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Individualized, accelerated continuous theta burst stimulation (cTBS) targeting the right dorsolateral prefrontal cortex (R.DLPFC) may offer a potential therapeutic approach for concurrently improving clinical and psychosocial outcomes in MDD. In this randomized, double-blind, sham-controlled trial, 70 patients with MDD were randomly assigned to receive either active (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200937) or sham (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933) accelerated cTBS for 2 weeks. The treatments targeted individualized R.DLPFC sites, which were identified by task-evoked brain activation during a social interactive task (Ultimatum Game, UG). Depressive and anxiety symptoms, general social functioning, UG-derived behavioral and computational modeling indices (e.g., learning rates), and effective connectivity in social processing networks were assessed pre- and post-treatment. Active accelerated cTBS significantly outperformed sham stimulation in reducing depressive and anxiety symptoms and improving general social functioning (all\n                    <jats:italic>ps<\/jats:italic>\n                    \u2009&lt;\u20090.001). The active group also demonstrated enhanced cooperation behavior (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) and increased learning rates (89% HDI: [0.01, 0.21]). And the active group exhibited increased effective connectivity from the right insula to the R.DLPFC and stable effective connectivity from the anterior cingulate cortex (ACC) to the left insula after treatment, which was different from the sham group (\n                    <jats:italic>Pp<\/jats:italic>\n                    \u2009&gt;\u20090.95). No severe adverse events occurred. Individualized, accelerated cTBS targeting task-evoked activation in the R.DLPFC safely and effectively improves clinical symptoms and social dysfunction in MDD. Altered effective connectivity among the DLPFC, insula and ACC may provide mechanistic insights into its therapeutic effects. Trial Registration: chictr.org.cn; ChiCTR2300068273.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02365-7","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:36:12Z","timestamp":1771598172000},"page":"1290-1299","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Task-guided accelerated cTBS simultaneously treats depression and social dysfunction in patients with major depressive disorder: a randomized clinical trial"],"prefix":"10.1038","volume":"51","author":[{"given":"Jing","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuening","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Zeidman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6378-1711","authenticated-orcid":false,"given":"Yuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-1188","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"2365_CR1","first-page":"1517","volume":"317","author":"MJ Friedrich","year":"2017","unstructured":"Friedrich MJ. 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(2025, July 15): Proximity to an SGC-DLPFC individualized functional target and outcomes in large rTMS clinical trials for treatment-resistant depression. bioRxiv, p 2025.07.09.662866.","DOI":"10.1101\/2025.07.09.662866"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02365-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02365-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02365-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T04:35:10Z","timestamp":1779856510000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02365-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2365"],"URL":"https:\/\/doi.org\/10.1038\/s41386-026-02365-7","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"10 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the last 3 years, PBF has received equipment for research from Neurosoft and Nexstim. He has served on a scientific advisory board for Magstim and received speaker fees from Otsuka. He has also acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This manuscript is original, and none of the materials in this paper has been previously published or are under consideration for publication elsewhere. All the listed authors have reviewed and approved the content.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}