Inflammation is associated with depressive symptoms, and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure; however, how these are related remains unclear. This study investigated the association between peripheral inflammation (measured by C-reactive protein, CRP), brain microstructure (proton density, PD), and functional connectivity in depression. Results showed CRP was significantly associated with PD in the precuneus, posterior cingulate cortex (PCC), and medial prefrontal cortex (mPFC); and with functional connectivity between PCC, mPFC, and hippocampus. Depression was associated with reduced weighted degree of PCC, mPFC, and other default mode network (DMN) nodes. CRP-related increases in PD and changes in functional connectivity were co-localized with DMN nodes showing reduced hubness in depression, suggesting that inflammation's effects on DMN microstructure and connectivity may mediate its effects on depression.

Manfred G. Kitzbichler, Athina R. Aruldass, Gareth J. Barker, Tobias C. Wood, Nicholas G. Dowell, Samuel A. Hurley, John McLean, Marta Correia, Charlotte Clarke, Linda Pointon, Jonathan Cavanagh, Phil Cowen, Carmine Pariante, Mara Cercignani, Edward T. Bullmore, Neil A. Harrison