Skip to main content
SpringerLink
Log in

Exploiting Circulating MicroRNAs as Biomarkers in Psychiatric Disorders

  • Review Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Non-invasive peripheral biomarkers play a significant role in both disease diagnosis and progression. In the past few years, microRNA (miRNA) expression changes in circulating peripheral tissues have been found to be correlative with changes in neuronal tissues from patients with neuropsychiatric disorders. This is a notable quality of a biomolecule to be considered as a biomarker for both prognosis and diagnosis of disease. miRNAs, members of the small non-coding RNA family, have recently gained significant attention due to their ability to epigenetically influence almost every aspect of brain functioning. Empirical evidence suggests that miRNA-associated changes in the brain are often translated into behavioral changes. Current clinical understanding further implicates their role in the management of major psychiatric conditions, including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). This review aims to critically evaluate the potential advantages and disadvantages of miRNAs as diagnostic/prognostic biomarkers in psychiatric disorders as well as in treatment response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rosado M, Silva R, Manadas B, Anjo SI. Advances in biomarker detection: alternative approaches for blood-based biomarker detection. Adv Clin Chem. 2019;92:141–99.

    Article  PubMed  Google Scholar 

  2. Wiktorowicz JE, Soman KV. Discovery of candidate biomarkers. Adv Exp Med Biol. 2016;919:443–62.

    Article  CAS  PubMed  Google Scholar 

  3. Pinto JV, Moulin TC, Amaral OB. On the transdiagnostic nature of peripheral biomarkers in major psychiatric disorders: a systematic review. Neurosci Biobehav Rev. 2017;83:97–108.

    Article  CAS  PubMed  Google Scholar 

  4. Hayashi-Takagi A, Vawter MP, Iwamoto K. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research. Biol Psychiatry. 2014;75(12):920–8.

    Article  CAS  PubMed  Google Scholar 

  5. Ramocki MB, Zoghbi HY. Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature. 2008;455(7215):912–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Geaghan M, Cairns MJ. MicroRNA and posttranscriptional dysregulation in psychiatry. Biol Psychiatry. 2015;78(4):231–9.

    Article  CAS  PubMed  Google Scholar 

  7. Follert P, Cremer H, Beclin C. MicroRNAs in brain development and function: a matter of flexibility and stability. Front Mol Neurosci. 2014;7:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Maffioletti E, Tardito D, Gennarelli M, Bocchio-Chiavetto L. Micro spies from the brain to the periphery: new clues from studies on microRNAs in neuropsychiatric disorders. Front Cell Neurosci. 2014;8:75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Gururajan A, Naughton ME, Scott KA, O'Connor RM, Moloney G, Clarke G, et al. MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c. Transl Psychiatry. 2016;6(8):e862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Roy B, Dunbar M, Shelton RC, Dwivedi Y. Identification of microRNA-124-3p as a putative epigenetic signature of major depressive disorder. Neuropsychopharmacology. 2017;42(4):864–75.

    Article  CAS  PubMed  Google Scholar 

  11. Maffioletti E, Cattaneo A, Rosso G, Maina G, Maj C, Gennarelli M, et al. Peripheral whole blood microRNA alterations in major depression and bipolar disorder. J Affect Disord. 2016;200:250–8.

    Article  CAS  PubMed  Google Scholar 

  12. Lai CY, Lee SY, Scarr E, Yu YH, Lin YT, Liu CM, et al. Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue. Transl Psychiatry. 2016;6:e717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mayeux R. Biomarkers: potential uses and limitations. NeuroRx. 2004;1(2):182–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kuehner JN, Bruggeman EC, Wen Z, Yao B. Epigenetic regulations in neuropsychiatric disorders. Front Genet. 2019;10:268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. LaSalle JM, Powell WT, Yasui DH. Epigenetic layers and players underlying neurodevelopment. Trends Neurosci. 2013;36(8):460–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bartel DP. Metazoan microRNAs. Cell. 2018;173(1):20–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509–24.

