Inflammation in Psychiatric Disorders: Sources and Symptoms
Mechanisms and Prevalence of Increased Inflammation in Psychiatric Patients
Peripheral-Central Immune Crosstalk at the Blood-Brain Interface
Increased Inflammation and Transdiagnostic Symptoms: Cause-Effect Relationships
Inflammatory Cytokines Induce Symptoms of Reduced Motivation, Motor Slowing, and Anxiety
Endogenous Inflammation, Transdiagnostic Symptoms, and Reversal With Anticytokine Therapies
- Milaneschi Y.
- Kappelmann N.
- Ye Z.
- Lamers F.
- Moser S.
- Jones P.B.
- et al.
- Salvadore G.
- Nash A.
- Bleys C.
- Hsu B.
- Saad Z.
- Gause A.
- et al.
Impact of Inflammatory Stimuli on Brain Regions and Circuits: From the Clinic to the Laboratory
Impact of Inflammation on Reward and Motor Regions and Circuits
Impact of Inflammation on Regions and Circuits for Threat Detection, Anxiety, and Emotional and Interoceptive Processing
Structural and Functional Dysconnectivity in Patients With High Inflammation
|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 (|
|MDD||CRP||↓ Seed-to-voxel and seed-to-ROI, resting-state FC||Left VS–vmPFC|
|Dorsal striatum and vmPFC, presupplementary motor area|
|Yin et al., 2019 (|
|MDD||CRP||↓ Voxelwise GBC and PBA of 100 ROIs, resting-state FC||Network with central hubs in vmPFC followed by VS|
|Mehta et al., 2020 (|
|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 (|
|BD (current episode depressed)||IL-8||↓ ICA, resting-state FC||Right precentral gyrus (somatomotor network)|
|Tseng et al., 2021 (|
|BD (euthymic)||CRP||↑ Seed-to-voxel, resting-state FC||Right dorsal caudal putamen–middle orbitofrontal gyrus|
|Rengasamy et al., 2022 (|
|TRD||IL-6||↓ Seed-to-ROI, resting-state FC||Left VS–vmPFC|
|Haroon et al., 2018 (|
|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 (|
|Adolescents presenting with clinically significant psychiatric symptoms||Inflammatory composite factors||↓ Activation to reward attainment and anticipation||Basal ganglia (ROI), angular gyrus (whole-brain)|
|Liu et al., 2020 (|
|Adolescents presenting with clinically significant psychiatric symptoms||CRP||↑ Activation to reward attainment||Visual and dorsal attention networks (whole-brain)|
|↓ Activation to reward anticipation||dACC (ROI)|
|↑ Activation to positive prediction error||NAc (ROI)|
|Burrows et al., 2021 (|
|MDD||CRP||↓ Activation to anticipation of small rewards||Dorsal caudate, thalamus, left insula, left precuneus (whole-brain)|
|Costi et al., 2021 (|
|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 (|
|MDD with or without comorbid anxiety disorders or PTSD||CRP, IL-6, IL-1Ra||↓ ROI-to-voxel and ROI-to-ROI, resting-state FC||Right amygdala–vmPFC|
|Right amygdala–left precentral gyrus|
|Gong et al., 2022 (|
|BD (>75% depressive episode)||TNF||↓ Seed-to-voxel, resting-state FC||Right amygdala–bilateral mPFC|
|Left amygdala-left temporal pole|
|Mehta et al., 2022 (|
|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 (|
Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.
Brain Behav Immun. 2013; 31: 161-171
|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 (|
|MDD||CRP||No association with reactivity to negative faces||Bilateral amygdala (ROI)|
|Poletti et al., 2017 (|
|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 (|
|Women with history of MDD and/or SA and healthy controls||IL-1β, IL-2||↓ Activation related to IL-1β||Right orbitofrontal cortex|
|↑ Activation related to IL-2 during social exclusion||Right orbitofrontal cortex, insula, and ACC (ROI)|
|Boukezzi et al., 2022 (|
|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 (|
|BD (current episode depressed)||IL-6||↓ Seed-to-voxel, resting-state FC||Right posterior insula–left postcentral gyrus|
|Aruldass et al., 2021 (|
|MDD||CRP, IL-6, neutrophils, CD4+ T cells||↓ NBS of 8 networks, resting-state FC||Within insular/frontal opercular cortex (VAN) and posterior cingulate cortex (DMN)|
|Kitzbichler et al., 2021 (|
|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 (|
|SZ||IL-6||↓ Seed-to-voxel, resting-state FC||Left lateral parietal cortex–precuneus of DMN|
|Beckmann et al., 2022 (|
C-reactive protein is related to a distinct set of alterations in resting-state functional connectivity contributing to a differential pathophysiology of major depressive disorder.
Psychiatry Res Neuroimaging. 2022; 321111440
|MDD||CRP||↑ Seed-based analysis of 5 networks, resting-state FC||Internetwork DMN to AN|
|Structural Connectivity Studies|
|Prasad et al., 2015 (|
|SZ||CRP, IL-6||↓ FA, ↑ RD||Inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps major (RD to IL-6 only)|
|Benedetti et al., 2016 (|
|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 (|
Relationship between white matter integrity and serum inflammatory cytokine levels in drug-naive patients with major depressive disorder: Diffusion tensor imaging study using tract-based spatial statistics.
Transl Psychiatry. 2018; 8: 141
|MDD||IL-1β||↓ FA||Inferior fronto-occipital fasciculi, left uncinate fasciculus|
|Wang et al., 2020 (|
|SZ||IL-6||↓ FA||Genu and body of corpus callosum, anterior/posterior limbs of internal capsule|
|Lim et al., 2021 (|
|MDD||TNF||↓ FA||Genu of corpus callosum, left anterior and superior corona radiata|
|Thomas et al., 2021 (|
|MDD||CRP||↓ QA||Corticostriatal tracts, thalamic radiations, inferior longitudinal fasciculi, corpus callosum, cingulum, and left superior longitudinal fasciculus|
Inflammation and Low rsFC in Nonpsychiatric Populations: Risk Factors Across the Life Span
Frontostriatal Circuits and Transdiagnostic Symptoms of Reduced Motivation and Psychomotor Slowing
Inflammation and Low rsFC in Reward and Motor Circuits
Complementary Task fMRI, Neurotransmitter, and Structural Studies
- Bekhbat M.
- Li Z.
- Mehta N.D.
- Treadway M.T.
- Lucido M.J.
- Woolwine B.J.
- et al.
- Sugimoto K.
- Kakeda S.
- Watanabe K.
- Katsuki A.
- Ueda I.
- Igata N.
- et al.
Amygdala-Prefrontal Circuits Involved in Threat Detection, Anxiety, and Emotional Processing
Inflammation and Low Amygdala-PFC rsFC
Complementary Task fMRI Studies
- Savitz J.
- Frank M.B.
- Victor T.
- Bebak M.
- Marino J.H.
- Bellgowan P.S.
- et al.
Interoceptive, Default Mode, and Other Large-Scale Networks
- Beckmann F.E.
- Seidenbecher S.
- Metzger C.D.
- Gescher D.M.
- Carballedo A.
- Tozzi L.
- et al.
Conclusions and Translational Implications
- Sugimoto K.
- Kakeda S.
- Watanabe K.
- Katsuki A.
- Ueda I.
- Igata N.
- et al.
- Bekhbat M.
- Li Z.
- Mehta N.D.
- Treadway M.T.
- Lucido M.J.
- Woolwine B.J.
- et al.
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