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Currently, tRNA\u2010derived small ribonucleic acids (tsRNAs) have been established as promising non\u2010invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA\u2010Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up\u2010regulated and 4 down\u2010regulated). qRT\u2010PCR was used to validate the expression of six tsRNAs that were up\u2010regulated in MDD (tiRNA\u20101:20\u2010chrM.Ser\u2010GCT, tiRNA\u20101:33\u2010Gly\u2010GCC\u20101, tRF\u20101:22\u2010chrM.Ser\u2010GCT, tRF\u20101:31\u2010Ala\u2010AGC\u20104\u2010M6, tRF\u20101:31\u2010Pro\u2010TGG\u20102 and tRF\u20101:32\u2010chrM.Gln\u2010TTG). Interestingly, serum tiRNA\u2010Gly\u2010GCC\u2010001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA\u2010Gly\u2010GCC\u2010001 is predicted to suppress brain\u2010derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA\u2010Gly\u2010GCC\u2010001 down\u2010regulation was evident following an 8\u2010week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our current work reports for the first time that tiRNA\u2010Gly\u2010GCC\u2010001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16319","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T07:14:30Z","timestamp":1709622870000},"page":"1952-1972","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["tiRNA\u2010Gly\u2010GCC\u2010001 in major depressive disorder: Promising diagnostic and therapeutic biomarker"],"prefix":"10.1111","volume":"181","author":[{"given":"Haihua","family":"Tian","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Pathophysiology, Health Center Ningbo University  Ningbo Zhejiang China"},{"name":"Department of Psychiatry Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang China"},{"name":"Department of Psychiatry Ningbo Kangning Hospital  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shugui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang China"},{"name":"Department of Psychiatry Ningbo Kangning Hospital  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang China"},{"name":"Department 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