    Article  CAS  PubMed  Google Scholar 

  18. Paraskevopoulou MD, Hatzigeorgiou AG. Analyzing miRNA-lncRNA interactions. Methods Mol Biol. 2016;1402:271–86.

    Article  CAS  PubMed  Google Scholar 

  19. Gosline SJ, Gurtan AM, JnBaptiste CK, Bosson A, Milani P, Dalin S, et al. Elucidating microRNA regulatory networks using transcriptional, post-transcriptional, and histone modification measurements. Cell Rep. 2016;14(2):310–9.

    Article  CAS  PubMed  Google Scholar 

  20. Liu Y, Chang X, Hahn CG, Gur RE, Sleiman PAM, Hakonarson H. Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease. Transl Psychiatry. 2018;8(1):44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Roy B, Wang Q, Palkovits M, Faludi G, Dwivedi Y. Altered miRNA expression network in locus coeruleus of depressed suicide subjects. Sci Rep. 2017;7(1):4387.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. O'Connor RM, Gururajan A, Dinan TG, Kenny PJ, Cryan JF. All roads lead to the miRNome: miRNAs have a central role in the molecular pathophysiology of psychiatric disorders. Trends Pharmacol Sci. 2016;37(12):1029–44.

    Article  CAS  PubMed  Google Scholar 

  23. Hu Z, Gao S, Lindberg D, Panja D, Wakabayashi Y, Li K, et al. Temporal dynamics of miRNAs in human DLPFC and its association with miRNA dysregulation in schizophrenia. Transl Psychiatry. 2019;9(1):196.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Forstner AJ, Hofmann A, Maaser A, Sumer S, Khudayberdiev S, Muhleisen TW, et al. Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder. Transl Psychiatry. 2015;5:e678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. 2016;17(10):1.

    Article  CAS  Google Scholar 

  26. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–D162162.

    Article  CAS  PubMed  Google Scholar 

  28. Golan D, Levy C, Friedman B, Shomron N. Biased hosting of intronic microRNA genes. Bioinformatics. 2010;26(8):992–5.

    Article  CAS  PubMed  Google Scholar 

  29. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14(10A):1902–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Daugaard I, Hansen TB. Biogenesis and function of Ago-associated RNAs. Trends Genet. 2017;33(3):208–19.

    Article  CAS  PubMed  Google Scholar 

  31. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–34.

    Article  CAS  PubMed  Google Scholar 

  32. Issler O, Chen A. Determining the role of microRNAs in psychiatric disorders. Nat Rev Neurosci. 2015;16(4):201–12.

    Article  CAS  PubMed  Google Scholar 

  33. Nowakowski TJ, Rani N, Golkaram M, Zhou HR, Alvarado B, Huch K, et al. Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development. Nat Neurosci. 2018;21(12):1784–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology. 2008;33(1):88–109.

    Article  CAS  PubMed  Google Scholar 

  35. Nadim WD, Simion V, Benedetti H, Pichon C, Baril P, Morisset-Lopez S. MicroRNAs in neurocognitive dysfunctions: new molecular targets for pharmacological treatments? Curr Neuropharmacol. 2017;15(2):260–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Forrest MP, Parnell E, Penzes P. Dendritic structural plasticity and neuropsychiatric disease. Nat Rev Neurosci. 2018;19(4):215–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Konopka W, Kiryk A, Novak M, Herwerth M, Parkitna JR, Wawrzyniak M, et al. MicroRNA loss enhances learning and memory in mice. J Neurosci. 2010;30(44):14835–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Devaraju P, Yu J, Eddins D, Mellado-Lagarde MM, Earls LR, Westmoreland JJ, et al. Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium. Mol Psychiatry. 2017;22(9):1313–26.

    Article  CAS  PubMed  Google Scholar 

  39. Aksoy-Aksel A, Zampa F, Schratt G. MicroRNAs and synaptic plasticity: a mutual relationship. Philos Trans R Soc Lond B Biol Sci. 2014;369:1652.

