Neuroinflammation in the amygdala is associated with recent depressive symptoms

Abstract

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, β=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.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice

“…Second, we examined the preventive mechanisms of zymosan A on CSDS-induced depression-like behaviors by examining only the changes in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. In addition to the hippocampus and prefrontal cortex, there are many other brain regions involved in the pathogenesis of neuroinflammation and depression, such as the amygdala (Zhang et al ., 2023), nucleus accumbens (Wang et al ., 2022b), and hypothalamus (Cheiran Pereira et al ., 2022). Future studies should carefully investigate the causal relationship between the prophylactic effect of zymosan A on chronic stress-induced depression-like behaviors and neuroinflammatory responses in different brain regions.…”

Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study

“…It demonstrated associations with inflammation-related cellularity derived from immunohistochemistry in an experimental mouse model of induced autoimmune encephalomyelitis ( Wang et al, 2014 ), and with stain-quantitated nuclei and microglia density (i.e., cellularity) from post-mortem human brain tissues ( Wu et al, 2022 ). Higher levels of DBSI-RF have also been linked to inflammation-related conditions, including multiple sclerosis ( Cross and Song, 2017 ; Wang et al, 2015 ; Shirani et al, 2019a ; Ye et al, 2020 ), obesity ( Ly et al, 2021 ; Samara et al, 2020 ), HIV ( Strain et al, 2017 ), Alzheimer's disease ( Wu et al, 2022 ; Ly et al, 2021 ; Wang et al, 2019 ), and depression ( Zhang et al, 2023 ), as well as markers of disease progression ( Wu et al, 2022 ; Vavasour et al, 2022 ). In addition to DBSI-RF, hindered fraction from the DBSI estimation (DBSI-HF) has shown promise as a putative marker for indicating inflammation-related cerebral edema ( Cross and Song, 2017 ; Zhan et al, 2018 ), and has been linked to inflammatory conditions including obesity ( Ly et al, 2021 ; Samara et al, 2020 ), and Alzheimer Disease ( Wang et al, 2019 ).…”