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

Published:April 03, 2019DOI:



      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.


      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 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.


      These findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression.


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      Linked Article

      • Can Immunopsychiatry Help in Understanding the Basis of Sex Differences in Major Depressive Disorder?
        Biological Psychiatry: Cognitive Neuroscience and NeuroimagingVol. 4Issue 7
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          While it is commonly recognized that the prevalence of major depressive disorder (MDD) is about twice as high in women than in men, the reasons underlying this difference are the subject of many of the controversies that surround the issue of sex and gender. At the sociocultural and economic level, it is important to remember that gender inequality significantly contributes to depressive symptoms in women. MDD affects mainly women who are younger, are nonwhite, are not currently married, are less educated, and have lower household incomes (1).
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