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miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders

The Pharmacogenomics Journal volume 22, pages 211–222 (2022)Cite this article

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Abstract

The heterogeneity of psychiatric disorders and the lack of reliable biomarkers for prediction and treatments follow-up pose difficulties towards recognition and understanding of the molecular basis of psychiatric diseases. However, several studies based on NGS approaches have shown that miRNAs could regulate gene expression during onset and disease progression and could serve as potential diagnostic and pharmacogenomics biomarkers during treatment. We provide herein a detailed overview of circulating miRNAs and their expression profiles as biomarkers in schizophrenia, bipolar disorder and major depressive disorder and their role in response to specific treatments. Bioinformatics analysis of miR-34a, miR-106, miR-134 and miR-132, which are common among SZ, BD and MDD patients, showed brain enrichment and involvement in the modulation of critical signaling pathways, which are often deregulated in psychiatric disorders. We propose that specific miRNAs support accurate diagnosis and effective precision treatment of psychiatric disorders.

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Fig. 1: Role of epigenomics in the development of psychiatric disorders.

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All data generated or analyzed during this study are included in this published article [and its supplementary information files].

References

  1. James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–858.

    Article  Google Scholar 

  2. Giannopoulou E, Katsila T, Mitropoulou C, Tsermpini E-E, Patrinos GP Integrating next-generation sequencing in the clinical pharmacogenomics workflow. Front Pharmacol. 2019; 10. https://doi.org/10.3389/fphar.2019.00384.

  3. Hoehe MR, Morris-Rosendahl DJ. The role of genetics and genomics in clinical psychiatry. Dialogues Clin Neurosci. 2018;20:169–77.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Peedicayil J, Kumar A. Epigenetic drugs for mood disorders. Prog Mol Biol Transl Sci. 2018;157:151–74.

    Article  CAS  PubMed  Google Scholar 

  5. Pisanu C, Tsermpini EE, Skokou M, Kordou Z, Gourzis P, Assimakopoulos K, et al. Leukocyte telomere length is reduced in patients with major depressive disorder. Drug Dev Res. 2020;81:268–73.

    Article  CAS  PubMed  Google Scholar 

  6. Karam CS, Ballon JS, Bivens NM, Freyberg Z, Girgis RR, Lizardi-Ortiz JE, et al. Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. Trends Pharm Sci. 2010;31:381–90.

    Article  CAS  PubMed  Google Scholar 

  7. Tsermpini EE, Assimakopoulos K, Bartsakoulia M, Iconomou G, Papadima EM, Mitropoulos K, et al. Individualizing clozapine and risperidone treatment for schizophrenia patients. Pharmacogenomics. 2014;15:95–110.

    Article  CAS  PubMed  Google Scholar 

  8. O’Tuathaigh CMP, Moran PM, Zhen XC, Waddington JL. Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies. Br J Pharm. 2017;174:3173–90.

    Article  CAS  Google Scholar 

  9. Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, et al. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells. 2020;9:276.

    Article  CAS  PubMed Central  Google Scholar 

  10. Beveridge NJ, Cairns MJ. MicroRNA dysregulation in schizophrenia. Neurobiol Dis. 2012;46:263–71.

    Article  CAS  PubMed  Google Scholar 

  11. 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;69:180–7.

    Article  CAS  PubMed  Google Scholar 

  12. 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;69:188–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mor E, Kano S-I, Colantuoni C, Sawa A, Navon R, Shomron N. MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients. Neurobiol Dis. 2013;55:1–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. de la Morena MT, Eitson JL, Dozmorov IM, Belkaya S, Hoover AR, Anguiano E, et al. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. Clin Immunol. 2013;147:11–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Lai C-Y, Lee S-Y, Scarr E, Yu Y-H, Lin Y-T, Liu C-M, 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 

  16. Shi W, Du J, Qi Y, Liang G, Wang T, Li S, et al. Aberrant expression of serum miRNAs in schizophrenia. J Psychiatr Res. 2012;46:198–204.

    Article  PubMed  Google Scholar 

  17. Sun X, Lu J, Zhang LLLLL, Song H, Zhao L, Fan H, et al. Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients. J Clin Neurosci. 2015;22:570–4.

    Article  CAS  PubMed  Google Scholar 

  18. Sun X, Zhang J, Niu W, Guo W, Song H, Li H, et al. A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2015;168B:170–8.

    Article  PubMed  CAS  Google Scholar 

  19. Gardiner E, Beveridge NJ, Wu JQ, Carr V, Scott RJ, Tooney PA, et al. Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. Mol Psychiatry. 2012;17:827–40.

