title: Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications.
abstract: Major depressive disorder (MDD) is a major public health concern. Despite tremendous advances, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by modulating translation, messenger RNA (mRNA) degradation, or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recent studies demonstrating the involvement of miRNAs in several aspects of neural plasticity, neurogenesis, and stress response, and more direct studies in human postmortem brain provide strong evidence that miRNAs can not only play a critical role in MDD pathogenesis, but can also open up new avenues for the development of therapeutic targets. Circulating miRNAs are now being considered as possible biomarkers in disease pathogenesis and in monitoring therapeutic responses because of the presence and/or release of miRNAs in blood cells as well as in other peripheral tissues. In this review, these aspects are discussed in a comprehensive and critical manner.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarker; depression; miRNA; neural plasticity; neurogenesis; stress
references.citation: Anal Biochem. 2009 Apr 15;387(2):303-14
references.pmid: 19454234
references.citation: Eur J Neurosci. 2008 May;27(9):2250-61
references.pmid: 18445216
references.citation: Mol Cell. 2011 May 20;42(4):500-10
references.pmid: 21596314
references.citation: J Affect Disord. 2011 Jul;132(1-2):99-103
references.pmid: 21371756
references.citation: EMBO J. 2009 Mar 18;28(6):697-710
references.pmid: 19197241
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5395-400
references.pmid: 9144248
references.citation: Genome Biol. 2004;5(3):R13
references.pmid: 15003116
references.citation: Eur J Neurosci. 2005 Mar;21(5):1299-303
references.pmid: 15813939
references.citation: Int J Neuropsychopharmacol. 2009 Nov;12(10):1337-54
references.pmid: 19835659
references.citation: Development. 2008 Dec;135(23):3911-21
references.pmid: 18997113
references.citation: BMC Genomics. 2009 Jul 29;10:340
references.pmid: 19640296
references.citation: Biochem Pharmacol. 2010 Dec 15;80(12):1860-8
references.pmid: 20599772
references.citation: PLoS One. 2012;7(3):e30679
references.pmid: 22427800
references.citation: PLoS One. 2012;7(3):e33201
references.pmid: 22427989
references.citation: ScientificWorldJournal. 2010 Apr 13;10:713-26
references.pmid: 20419280
references.citation: Eur Neuropsychopharmacol. 2013 Jan;23(1):55-62
references.pmid: 23154052
references.citation: J Neurosci. 2008 Apr 23;28(17):4322-30
references.pmid: 18434510
references.citation: J Affect Disord. 2011 Mar;129(1-3):47-55
references.pmid: 20708276
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16426-31
references.pmid: 16260724
references.citation: Science. 1997 Mar 14;275(5306):1586-93
references.pmid: 9054346
references.citation: Clin Chem. 2010 Nov;56(11):1733-41
references.pmid: 20847327
references.citation: Front Neurosci. 2012 May 21;6:71
references.pmid: 22661924
references.citation: J Neurobiol. 2005 Jul;64(1):116-31
references.pmid: 15883999
references.citation: Expert Opin Investig Drugs. 2013 Feb;22(2):217-33
references.pmid: 23253113
references.citation: Nat Cell Biol. 2009 Jun;11(6):705-16
references.pmid: 19465924
references.citation: Cell. 2006 Jan 13;124(1):191-205
references.pmid: 16413491
references.citation: Curr Mol Med. 2013 Nov;13(9):1432-45
references.pmid: 23971736
references.citation: Genes Dev. 2002 Oct 1;16(19):2497-508
