{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:39:55Z","timestamp":1790386795164,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["No. 23591684"],"award-info":[{"award-number":["No. 23591684"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Major depressive disorder (MDD) is a life-impairing disorder, and early successful treatment is important for a favorable prognosis. However, early response to antidepressants differs widely among individuals, and is difficult to predict pre-treatment. As miRNAs have been reported to play important roles in depression, identification of miRNAs associated with antidepressant treatment responses and their interacting genes and pathways will be beneficial in understanding the predictors and molecular mechanisms of depression treatment. This randomized control trial examined miRNAs correlated with the early therapeutic effect of selective serotonin reuptake inhibitors (SSRIs; paroxetine or sertraline) and mirtazapine monotherapy. Before medication, we comprehensively analyzed the miRNA expression of 92 depressed participants and identified genes and pathways interacting with miRNAs. A total of 228 miRNAs were significantly correlated with depressive symptoms improvements after 2 weeks of SSRIs treatment, with miR-483.5p showing the most robust correlation. These miRNAs are involved in 21 pathways, including TGF-\u03b2, glutamatergic synapse, long-term depression, and the mitogen-activated protein kinase (MAPK) signaling pathways. Using these miRNAs enabled us to predict SSRI response at week 2 with a 57% difference. This study shows that pre-treatment levels of miRNAs could be used to predict early responses to antidepressant administration, a knowledge of genes, and an identification of genes and pathways associated with the antidepressant response.<\/jats:p>","DOI":"10.3390\/ijms23073873","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:34:29Z","timestamp":1648762469000},"page":"3873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Multiple Pre-Treatment miRNAs Levels in Untreated Major Depressive Disorder Patients Predict Early Response to Antidepressants and Interact with Key Pathways"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-7272","authenticated-orcid":false,"given":"Masaki","family":"Kato","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":"Department of Cellular and Molecular Biology, 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":"Keiichiro","family":"Nishida","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 University of Health Sciences, Kobe 650-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Higasa","sequence":"additional","affiliation":[{"name":"Department of Genome Analysis, Institute of Biomedical Science, 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"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1017\/S0033291712001511","article-title":"Global variation in the prevalence and incidence of major depressive disorder: A systematic review of the epidemiological literature","volume":"43","author":"Ferrari","year":"2013","journal-title":"Psychol. Med."},{"key":"ref_2","unstructured":"Stein, D.J., Scott, K.M., de Jonge, P., and Kessler, R.C. (2018). Major Depressive Disorder. Mental Disorders Around the World: Facts and Figures from the WHO World Mental Health Surveys, Cambridge University Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1017\/S0033291709991036","article-title":"How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment","volume":"40","author":"Moffitt","year":"2010","journal-title":"Psychol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)02141-3","article-title":"Time for united action on depression: A Lancet-World Psychiatric Association Commission","volume":"399","author":"Herrman","year":"2022","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-020-0200-2","article-title":"Comorbid depression in medical diseases","volume":"6","author":"Gold","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1017\/S0033291718000624","article-title":"The prevalence of depression in general hospital inpatients: A systematic review and meta-analysis of interview-based studies","volume":"48","author":"Walker","year":"2018","journal-title":"Psychol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e017173","DOI":"10.1136\/bmjopen-2017-017173","article-title":"Prevalence of depression and depressive symptoms among outpatients: A systematic review and meta-analysis","volume":"7","author":"Wang","year":"2017","journal-title":"BMJ Open"},{"key":"ref_8","unstructured":"World Health Organization (2018, December 13). The Mental Health Gap Action Program (mhGAP), Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241596206:."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jpsychires.2005.06.005","article-title":"Management of depression relapse: Re-initiation of duloxetine treatment or dose increase","volume":"40","author":"Fava","year":"2006","journal-title":"J. Psychiatry Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jpsychires.2017.02.003","article-title":"Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT","volume":"89","author":"Kato","year":"2017","journal-title":"J. Psychiatry Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41380-020-0843-0","article-title":"Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: A systematic review and meta-analysis","volume":"26","author":"Kato","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Penninx, B.W., Milaneschi, Y., Lamers, F., and Vogelzangs, N. (2013). Understanding the somatic consequences of depression: Biological mechanisms and the role of depression symptom profile. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-129"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1037\/0278-6133.14.5.374","article-title":"Pathways linking affective disturbances and physical disorders","volume":"14","author":"Cohen","year":"1995","journal-title":"Health Psychol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"S\u00e1iz-V\u00e1zquez, O., Gracia-Garc\u00eda, P., Ubillos-Landa, S., Puente-Mart\u00ednez, A., Casado-Yusta, S., Olaya, B., and Santab\u00e1rbara, J. (2021). Depression as a Risk Factor for Alzheimer\u2019s Disease: A Systematic Review of Longitudinal Meta-Analyses. J. Clin. Med., 10.","DOI":"10.3390\/jcm10091809"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1176\/appi.ajp.2012.12020250","article-title":"Increase in work productivity of depressed individuals with improvement in depressive symptom severity","volume":"170","author":"Trivedi","year":"2013","journal-title":"Am J. Psychiatry"},{"key":"ref_17","first-page":"295","article-title":"Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment","volume":"18","author":"Habert","year":"2016","journal-title":"Prim. Care Companion CNS Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e513","DOI":"10.1038\/tp.2015.6","article-title":"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","volume":"5","author":"Kato","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"344","DOI":"10.4088\/JCP.07m03780","article-title":"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","volume":"70","author":"Szegedi","year":"2009","journal-title":"J. Clin. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3109\/15622975.2013.804195","article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders","volume":"14","author":"Bauer","year":"2013","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1177\/0706743716659417","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments","volume":"61","author":"Kennedy","year":"2016","journal-title":"Can. J. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.4088\/JCP.v69n0908","article-title":"Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: Systematic review and meta-analysis","volume":"69","author":"Watanabe","year":"2008","journal-title":"J. Clin. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1527-3458.2001.tb00198.x","article-title":"A review of the pharmacological and clinical profile of mirtazapine","volume":"7","author":"Anttila","year":"2001","journal-title":"CNS Drug Rev."},{"key":"ref_24","first-page":"861","article-title":"Effect of the alpha-2 adrenoceptor antagonist mirtazapine on the 5-hydroxytryptamine system in the rat brain","volume":"277","author":"Haddjeri","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tanaka, M., T\u00f3th, F., Poly\u00e1k, H., Szab\u00f3, \u00c1., M\u00e1ndi, Y., and V\u00e9csei, L. (2021). Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines, 9.","DOI":"10.20944\/preprints202106.0344.v1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1176\/appi.ajp.2020.20060845","article-title":"The State of Our Understanding of the Pathophysiology and Optimal Treatment of Depression: Glass Half Full or Half Empty?","volume":"177","author":"Nemeroff","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sakurai, H., Yonezawa, K., Tani, H., Mimura, M., Bauer, M., and Uchida, H. (2022). Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry. Pharmacopsychiatry.","DOI":"10.1055\/a-1714-9097"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/npp.2015.85","article-title":"Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors","volume":"40","author":"Hill","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","first-page":"1","article-title":"Pretreatment plasma cytokine levels as potential predictors of short-term remission of depression","volume":"40","author":"Atake","year":"2022","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/7854_2012_216","article-title":"Molecular and cellular mechanisms of antidepressant action","volume":"14","author":"Sharp","year":"2013","journal-title":"Curr. Top Behav. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pena-Vargas, C., Armaiz-Pena, G., and Castro-Figueroa, E. (2021). A Biopsychosocial Approach to Grief, Depression, and the Role of Emotional Regulation. Behav. Sci., 11.","DOI":"10.3390\/bs11080110"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tanaka, M., and Vecsei, L. (2021). Editorial of Special Issue \u201cCrosstalk between Depression, Anxiety, and Dementia: Comorbidity in Behavioral Neurology and Neuropsychiatry\u201d. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050517"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrd2462","article-title":"Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders","volume":"7","author":"Sanacora","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1080\/14728222.2016.1238899","article-title":"Ketamine\u2019s antidepressant action: Beyond NMDA receptor inhibition","volume":"20","author":"Hashimoto","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000356549","article-title":"Targeting the inflammatory pathway as a therapeutic tool for major depression","volume":"21","author":"Noto","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrn3234","article-title":"Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease","volume":"13","author":"Qureshi","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fgene.2014.00041","article-title":"Brain-expressed 3\u2032UTR extensions strengthen miRNA cross-talk between ion channel\/transporter encoding mRNAs","volume":"5","author":"Wehrspaun","year":"2014","journal-title":"Front. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jpsychires.2016.07.009","article-title":"Predisposition to treatment response in major depressive episode: A peripheral blood gene coexpression network analysis","volume":"81","author":"Belzeaux","year":"2016","journal-title":"J. Psychiatry Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1002\/jcb.26599","article-title":"MicroRNAs and exosomes in depression: Potential diagnostic biomarkers","volume":"119","author":"Tavakolizadeh","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Smalheiser, N.R., Lugli, G., Rizavi, H.S., Torvik, V.I., Turecki, G., and Dwivedi, Y. (2012). MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033201"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jpsychires.2014.08.007","article-title":"Differential expression of microRNA in peripheral blood mononuclear cells as specific biomarker for major depressive disorder patients","volume":"59","author":"Fan","year":"2014","journal-title":"J. Psychiatry Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/s41386-020-00861-y","article-title":"Differential and unique patterns of synaptic miRNA expression in dorsolateral prefrontal cortex of depressed subjects","volume":"46","author":"Yoshino","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Cao, D.D., Li, L., and Chan, W.Y. (2016). MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060842"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"556","DOI":"10.4088\/JCP.18m12556","article-title":"Predicting Worsening Suicidal Ideation with Clinical Features and Peripheral Expression of Messenger RNA and MicroRNA during Antidepressant Treatment","volume":"80","author":"Belzeaux","year":"2019","journal-title":"J. Clin. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nm.3582","article-title":"miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment","volume":"20","author":"Lopez","year":"2014","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e185","DOI":"10.1038\/tp.2012.112","article-title":"Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode","volume":"2","author":"Belzeaux","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.neuron.2014.05.042","article-title":"MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity","volume":"83","author":"Issler","year":"2014","journal-title":"Neuron"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jpsychires.2016.03.015","article-title":"Alterations of microRNA-124 expression in peripheral blood mononuclear cells in pre- and post-treatment patients with major depressive disorder","volume":"78","author":"He","year":"2016","journal-title":"J. Psychiatry Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/ijnp\/pyx034","article-title":"Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response","volume":"20","author":"Fiori","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jpsychires.2017.07.003","article-title":"Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis","volume":"94","author":"Wagner","year":"2017","journal-title":"J. Psychiatry Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/npp.2017.9","article-title":"Co-Variation of Peripheral Levels of miR-1202 and Brain Activity and Connectivity during Antidepressant Treatment","volume":"42","author":"Lopez","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jad.2016.10.008","article-title":"A genetic variant in miRNA binding site of glutamate receptor 4, metabotropic (GRM4) is associated with increased risk of major depressive disorder","volume":"208","author":"Dadkhah","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1101\/gad.1884710","article-title":"Mammalian microRNAs: Experimental evaluation of novel and previously annotated genes","volume":"24","author":"Chiang","year":"2010","journal-title":"Genes Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nsmb.3050","article-title":"Small-RNA asymmetry is directly driven by mammalian Argonautes","volume":"22","author":"Suzuki","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1101\/gad.224170.113","article-title":"The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis","volume":"27","author":"Liu","year":"2013","journal-title":"Genes Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11909","DOI":"10.1038\/srep11909","article-title":"miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA\/ROCK1\/ERK1\/2 pathway in multiple symmetric lipomatosis","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pepe, F., Visone, R., and Veronese, A. (2018). The Glucose-Regulated MiR-483-3p Influences Key Signaling Pathways in Cancer. Cancers, 10.","DOI":"10.3390\/cancers10060181"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15497","DOI":"10.1038\/ncomms15497","article-title":"MicroRNAs 146a\/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK\/Wnt-system genes","volume":"8","author":"Lopez","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_60","unstructured":"American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [4th ed.]."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.2044-8260.1967.tb00530.x","article-title":"Development of a rating scale for primary depressive illness","volume":"6","author":"Hamilton","year":"1967","journal-title":"Br. J. Soc. Clin. Psychol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W460","DOI":"10.1093\/nar\/gkv403","article-title":"DIANA-miRPath v3.0: Deciphering microRNA function with experimental support","volume":"43","author":"Vlachos","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.phrs.2018.02.007","article-title":"Neurobiological links between depression and AD: The role of TGF-\u03b21 signaling as a new pharmacological target","volume":"130","author":"Caraci","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108916","DOI":"10.1016\/j.neuropharm.2021.108916","article-title":"2-Arachidonoylglycerol mobilization following brief synaptic stimulation in the dorsal lateral striatum requires glutamatergic and cholinergic neurotransmission","volume":"205","author":"Liput","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hiew, L.F., Poon, C.H., You, H.Z., and Lim, L.W. (2021). TGF-\u03b2\/Smad Signalling in Neurogenesis: Implications for Neuropsychiatric Diseases. Cells, 10.","DOI":"10.3390\/cells10061382"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.tins.2011.06.002","article-title":"More than being protective: Functional roles for TGF-\u03b2\/activin signaling pathways at central synapses","volume":"34","author":"Krieglstein","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"112545","DOI":"10.1016\/j.biopha.2021.112545","article-title":"Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression","volume":"146","author":"Behl","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12264-019-00358-9","article-title":"Regulation of Circadian Genes by the MAPK Pathway: Implications for Rapid Antidepressant Action","volume":"36","author":"Wang","year":"2020","journal-title":"Neurosci. Bull."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S2215-0366(20)30137-1","article-title":"Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: A systematic review and network meta-analysis","volume":"7","author":"Zhou","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.neubiorev.2021.04.036","article-title":"Memories are not written in stone: Re-writing fear memories by means of non-invasive brain stimulation and optogenetic manipulations","volume":"127","author":"Borgomaneri","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1001\/jamapsychiatry.2013.143","article-title":"Toward a neuroimaging treatment selection biomarker for major depressive disorder","volume":"70","author":"McGrath","year":"2013","journal-title":"JAMA Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:47:36Z","timestamp":1760136456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":71,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073873"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073873","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]}}}