A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.

Stress research typically emphasizes the toxic effects of stress, but recent evidence has suggested that stress exposure, in moderation, can facilitate resilience. To test whether moderate stress exposure promotes psychological resilience to cancer, we examined the relationship between lifetime stress exposure prior to cancer diagnosis and postdiagnosis psychological functioning among 122 breast cancer survivors. Lifetime acute and chronic stress was assessed using an interview-based measure, and psychological functioning was assessed using measures of cancer-related intrusive thoughts and positive and negative affect. Results indicated that acute stress exposure was associated with cancer-related intrusive thoughts in a quadratic fashion (p = .016), such that participants with moderate acute stress reported fewer intrusive thoughts compared to those with low or high acute stress. Similarly, a quadratic relationship emerged between acute stress exposure and positive affect (p = .009), such that individuals with moderate acute stress reported the highest levels of positive affect. In contrast, acute and chronic stress were related to negative affect in a positive, linear fashion (ps < .05). In conclusion, moderate stress exposure was associated with indicators of psychological resilience among breast cancer survivors, supporting stress exposure as a key factor influencing adjustment to breast cancer and providing evidence for stress-induced resilience in a novel population.

Minor increases in inflammation were associated with corresponding increases in features of depression, and these associations occurred in the absence of any physical symptoms. The influenza vaccine could be used to probe causal relationships with a high degree of ecological validity, even in high-risk and vulnerable populations, to better understand the role of inflammation in the pathogenesis of depression.

Background: Alterations in reward processing are a central feature of depression and may be influenced by inflammation. Indeed, inflammation is associated with deficits in reward-related processes in animal models and with dysregulation in reward-related neural circuitry in humans. However, the downstream behavioral manifestations of such impairments are rarely examined in humans. Methods: The influenza vaccination was used to elicit a mild inflammatory response in 41 healthy young adults (age range: 18-22, 30 female). Participants provided blood samples and completed behavioral measures of three key aspects of reward-reward motivation, reward learning, and reward sensitivity-before and 1 day after receiving the influenza vaccine.

Background Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation. Methods Participants (ages 18–22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin‐6 (IL‐6) were measured immediately before and 24 hr after vaccination. Results ELS was not associated with the magnitude of change in IL‐6 from pre‐ to post‐vaccine, however, exposure to ELS moderated the association between change in IL‐6 from pre‐ to post‐vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL‐6. Conclusions Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.