    Article  CAS  Google Scholar 

  40. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, et al. A brain-specific microRNA regulates dendritic spine development. Nature. 2006;439(7074):283–9.

    Article  CAS  PubMed  Google Scholar 

  41. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466(7310):1105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bicker S, Khudayberdiev S, Weiss K, Zocher K, Baumeister S, Schratt G. The DEAH-box helicase DHX36 mediates dendritic localization of the neuronal precursor-microRNA-134. Genes Dev. 2013;27(9):991–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hu Z, Li Z. miRNAs in synapse development and synaptic plasticity. Curr Opin Neurobiol. 2017;45:24–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kiltschewskij D, Cairns MJ. Temporospatial guidance of activity-dependent gene expression by microRNA: mechanisms and functional implications for neural plasticity. Nucleic Acids Res. 2019;47(2):533–45.

    Article  CAS  PubMed  Google Scholar 

  45. Schratt G. MicroRNAs at the synapse. Nat Rev Neurosci. 2009;10(12):842–9.

    Article  CAS  PubMed  Google Scholar 

  46. Pompili M, Shrivastava A, Serafini G, Innamorati M, Milelli M, Erbuto D, et al. Bereavement after the suicide of a significant other. Indian J Psychiatry. 2013;55(3):256–63.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Smalheiser NR, Lugli G, Rizavi HS, Torvik VI, Turecki G, Dwivedi Y. MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS ONE. 2012;7(3):e33201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Smalheiser NR, Lugli G, Zhang H, Rizavi H, Cook EH, Dwivedi Y. Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects. PLoS ONE. 2014;9(1):e86469.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B, et al. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat Med. 2014;20(7):764–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Azevedo JA, Carter BS, Meng F, Turner DL, Dai M, Schatzberg AF, et al. The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression. J Psychiatr Res. 2016;82:58–67.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Choi JL, Kao PF, Itriago E, Zhan Y, Kozubek JA, Hoss AG, et al. miR-149 and miR-29c as candidates for bipolar disorder biomarkers. Am J Med Genet B Neuropsychiatr Genet. 2017;174(3):315–23.

    Article  CAS  PubMed  Google Scholar 

  52. Banigan MG, Kao PF, Kozubek JA, Winslow AR, Medina J, Costa J, et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS ONE. 2013;8(1):e48814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Miller BH, Zeier Z, Xi L, Lanz TA, Deng S, Strathmann J, et al. MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proc Natl Acad Sci USA. 2012;109(8):3125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bavamian S, Mellios N, Lalonde J, Fass DM, Wang J, Sheridan SD, et al. Dysregulation of miR-34a links neuronal development to genetic risk factors for bipolar disorder. Mol Psychiatry. 2015;20(5):573–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, et al. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol. 2007;8(2):R27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ, et al. Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet. 2008;17(8):1156–68.

    Article  CAS  PubMed  Google Scholar 

  57. Moreau MP, Bruse SE, David-Rus R, Buyske S, Brzustowicz LM. Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry. 2011;69(2):188–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ. Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry. 2010;15(12):1176–89.

    Article  CAS  PubMed  Google Scholar 

  59. Kim AH, Reimers M, Maher B, Williamson V, McMichael O, McClay JL, et al. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res. 2010;124(1–3):183–91.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Zhu Y, Kalbfleisch T, Brennan MD, Li Y. A MicroRNA gene is hosted in an intron of a schizophrenia-susceptibility gene. Schizophr Res. 2009;109(1–3):86–9.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Santarelli DM, Beveridge NJ, Tooney PA, Cairns MJ. Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry. 2011;69(2):180–7.

    Article  CAS  PubMed  Google Scholar 

  62. Guella I, Sequeira A, Rollins B, Morgan L, Torri F, van Erp TG, et al. Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. J Psychiatr Res. 2013;47(9):1215–21.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Cohen RA, Hitsman BL, Paul RH, McCaffery J, Stroud L, Sweet L, et al. Early life stress and adult emotional experience: an international perspective. Int J Psychiatry Med. 2006;36(1):35–52.

