Table 1.
Summary of studies assessing relationships between endogenous inflammation and functional or structural neuroimaging outcomes in the context of significant psychiatric symptoms or diagnoses.
| Study | Population | Inflammatory Markers | Outcome | Brain Region/White Matter Tract |
|---|---|---|---|---|
| Resting State Functional Connectivity and Supporting fMRI Studies | ||||
| Circuits and Regions Relevant to Reduced Motivation or Psychomotor Slowing | ||||
| Felger et al., 2016 (55) | MDD | CRP | ↓ seed-to-voxel and seed-to-ROI, resting-state FC | (1) Left VS-vmPFC (2) Dorsal striatum and vmPFC, presupplementary motor area |
| Yin et al., 2019 (110) | MDD | CRP | ↓ Voxel-wise GBC and PBA of 100 ROIs, resting-state FC | Network with central hubs in vmPFC followed by VS |
| Mehta et al., 2020 (112) | Trauma-exposed women with or without clinically significant PTSD symptoms | CRP, inflammatory cytokine composite score | ↓ seed-to-ROI, resting-state FC | VS-vmPFC |
| Tang et al., 2021 (114) | BD (current episode depressed) | IL-8 | ↓ ICA, resting-state FC | Right precentral gyrus (somatomotor network) |
| Tseng et al., 2021 (113) | BD (euthymic) | CRP | ↑ seed-to-voxel, resting-state FC | Right dorsal caudal putamen-middle orbitofrontal gyrus |
| Rengasamy et al, 2022 (111) | TRD | IL-6 | ↓ seed-to-ROI, resting-state FC | Left VS-vmPFC |
| Haroon et al., 2018 (120) | MDD | CRP | ↓ local and network, resting-state ReHo functional integrity | Left basal ganglia and network varying by levels of CRP and MRS glutamate |
| Bradley et al., 2019 (118) | Adolescents presenting with clinically significant psychiatric symptoms | Inflammatory composite factors | ↓ activation to reward attainment (1) and anticipation (2) | (1)Basal ganglia (ROI), angular gyrus (whole-brain) (2) Precuneus/PCC (whole-brain) |
| Liu et al., 2020 (117) | Adolescents presenting with clinically significant psychiatric symptoms | CRP | ↑activation to reward attainment (1) ↓ activation to reward anticipation (2) ↑ activation to positive prediction error (3) |
(1) Visual and dorsal attention networks (whole-brain) (2) dACC (ROI) (3) NAc (ROI) |
| Burrows et al., 2021 (115) | MDD | CRP | ↓ activation to anticipation of small rewards | Dorsal caudate, thalamus, left insula, left precuneus (whole-brain) |
| Costi et al., 2021 (116) | MDD and healthy adults | Stimulated blood immune markers | ↓ activation to reward anticipation | VS (ROI) |
| Circuits and Regions Relevant to Threat, Anxiety and Emotional Processing | ||||
| Mehta et al., 2018 (126) | MDD with or without comorbid anxiety disorders or PTSD | CRP, IL-6, IL-1ra | ↓ ROI-to-voxel and ROI-to-ROI, resting-state FC | (1) Right amygdala-vmPFC (2) Right amygdala-left precentral gyrus |
| Gong et al., 2022 (128) | BD (>75% depressive episode) | TNF | ↓ seed-to-voxel, resting-state FC | (1) Right amygdala-bilateral medial PFC (2) Left amygdala-left temporal pole |
| Mehta et al., 2022 (127) | Trauma-exposed women with or without clinically significant PTSD symptoms | CRP, inflammatory cytokine composite score | ↓ ROI-to-ROI, resting-state FC | Right amygdala-vmPFC |
| Savitz et al., 2013 (131) | MDD | Expression of immune-related PBMC genes | ↑ activation to sad vs happy faces | Amygdala, left hippocampus, and vmPFC (ROIs from whole-brain MDD > HC) |
| Mocking et al, 2017 (130) | MDD | CRP | No association with reactivity to negative faces | Bilateral amygdala (ROI) |
