{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:37:50Z","timestamp":1791981470510,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":241,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472057"],"award-info":[{"award-number":["82472057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971597"],"award-info":[{"award-number":["81971597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004000","name":"Guangzhou Science and Technology Program key projects","doi-asserted-by":"publisher","award":["2024B03J1299"],"award-info":[{"award-number":["2024B03J1299"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Depression and Anxiety"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The therapeutic effects of vortioxetine on mood and cognition have been documented in major depressive disorder (MDD). This study aims to examine whether vortioxetine can improve brain glymphatic system function and connections among functional brain networks and to explore the underlying relationships among these changes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    A total of 34 patients with MDD and 41 healthy controls (HCs) were recruited in the study. All participants underwent mood and cognitive assessment, and diffusion tensor imaging (DTI) and resting\u2010state functional MRI scans at baseline and 8\u2010week follow\u2010up. The DTI analysis along the perivascular space (DTI\u2010ALPS) index, and functional connectivity (FC) were assessed. Cognitive assessment was conducted using the Chinese version of Measurement Consensus Cognitive Battery (MCCB). Correlation analysis was subsequently performed to explore underlying association among these indexes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Compared to HCs, patients with MDD showed decreased DTI\u2010ALPS indexes at baseline; patients with MDD showed increased the default mode network (DMN) FC between the posterior cingulate cortex (PCC)\u2013precuneus; patients with MDD displayed decreased attention\/vigilance, verbal learning, visual learning, social cognition, and global cognition. Treatment with vortioxetine, patients with MDD displayed reduced depressive symptoms, increased DTI\u2010ALPS indexes, decreased DMN FC, and improved attention\/vigilance, verbal learning, visual learning, social cognition, and global cognition. Moreover, the increased DTI\u2010ALPS indexes correlated with improved global cognition, and decreased DMN FC in MDD, respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The current study indicated vortioxetine improves glymphatic system function and brain connections within the DMN in MDD. Furthermore, the restoration of glymphatic function is linked to improved brain function and cognition.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration<\/jats:bold>\n                    :\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: ChiCTR2200057820\n                  <\/jats:p>","DOI":"10.1155\/da\/1990117","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T08:52:40Z","timestamp":1756543960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Vortioxetine Improves Brain Glymphatic System Function, Functional Connectivity, and Cognitive Functions in Major Depressive Disorder"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6772-1131","authenticated-orcid":false,"given":"Zixuan","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuming","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanmao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-8097","authenticated-orcid":false,"given":"Yanbin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-4177","authenticated-orcid":false,"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"e_1_2_12_1_2","unstructured":"WHO Depression and Other Common Mental Disorders: Global Health Estimates 2017 World Health Organization."},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30291-3"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.07.022"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0655-3"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.07.001"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30318-1"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8739"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbae039"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232274"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26710"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2024.05.009"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013215"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.002"},{"key":"e_1_2_12_14_2","doi-asserted-by":"crossref","unstructured":"LiuY. D. ChangY. H. andXieX. T. et al.PET Imaging Unveils Neuroinflammatory Mechanisms in Psychiatric Disorders: From Microglial Activation to Therapeutic Innovation 2025 https:\/\/doi.org\/10.1007\/s12035-025-05177-w.","DOI":"10.1007\/s12035-025-05177-w"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11112296"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080743"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.21037\/qims-24-510"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01995-x"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2023-101371"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-03207-0"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2015.0071"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2012.04.013"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.12.002"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.01.010"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1900390116"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.21070727"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.08.055"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.3867"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijchp.2024.100483"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12021-011-9109-y"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011121"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4473-9"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-023-02614-z"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2021202043"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70218"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.02.020"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0212"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.9.877"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.104"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02778-0"},{"key":"e_1_2_12_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.10.011"},{"key":"e_1_2_12_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14458"},{"key":"e_1_2_12_44_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209306"},{"key":"e_1_2_12_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14149"}],"container-title":["Depression and Anxiety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/da\/1990117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/da\/1990117","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/da\/1990117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:40:54Z","timestamp":1772966454000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/da\/1990117"}},"subtitle":[],"editor":[{"given":"Marlene","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/da\/1990117"],"URL":"https:\/\/doi.org\/10.1155\/da\/1990117","archive":["Portico"],"relation":{},"ISSN":["1091-4269","1520-6394"],"issn-type":[{"value":"1091-4269","type":"print"},{"value":"1520-6394","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1990117"}}