    Article  PubMed  Google Scholar 

  64. Targum SD, Nemeroff CB. The effect of early life stress on adult psychiatric disorders. Innov Clin Neurosci. 2019;16(1–2):35–7.

    PubMed  PubMed Central  Google Scholar 

  65. Herbison CE, Allen K, Robinson M, Newnham J, Pennell C. The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure. Dev Psychopathol. 2017;29(4):1443–544.

    Article  PubMed  Google Scholar 

  66. Allen L, Dwivedi Y. MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior. Mol Psychiatry. 2020;25(2):308–20.

    Article  CAS  PubMed  Google Scholar 

  67. Cattane N, Mora C, Lopizzo N, Borsini A, Maj C, Pedrini L, et al. Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: new insights for the key role of miR-125b-1-3p in neurodevelopmental processes. Schizophr Res. 2019;205:63–75.

    Article  PubMed  Google Scholar 

  68. Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, et al. Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron. 2010;65(3):373–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pompili M, Gibiino S, Innamorati M, Serafini G, Del Casale A, De Risio L, et al. Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients. Psychiatry Res. 2012;200(2–3):389–94.

    Article  CAS  PubMed  Google Scholar 

  70. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Pandey SC, Pesold C, et al. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry. 2002;159(3):419–29.

    Article  PubMed  Google Scholar 

  71. Kaminsky Z, Wilcox HC, Eaton WW, Van Eck K, Kilaru V, Jovanovic T, et al. Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder. Transl Psychiatry. 2015;5:e627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Belzeaux R, Lin R, Turecki G. Potential use of microRNA for monitoring therapeutic response to antidepressants. CNS Drugs. 2017;31(4):253–62.

    Article  CAS  PubMed  Google Scholar 

  73. Dwivedi Y. Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications. Dialogues Clin Neurosci. 2014;16(1):43–61.

    PubMed  PubMed Central  Google Scholar 

  74. Dwivedi Y. Pathogenetic and therapeutic applications of microRNAs in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:341–8.

    Article  CAS  PubMed  Google Scholar 

  75. Dwivedi Y. MicroRNAs in depression and suicide: recent insights and future perspectives. J Affect Disord. 2018;240:146–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Fries GR, Carvalho AF, Quevedo J. The miRNome of bipolar disorder. J Affect Disord. 2018;233:110–6.

    Article  CAS  PubMed  Google Scholar 

  77. Narahari A, Hussain M, Sreeram V. MicroRNAs as biomarkers for psychiatric conditions: a review of current research. Innov Clin Neurosci. 2017;14(1–2):53–5.

    PubMed  PubMed Central  Google Scholar 

  78. Saavedra K, Molina-Marquez AM, Saavedra N, Zambrano T, Salazar LA. Epigenetic modifications of major depressive disorder. Int J Mol Sci. 2016;17(8):1.

    Article  CAS  Google Scholar 

  79. Tavakolizadeh J, Roshanaei K, Salmaninejad A, Yari R, Nahand JS, Sarkarizi HK, et al. MicroRNAs and exosomes in depression: potential diagnostic biomarkers. J Cell Biochem. 2018;119(5):3783–97.

    Article  CAS  PubMed  Google Scholar 

  80. Yuan H, Mischoulon D, Fava M, Otto MW. Circulating microRNAs as biomarkers for depression: many candidates, few finalists. J Affect Disord. 2018;233:68–78.

    Article  CAS  PubMed  Google Scholar 

  81. Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, et al. MicroRNAs 146a/b-5 and 425–3p and 24–3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat Commun. 2017;8:15497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Duman RS, Voleti B. Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci. 2012;35(1):47–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Roy B, Dunbar M, Agrawal J, Allen L, Dwivedi Y. Amygdala based altered miRNome and epigenetic contribution of miR-128-3p in conferring susceptibility to depression-like behavior via Wnt signaling. Int J Neuropsychopharmacol. 2019 (in press).

