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Thursday

 

Hippocampal neuroinflammation, functional connectivity and depressive symptoms in MS: STUDY
















































Image Source: STEVESEAY


Abstract

Background:
Depression, a common co-morbidity of multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression in MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in MS patients using the TSPO radioligand [18F]-PBR111 in MS patients. To evaluate pathophysiological mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms and hippocampal functional connectivities defined by resting state fMRI.

Methods:
Eleven MS patients and twenty-two healthy controls were administered the Beck’s Depression Inventory (BDI) before PET and fMRI scanning. We tested for higher [18F]-PBR111 uptake in the hippocampus of MS patients relative to healthy controls and examined the correlations between [18F]-PBR111 uptake, BDI scores, and hippocampal functional connectivities in the MS patients.

Results:
MS patients had an increased hippocampal [18F]-PBR111 distribution volume ratio (DVR) relative to healthy controls (p=0.024), and in MS patients the hippocampal DVR was strongly correlated with the BDI score (r=0.86, p=0.006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with both BDI scores and [18F]-PBR111 DVR.

Conclusions:
Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. They suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally.

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