references.pmid: 12368261
references.citation: Curr Biol. 2002 Apr 30;12(9):735-9
references.pmid: 12007417
references.citation: Front Genet. 2012 May 17;3:82
references.pmid: 22629284
references.citation: Metab Eng. 2006 Nov;8(6):672-83
references.pmid: 16996764
references.citation: Transl Psychiatry. 2011 Nov 22;1:e56
references.pmid: 22833211
references.citation: Circ Res. 2010 Sep 3;107(5):677-84
references.pmid: 20595655
references.citation: Bioinformatics. 2005 Dec 15;21(24):4348-55
references.pmid: 16234317
references.citation: Biol Psychiatry. 2000 Oct 15;48(8):721-31
references.pmid: 11063969
references.citation: Arch Gen Psychiatry. 2001 Jun;58(6):545-53
references.pmid: 11386983
references.citation: Nat Genet. 2008 Jun;40(6):751-60
references.pmid: 18469815
references.citation: J Exp Med. 2007 Jul 9;204(7):1553-8
references.pmid: 17606634
references.citation: Prog Brain Res. 2008;169:145-58
references.pmid: 18394472
references.citation: J Neurochem. 2005 Aug;94(4):896-905
references.pmid: 16092937
references.citation: J Chem Neuroanat. 2011 Oct;42(2):142-56
references.pmid: 21515361
references.citation: Urol Oncol. 2010 Nov-Dec;28(6):655-61
references.pmid: 19375957
references.citation: Nat Cell Biol. 2011 Apr;13(4):423-33
references.pmid: 21423178
references.citation: Pharmacogenomics. 2012 Jul;13(10):1129-39
references.pmid: 22909203
references.citation: Pharmacogenomics. 2011 Feb;12(2):171-84
references.pmid: 21332311
references.citation: Nat Neurosci. 2004 Feb;7(2):113-7
references.pmid: 14703574
references.citation: PLoS One. 2012;7(5):e38174
references.pmid: 22693596
references.citation: Behav Brain Res. 2010 Mar 17;208(1):265-9
references.pmid: 19913057
references.citation: J Neurosci. 2006 Oct 11;26(41):10508-13
references.pmid: 17035535
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8
references.pmid: 21383194
references.citation: Bipolar Disord. 2002 Jun;4(3):183-94
references.pmid: 12180273
references.citation: Prog Brain Res. 2000;126:397-412
references.pmid: 11105659
references.citation: Eur Neuropsychopharmacol. 2004 Oct;14(5):393-405
references.pmid: 15336301
references.citation: Endocrinology. 2009 May;150(5):2220-8
references.pmid: 19131573
references.citation: J Neurosci. 2010 Nov 10;30(45):15007-18
references.pmid: 21068306
references.citation: Trends Neurosci. 2012 May;35(5):325-34
references.pmid: 22436491
references.citation: Genome Biol. 2007;8(8):R173
references.pmid: 17711588
references.citation: J Psychiatr Res. 2010 Oct;44(14):971-8
references.pmid: 20398908
references.citation: Neuron. 2009 Sep 24;63(6):803-17
references.pmid: 19778509
references.citation: Mol Psychiatry. 1998 May;3(3):190-1
references.pmid: 9672886
references.citation: Trends Cell Biol. 2004 Aug;14(8):461-9
references.pmid: 15308213
references.citation: Psychiatr Clin North Am. 1996 Jun;19(2):179-200
references.pmid: 8827185
references.citation: Curr Top Behav Neurosci. 2013;14:153-79
references.pmid: 22903751
references.citation: Eur Neuropsychopharmacol. 2013 Jul;23(7):602-11
references.pmid: 22925464
references.citation: CNS Drugs. 2002;16(6):361-72
references.pmid: 12027783
references.citation: Biol Psychiatry. 2001 Mar 1;49(5):391-404
references.pmid: 11274650
references.citation: J Neurol Neurosurg Psychiatry. 1993 Dec;56(12):1290-4
references.pmid: 8270929
references.citation: Exp Cell Res. 2008 Aug 15;314(14):2618-33
references.pmid: 18619591
references.citation: Neuron. 2009 Dec 24;64(6):871-84