  84. Sun XY, Zhang J, Niu W, Guo W, Song HT, Li HY, et al. A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2015;168B(3):170–8.

    Article  PubMed  CAS  Google Scholar 

  85. Liu S, Zhang F, Shugart YY, Yang L, Li X, Liu Z, et al. The early growth response protein 1-miR-30a-5p-neurogenic differentiation factor 1 axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring. Transl Psychiatry. 2017;7(1):e998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wu S, Zhang R, Nie F, Wang X, Jiang C, Liu M, et al. MicroRNA-137 inhibits EFNB2 expression affected by a genetic variant and is expressed aberrantly in peripheral blood of schizophrenia patients. EBioMedicine. 2016;12:133–42.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Wei H, Yuan Y, Liu S, Wang C, Yang F, Lu Z, et al. Detection of circulating miRNA levels in schizophrenia. Am J Psychiatry. 2015;172(11):1141–7.

    Article  PubMed  Google Scholar 

  88. Wang Q, Roy B, Turecki G, Shelton RC, Dwivedi Y. Role of complex epigenetic switching in tumor necrosis factor-alpha upregulation in the prefrontal cortex of suicide subjects. Am J Psychiatry. 2018;175(3):262–74.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Turchinovich A, Burwinkel B. Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma. RNA Biol. 2012;9(8):1066–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dufourd T, Robil N, Mallet D, Carcenac C, Boulet S, Brishoual S, et al. Plasma or serum? A qualitative study on rodents and humans using high-throughput microRNA sequencing for circulating biomarkers. Biol Methods Protoc. 2019;4(1):1.

    Article  CAS  Google Scholar 

  91. Fang Z, He QW, Li Q, Chen XL, Baral S, Jin HJ, et al. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. FASEB J. 2016;30(6):2097–107.

    Article  CAS  PubMed  Google Scholar 

  92. Saeedi S, Israel S, Nagy C, Turecki G. The emerging role of exosomes in mental disorders. Transl Psychiatry. 2019;9(1):122.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, et al. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study. Alzheimers Dement. 2015;11(6):600.

    Article  PubMed  Google Scholar 

  94. Yang TT, Liu CG, Gao SC, Zhang Y, Wang PC. The serum exosome derived microRNA-135a, -193b, and -384 were potential Alzheimer's disease biomarkers. Biomed Environ Sci. 2018;31(2):87–96.

    PubMed  Google Scholar 

  95. Yao YF, Qu MW, Li GC, Zhang FB, Rui HC. Circulating exosomal miRNAs as diagnostic biomarkers in Parkinson's disease. Eur Rev Med Pharmacol Sci. 2018;22(16):5278–83.

    PubMed  Google Scholar 

  96. Ceylan D, Tufekci KU, Keskinoglu P, Genc S, Ozerdem A. Circulating exosomal microRNAs in bipolar disorder. J Affect Disord. 2020;262:99–107.

    Article  CAS  PubMed  Google Scholar 

  97. van den Berg MMJ, Krauskopf J, Ramaekers JG, Kleinjans JCS, Prickaerts J, Briede JJ. Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Prog Neurobiol. 2019;7:101732.

