{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:59:16Z","timestamp":1790481556354,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The serotonin transporter gene (SLC6A4; 5-HTT; SERT) is considered a prime candidate in pharmacogenetic research in major depressive disorder (MDD). Besides genetic variation, recent advances have spotlighted the involvement of epigenetic mechanisms such as DNA methylation in predicting antidepressant treatment response in \u201cpharmaco-epigenetic\u201d approaches. In MDD, lower SLC6A4 promoter methylation has been suggested to predict impaired response to serotonergic antidepressants. The present study sought to replicate and extend this finding in a large, independent sample of MDD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The sample comprised n\u2009=\u2009236 Caucasian patients with MDD receiving antidepressant medication in a naturalistic treatment setting. Functional DNA methylation of 9 CpG sites located in the SLC6A4 promoter region was analyzed via direct sequencing of sodium bisulfite\u2013 treated DNA extracted from blood cells. Patients were assessed over the course of a 6-week in-patient treatment using the Hamilton Depression Scale (HAM-D).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Results confirm relative SLC6A4 hypomethylation to predict impaired antidepressant response both dimensionally and categorically (HAM-D reductions &amp;lt; 50%) and to furthermore be indicative of nonremission (HAM-D &amp;gt; 7). This also held true in a homogenous subgroup of patients continuously treated with selective serotonin reuptake inhibitors or serotonin\/noradrenaline reuptake inhibitors (n\u2009=\u2009110).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Impaired response to serotonergic antidepressants via SLC6A4 hypomethylation may be conveyed by increased gene expression and consequently decreased serotonin availability, which may counteract the effects of serotonergic antidepressants. The present results could in the future inform clinical decision-making towards a more personalized treatment of MDD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaa081","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T03:32:13Z","timestamp":1603510333000},"page":"191-199","source":"Crossref","is-referenced-by-count":49,"title":["Serotonin Transporter Gene Promoter Hypomethylation as a Predictor of Antidepressant Treatment Response in Major Depression: A Replication Study"],"prefix":"10.1093","volume":"24","author":[{"given":"M A","family":"Schiele","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Zwanzger","sequence":"additional","affiliation":[{"name":"kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Schwarte","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Arolt","sequence":"additional","affiliation":[{"name":"Institute of Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B T","family":"Baune","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of M\u00fcnster, M\u00fcnster, Germany"},{"name":"Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia"},{"name":"The Florey Institute of 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