RT Journal Article SR Electronic T1 The functional and structural associations of aberrant microglial activity in major depressive disorder JF Journal of Psychiatry and Neuroscience JO JPN FD Canadian Medical Association SP E197 OP E208 DO 10.1503/jpn.210124 VO 47 IS 3 A1 Jasmine D. Cakmak A1 Linshan Liu A1 Stefan E. Poirier A1 Betsy Schaefer A1 Raju Poolacherla A1 Amer M. Burhan A1 Priyadharshini Sabesan A1 Keith St. Lawrence A1 Jean Théberge A1 Justin W. Hicks A1 Elizabeth Finger A1 Lena Palaniyappan A1 Udunna C. Anazodo YR 2022 UL http://jpn.ca/content/47/3/E197.abstract AB Background: Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dysconnectivity in treatment-resistant MDD by concurrently measuring the following: microglial activity with [18F]N-2-(fluoroethoxyl)benzyl-N-(4phenoxypyridin-3-yl)acetamide ([18F]FEPPA) positron emission tomography (PET); the severity of MDD; and functional or structural connectivity among insula or sgACC nodes.Methods: Twelve patients with treatment-resistant MDD (8 female, 4 male; mean age ± standard deviation 54.9 ± 4.5 years and 23 healthy controls (11 female, 12 male; 60.3 ± 8.5 years) completed a hybrid [18F]FEPPA PET and MRI acquisition. From these, we extracted relative standardized uptake values for [18F]FEPPA activity and Pearson r-to-z scores representing functional connectivity from our regions of interest. We extracted diffusion tensor imaging metrics from the cingulum bundle, a key white matter bundle in MDD. We performed regressions to relate microglial activity with functional connectivity, structural connectivity and scores on the 17-item Hamilton Depression Rating Scale.Results: We found significantly increased [18F]FEPPA uptake in the left sgACC in patients with treatment-resistant MDD compared to healthy controls. Patients with MDD also had a reduction in connectivity between the sgACC and the insula. The [18F]FEPPA uptake in the left sgACC was significantly related to functional connectivity with the insula, and to the structural connectivity of the cingulum bundle. [18F]FEPPA uptake also predicted scores on the Hamilton Depression Rating Scale.Limitations: A relatively small sample size, lack of functional task data and concomitant medication use may have affected our findings.Conclusion: We present preliminary evidence linking a network-level dysfunction relevant to the pathophysiology of depression and related to increased microglial activity in MDD.