    Article  CAS  PubMed  Google Scholar 

  20. Alevizos I, Illei GG. MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol. 2010;6:391–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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 

  22. 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;7:15328.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. You X, Zhang Y, Long Q, Liu Z, Ma X, Lu Z et al. Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment‑resistant schizophrenia using miRNA sequencing and integrated bioinformatics. Mol Med Rep. 2020. https://doi.org/10.3892/mmr.2020.11513.

  24. Ma J, Shang S, Wang J, Zhang T, Nie F, Song X, et al. Identification of miR-22-3p, miR-92a-3p, and miR-137 in peripheral blood as biomarker for schizophrenia. Psychiatry Res. 2018;265:70–76.

    Article  CAS  PubMed  Google Scholar 

  25. Gallego J, Alsop E, Lencz T, Van Keuren-Jensen K, Malhotra A. F10. Differential Expression Of Micrornas In Cerebrospinal Fluid And Plasma Samples In Schizophrenia. Schizophr Bull. 2018;44:S221–22.

    Article  PubMed Central  Google Scholar 

  26. 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:e998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang Y, Wang J, Guo T, Peng Y, Wang K, Bai K, et al. Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin β1. Med (Baltim). 2019;98:e14332.

    Article  CAS  Google Scholar 

  28. Lai C-Y, Yu S-L, Hsieh MH, Chen C-H, Chen H-Y, Wen C-C, et al. MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One. 2011;6:e21635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. He K, Guo C, Guo M, Tong S, Zhang Q, Sun H, et al. Identification of serum microRNAs as diagnostic biomarkers for schizophrenia. Hereditas. 2019;156:23.

    Article  PubMed  PubMed Central  Google Scholar 

  30. He K, Guo C, He L, Shi Y. MiRNAs of peripheral blood as the biomarker of schizophrenia. Hereditas. 2018;155:9.

    Article  PubMed  Google Scholar 

  31. Xu Y, Li F, Zhang B, Zhang K, Zhang F, Huang X, et al. MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia. Schizophr Res. 2010;119:219–27.

    Article  PubMed  Google Scholar 

  32. Song H, Sun X, Zhang L, Zhao L, Guo Z, Fan H, et al. A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment. J Psychiatr Res. 2014;54:134–40.

    Article  PubMed  Google Scholar 

  33. Yu H, Wu J, Zhang H, Zhang G, Sui J, Tong W, et al. Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. 2015;63:23–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  35. Camkurt MA, Karababa F, Erdal ME, Bayazıt H, Kandemir SB, Ay ME, et al. Investigation of Dysregulation of Several MicroRNAs in Peripheral Blood of Schizophrenia Patients. Clin Psychopharmacol Neurosci. 2016;14:256–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Geaghan MP, Atkins JR, Brichta AM, Tooney PA, Scott RJ, Carr VJ, et al. Alteration of miRNA-mRNA interactions in lymphocytes of individuals with schizophrenia. J Psychiatr Res. 2019;112:89–98.

    Article  PubMed  Google Scholar 

  37. Kalia M, Costa E, Silva J. Biomarkers of psychiatric diseases: current status and future prospects. Metabolism. 2015;64:S11–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  39. Fries GR, Lima CNC, Valvassori SS, Zunta-Soares G, Soares JC, Quevedo J. Preliminary investigation of peripheral extracellular vesicles’ microRNAs in bipolar disorder. J Affect Disord. 2019;255:10–14.

    Article  CAS  PubMed  Google Scholar 

  40. 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 

  41. Lee S-Y, Lu R-B, Wang L-J, Chang C-H, Lu T, Wang T-Y, et al. Serum miRNA as a possible biomarker in the diagnosis of bipolar II disorder. Sci Rep. 2020;10:1131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tabano S, Caldiroli A, Terrasi A, Colapietro P, Grassi S, Carnevali GS, et al. A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls. Eur Arch Psychiatry Clin Neurosci. 2020;270:893–900.

    Article  PubMed  Google Scholar 

  43. Camkurt MA, Karababa İF, Erdal ME, Kandemir SB, Fries GR, Bayazıt H, et al. MicroRNA dysregulation in manic and euthymic patients with bipolar disorder. J Affect Disord. 2020;261:84–90.

    Article  CAS  PubMed  Google Scholar 

  44. Walker RM, Rybka J, Anderson SM, Torrance HS, Boxall R, Sussmann JE, et al. Preliminary investigation of miRNA expression in individuals at high familial risk of bipolar disorder. J Psychiatr Res. 2015;62:48–55.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Belzeaux R, Lin R, Turecki G. Potential Use of MicroRNA for Monitoring Therapeutic Response to Antidepressants. CNS Drugs. 2017;31:253–62.

