{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:18:54Z","timestamp":1787725134886,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF\u2010\u03b1 levels, hippocampal volume, beta\u2010amyloid (A\u03b2) burden, and cognitive abilities in MDD patients, aiming to illuminate the complex interplay among inflammatory markers, pathology indicators, structural brain alterations, and cognitive performance in non\u2010demented MDD individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Fifty\u2010two non\u2010demented MDD patients, comprising 25 with mild cognitive impairment (MCI), were recruited along with 10 control subjects. Each participant underwent a thorough assessment encompassing TNF\u2010\u03b1 blood testing, <jats:sup>18<\/jats:sup>F\u2010florbetapir positron emission tomography, magnetic resonance imaging scans, and neuropsychological testing. Statistical analyses, adjusted for age and education, were performed to investigate the associations between TNF\u2010\u03b1 levels, adjusted hippocampal volume (HVa), global A\u03b2 burden, and cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MCI MDD patients displayed elevated TNF\u2010\u03b1 levels and reduced HVa relative to controls. Correlation analyses demonstrated inverse relationships between TNF\u2010\u03b1 level and HVa in MCI MDD, all MDD, and all subjects groups. Both TNF\u2010\u03b1 level and HVa exhibited significant correlations with processing speed across all MDD and all subjects. Notably, global <jats:sup>18<\/jats:sup>F\u2010florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF\u2010\u03b1 level, HVa, and cognitive measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights elevated TNF\u2010\u03b1 levels and reduced hippocampal volume in MCI MDD patients, indicating a potential association between peripheral inflammation and structural brain alterations in depression. Furthermore, our results suggest that certain cases of MDD may be affected by non\u2010amyloid\u2010mediated process, which impacts their TNF\u2010\u03b1 and hippocampal volume. These findings emphasize the importance of further investigating the complex interplay among inflammation, neurodegeneration, and cognitive function in MDD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70016","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T17:58:36Z","timestamp":1725559116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Relationships among tumor necrosis factor\u2010alpha levels, beta\u2010amyloid accumulation, and hippocampal atrophy in patients with late\u2010life major depressive disorder"],"prefix":"10.1002","volume":"14","author":[{"given":"Szu\u2010Kai","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Psychiatry Chang Gung Memorial Hospital and College of Medicine Chang Gung University  Taoyuan 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