UCLA

Depression is a leading cause of disability worldwide. A strong empirical literature has identified a role for inflammation in the pathophysiology of depression, yet evidence suggests that the precise nature of this relationship is complex and still largely undefined. It has been suggested that a barrier to understanding the role of inflammation in depression is the tendency to conceptualize and measure depression as a homogeneous, unitary construct. Instead, an approach that “deconstructs the construct” of depression and examines how inflammation impacts core processes or endophenotypes of depression may lead to new insights into the nature of the inflammation-depression link.

The first part of this dissertation consists of an integrative review of the literature linking inflammation and core processes of depression. The purpose of the review is to bring together the depression, endophenotype, and inflammation literatures in order to identify core processes of depression likely to be impacted by inflammation, which can be targets of investigation in future work. The review first identifies key endophenotypes of depression that have been evaluated in at least preliminary work within the context of inflammation; then, the evidence examining a potential role for inflammation in each of these core processes of depression is reviewed and evaluated. Overall, existing evidence supports a role of inflammation in modulating several key domains relevant to depression, including cognitive biases, reward processing, and somatic symptoms.

The second section of this dissertation presents an empirical study aimed at testing several of the inflammation-depression endophenotype links identified in the review paper. In this study, an influenza vaccine was used to elicit increases in circulating inflammation, and resulting effects on multiple processes relevant to depression were examined, including mood, fatigue, reward processing, cognitive functioning, and attentional bias. Findings indicated that increases in inflammation were associated with attentional avoidance of positive stimuli, as well as improvements in working memory and reward learning. These findings suggest a novel mechanism by which inflammation may contribute to depression (attentional bias), as well as provide insight into the effects of low-grade inflammation on aspects of memory and reward processing.