    Article  CAS  PubMed  Google Scholar 

  46. Zhang H-P, Liu X-L, Chen J-J, Cheng K, Bai S-J, Zheng P, et al. Circulating microRNA 134 sheds light on the diagnosis of major depressive disorder. Transl Psychiatry. 2020;10:95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Belzeaux R, Bergon A, Jeanjean V, Loriod B, Formisano-Tréziny C, Verrier L, et al. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Transl Psychiatry. 2012;2:e185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kuang W-H, Dong Z-Q, Tian L-T, Li J. MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment. Braz J Med Biol Res = Rev Bras Pesqui medicas e Biol. 2018;51:e7212.

    Article  CAS  Google Scholar 

  49. He S, Liu X, Jiang K, Peng D, Hong W, Fang Y, et al. Alterations of microRNA-124 expression in peripheral blood mononuclear cells in pre- and post-treatment patients with major depressive disorder. J Psychiatr Res. 2016;78:65–71.

    Article  PubMed  Google Scholar 

  50. Wang X, Wang B, Zhao J, Liu C, Qu X, Li Y MiR-155 is involved in major depression disorder and antidepressant treatment via targeting SIRT1. Biosci Rep. 2018; 38. https://doi.org/10.1042/BSR20181139.

  51. Qi S, Yang X, Zhao L, Calhoun VD, Perrone-Bizzozero N, Liu S, et al. MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder. Brain. 2018;141:916–26.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Liu X, Zhang L, Cheng K, Wang X, Ren G, Xie P. Identification of suitable plasma-based reference genes for miRNAome analysis of major depressive disorder. J Affect Disord. 2014;163:133–9.

    Article  CAS  PubMed  Google Scholar 

  53. Wan Y, Liu Y, Wang X, Wu J, Liu K, Zhou J, et al. Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder. PLoS One. 2015;10:e0121975.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Liang J-Q, Liao H-R, Xu C-X, Li X-L, Wei Z-X, Xie G-J, et al. Serum Exosome-Derived miR-139-5p as a Potential Biomarker for Major Depressive Disorder. Neuropsychiatr Dis Treat. 2020;16:2689–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Camkurt MA, Acar Ş, Coşkun S, Güneş M, Güneş S, Yılmaz MF, et al. Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls. J Psychiatr Res. 2015;69:67–71.

    Article  PubMed  Google Scholar 

  56. Fan H, Sun X, Guo W, Zhong A, Niu W, Zhao L, et al. Differential expression of microRNA in peripheral blood mononuclear cells as specific biomarker for major depressive disorder patients. J Psychiatr Res. 2014;59:45–52.

    Article  CAS  PubMed  Google Scholar 

  57. Lian N, Niu Q, Lei Y, Li X, Li Y, Song X. MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons. Cell Cycle. 2018;17:2745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sun N, Lei L, Wang Y, Yang C, Liu Z, Li X, et al. Preliminary comparison of plasma notch-associated microRNA-34b and -34c levels in drug naive, first episode depressed patients and healthy controls. J Affect Disord. 2016;194:109–14.

    Article  CAS  PubMed  Google Scholar 

  59. Wang Q, Zhao G, Yang Z, Liu X, Xie P. Downregulation of microRNA‑124‑3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder. Int J Mol Med. 2018;41:493–500.

    CAS  PubMed  Google Scholar 

  60. 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 

  61. Hung Y-Y, Wu M-K, Tsai M-C, Huang Y-L, Kang H-Y Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment. Cells. 2019; 8. https://doi.org/10.3390/cells8070647.

  62. 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:e862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fiori LM, Lopez JP, Richard-Devantoy S, Berlim M, Chachamovich E, Jollant F, et al. Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response. Int J Neuropsychopharmacol. 2017;20:619–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Roy B, Dunbar M, Shelton RC, Dwivedi Y. Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder. Neuropsychopharmacology. 2017;42:864–75.

    Article  CAS  PubMed  Google Scholar 

  65. Möller H-J, Seemüller F, Schennach-Wolff R, Stübner S, Rüther E, Grohmann R. History, background, concepts and current use of comedication and polypharmacy in psychiatry. Int J Neuropsychopharmacol. 2014;17:983–96.

    Article  PubMed  Google Scholar 

  66. Chen S-D, Sun X-Y, Niu W, Kong L-M, He M-J, Fan H-M, et al. A preliminary analysis of microRNA-21 expression alteration after antipsychotic treatment in patients with schizophrenia. Psychiatry Res. 2016;244:324–32.

