{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:36:19Z","timestamp":1791916579800,"version":"4.3.4"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Bror Gadelius Memorial Foundation"},{"name":"The Swedish Mental Health Fund"},{"name":"Ellen and Henrik Sj\u00f6bring Memorial Foundation"},{"name":"Ellen and Henrik Sj\u00f6bring Memorial Foundation"},{"DOI":"10.13039\/501100001862","name":"The Swedish Research Council","doi-asserted-by":"crossref","award":["2020-01428"],"award-info":[{"award-number":["2020-01428"]}],"id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"crossref"}]},{"name":"state grants from the province of Scania, Sweden"},{"name":"state grants from the province of Scania, Sweden"},{"name":"Ellen and Sj\u00f6bring Memorial Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a personality disorder, 13% bipolar disorder. All analyses involving ccf-mtDNA were <jats:italic>a priori<\/jats:italic> adjusted for age and sex.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Mean levels in ccf-mtDNA were significantly different between patients with a current depressive episode (n = 236), remitted depressive episode (n = 45) and healthy controls (n = 49) (f = 8.3, p&lt;0.001). Post-hoc tests revealed that both patients with current (p&lt;0.001) and remitted (p = 0.002) depression had lower ccf-mtDNA compared to controls. Within the depressed group there was a positive correlation between ccf-mtDNA and \u201cinflammatory depression symptoms\u201d (r = 0.15, p = 0.02). We also found that treatment with mood stabilizers lamotrigine, valproic acid or lithium was associated with lower ccf-mtDNA (f = 8.1, p = 0.005).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>Decreased plasma ccf-mtDNA in difficult-to-treat depression may be partly explained by concurrent psychotropic medications and co-morbidity. Our findings suggest that ccf-mtDNA may be differentially regulated in different subtypes of depression, and this hypothesis should be pursued in future studies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0259591","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T17:46:46Z","timestamp":1636048006000},"page":"e0259591","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":49,"title":["Plasma circulating cell-free mitochondrial DNA in depressive 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