Dataset Information

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

ABSTRACT: 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. 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, 18F-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. 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 18F-florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF-α level, HVa, and cognitive measures. 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.

SUBMITTER: Ho SK

PROVIDER: S-EPMC11376440 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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

Ho Szu-Kai SK Hsiao Ing-Tsung IT Lin Kun-Ju KJ Wu Yi-Ming YM Wu Kuan-Yi KY

Brain and behavior 20240901 9

<h4>Background</h4>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 indica ...[more]

PMID: 39236111

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

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

Publications

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

Similar Datasets

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