Changes in Multiple MicroRNA Levels with Antidepressant Treatment Are Associated with Remission and Interact with Key Pathways: A Comprehensive MicroRNA Analysis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Aug 12

PMID 37569574

Authors

Toshiya Funatsuki

Haruhiko Ogata

Hidetoshi Tahara

Akira Shimamoto

Yoshiteru Takekita

Yosuke Koshikawa

Shinpei Nonen

Koichiro Higasa

Toshihiko Kinoshita

Masaki Kato

Affiliations

Soon will be listed here.

Abstract

Individual treatment outcomes to antidepressants varies widely, yet the determinants to this difference remain elusive. MicroRNA (miRNA) gene expression regulation in major depressive disorder (MDD) has attracted interest as a biomarker. This 4-week randomized controlled trial examined changes in the plasma miRNAs that correlated with the treatment outcomes of mirtazapine (MIR) and selective serotonin reuptake inhibitor (SSRI) monotherapy. Pre- and post- treatment, we comprehensively analyzed the miRNA levels in MDD patients, and identified the gene pathways linked to these miRNAs in 46 patients. Overall, 141 miRNA levels significantly demonstrated correlations with treatment remission after 4 weeks of MIR, with miR-1237-5p showing the most robust and significant correlation after Bonferroni correction. These 141 miRNAs displayed a negative correlation with remission, indicating a decreasing trend. These miRNAs were associated with 15 pathways, including TGF-β and MAPK. Through database searches, the genes targeted by these miRNAs with the identified pathways were compared, and it was found that , , , and matched. Alterations in specific miRNAs levels before and after MIR treatment correlated with remission. The miRNAs mentioned in this study have not been previously reported. No other studies have investigated treatment with MIR. The identified miRNAs also correlated with depression-related genes and pathways.

Citing Articles

MicroRNAs as Diagnostic Biomarkers and Predictors of Antidepressant Response in Major Depressive Disorder: A Systematic Review.

Carneiro B, Franco Guerreiro-Costa L, Lins-Silva D, Faria Guimaraes D, Souza L, Leal G Cureus. 2024; 16(3):e56910.

PMID: 38665721 PMC: 11043793. DOI: 10.7759/cureus.56910.

Clinical Insights into MicroRNAs in Depression: Bridging Molecular Discoveries and Therapeutic Potential.

Kaurani L Int J Mol Sci. 2024; 25(5).

PMID: 38474112 PMC: 10931847. DOI: 10.3390/ijms25052866.

References

Fang Y, Qiu Q, Zhang S, Sun L, Li G, Xiao S . Changes in miRNA-132 and miR-124 levels in non-treated and citalopram-treated patients with depression. J Affect Disord. 2018; 227:745-751. DOI: 10.1016/j.jad.2017.11.090. View

Szegedi A, Jansen W, Van Willigenburg A, van der Meulen E, Stassen H, Thase M . Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009; 70(3):344-53. DOI: 10.4088/jcp.07m03780. View

Tzanakakis G, Neagu M, Tsatsakis A, Nikitovic D . Proteoglycans and Immunobiology of Cancer-Therapeutic Implications. Front Immunol. 2019; 10:875. PMC: 6491844. DOI: 10.3389/fimmu.2019.00875. View

Lopez J, Fiori L, Cruceanu C, Lin R, Labonte B, Cates H . 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. PMC: 5477510. DOI: 10.1038/ncomms15497. View

Maeda N . Proteoglycans and neuronal migration in the cerebral cortex during development and disease. Front Neurosci. 2015; 9:98. PMC: 4369650. DOI: 10.3389/fnins.2015.00098. View

Young E, Kornstein S, Marcus S, Harvey A, Warden D, Wisniewski S . Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res. 2008; 43(5):503-11. PMC: 2681489. DOI: 10.1016/j.jpsychires.2008.07.002. View

Tavakolizadeh J, Roshanaei K, Salmaninejad A, Yari R, Nahand J, Sarkarizi H . MicroRNAs and exosomes in depression: Potential diagnostic biomarkers. J Cell Biochem. 2017; 119(5):3783-3797. DOI: 10.1002/jcb.26599. View

Vlachos I, Zagganas K, Paraskevopoulou M, Georgakilas G, Karagkouni D, Vergoulis T . DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res. 2015; 43(W1):W460-6. PMC: 4489228. DOI: 10.1093/nar/gkv403. View

Rana T, Behl T, Sehgal A, Mehta V, Singh S, Sharma N . Elucidating the Possible Role of FoxO in Depression. Neurochem Res. 2021; 46(11):2761-2775. DOI: 10.1007/s11064-021-03364-4. View

10.

Kraus C, Kadriu B, Lanzenberger R, Zarate Jr C, Kasper S . Prognosis and improved outcomes in major depression: a review. Transl Psychiatry. 2019; 9(1):127. PMC: 6447556. DOI: 10.1038/s41398-019-0460-3. View

11.

Satomi-Tsushita N, Shimomura A, Matsuzaki J, Yamamoto Y, Kawauchi J, Takizawa S . Serum microRNA-based prediction of responsiveness to eribulin in metastatic breast cancer. PLoS One. 2019; 14(9):e0222024. PMC: 6726239. DOI: 10.1371/journal.pone.0222024. View

12.

Kozomara A, Birgaoanu M, Griffiths-Jones S . miRBase: from microRNA sequences to function. Nucleic Acids Res. 2018; 47(D1):D155-D162. PMC: 6323917. DOI: 10.1093/nar/gky1141. View

13.

Habert J, Katzman M, Oluboka O, McIntyre R, McIntosh D, Macqueen G . Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment. Prim Care Companion CNS Disord. 2016; 18(5). DOI: 10.4088/PCC.15r01926. View

14.

Nemeroff C . The State of Our Understanding of the Pathophysiology and Optimal Treatment of Depression: Glass Half Full or Half Empty?. Am J Psychiatry. 2020; 177(8):671-685. DOI: 10.1176/appi.ajp.2020.20060845. View

15.

Belzeaux R, Fiori L, Lopez J, Boucekine M, Boyer L, Blier P . Predicting Worsening Suicidal Ideation With Clinical Features and Peripheral Expression of Messenger RNA and MicroRNA During Antidepressant Treatment. J Clin Psychiatry. 2019; 80(3). DOI: 10.4088/JCP.18m12556. View

16.

Smalheiser N, Lugli G, Rizavi H, Torvik V, Turecki G, Dwivedi Y . MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS One. 2012; 7(3):e33201. PMC: 3302855. DOI: 10.1371/journal.pone.0033201. View

17.

Kato M, Takekita Y, Koshikawa Y, Sakai S, Bandou H, Nishida K . Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT. J Psychiatr Res. 2017; 89:97-104. DOI: 10.1016/j.jpsychires.2017.02.003. View

18.

Kozomara A, Griffiths-Jones S . miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2013; 42(Database issue):D68-73. PMC: 3965103. DOI: 10.1093/nar/gkt1181. View

19.

Kato M, Serretti A, Nonen S, Takekita Y, Wakeno M, Azuma J . Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder: the result of two pooled RCTs. Transl Psychiatry. 2015; 5:e513. PMC: 4445755. DOI: 10.1038/tp.2015.6. View

20.

Otte C, Gold S, Penninx B, Pariante C, Etkin A, Fava M . Major depressive disorder. Nat Rev Dis Primers. 2016; 2:16065. DOI: 10.1038/nrdp.2016.65. View