    Google Scholar 

  98. Raoof R, Jimenez-Mateos EM, Bauer S, Tackenberg B, Rosenow F, Lang J, et al. Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus. Sci Rep. 2017;7(1):3328.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Wiegand C, Heusser P, Klinger C, Cysarz D, Bussing A, Ostermann T, et al. Stress-associated changes in salivary microRNAs can be detected in response to the Trier Social Stress Test: an exploratory study. Sci Rep. 2018;8(1):7112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Xia X, Wang Y, Huang Y, Zhang H, Lu H, Zheng JC. Exosomal miRNAs in central nervous system diseases: biomarkers, pathological mediators, protective factors and therapeutic agents. Prog Neurobiol. 2019;183:101694.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  101. Mustapic M, Eitan E, Werner JK Jr, Berkowitz ST, Lazaropoulos MP, Tran J, et al. Plasma extracellular vesicles enriched for neuronal origin: a potential window into brain pathologic processes. Front Neurosci. 2017;11:278.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Kok MGM, de Ronde MWJ, Moerland PD, Ruijter JM, Creemers EE, Pinto-Sietsma SJ. Small sample sizes in high-throughput miRNA screens: a common pitfall for the identification of miRNA biomarkers. Biomol Detect Quantif. 2018;15:1–5.

    Article  CAS  PubMed  Google Scholar 

  103. Zampetaki A, Mayr M. Analytical challenges and technical limitations in assessing circulating miRNAs. Thromb Haemost. 2012;108(4):592–8.

    CAS  PubMed  Google Scholar 

  104. Witwer KW. Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin Chem. 2015;61(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  105. Martin AR, Daly MJ, Robinson EB, Hyman SE, Neale BM. Predicting polygenic risk of psychiatric disorders. Biol Psychiatry. 2019;86(2):97–109.

    Article  PubMed  Google Scholar 

  106. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.

    Article  CAS  PubMed  Google Scholar 

  107. Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC. 2019;30(2):114–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005;438(7068):685–9.

    Article  PubMed  CAS  Google Scholar 

  109. Song MF, Dong JZ, Wang YW, He J, Ju X, Zhang L, et al. CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system. J Affect Disord. 2015;178:25–31.

    Article  CAS  PubMed  Google Scholar 

  110. Suryawanshi H, Sarangdhar MA, Vij M, Roshan R, Singh VP, Ganguli M, et al. A simple alternative to stereotactic injection for brain specific knockdown of miRNA. J Vis Exp. 2015;106:e53307.

    Google Scholar 

  111. Oswald M, Geissler S, Goepferich A. Targeting the central nervous system (CNS): a review of rabies virus-targeting strategies. Mol Pharm. 2017;14(7):2177–96.

    Article  CAS  PubMed  Google Scholar 

  112. Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids. 2017;7:278–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Labourier E, Shifrin A, Busseniers AE, Lupo MA, Manganelli ML, Andruss B, et al. Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab. 2015;100(7):2743–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Meiri E, Mueller WC, Rosenwald S, Zepeniuk M, Klinke E, Edmonston TB, et al. A second-generation microRNA-based assay for diagnosing tumor tissue origin. Oncologist. 2012;17(6):801–12.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Margis R, Margis R, Rieder CR. Identification of blood microRNAs associated to Parkinson's disease. J Biotechnol. 2011;152(3):96–101.

    Article  CAS  PubMed  Google Scholar 

  116. Sheinerman KS, Toledo JB, Tsivinsky VG, Irwin D, Grossman M, Weintraub D, et al. Circulating brain-enriched microRNAs as novel biomarkers for detection and differentiation of neurodegenerative diseases. Alzheimers Res Ther. 2017;9(1):89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Amur S, LaVange L, Zineh I, Buckman-Garner S, Woodcock J. Biomarker qualification: toward a multiple stakeholder framework for biomarker development, regulatory acceptance, and utilization. Clin Pharmacol Ther. 2015;98(1):34–46.

    Article  CAS  PubMed  Google Scholar 

  118. Liu S, Zhang F, Wang X, Shugart YY, Zhao Y, Li X, et al. Diagnostic value of blood-derived microRNAs for schizophrenia: results of a meta-analysis and validation. Sci Rep. 2017;7(1):15328.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Perez-Gracia JL, Sanmamed MF, Bosch A, Patino-Garcia A, Schalper KA, Segura V, et al. Strategies to design clinical studies to identify predictive biomarkers in cancer research. Cancer Treat Rev. 2017;53:79–977.