| Poletti et al., 2017 (133) | BD (current episode depressed) | T regulatory cells | ↓ activation to negative vs. positive stimuli | Right dorsolateral PFC/inferior frontal gyrus (whole-brain) |
| Conejero et al., 2019 (132) | Women with history of MDD and/or SA and healthy controls | IL-1β, IL-2 | ↓ activation related to IL-1β (1) ↑ activation related to IL-2 (2) during social exclusion |
(1) Right orbitofrontal cortex (2) Right orbitofrontal cortex, insula and ACC (ROI) |
| Boukezzi et al., 2022 (129) | MDD | Stimulated blood immune markers | ↑ activation to fear vs happy faces | Amygdala (ROI) |
| Interoceptive, Default Mode and other Large-Scale Networks | ||||
| Chen et al., 2020 (143) | BD (current episode depressed) | IL-6 | ↓ seed-to-voxel, resting-state FC | Right posterior insula-left postcentral gyrus |
| Aruldass et al., 2021 (140) | MDD | CRP, IL-6, neutrophils, CD4+ T-cells | ↓ NBS of 8 networks, resting-state FC | Within insular/frontal opercular cortex (VAN) and the posterior cingulate cortex (DMN) |
| Kitzbichler et al., 2021 (141) | MDD | CRP | ↓↑ PBA of 360 cortical and 16 subcortical ROIs, resting-state FC |
Lower within DMN, higher DMN-hippocampus, in association with PD free water edema signal |
| King et al., 2021 (144) | SZ | IL-6 | ↓ seed-to-voxel, resting-state FC | Left lateral parietal cortex-precuneus of DMN |
| Beckmann et al., 2022 (142) | MDD | CRP | ↑ seed-based analysis of 5 networks, resting-state FC | Internetwork DMN to AN |
| Structural Connectivity Studies | ||||
| Prasad et al., 2015 (100) | SZ | CRP, IL-6 | ↓ FA, ↑ RD | Inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps major (RD to IL-6 only) |
| Benedetti et al., 2016 (125) | BD (current episode depressed) | TNF, IL-8, IFN-γ | ↓ FA ↑ RD | Corpus callosum, cingulum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, uncinate, forceps, corona radiata, thalamic radiation, internal capsule |
| Sugimoto et al., 2018 (123) | MDD | IL-1β | ↓ FA | Inferior fronto-occipital fasciculi, left uncinate fasciculus |
| Wang et al., 2020 (102) | SZ | IL-6 | ↓ FA | Genu and body of corpus callosum, anterior/posterior limbs of internal capsule |
| Lim et al., 2021 (124) | MDD | TNF | ↓ FA | Genu of corpus callosum, left anterior and superior corona radiata |
| Thomas et al., 2021 (122) | MDD | CRP | ↓ QA | Corticostriatal tracts, thalamic radiations, inferior longitudinal fasciculi, corpus callosum, cingulum, and left superior longitudinal fasciculus |
AN - affective network; BD - bipolar disorder; CRP - C-reactive protein; dACC - dorsal anterior cingulate cortex; DMN - default mode network; FA - fractional anisotropy; FC - functional connectivity; GBC - global brain connectivity; HC - healthy controls; IFN - interferon; IL - interleukin; L-DOPA - levodopa; MDD - major depressive disorder; MRS - magnetic resonance spectroscopy; NAc - nucleus accumbens; NBS - network-based statistics; PBA - parcellation-based analysis; PBMC - peripheral blood mononuclear cells; PCC - posterior cingulate cortex; PD - proton density; PTSD - post-traumatic stress disorder; QA - quantitative anisotropy; ra - receptor antagonist; RD - radial diffusivity; ReHo - regional homogeneity; SA - suicide attempt; SZ - schizophrenia; TNF - tumor necrosis factor; TRD - treatment-resistant depression; VAN - ventral attention network; vmPFC - ventromedial prefrontal cortex; VS - ventral striatum