Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis

Colasanti, Alessandro, Guo, Qi, Giannetti, Paolo, Wall, Matthew B, Newbould, Rexford D, Bishop, Courtney, Onega, Mayca, Nicholas, Richard, Ciccarelli, Olga, Muraro, Paolo A, Malik, Omar, Owen, David R, Young, Allan H, Gunn, Roger N, Piccini, Paola, Matthews, Paul M and Rabiner, Eugenii A (2016) Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis. Biological Psychiatry, 80 (1). pp. 62-72. ISSN 0006-3223

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Abstract

Depression, a condition commonly comorbid with 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 associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.

Methods
The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.

Results
Patients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio.

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. Our results 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.

Item Type: Article
Keywords: Depression, Hippocampus, Multiple sclerosis, Neuroimaging, Neuroinflammation, TSPO
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Depositing User: Alexei Fisk
Date Deposited: 07 Sep 2018 16:06
Last Modified: 02 Jul 2019 14:35
URI: http://sro.sussex.ac.uk/id/eprint/78578

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Project NameSussex Project NumberFunderFunder Ref
Clinical Training Fellowship in Translational Medicine and Therapeuticsn/a - Imperial College LondonWellcome TrustUnset