references.pmid: 20064393
references.citation: Nat Rev Clin Oncol. 2011 Jun 07;8(8):467-77
references.pmid: 21647195
references.citation: J Neurochem. 2001 May;77(3):916-28
references.pmid: 11331420
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9093-8
references.pmid: 18577589
references.citation: Arch Gen Psychiatry. 2003 Aug;60(8):804-15
references.pmid: 12912764
references.citation: Transl Psychiatry. 2012 Nov 13;2:e185
references.pmid: 23149449
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2422-7
references.pmid: 16461918
references.citation: Front Psychiatry. 2013 Jul 10;4:66
references.pmid: 23847554
references.citation: Science. 2010 Sep 17;329(5998):1537-41
references.pmid: 20847275
references.citation: Cell Mol Life Sci. 2012 Jan;69(1):89-102
references.pmid: 21833581
references.citation: Nat Neurosci. 2009 Apr;12(4):399-408
references.pmid: 19287386
references.citation: Nature. 2010 Aug 26;466(7310):1105-9
references.pmid: 20622856
references.citation: J Neurosci. 2013 May 29;33(22):9408-19
references.pmid: 23719809
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13290-5
references.pmid: 9789081
references.citation: Arch Gen Psychiatry. 2003 Mar;60(3):273-82
references.pmid: 12622660
references.citation: Genome Biol. 2004;5(9):R68
references.pmid: 15345052
references.citation: Nature. 1999 Nov 25;402(6760):421-5
references.pmid: 10586883
references.citation: Cell. 2012 Mar 16;148(6):1172-87
references.pmid: 22424228
references.citation: Nat Rev Neurosci. 2006 Dec;7(12):911-20
references.pmid: 17115073
references.citation: Mol Cell Neurosci. 2010 Jan;43(1):146-56
references.pmid: 19850129
references.citation: Biochim Biophys Acta. 2014 Jan;1844(1 Pt B):191-7
references.pmid: 23954304
references.citation: PLoS One. 2011;6(12):e28656
references.pmid: 22194877
references.citation: Nature. 2011 Aug 03;476(7361):458-61
references.pmid: 21814201
references.citation: Neural Plast. 2012;2012:854285
references.pmid: 23346419
references.citation: J Neurosci. 2012 Jun 27;32(26):8879-89
references.pmid: 22745489
references.citation: Mol Psychiatry. 2007 Sep;12(9):815-25
references.pmid: 17440432
references.citation: Nature. 2006 Jan 19;439(7074):283-9
references.pmid: 16421561
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14374-8
references.pmid: 14614133
references.citation: Nat Neurosci. 2011 Sep 04;14(10):1240-2
references.pmid: 21892155
references.citation: Science. 2012 Oct 5;338(6103):72-5
references.pmid: 23042885
references.citation: Neuroscience. 2012 Oct 25;223:285-95
references.pmid: 22898830
references.citation: J Psychiatry Neurosci. 1999 Mar;24(2):116-21
references.pmid: 10212553
references.citation: Neurosci Behav Physiol. 1992 Jan-Feb;22(1):59-65
references.pmid: 1614620
references.citation: J Cell Biol. 2010 Apr 5;189(1):127-41
references.pmid: 20368621
references.citation: J Psychiatr Res. 2011 Jan;45(1):92-5
references.pmid: 20546789
references.citation: Genomics Proteomics Bioinformatics. 2012 Oct;10(5):285-94
references.pmid: 23200138
references.citation: RNA. 2010 Aug;16(8):1516-29
references.pmid: 20584895
references.citation: Biochim Biophys Acta. 2008 Aug;1779(8):471-8
references.pmid: 18194678
references.citation: Front Genet. 2012 Sep 26;3:194
references.pmid: 23056009
references.citation: Acta Biochim Biophys Sin (Shanghai). 2007 Sep;39(9):708-14
references.pmid: 17805466
references.citation: Int J Neuropsychopharmacol. 2011 Nov;14(10):1315-25
