Neuroinflammation in the amygdala is associated with recent depressive symptoms.

Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral and neuro~inflammation in depression is unclear. Here using data from the UK Biobank (n=11,512), we estimated associations among depression, C~reactive protein as a measure of peripheral inflammation (CRP), and neuroinflammation as indexed by diffusion~basis spectral imaging-based restricted fraction (DBSI~RF). DBSI~RF was derived from diffusion-weighted imaging data for whole~brain gray matter (global~RF), and regions of interest in bilateral amygdala (amygdala~RF) and hippocampus (hippocampus~RF), and CRP was estimated from blood (serum) samples. Self~reported recent depression symptoms were measured using a 4~item assessment. Linear regressions were used to estimate associations between CRP and DBSI~RFs with depression, while adjusting for the following covariates: Age, sex, body mass index, smoking, drinking, and medical conditions. Elevated CRP was associated with higher depression symptoms (r=0.03, p<0.001) and reduced global~RF (r=-0.03, p<0.005). Higher amygdala~RF was associated with elevated depression ~ an effect resilient to added covariates and CRP (t=2.53, {beta}=0.02, p<0.05). Interestingly, this association was stronger in individuals with a lifetime history of depression (t=3.02, beta=0.07, p<0.005) than in those without (t=2.32, beta=0.03, p<0.05). Associations between global-RF or hippocampus-RF with depression were not significant, and no DBSI~RF indices indirectly linked CRP with depression (i.e., mediation effect). Peripheral inflammation and DBSI~RF neuroinflammation in the amygdala are independently associated with depression, consistent with animal studies suggesting distinct pathways of peripheral and neuro~inflammation in the pathophysiology of depression, and with investigations highlighting the role of the amygdala in stress-induced inflammation and depression.