    Article  PubMed  Google Scholar 

  120. Venkatasubramanian G, Keshavan MS. Biomarkers in psychiatry: a critique. Ann Neurosci. 2016;23(1):3–5.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Khandelwal N, Dey SK, Chakravarty S, Kumar A. miR-30 family miRNAs mediate the effect of chronic social defeat stress on hippocampal neurogenesis in mouse depression model. Front Mol Neurosci. 2019;12:188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lo Iacono L, Ielpo D, Accoto A, Di Segni M, Babicola L, D’Addario SL, et al. MicroRNA-34a Regulates the depression-like behavior in mice by modulating the expression of target genes in the dorsal raphè. Mol Neurobiol. 2020;57(2):823–36.

    Article  CAS  PubMed  Google Scholar 

  123. Higuchi F, Uchida S, Yamagata H, Abe-Higuchi N, Hobara T, Hara K, et al. Hippocampal microRNA-124 enhances chronic stress resilience in mice. J Neurosci. 2016;36(27):7253–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Smalheiser NR, Zhang H, Dwivedi Y. Enoxacin elevates microRNA levels in rat frontal cortex and prevents learned helplessness. Front Psychiatry. 2014;5:6.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Bocchio-Chiavetto L, Maffioletti E, Bettinsoli P, Giovannini C, Bignotti S, Tardito D, et al. Blood microRNA changes in depressed patients during antidepressant treatment. Eur Neuropsychopharmacol. 2013;23(7):602–11.

    Article  CAS  PubMed  Google Scholar 

  126. Li J, Meng H, Cao W, Qiu T. miR-335 is involved in major depression disorder and antidepressant treatment through targeting GRM4. Neurosci Lett. 2015;606:167–72.

    Article  CAS  PubMed  Google Scholar 

  127. Gheysarzadeh A, Sadeghifard N, Afraidooni L, Pooyan F, Mofid MR, Valadbeigi H, et al. Serum-based microRNA biomarkers for major depression: MiR-16, miR-135a, and miR-1202. J Res Med Sci. 2018;23:69.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Lee SY, Lu RB, Wang LJ, Chang CH, Lu T, Wang TY, et al. Serum miRNA as a possible biomarker in the diagnosis of bipolar II disorder. Sci Rep. 2020;10(1):1131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Chen JJ, Zhao B, Zhao J, Li S. Potential roles of exosomal microRNAs as diagnostic biomarkers and therapeutic application in Alzheimer's disease. Neural Plast. 2017;2017:7027380.

    PubMed  PubMed Central  Google Scholar 

  130. Roser AE, Caldi Gomes L, Schunemann J, Maass F, Lingor P. Circulating miRNAs as diagnostic biomarkers for Parkinson's disease. Front Neurosci. 2018;12:625.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Translational Research, UAB Mood Disorders Program, UAB Depression and Suicide Center, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, SC711 Sparks Center, 1720 7th Avenue South, Birmingham, AL, 35294, USA

    Bhaskar Roy, Yuta Yoshino, Lauren Allen, Kevin Prall, Grant Schell & Yogesh Dwivedi

Authors
  1. Bhaskar Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuta Yoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lauren Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevin Prall
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Grant Schell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yogesh Dwivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yogesh Dwivedi.

Ethics declarations

Conflict of Interest

All authors, Bhaskar Roy, Yuta Yoshino, Lauren Allen, Kevin Prall, Grant Schell, and Yogesh Dwivedi, declare no conflicts of interest.

Funding

The research was partly supported by grants from the National Institute of Mental Health (R01MH082802; 1R01MH101890; R01MH100616; 1R01MH107183-01) and the American Foundation for Suicide Prevention (SRG-1-042-14) to Dr. Dwivedi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roy, B., Yoshino, Y., Allen, L. et al. Exploiting Circulating MicroRNAs as Biomarkers in Psychiatric Disorders. Mol Diagn Ther 24, 279–298 (2020). https://doi.org/10.1007/s40291-020-00464-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-020-00464-9

Search

Navigation