{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:39:56Z","timestamp":1790386796263,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["23591684"],"award-info":[{"award-number":["23591684"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["22K07607"],"award-info":[{"award-number":["22K07607"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b2 and MAPK. Through database searches, the genes targeted by these miRNAs with the identified pathways were compared, and it was found that MAPK1, IGF1, IGF1R, and BRAF 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.<\/jats:p>","DOI":"10.3390\/ijms241512199","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:26:40Z","timestamp":1690766800000},"page":"12199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Changes in Multiple microRNA Levels with Antidepressant Treatment Are Associated with Remission and Interact with Key Pathways: A Comprehensive microRNA Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Toshiya","family":"Funatsuki","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3054-4175","authenticated-orcid":false,"given":"Hidetoshi","family":"Tahara","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8533, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimamoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda 756-0084, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-4033","authenticated-orcid":false,"given":"Yoshiteru","family":"Takekita","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-092X","authenticated-orcid":false,"given":"Yosuke","family":"Koshikawa","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinpei","family":"Nonen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hyogo Medical University, Nishinomiya 650-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Higasa","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Science, Department of Genome Analysis, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-7272","authenticated-orcid":false,"given":"Masaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Kansai Medical University, Osaka 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-publhealth-031912-114409","article-title":"The epidemiology of depression across cultures","volume":"34","author":"Kessler","year":"2013","journal-title":"Annu. 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