The Neurocircuitry of Inflammation in Depression Pubblico
Felger, Jennifer (2015)
Published
Abstract
Inflammatory stimuli exogenously administered to humans affects neural activity in reward-related brain regions and causes symptoms of anhedonia, a core symptom of depression that has been associated with treatment non-response to conventional antidepressant therapies. A substantial proportion of patients with depression exhibit high inflammation, as measured by peripheral inflammatory markers such as the acute phase reactant, C-reactive protein (CRP). However, whether endogenous inflammation in patients with depression is associated with alterations in reward circuitry that lead to symptoms of anhedonia has yet to be explored. This study examined whether endogenous inflammation is related to disrupted reward circuitry in 48 patients with depression. Striatal seed-to-whole brain correlations were computed to identify associations between ventral and dorsal striatal functional connectivity with plasma high sensitivity (hs) CRP concentrations, using resting state blood oxygen level dependent MRI. We found that increasing levels of inflammation predicted decreasing functional connectivity between ventral and dorsal striatum and the ventromedial prefrontal cortex (adjusted r=-0.39 to -0.61, whole brain corrected p <0.05). In addition to hsCRP, the interleukin (IL)-1 family protein, IL-1 receptor antagonist, was a significant predictor of reduced corticostriatal connectivity (adjusted r=-0.30, p<0.05). Attenuated connectivity between ventral striatum and vmPFC was associated with increased anhedonia (adjusted r=-0.43, p<0.01), whereas decreased connectivity between dorsal striatum and vmPFC was associated with decreased motor speed (adjusted r=0.37, p <0.05). Relationships between corticostriatal connectivity and behavior remained significant when functional connectivity data was extracted using coordinates for vmPFC identified by meta-analysis as a key contributor to the neural circuitry of hedonic reward. Collectively, we found that increased inflammation predicts alterations in frontostriatal circuitry related to motivational and motor deficits in depression. Further research is required to understand the mechanisms by which inflammation may disrupt connectivity in reward-related brain regions to cause anhedonia, which may lead to new treatments for depression, particularly in patients with high inflammation.
Table of Contents
Section 1. Introduction (p. 1-2)
Section 2. Background (p. 3-8)
Section 3. Methods (p. 9-16)
Section 4. Results (p. 17-21)
Section 5. Discussion (p. 22-28)
Section 6. References (p. 29-43)
Section 7. Tables & Figures (p. 44-56)
Table 1: Clinical characteristics. p. 45
Table 2: Relationships between hsCRP and corticostriatal connectivity. p. 46
Table 3: Cytokines and their receptors that predicted connectivity. p. 47
Table 4: Ventral striatal connectivity - associations with anhedonia. p. 48
Table 5: Dorsal striatal connectivity - associations with psychomotor slowing. p. 49
Table 6: Left VS to vmPFC - associations with anhedonia and inflammation. p. 50
Table 7: Right dcP to vmPFC - associations with motor speed and inflammation. p.51
Table 8: Right dC to vmPFC - associations with psychomotor processing and inflammation. p. 52
Figure 1: Working model. p. 53
Figure 2: Ventral and dorsal striatal seeding regions. p. 54
Figure 3: Corticostriatal connectivity that was associated with inflammation. p. 55
Figure 4: Functional connectivity maps in patients with low, moderate and high inflammation. p. 56
About this Master's Thesis
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