The Functional and Structural Consequences of Aberrant Microglial Activity in Major Depressive Disorder

Jasmine D. Cakmak, The University of Western Ontario

Abstract

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [¹⁸F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [¹⁸F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show overall decreased connectivity between the sgACC and the insula. To test the relationship between inflammation and brain connectivity, we performed regressions which found functional (sgACC-insula) and structural (cingulum bundle) connectivity to be significant factors in explaining the microglial activity in the left sgACC. Our study suggests that neuroinflammation relates to network function in MDD.