references.pmid: 21275079
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):7964-9
references.pmid: 18524951
references.citation: Neuron. 2012 Jan 12;73(1):35-48
references.pmid: 22243745
references.citation: Trends Neurosci. 2010 Dec;33(12):569-79
references.pmid: 20961627
references.citation: Neurosci Res. 2012 Jul;73(3):179-90
references.pmid: 22521503
references.citation: Hum Mol Genet. 2011 Jun 1;20(11):2225-37
references.pmid: 21421997
references.citation: J Evol Biol. 2006 Nov;19(6):1768-74
references.pmid: 17040373
references.citation: Neuroscience. 2010 Feb 17;165(4):1301-11
references.pmid: 19958814
references.citation: Zhongguo Zhong Yao Za Zhi. 2013 May;38(10):1585-9
references.pmid: 23947143
references.citation: Front Neuroendocrinol. 2010 Apr;31(2):128-33
references.pmid: 19683017
references.citation: Science. 2007 Sep 21;317(5845):1764-7
references.pmid: 17656684
references.citation: Nucleic Acids Res. 2011 Feb;39(3):825-36
references.pmid: 20929877
references.citation: J Affect Disord. 2012 Feb;136(3):405-11
references.pmid: 22177743
references.citation: Arch Gen Psychiatry. 1994 Jan;51(1):8-19
references.pmid: 8279933
references.citation: PLoS One. 2012;7(10):e46921
references.pmid: 23056528
references.citation: Neuron. 2008 Jan 10;57(1):41-55
references.pmid: 18184563
references.citation: Neuron. 2010 Feb 11;65(3):373-84
references.pmid: 20159450
references.citation: Psychiatry Res. 2006 Jun 15;142(2-3):139-50
references.pmid: 16631256
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11650-5
references.pmid: 21697510
references.citation: Biol Psychiatry. 2000 Oct 15;48(8):791-800
references.pmid: 11063975
references.citation: Int J Oncol. 2013 Oct;43(4):985-94
references.pmid: 23939688
references.citation: Cell. 2007 Jun 29;129(7):1401-14
references.pmid: 17604727
references.citation: DNA Cell Biol. 2012 Sep;31(9):1499-506
references.pmid: 22694265
references.citation: Int J Mol Sci. 2013 Mar 06;14(3):5338-66
references.pmid: 23466882
references.citation: ScientificWorldJournal. 2007 Nov 02;7:146-54
references.pmid: 17982588
references.citation: Nat Rev Mol Cell Biol. 2009 Feb;10(2):141-8
references.pmid: 19145236
references.citation: Cell Tissue Res. 2012 Aug;349(2):405-13
references.pmid: 22622804
references.citation: Genes Dev. 2002 Oct 1;16(19):2491-6
references.pmid: 12368260
references.citation: Nature. 2004 Sep 16;431(7006):350-5
references.pmid: 15372042
references.citation: Nature. 2005 Aug 4;436(7051):740-4
references.pmid: 15973356
references.citation: Cell Res. 2008 Oct;18(10):997-1006
references.pmid: 18766170
references.citation: Eur Neuropsychopharmacol. 2010 Jan;20(1):1-17
references.pmid: 19748235
references.citation: Front Mol Neurosci. 2013 Aug 30;6:24
references.pmid: 24009553
references.citation: J Psychiatr Res. 2012 Feb;46(2):198-204
references.pmid: 22094284
references.citation: Schizophr Res. 2010 Dec;124(1-3):183-91
references.pmid: 20675101
references.citation: JAMA. 1990 Nov 21;264(19):2524-8
references.pmid: 2146410
references.citation: Development. 2008 Apr;135(7):1201-14
references.pmid: 18287206
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: Pharmacol Ther. 2011 Apr;130(1):26-37
references.pmid: 21256154
references.citation: Neuropharmacology. 2010 May;58(6):884-93
references.pmid: 20060007
references.citation: Genome Biol. 2006;7(9):R85
references.pmid: 17002790
references.citation: Eur J Neurosci. 2012 Oct;36(7):2941-8
references.pmid: 22845676