    Article  CAS  PubMed  Google Scholar 

  67. Liu S, Yuan Y, Guan L, Wei H, Cheng Z, Han X, et al. MiRNA-365 and miRNA-520c-3p respond to risperidone treatment in first-episode schizophrenia after a 1 year remission. Chin Med J (Engl). 2013;126:2676–80.

    CAS  Google Scholar 

  68. Burns KE, Deane-Alder KD, Bellissima BL, Tingle MD. Circulating microRNA as biomarkers of clozapine-induced cardiotoxicity. Biomarkers. 2020;25:76–85.

    Article  CAS  PubMed  Google Scholar 

  69. Alacam H, Akgun S, Akca H, Ozturk O, Kabukcu BB, Herken H. miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia. Psychiatry Res. 2016;245:200–6.

    Article  CAS  PubMed  Google Scholar 

  70. Huang X, Bao C, Lv Q, Zhao J, Hu G, Wu H, et al. MicroRNA-195 predicts olanzapine response in drug-free patients with schizophrenia: A prospective cohort study. J Psychopharmacol. 2021;35:23–30.

    Article  PubMed  CAS  Google Scholar 

  71. Lin C-C, Tsai M-C, Lee C-T, Sun M-H, Huang T-L. Antidepressant treatment increased serum miR-183 and miR-212 levels in patients with major depressive disorder. Psychiatry Res. 2018;270:232–7.

    Article  CAS  PubMed  Google Scholar 

  72. 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 

  73. Yrondi A, Fiori LM, Frey BN, Lam RW, MacQueen GM, Milev R, et al. Association Between Side Effects and Blood microRNA Expression Levels and Their Targeted Pathways in Patients With Major Depressive Disorder Treated by a Selective Serotonin Reuptake Inhibitor, Escitalopram: A CAN-BIND-1 Report. Int J Neuropsychopharmacol. 2020;23:88–95.

    Article  CAS  PubMed  Google Scholar 

  74. 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;23:602–11.

    Article  CAS  PubMed  Google Scholar 

  75. Enatescu VR, Papava I, Enatescu I, Antonescu M, Anghel A, Seclaman E, et al. Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study. Psychiatry Investig. 2016;13:549–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Oved K, Morag A, Pasmanik-Chor M, Oron-Karni V, Shomron N, Rehavi M, et al. Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers. Pharmacogenomics. 2012;13:1129–39.

    Article  CAS  PubMed  Google Scholar 

  77. Marshe VS, Islam F, Maciukiewicz M, Fiori LM, Yerko V, Yang J, et al. Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109867.

    Article  CAS  PubMed  Google Scholar 

  78. Malhi GS, Tanious M, Das P, Coulston CM, Berk M. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs. 2013;27:135–53.

    Article  PubMed  Google Scholar 

  79. Ayano G Bipolar Disorders and Valproate: Pharmacokinetics,Pharmacodynamics, Therapeutic Effects and Indications of Valproate: Review of Articles. Bipolar Disord Open Access. 2016; 02. https://doi.org/10.4172/2472-1077.1000109.

  80. Zhang Z, Convertini P, Shen M, Xu X, Lemoine F, de la Grange P, et al. Valproic Acid Causes Proteasomal Degradation of DICER and Influences miRNA Expression. PLoS One. 2013;8:e82895.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA Targets. PLoS Biol. 2004;2:e363.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Pisanu C, Merkouri Papadima E, Melis C, Congiu D, Loizedda A, Orrù N, et al. Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder. Int J Mol Sci. 2019; 20. https://doi.org/10.3390/ijms20236040.

  83. Chen H, Wang N, Burmeister M, McInnis MG. MicroRNA expression changes in lymphoblastoid cell lines in response to lithium treatment. Int J Neuropsychopharmacol. 2009;12:975.

    Article  CAS  PubMed  Google Scholar 

  84. Rong H, Liu TB, Yang KJ, Yang HC, Wu DH, Liao CP, et al. MicroRNA-134 plasma levels before and after treatment for bipolar mania. J Psychiatr Res. 2011;45:92–5.

    Article  PubMed  Google Scholar 

  85. Lim CH, Zainal NZ, Kanagasundram S, Zain SM, Mohamed Z. Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment. Am J Med Genet B Neuropsychiatr Genet. 2016;171:867–74.

    Article  CAS  PubMed  Google Scholar 

  86. Alural B, Genc S, Haggarty SJ. Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future. Prog Neuropsychopharmacol Biol Psychiatry. 2017;73:87–103.

