Affiliation:
1. Department of Psychiatry Chang Gung Memorial Hospital and College of Medicine Chang Gung University Taoyuan Taiwan
2. Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation Chang Gung Memorial Hospital Taoyuan Taiwan
3. Department of Medical Imaging and Radiological Sciences and Healthy Aging Research Center Chang Gung University Taoyuan Taiwan
4. Neuroscience Research Center Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
5. Department of Radiology Chang Gung Memorial Hospital Taoyuan Taiwan
Abstract
AbstractBackgroundMajor 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.MethodFifty‐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.ResultsMCI 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.ConclusionThis 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.