: Wingless-related integration site, member 5B.