Elevated VCAM-1 levels in peripheral blood are associated with brain structural and functional alterations in major
Jingjing Zhou1, Rui Liu1, Jia Zhou1
1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Insights
Major depressive disorder (MDD) patients show elevated levels of vascular cell adhesion molecule-1 (VCAM-1). This molecule is linked to reduced gray matter volume and altered brain connectivity, suggesting a role in MDD pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Vascular cell adhesion molecule-1 (VCAM-1) is a key marker of endothelial activation.
- Endothelial dysfunction and inflammation are increasingly implicated in the pathophysiology of major depressive disorder (MDD).
Purpose of the Study:
- To investigate peripheral VCAM-1 levels in patients with MDD.
- To explore the relationship between VCAM-1, brain structure (gray matter volume), and functional connectivity in MDD.
Main Methods:
- Recruited 165 participants (85 MDD patients, 80 healthy controls).
- Measured serum VCAM-1 using ELISA.
- Acquired magnetic resonance imaging (MRI) data for 133 participants to assess gray matter volume (GMV) and functional connectivity (FC).
Main Results:
- MDD patients exhibited significantly higher VCAM-1 levels compared to healthy controls.
- VCAM-1 levels negatively correlated with GMV in the right medial frontal cortex and postcentral gyrus.
- VCAM-1 mediated the association between group status and GMV of the postcentral gyrus, and FC between the left ventral prefrontal cortex and right inferior parietal lobe.
Conclusions:
- Elevated VCAM-1 is associated with structural and functional brain alterations in MDD.
- VCAM-1 may play a role in the etiology of MDD by affecting brain structure and function.
- Findings suggest VCAM-1 as a potential biomarker linking immune activation to neurobiological changes in depression.
Background:
Vascular cell adhesion molecule-1 (VCAM-1) is a well-known biomarker of endothelial activation. This study aimed to determine whether changes in peripheral VCAM-1 levels occurred in major depressive disorder (MDD) patients and explored immune-brain interactions based on neuroimaging.
Methods:
This study included 165 subjects (80 healthy controls [HCs] and 85 MDD patients). Of them, 133 underwent magnetic resonance imaging. VCAM-1 was measured using a commercially available Enzyme-Linked Immunosorbent Assay kit following the manufacturer's instructions. The gray matter volume (GMV) and surface-based functional connectivity (FC) were calculated based on Schaefer parcellation 400 parcels.
Results:
Compared with the HCs, MDD patients exhibited significantly higher level of VCAM-1. The correlation analysis showed that VCAM-1 had a significant negative correlation with GMV of the right medial frontal cortex (MFC) and postcentral (PostCG). The mediation analyses showed that VCAM-1 mediated the association between group and GMV of PostCG and the FC of left ventral prefrontal cortex (vPFC) with right inferior parietal lobe (IPL).
Conclusions:
This study showed that a high level of VCAM-1 was associated to the decreased GMV in the right MFC and PostCG, and mediated the FC of the left vPFC with right IPL. These findings suggested that VCAM-1 might contribute to the etiology of MDD by influencing brain structure and function.
Limitations:
The cross-sectional design makes it difficult to determine the causal relationship and dynamic effect among VCAM-1, brain structure/function features, and depressive symptoms.
