The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation

Abstract

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.

Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation

“…Indeed, experimental animal models have shown that vulnerability to the behavioral effects of stress are linked to greater permeability in the BBB (Menard et al, ). Through these and other mechanisms, neuroinflammation during critical phases of development may alter functional circuits in the brain (Ganguly & Brenhouse, ) and have profound implications for several neurotransmitters, including glutamate, serotonin, and dopamine (Dooley et al, ; Miller, Haroon, Raison, & Felger, ). Of course, these mechanisms are not mutually exclusive, and more translational research is needed to better characterize the development of functional circuits in the context of these developmental neuroimmune processes.…”

“…There are a number of indices of inflammatory signaling that are more sensitive than IL‐6 alone, including multiplex assays that measure multiple circulating inflammatory proteins, expression of genes associated with the production and regulation of inflammation, and expression of RNA transcription factors that are linked to inflammation (Cole, ; Slavich & Cole, ). Similarly, psychological sensitivity to inflammatory signaling could be manifested at many levels of analysis, such as through structural and functional connectivity of neural circuits that govern mood, or through performance on behavioral and neuropsychological tasks (See Dooley et al, for review). Furthermore, our interpretations of psychological sensitivity to the influenza vaccine are limited by the imbalance in sampling frequency between our mood and inflammatory measures.…”

“…Cumulative exposure to early life stress (ELS), such as maltreatment, neglect, poverty, and family violence, is associated with elevated risk for psychiatric disorders (Kessler et al, ; McLaughlin et al, ), particularly depression (Chapman et al, ). Inflammation has been identified as a biological process through which depression and other internalizing psychiatric disorders develop (Dantzer, O’Connor, Freund, Johnson, & Kelley, ; Dooley et al, ; Miller & Raison, ). The purpose of this study was to explore two plausible, competing pathways through which ELS may lead to depressive symptoms via inflammation; whether exposure to ELS was associated with greater inflammatory responses to external stimulation or whether ELS was associated with greater sensitivity to the link between inflammation and mood.…”

“…This is important because inflammation is considered to be one putative mechanism through which depression develops (Raison, Capuron, & Miller, ). For example, prospective longitudinal studies have shown that elevated systemic markers predict depression over time (Gimeno et al, ), acute activation of the inflammatory arm of the immune system can induce many of the behavioral features of depression (Dooley et al, ), and individuals with depression tend to have higher systemic inflammation than individuals without depression (Dowlati et al, ; Howren, Lamkin, & Suls, ).…”

Why inflammation and the activities of the immune system matter for social and personality psychology (and not only for those who study health)

“…Several researchers have now proposed that proinflammatory cytokines may play a role in the pathogenesis of depression (Capuron & Miller, ; Dantzer, O'Connor, Freund, Johnson, & Kelley, ; Dooley et al, ; Miller & Raison, ; Raison & Miller, ). Consistent with this hypothesis, research finds that patients with major depressive disorder have higher levels of inflammation in their peripheral blood and cerebrospinal fluid than do healthy controls (Berk et al, ; Raison & Miller, ).…”