Summary of findings from neuroimaging studies exploring the effect of inflammation on glutamate/dopamine and/or reward circuitry
| Study | Neuroimaging technique | Participants | Findings |
| Slavich et al (2010) | fMRI | 31 healthy subjects | Exposure to the laboratory-based social stressor: sTNFαRII ↑ ∝↑ dorsal anterior cingulate cortex and anterior insula activity |
| Muscatell et al (2015) | fMRI | 31 healthy female subjects | Exposure to the laboratory-based social stressor: IL-6 ↑∝↑ amygdala, subACC, middle temporal gyrus, and dmPFC activity |
| Haroon et al (2016) | MRS,CSI | 50 medication-free MDD | log plasma CRP ↑ ∝log left basal ganglia glutamate↑; log left basal ganglia glutamate ∝ anhedonia and psychomotor slowing; plasma and CSF CRP ∝ CSI measures of basal ganglia glutamate and the glial marker myoinositol |
| Felger et al (2016) | fMRI | 48 medication-free MDD | CRP ↑∝↓ connectivity between ventral striatum and vmPFC, which in turn correlated with anhedonia↑; CRP ↑ ∝↓dorsal striatal to vmPFC and presupplementary motor area connectivity, which correlated with ↑ motor speed and ↓ psychomotor slowing |
| Lapidus et al (2014) | 1H MRS | 17 MDD vs 17 HC | Anhedonia severity ∝↓ occipital GSH levels, which indirectly reflect oxidative stress in neuroinflammation |
| Harrison et al (2015) | qMTI | 20 healthy subjects | After typhoid vaccination injection: inflammation-induced change in insular microstructure ∝ inflammation-induced motor activity (eg, fatigue) ↓ |
| Harroon et al (2014) | MRS | 31 patients with hepatitis C | After IFN-α treatment: IFN-α ∝↑ glutamate in dACC and basal ganglia, which were correlated with motivation ↓ |
| Dowell et al (2016) | qMTI | 23 patients with hepatitis C | After IFN-α injection: inflammation-induced acute change in striatal microstructure predicted development of fatigue but not mood symptoms |
| Capuron et al (2012) | 18F-dopa PET fMRI | 28 patients with hepatitis C | Cross-sectional studies: after IFN-α treatment, inflammation-induced activation of the ventral striatum↓∝ anhedonia and fatigue Longitudinal studies: ↑ 18F-dopa uptake and ↓18F-dopa turnover in caudate, putamen and ventral striatum; baseline and percentage change in 18F-dopa uptake and turnover ∝depression, fatigue and neurotoxicity |
| Swarz et al (2017) | fMRI | 448 healthy subjects | IL-18 risk haplotype ∝ anhedonia in women through ↑ threat-related amygdala reactivity |
∝: significant correlation; ↑: increased; ↓: decreased.
CRP, C reactive protein; CSF, cerebrospinal fluid; CSI, chemical shift imaging; HC, healthy controls; 1H MRS, proton MRS; IL-6, interleukin 6 ; IL-18, interleukin 18; MDD, major depressive disorder; MRS, magnetic resonance spectroscopy; PET, positron emission tomography; dmPFC, dorsomedial prefrontal cortex; fMRI, functional MRI; qMTI, quantitative magnetisation transfer imaging; qMTI, quantitative magnetisation transfer imaging; sTNFαRII, a soluble receptor for tumour necrosis factor-α; subACC, subgenera region of the anterior cingulate cortex.