Recent research has demonstrated a relationship between depression and immune system
activity, specifically proinflammatory cytokine activity. Although experimentally-induced
immune activation leads to increases in depressed mood, the neural correlates associated with
these changes have remained largely unexplored. Based on relationships between cytokine
activity, depression, and heightened physical and social pain sensitivity, I propose to
investigate the effect of proinflammatory cytokine activation on the neural correlates of
socially painful experience that may contribute to depression. Our previous work has shown
that the dorsal anterior cingulate cortex (dACC), typically associated with physical pain
distress, also plays a role in the distressing feelings associated with social rejection or
social loss. Moreover, recent pilot data has revealed that individuals with elevated levels
of baseline proinflammatory cytokines report feeling more distressed and show more dACC
activity during social rejection. To investigate the causal role that cytokines may play in
the heightened social pain sensitivity that can contribute to depression, participants will
be randomly assigned to receive either endotoxin (which increases proinflammatory cytokine
activity) or placebo. Subsequently, participants will complete a neuroimaging study in which
they will be rejected during an online ball-tossing game. We hypothesize that individuals
exposed to endotoxin will report more social distress and depression following rejection and
will show more dACC reactivity during rejection. The proposed study is the first to
investigate the effect of systemic inflammation on neural reactivity related to social and
affective processes that may increase the risk of depression.