Abstract
Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks
Highlights
We tested the prior hypotheses that peripheral inflammation is associated with disruptions in human brain micro-structure and functional connectivity that co-locate with depression-related changes in functional networks
Inflammation-related changes in proton density The clearest signal of inflammation-related change was provided by the micro-structural magnetic resonance imaging (MRI) measurements of proton density (PD) at global (Fig. 1A) and regional scales of analysis (Fig. 1C)
Where PD scaled positively or to a lesser extent negatively (DLPFC) with C-reactive protein (CRP). These results were robust to multiple comparisons correction at PFDR < 0.05 and to sensitivity analyses including correction for potentially confounding variables and restriction to data from depressed cases only (Fig. S4)
Summary
Cohorts of patients with depression have increased blood concentrations of C-reactive protein (CRP) and pro-inflammatory cytokines compared to healthy controls. Some of the clearest evidence that peripheral inflammation can cause changes in the human brain has come from functional magnetic resonance imaging (fMRI) studies of emotional or cognitive task-related activation. Experimental studies have collected fMRI data before and after controlled administration of a safe inflammatory challenge, e.g., typhoid vaccination of healthy volunteers, so that any before-after differences in brain function can be considered causal effects of peripheral inflammation [9]. Meta-analysis of 24 experimental and observational studies (total N~457) demonstrated replicable and significant effects of inflammation on task-related activation in dorsal anterior cingulate cortex (dACC), subgenual anterior cingulate cortex (sgACC) and adjacent areas of medial prefrontal cortex (mPFC), insula, hippocampus, amygdala, and striatum [12]
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