Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin

Abstract

BACKGROUND: There are robust sex differences in the prevalence of depression. Inflammation and anhedonia may play a role in understanding these sex differences. Indeed, sex differences in inflammation-induced neural responses to reward may provide insight into the sex gaps in depression, but no study has examined this question. METHODS: As such, the current study examined whether there were sex differences in reward-related neural activity (i.e., ventral striatum [VS] activity) in response to an experimental inflammatory challenge. Human participants (N = 115; 69 female) were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammation in a safe, time-limited manner. Two hours after receiving placebo or endotoxin (the height of the inflammatory response to endotoxin), participants completed a task in which they anticipated monetary reward in a functional magnetic resonance imaging scanner. RESULTS: Results demonstrated that endotoxin (vs. placebo) led to reduced VS activity in anticipation of reward and that there were sex differences in this effect. Specifically, in female participants, endotoxin (vs. placebo) led to decreased VS activity in anticipation of reward, but this effect was not present in male participants. In addition, within the endotoxin condition, decreases in VS activity in anticipation of reward were related to increases in inflammation for female but not male participants. CONCLUSIONS: These findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression.

Kynurenine metabolism and inflammation-induced depressed mood: A human experimental study

“…KYN increased by the 2 h time point, and by the six hour time point KYN concentrations were decreasing back toward baseline levels. This is similar to our findings regarding cytokine concentrations, which peaked at the 2 h time point following endotoxin administration (Eisenberger et al, 2010a;Inagaki et al, 2012;Moieni et al, 2019). However, changes in concentrations of KynA and Trp were largely driven by later change, occurring between the 2 h and the 6 h time points (Fig.…”

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images

“…Our first set of findings showing that greater inflammation is associated with lower neural activity in the amygdala, hippocampus, insula and temporal pole activity in response to positive stimuli is consistent with a growing literature documenting associations between inflammation and blunted neural reactivity to positive stimuli ( Capuron et al., 2012 ; Eisenberger et al ., 2010a ; Moieni et al., 2019 ). Lower reactivity to positive images in canonical regions implicated in the detection of and attention to salient stimuli suggests that less sensitivity to positive stimuli may be linked to higher low-grade inflammation.…”

“…These studies generally find that inflammation causes a decrease in neural activity in reward-related regions (i.e. ventral striatum) in response to monetary gain ( Eisenberger et al ., 2010a ; Capuron et al., 2012 ; Moieni et al., 2019 , c.f. Inagaki et al., 2015 ; Muscatell et al ., 2016b ).…”

Sex Differences in the Effect of Inflammation on Subjective Social Status: A Randomized Controlled Trial of Endotoxin in Healthy Young Adults

“…Detailed descriptions of study procedures have already been reported (Moieni et al, 2015a, c), but are summarized here. None of the subjective social status data in this paper have been reported on previously; however, other results from the parent study have been published (Inagaki et al, 2015; Moieni et al, 2015a,b,c, 2019; Muscatell et al, 2016; Cho et al, 2017, 2019; Irwin et al, 2019). Thus, this is a secondary analysis of these data.…”