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However, whether these processes are related, either to each other or to eventual treatment outcomes, has yet to be determined. We examined the relationship between levels of peripheral pro-inflammatory cytokines and diffusion imaging-indexed changes in WM microstructure in individuals with treatment-resistant depression (TRD) who underwent ECT. Forty-two patients were assessed at baseline, after their second ECT (T2), and after completion of ECT (T3). A Montgomery \u00c5sberg Depression Rating Scale improvement of &gt;50% post-ECT defined ECT-responders (<jats:italic>n<\/jats:italic>\u2009=\u200919) from non-responders (<jats:italic>n<\/jats:italic>\u2009=\u200923). Thirty-four controls were also examined. Tissue-specific fractional anisotropy (FAt) was estimated using diffusion imaging data and the Free-Water method in 17 WM tracts. Inflammatory panels were evaluated from peripheral blood. Cytokines were examined to characterize the association between potential ECT-induced changes in an inflammatory state and WM microstructure. Longitudinal trajectories of both measures were also examined separately for ECT-responders and non-responders. Patients exhibited elevated Interleukin-8 (IL-8) levels at baseline compared to controls. In patients, correlations between IL-8 and FAt changes from baseline to T2 were significant in the positive direction in the right superior longitudinal fasciculus (R-SLF) and right cingulum (R-CB) (<jats:italic>p<\/jats:italic><jats:sub>sig<\/jats:sub>\u2009=\u20090.003). In these tracts, linear mixed-effects models revealed that trajectories of IL-8 and FAt were significantly positively correlated across all time points in responders, but not non-responders (R-CB-p\u2009=\u2009.001; R-SLF-p\u2009=\u20090.008). Our results suggest that response to ECT in TRD may be mediated by IL-8 and WM microstructure.<\/jats:p>","DOI":"10.1038\/s41398-022-01960-8","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T04:02:54Z","timestamp":1651896174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Longitudinal trajectory of response to electroconvulsive therapy associated with transient immune response &amp; white matter alteration post-stimulation"],"prefix":"10.1038","volume":"12","author":[{"given":"Blake","family":"Andreou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-516X","authenticated-orcid":false,"given":"Amanda E.","family":"Lyall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3315-5821","authenticated-orcid":false,"given":"Suheyla","family":"Cetin-Karayumak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Kubicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-4212","authenticated-orcid":false,"given":"Randall","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0628-3921","authenticated-orcid":false,"given":"Jennifer","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Narr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-8212","authenticated-orcid":false,"given":"Marek","family":"Kubicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"key":"1960_CR1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s11121-011-0231-8","volume":"12","author":"KA McLaughlin","year":"2011","unstructured":"McLaughlin KA. 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