Neuroinflammation in the Amygdala Is Associated With Recent Depressive Symptoms

Background: Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral inflammation and neuroinflammation in depression is unclear. Here, using data from the UK Biobank, we estimated associations among depression, C-reactive protein (CRP) as a measure of peripheral inflammation, and neuroinflammation as indexed by diffusion basis spectral imaging–based restricted fraction (DBSI-RF). Methods: DBSI-RF was derived from diffusion-weighted imaging data (N = 11,512) for whole-brain gray matter (global-RF), and regions of interest in the 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. Results: Elevated CRP was associated with higher depression symptoms (β = 0.04, false discovery rate–corrected p <.005) and reduced global-RF (β = −0.03, false discovery rate–corrected p <.001). Higher amygdala-RF was associated with elevated depression—an effect resilient to added covariates and CRP (β = 0.02, false discovery rate–corrected p <.05). Interestingly, this association was stronger in individuals with a lifetime history of depression (β = 0.07, p <.005) than in those without (β = 0.03, p <.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). Conclusions: Peripheral inflammation and DBSI-RF neuroinflammation in the amygdala are independently associated with depression, consistent with animal studies suggesting distinct pathways of peripheral inflammation and neuroinflammation in the pathophysiology of depression and with investigations highlighting the role of the amygdala in stress-induced inflammation and depression.