Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

Burrows, Kaiping; Stewart, Jennifer L.; Kuplicki, Rayus; Figueroa-Hall, Leandra K.; Spechler, Philip A.; Zheng, Haixia; Guinjoan, Salvador M.; Savitz, Jonathan; Teague, T. Kent; Paulus, Martin P.

doi:10.1016/j.bbi.2021.01.016

Cited by 56 publications

(32 citation statements)

References 93 publications

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“…Given the aforementioned neuroimaging findings in the nonpsychiatric population and the hypothesis that the peripheral inflammatory state is associated with the neuroinflammatory state, 53 MRI has been used increasingly to investigate the association between blood levels of peripheral inflammatory markers and functional neuroimaging markers in patients with depression. 38 97 98 99 100 101 102 Regarding reward-processing neural-circuit dysfunction, striatal activity was found to be negatively correlated with serum CRP levels in patients with depression. Burrows et al 102 found that patients with MDD and a high CRP level (>3 mg/L) showed lower activation of the dorsal caudate, thalamus, left insula, and left precuneus compared with patients with MDD and a low CRP level (≤3 mg/L) when anticipating a win in the monetary incentive delay task.…”

Section: Peripheral Inflammatory Markers and Depression: Functional Neuroimaging Findingsmentioning

confidence: 99%

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Han

Ham

2021

J Clin Neurol

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This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamate-mediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depression-related neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

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Section: Peripheral Inflammatory Markers and Depression: Functional Neuroimaging Findingsmentioning

confidence: 99%

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Han

Ham

2021

J Clin Neurol

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“…In this work, we provide exemplar results 11 different pipelines (three pipelines on each of two fMRI tasks, four pipelines on resting-state fMRI, and one pipeline on resting EEG) to demonstrate the utility of our infrastructure. Additionally, ROI-level results from our standard pipelines have been used in studies of cannabis ( 29 ) and stimulant/opioid use ( 30 ), while voxelwise results have appeared in studies of neighborhood effects ( 31 ) and inflammation ( 32 ), and clinical data have been used to predict head motion during scanning ( 33 ). We have also used EEG derived features have to differentiate participants with mood and anxiety disorders from healthy controls ( 34 ) and to predict participant age ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Hz, Hz, Theta[4][5][6][7] Hz, Delta [0.5-4] Hz, Gamma[30][31][32][33][34][35][36][37][38][39][40] Hz and whole range of EEG frequency [0. Hz.…”

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confidence: 99%

Common Data Elements, Scalable Data Management Infrastructure, and Analytics Workflows for Large-Scale Neuroimaging Studies

et al. 2021

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Neuroscience studies require considerable bioinformatic support and expertise. Numerous high-dimensional and multimodal datasets must be preprocessed and integrated to create robust and reproducible analysis pipelines. We describe a common data elements and scalable data management infrastructure that allows multiple analytics workflows to facilitate preprocessing, analysis and sharing of large-scale multi-level data. The process uses the Brain Imaging Data Structure (BIDS) format and supports MRI, fMRI, EEG, clinical, and laboratory data. The infrastructure provides support for other datasets such as Fitbit and flexibility for developers to customize the integration of new types of data. Exemplar results from 200+ participants and 11 different pipelines demonstrate the utility of the infrastructure.

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“…Clinical trials have investigated the antidepressant effects of NSAIDs, including selective cyclooxygenase (COX) inhibitors such as ibuprofen, given their strong anti-in ammatory properties 10 . Ibuprofen drives non-selective, reversible inhibition of COX enzymes, COX-1 and COX-2 11 . However, ibuprofen's exact mechanism of action is still under investigation with respect to the COX-independent effects on β-catenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPARγ), and p53-dependent molecular pathways 12 .…”

Section: Introductionmentioning

confidence: 99%

“…However, ibuprofen's exact mechanism of action is still under investigation with respect to the COX-independent effects on β-catenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPARγ), and p53-dependent molecular pathways 12 . Ibuprofen's effect on the central nervous system (CNS) may not be limited to its ability to inhibit COX-1 and prostaglandin (PG) synthesis 11 . In particular, Ibuprofen activates the transcription factor PPARγ in neuronal-like cells 13 , which is proposed as a potential mechanism for neural tissue maintenance 14 .…”

Section: Introductionmentioning

confidence: 99%

Neuronally-Enriched Exosomal miR-27b Reveals Mechanism for Ibuprofen-Induced Acute Effects on Reward-Related Brain Processing in a Randomized, Placebo-Controlled, Double-Blind Trial

Burrows

Figueroa-Hall

Kuplicki

et al. 2021

Preprint

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This double-blind, randomized, repeated measures study evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females,10 males) completed a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from plasma and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. Our findings indicate that miR-27b could be an important messaging molecule altered by anti-inflammatory drugs that relates to the processing of positive or negative valenced information.

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Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

Cited by 56 publications

References 93 publications

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Common Data Elements, Scalable Data Management Infrastructure, and Analytics Workflows for Large-Scale Neuroimaging Studies

Neuronally-Enriched Exosomal miR-27b Reveals Mechanism for Ibuprofen-Induced Acute Effects on Reward-Related Brain Processing in a Randomized, Placebo-Controlled, Double-Blind Trial

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