references.citation: Front Cell Neurosci. 2013 Jun 26;7:95
references.pmid: 23805071
references.citation: Pediatr Res. 2007 May;61(5 Pt 2):24R-29R
references.pmid: 17413852
references.citation: Biochem J. 2008 Aug 1;413(3):429-36
references.pmid: 18476811
references.citation: FEBS J. 2011 May;278(10):1598-609
references.pmid: 21395977
references.citation: PLoS One. 2009 Oct 06;4(10):e7225
references.pmid: 19806225
references.citation: Int J Neurosci. 2007 Apr;117(4):465-76
references.pmid: 17365129
references.citation: J Neurosci. 2007 Jun 20;27(25):6729-39
references.pmid: 17581960
references.citation: Neurosci Lett. 2013 Aug 9;549:125-9
references.pmid: 23721784
references.citation: Nucleic Acids Res. 2010 Nov;38(20):7248-59
references.pmid: 20615901
references.citation: Int J Neuropsychopharmacol. 2013 Sep;16(8):1885-92
references.pmid: 23684180
references.citation: Eur J Neurosci. 2007 Jan;25(2):341-50
references.pmid: 17284174
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4034-9
references.pmid: 16495412
references.citation: PLoS One. 2008 Apr 09;3(4):e1959
references.pmid: 18509506
references.citation: Arch Gen Psychiatry. 2001 Jul;58(7):649-50
references.pmid: 11448370
references.citation: BMC Neurosci. 2006 Oct 30;7 Suppl 1:S5
references.pmid: 17118159
references.citation: Front Psychiatry. 2013 Aug 07;4:80
references.pmid: 23966957
references.citation: Ann Pharm Fr. 2013 May;71(3):143-9
references.pmid: 23622692
references.citation: Dev Cell. 2008 Jun;14(6):926-39
references.pmid: 18539120
references.citation: Nature. 2007 Jun 14;447(7146):823-8
references.pmid: 17507929
references.citation: Nat Neurosci. 2004 Mar;7(3):244-53
references.pmid: 14770185
references.citation: Biol Psychiatry. 2009 Feb 15;65(4):319-28
references.pmid: 18930453
references.citation: Brain Res. 2008 Feb 8;1193:43-50
references.pmid: 18190899
references.citation: Neuromolecular Med. 2009;11(3):141-52
references.pmid: 19598002
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: J Neurochem. 2008 Jul;106(2):650-61
references.pmid: 18410515
references.citation: Front Neurosci. 2012 Feb 17;6:25
references.pmid: 22363255
references.citation: J Neurosci Res. 2004 May 1;76(3):306-14
references.pmid: 15079859
references.citation: Biol Direct. 2008 Oct 29;3:44
references.pmid: 18957138
references.citation: J Mol Neurosci. 2010 Jan;40(1-2):47-55
references.pmid: 19711202
references.citation: Mol Neurobiol. 2014 Feb;49(1):590-600
references.pmid: 23999871
references.citation: Neuroscience. 2001;104(1):33-40
references.pmid: 11311528
references.citation: Front Psychiatry. 2012 Apr 25;3:39
references.pmid: 22539927
references.citation: Eur J Neurosci. 2005 Mar;21(6):1469-77
references.pmid: 15845075
references.citation: Neuropharmacology. 2004 Oct;47(5):746-54
references.pmid: 15458846
references.citation: J Hematol Oncol. 2010 Oct 06;3:37
references.pmid: 20925959
references.citation: Neurobiol Dis. 2013 Sep;57:28-37
references.pmid: 22691453
references.citation: RNA. 2008 Mar;14(3):432-44
references.pmid: 18230762
references.citation: Neuroscience. 1997 May;78(1):99-110
references.pmid: 9135092
references.citation: CNS Neurol Disord Drug Targets. 2007 Jun;6(3):219-33
references.pmid: 17511618
references.citation: J Alzheimers Dis. 2008 May;14(1):27-41
references.pmid: 18525125
references.citation: Curr Opin Neurobiol. 2009 Apr;19(2):213-9
references.pmid: 19539460
references.citation: Mol Psychiatry. 2006 Jan;11(1):86-98
references.pmid: 16172610