    Article  CAS  PubMed  Google Scholar 

  87. van den Berg MMJ, Krauskopf J, Ramaekers JG, Kleinjans JCS, Prickaerts J, Briedé JJ. Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Prog Neurobiol. 2020;185:101732.

    Article  PubMed  Google Scholar 

  88. Nuzzo D, Picone P, Caruana L, Vasto S, Barera A, Caruso C, et al. Inflammatory mediators as biomarkers in brain disorders. Inflammation. 2014;37:639–48.

    CAS  PubMed  Google Scholar 

  89. Williamson VS, Mamdani M, McMichael GO, Kim AH, Lee D, Bacanu S, et al. Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals. Psychol Med. 2015;45:2557–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Shih W-L, Kao C-F, Chuang L-C, Kuo P-H. Incorporating Information of microRNAs into Pathway Analysis in a Genome-Wide Association Study of Bipolar Disorder. Front Genet. 2012;3:293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6:214–30.

    Article  CAS  PubMed  Google Scholar 

  92. Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci. 2008;105:13421–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Abdolmaleky HM, Yaqubi S, Papageorgis P, Lambert AW, Ozturk S, Sivaraman V, et al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr Res. 2011;129:183–90.

    Article  PubMed  Google Scholar 

  94. Gaughwin P, Ciesla M, Yang H, Lim B, Brundin P. Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134. Cereb Cortex. 2011;21:1857–69.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  96. Gao J, Wang W-Y, Mao Y-W, Gräff J, Guan J-S, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466:1105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, et al. From The Cover: A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci. 2005;102:16426–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wayman GA, Davare M, Ando H, Fortin D, Varlamova O, Cheng H-YM, et al. An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci. 2008;105:9093–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Magill ST, Cambronne XA, Luikart BW, Lioy DT, Leighton BH, Westbrook GL, et al. microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc Natl Acad Sci USA. 2010;107:20382–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Im H-I, Kenny PJ. MicroRNAs in neuronal function and dysfunction. Trends Neurosci. 2012;35:325–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kawashima H, Numakawa T, Kumamaru E, Adachi N, Mizuno H, Ninomiya M, et al. Glucocorticoid attenuates brain-derived neurotrophic factor-dependent upregulation of glutamate receptors via the suppression of microRNA-132 expression. Neuroscience. 2010;165:1301–11.

    Article  CAS  PubMed  Google Scholar 

  102. Khadimallah I, Jenni R, Cabungcal J-H, Cleusix M, Fournier M, Beard E, et al. Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia. Mol Psychiatry. 2021. https://doi.org/10.1038/s41380-021-01313-9.

  103. Chen Y, Shi J, Liu H, Wang Q, Chen X, Tang H, et al. Plasma microRNA Array Analysis Identifies Overexpressed miR-19b-3p as a Biomarker of Bipolar Depression Distinguishing From Unipolar Depression. Front psychiatry. 2020;11:757.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by INSPIRED (Grant MIS 5002550) which is implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure’, funded by the Operational Program ‘Competitiveness, Entrepreneurship and Innovation’ (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund).

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Author notes

  1. These authors contributed equally: Evangelia Eirini Tsermpini, Christina I. Kalogirou, George C. Kyriakopoulos.

Authors and Affiliations

  1. Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Evangelia Eirini Tsermpini

  2. Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece

    Christina I. Kalogirou, George C. Kyriakopoulos & Constantinos Stathopoulos

  3. Laboratory of Pharmacogenomics and Individualized Therapy, School of Health Sciences, Department of Pharmacy, University of Patras, Patras, Greece

    George P. Patrinos

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  1. Evangelia Eirini Tsermpini
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  2. Christina I. Kalogirou
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  3. George C. Kyriakopoulos
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  4. George P. Patrinos
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  5. Constantinos Stathopoulos
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Contributions

EET, CIK and GCK were responsible for designing the review protocol, writing - original draft preparation, conducting the bibliographic search, screening potentially eligible studies, extracting and analyzing data, interpreting results, updating reference lists, and creating the results tables. GPP was responsible for conceptualization, writing - review and editing, and supervision. CS was responsible for conceptualization, writing - review and editing, supervision, and project administration. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Constantinos Stathopoulos.

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Tsermpini, E.E., Kalogirou, C.I., Kyriakopoulos, G.C. et al. miRNAs as potential diagnostic biomarkers and pharmacogenomic indicators in psychiatric disorders. Pharmacogenomics J 22, 211–222 (2022). https://doi.org/10.1038/s41397-022-00283-7

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  • DOI: https://doi.org/10.1038/s41397-022-00283-7

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