Relationships among tumor necrosis factor-alpha levels, beta-amyloid accumulation, and hippocampal atrophy in patients with late-life major depressive disorder.

Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101570837 Publication Model: Print Cited Medium: Internet ISSN: 2162-3279 (Electronic) NLM ISO Abbreviation: Brain Behav Subsets: MEDLINE

Original Publication: Hoboken, NJ : John Wiley & Sons

Depressive Disorder, Major*/diagnostic imaging ; Depressive Disorder, Major*/metabolism ; Depressive Disorder, Major*/pathology ; Hippocampus*/diagnostic imaging ; Hippocampus*/pathology ; Hippocampus*/metabolism ; Tumor Necrosis Factor-alpha*/metabolism ; Tumor Necrosis Factor-alpha*/blood ; Amyloid beta-Peptides*/metabolism ; Positron-Emission Tomography* ; Atrophy*/pathology ; Cognitive Dysfunction*/etiology ; Cognitive Dysfunction*/metabolism ; Cognitive Dysfunction*/physiopathology ; Cognitive Dysfunction*/diagnostic imaging ; Magnetic Resonance Imaging*; Humans ; Male ; Female ; Aged ; Middle Aged ; Neuropsychological Tests ; Aniline Compounds ; Ethylene Glycols

Background: Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor-alpha (TNF-α) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF-α levels, hippocampal volume, beta-amyloid (Aβ) 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-demented MDD individuals.
Method: Fifty-two non-demented MDD patients, comprising 25 with mild cognitive impairment (MCI), were recruited along with 10 control subjects. Each participant underwent a thorough assessment encompassing TNF-α blood testing, ¹⁸ F-florbetapir 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-α levels, adjusted hippocampal volume (HVa), global Aβ burden, and cognitive performance.
Results: MCI MDD patients displayed elevated TNF-α levels and reduced HVa relative to controls. Correlation analyses demonstrated inverse relationships between TNF-α level and HVa in MCI MDD, all MDD, and all subjects groups. Both TNF-α level and HVa exhibited significant correlations with processing speed across all MDD and all subjects. Notably, global ¹⁸ F-florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF-α level, HVa, and cognitive measures.
Conclusion: This study highlights elevated TNF-α 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-amyloid-mediated process, which impacts their TNF-α and hippocampal volume. These findings emphasize the importance of further investigating the complex interplay among inflammation, neurodegeneration, and cognitive function in MDD.
(© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

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The Ministry of Science and Technology, Taiwan

Keywords: 18F‐florbetapir (AV‐45/Amyvid); TNF‐α; amyloid; hippocampal atrophy; major depressive disorder

0 (Tumor Necrosis Factor-alpha)
0 (Amyloid beta-Peptides)
6867Q6IKOD (florbetapir)
0 (Aniline Compounds)
0 (Ethylene Glycols)

Date Created: 20240905 Date Completed: 20240905 Latest Revision: 20240907

20250114

PMC11376440

10.1002/brb3.70016

39236111