Microglial Activation May Contribute to Depression in Multiple Sclerosis

Hippocampal microglial activation in a small group of patients with multiple sclerosis (MS) correlated with depression symptoms, suggesting that altered functional connectivity may contribute to the pathogenesis of depression.

Depression is more prevalent in people with MS compared to the general population.  Likewise, previous studies have suggested an association between MS disease burden and depressive symptoms. The authors of the current study, published in Biological Psychiatry, suggest that, “the association arises from a common, underlying factor that contributes to pathophysiological changes for both MS and depression.”

Alessandro Colasanti, MD, PhD, of the Centre for Affective Disorders at the Institute of Psychiatry, Psychology, and Neuroscience in London, and colleagues hypothesized that development of depression in MS is associated with an innate immune response in the hippocampus.

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Depression was assessed using the Beck’s Depression Inventory in 11 MS patients and 22 healthy control participants. Further, [¹⁸F]-PBR111 PET scans were used to highlight microglial activation within the hippocampus and functional MRI was used to assess the relationship between functional connectivity in the hippocampus and depression symptoms. Six of the MS patients were taking antidepressants and 10 were on disease-modifying drugs.

Overall, participants with MS had a higher mean Beck’s Depression Inventory score (15 versus 1.41, t=6.9, P<0.0001), with 6 patients meeting criteria for a major depressive episode.

Compared to the healthy controls, the [¹⁸F]-PBR111 Distribution Volume Ratio (DVR) was higher in MS patient’s hippocampus (1.083 versus 1.025, t=2.49, P=0.018). This remained significant even after adjusting for age and the rs6971 genotype (F=5.73, P=0.024).  

Current major depression was associated with higher [¹⁸F]-PBR111 DVR in the hippocampus of participants with MS compared to those without depression or resolved depression (t=2.48, P=0.044). Interestingly, MS patients without a history of depression (N=3) had [¹⁸F]-PBR111 DVR values that fell within the 95% confidence interval of healthy controls (MS range 1.03-1.06, healthy control 95% CI: 0.98-1.07).   

After adjustment, a strong positive correlation was observed between hippocampal [¹⁸F]-PBR111 DVR and Beck’s Depression Inventory in MS patients (Pearson’s partial correlation r=0.863, P=0.006).  

Finally, the authors noted correlations in MS patients between the Beck’s Depression Inventory scores and [¹⁸F]-PBR111 DVR with functional connectivity of the hippocampus to the parietal, prefrontal, and subgenual cingulate areas.

“…Our findings suggest that mediators of innate immunity in the hippocampus play a significant role in the pathophysiology of the affective dysregulation associated with MS.” 

Reference:

Colasanti A, Guo Q, Giannetti P. Hippocampal neuroinflammation, functional connectivity and depressive symptoms in multiple sclerosis, Biol Psychiatry. 2015; doi:10.1016/j.biopsych.2015.11.022.