Inflammation-related alterations in corticostriatal connectivity in depression: Reversal with levodopa?

Abstract

Neuroimaging studies indicate that inflammatory cytokines decrease activation of the ventral striatum in association with increased symptoms of anhedonia. Our in vivo microdialysis studies in non-human primates suggest that these effects are mediated by decreased striatal dopamine synthesis and release, which can be reversed by administration of the dopamine precursor, levodopa (L-DOPA). Herein, we examined inflammation-related alterations in functional connectivity with the ventral striatum in medically healthy, medication free patients with major depression (n = 48) in relation to symptoms of anhedonia. Pilot data was also collected from a subset of patients with high inflammation (as defined by plasma C-reactive protein [CRP]) who were administered L-DOPA before and after resting state fMRI. Increased inflammation (as determined by plasma CRP) was associated with decreased functional connectivity between the ventral striatum and ventromedial prefrontal cortex (vmPFC) in patients with major depression. These changes in functional connectivity were also associated with increased anhedonia (r = −0.48, df = 46, p = 0.001). Furthermore, preliminary data indicate that L-DOPA can reverse inflammation-associated decreases in corticostriatal connectivity. These data support the hypothesis that inflammation effects on dopamine synthesis and release may play a role in corticostriatal dysfunction that underlies symptoms of anhedonia in major depression. Ongoing work with L-DOPA will provide a foundation for future studies investigating therapeutic strategies that facilitate availability of dopamine precursors to improve symptoms of anhedonia in patients with major depression and increased inflammation.