{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:19:10Z","timestamp":1788236350996,"version":"build-2803163510"},"reference-count":0,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"unspecified","delay-in-days":293,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Spectr."],"published-print":{"date-parts":[[2025]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans and blood samples taken at baseline and 6 months. Brain volume was assessed using VolBrain2 and DSI studio.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared to controls, TRD patients initially showed lower volumes (mm\n 3<\/jats:sup>\n ) in key cortical regions such as the insula (p = 0.0156), the frontal lobe (p = 0.0228) the superior parietal lobe (p = 0.0402), both superior (p = 0.0216) and inferior (p = 0.0437) temporal lobes and subcortical regions such as the nucleus accumbens (p = 0.0056), putamen (p = 0.0083), thalamus (p = 0.0102) and the hippocampus (p = 0.0001). Brain volume increased in the frontal cortex (p = 0.0295), the anterior cingulate (p = 0.0496), and hippocampus (p = 0.0015), as well as in the volume and fiber tracts associated with emotional regulation, such as the frontoparahippocampal (p = 0.0156 and p = 0.0313, respectively), the frontoparietal (p = 0.0496 and p = 0.0156, respectively) and the frontal aslant tract after 6 months on treatment with ESK-IN. In parallel, sNfL levels decreased post-treatment, indicating potential neuroprotective effects.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n ESK-IN may promote structural changes in regions associated with mood regulation and neuroplasticity, while also reducing neuronal damage in TRD patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1017\/s1092852925100631","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:04:36Z","timestamp":1761048276000},"source":"Crossref","is-referenced-by-count":2,"title":["Rebuilding the atrophied brain: 6-month nasal esketamine therapy expands key frontal and hippocampal regions and reduces serum neurofilament levels in patients with major depressive disorder. A proof-of-concept study of the depTesk (DEPression treatment with ESKetamine) study"],"prefix":"10.1017","volume":"30","author":[{"given":"Ana","family":"Rodr\u00edguez Lorente","sequence":"first","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Pilar","family":"Campos-Navarro","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"},{"name":"Murcia Health Service"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Gil Montoya","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Mar\u00edn P\u00e9rez","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luisa","family":"Maso Navarro","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Orgaz Morales","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"L\u00f3pez Ramirez","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-7698","authenticated-orcid":false,"given":"Juan Antonio","family":"Garc\u00eda-Carmona","sequence":"additional","affiliation":[{"name":"Santa Luc\u00eda University Hospital"},{"name":"San Antonio Catholic University of Murcia (UCAM)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2025,10,21]]},"container-title":["CNS Spectrums"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1092852925100631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:23:06Z","timestamp":1762251786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1092852925100631\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025]]}},"alternative-id":["S1092852925100631"],"URL":"https:\/\/doi.org\/10.1017\/s1092852925100631","relation":{},"ISSN":["1092-8529","2165-6509"],"issn-type":[{"value":"1092-8529","type":"print"},{"value":"2165-6509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]},"article-number":"e83"}}