Association Between Interleukin-6 and Striatal Prediction-Error Signals Following Acute Stress in Healthy Female Participants

Abstract

Background Stress is widely known to alter behavioral responses to rewards and punishments. It is believed that stress may precipitate these changes through modulation of corticostriatal circuitry involved in reinforcement learning and motivation, although the intervening mechanisms remain unclear. One candidate is inflammation, which can rapidly increase following stress, and can disrupt dopamine-dependent reward pathways. Methods Here, in a sample of 88 healthy female participants, we first assessed the effect of an acute laboratory stress paradigm on levels of plasma interleukin-6 (IL-6), a cytokine known to be both responsive to stress and elevated in depression. In a second laboratory session, we examined the effects of a second laboratory stress paradigm on reward prediction error (RPE) signaling in the ventral striatum. Results We show that individual differences in stress-induced increases in IL-6 (session 1) were associated with decreased ventral striatal RPE signaling during reinforcement learning (session 2), though there was no main effect of stress on RPE. Further, changes in IL-6 following stress predicted intra-individual variability in perceived stress during a 4-month follow-up period. Conclusions Taken together, these data identify a novel link between IL-6 and striatal reward prediction errors during reinforcement learning in the context of acute psychological stress, as well as future appraisal of stressful life events.

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“…Further, elevated levels of CRP in this report were associated with increased levels of inflammatory cytokines in CSF [4]. Taken together, these findings suggest propagation of peripheral immune signals to central nervous system (CNS) which is reflected in reports linking peripheral inflammation to impaired reward behaviors and symptoms of anhedonia [5,6]. Thus, an improved understanding of how inflammation relates to BBB dysfunction may have immediate application in developing novel antidepressants and in antidepressant treatment selection, both of which continue to be a trial-and-error process [7][8][9].…”

The elusive effects of incidental anxiety on reinforcement-learning

“…per se(DeVido et al, 2009;Glienke et al, 2015;Treadway et al, 2017). However, our findings agree with our literature review of 13 studies on the effects of experimentally induced anxiety on instrumental learning, which also failed to identify a consensual, robust effect of anxiety on learning(Figure 1 and Supplementary-…”

Imaging the Role of Inflammation in Mood and Anxiety-related Disorders

“…Compared to saline control, Harrison and colleagues determined that vaccination reduced behavioral attractiveness of rewards while making punishments more aversive, effects that were related to decreased neural activation of ventral striatum to RPEs and increased activation of anterior insula to punishment prediction errors [ 123 ]. Healthy female control subjects who have heightened stress-induced production of IL-6 have also been found to exhibit decreased ventral striatal RPE signaling during reinforcement learning [ 184 ], suggesting that persons with chronically elevated inflammatory responses exhibit decreased neural sensitivity to reward. Of relevance to potential effects of inflammation on DA, the magnitude of response to prediction error signaling is fundamentally modulated by DA-dependent striatal activity as determined by administration of drugs that enhance (L-DOPA) or inhibit (haloperidol) DAergic function [ 185 ].…”