{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:02:18Z","timestamp":1789473738308,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Research Council of Lithuania","doi-asserted-by":"crossref","award":["S-MIP-25-125"],"award-info":[{"award-number":["S-MIP-25-125"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["G118588"],"award-info":[{"award-number":["G118588"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Diffusion-prepared pseudo-continuous arterial spin labelling (DP-pCASL) can quantify the cerebral blood flow (CBF) and the water exchange rate (kw) across the blood\u2013brain barrier (BBB). Little is known about the BBB water exchange in major depressive disorder (MDD). Objective: We aimed to explore the associations between kw, CBF, peripheral inflammation, and MDD. Methods: Using DP-pCASL, we measured the global and selected regional kw and CBF together with blood plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines in 85 patients with MDD and 51 controls. Results: The global CBF was significantly lower in MDD patients compared with controls (means of 51 and 57 mL\/100 g\/min, respectively; p = 0.006), with similar reductions found in the dorsolateral and ventromedial prefrontal, anterior, and posterior cingulate regions, while no differences were found in the amygdala and the isthmic cingulate. There were no differences in the kw between groups globally (means of 128 min\u22121; p = 0.958) and in the studied regions. Among MDD patients, the kw was weakly correlated with the MADRS scores (r = 0.231, p = 0.034). There were no associations between kw, CBF, and inflammatory markers (LPS, IL-6, IL-10, TNF-\u03b1, IFN-\u03b3). Logistic regression showed that a combination of the regional CBF &lt; 59.22 mL\/100 g\/min together with LPS &gt; 143.58 pg\/mL and\/or IL-10 &gt; 0 pg\/mL distinguished MDD patients from controls with a moderate accuracy of 83.1% (sensitivity = 94.1%, specificity = 64.7%, AUC = 0.876). Conclusions: DP-pCASL imaging confirmed previous findings of reduced CBF in MDD, which together with LPS and IL-10 concentrations were independent significant predictors of MDD. However, no changes in the BBB water exchange were found, suggesting that it may not be as significant as CBF in MDD pathophysiology.<\/jats:p>","DOI":"10.3390\/brainsci16010027","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:50:21Z","timestamp":1766710221000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebral Blood Flow and Blood\u2013Brain Barrier Water Exchange in Major Depressive Disorder: Evidence from Diffusion-Prepared Arterial Spin Labelling MRI"],"prefix":"10.3390","volume":"16","author":[{"given":"Simonas","family":"Jesmanas","sequence":"first","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3136-9064","authenticated-orcid":false,"given":"Egl\u0117","family":"Mila\u0161auskien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-2151","authenticated-orcid":false,"given":"Julius","family":"Burkauskas","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilmant\u0117","family":"Borutait\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"\u0160k\u0117mien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginija","family":"Adomaitien\u0117","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5086-8893","authenticated-orcid":false,"given":"Brigita","family":"Gradauskien\u0117","sequence":"additional","affiliation":[{"name":"Department of Immunology and Allergology, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saulius","family":"Luko\u0161evi\u010dius","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rymant\u0117","family":"Gleiznien\u0117","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-1730","authenticated-orcid":false,"given":"Guy C.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesta","family":"Steiblien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"},{"name":"Department of Psychiatry, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major Depressive Disorder: Hypothesis, Mechanism, Prevention and Treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. 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