Anhedonia transcends psychiatric diagnostic boundaries (e.g., depression, schizophrenia, PTSD) and is a marker of severe dysfunction and treatment resistance. However, the mechanisms through which vulnerability to anhedonia arises are poorly understood. Emerging convergent evidence from non-human animal models and initial human studies suggest that elevated inflammatory signaling may contribute to the development of anhedonia. However, the neural and behavioral mechanisms that may underlie the link between inflammation and anhedonia are largely unknown. Here, I propose to conduct two studies examining whether variability in reward-related neural circuitry and behavior may plausibly contribute to inflammation-related anhedonia. In the first study, I will collect fasting blood, electroencephalography (EEG), behavioral, and self-report data from young adults (n=150, 18-35 year olds) to test whether circulating cytokines are correlated with distinct aspects of behavioral (i.e., reward learning, delay discounting) and neural (i.e., feedback-related negativity [FRN]) indices of reward processing. In the second study, I will use data from the publicly available Adolescent Brain Cognitive Development (ABCD) longitudinal study of children (n=11,875 8-10 year olds at baseline) to test whether polygenic risk for heightened inflammatory signaling is associated with variability in reward-related corticostriatal circuit brain structure an anhedonia. The results of these projects would broadly inform our etiologic understanding of various forms of psychopathology that may ultimately contribute to refinements in diagnostic nosology and facilitate treatment and prevention approaches that target links within an etiologic chain. More immediately, this proposal would provide me with training in interdisciplinary research integrating inflammation, reward-related behavioral and neural phenotypes, and genomic approaches that would pave the way for the development of an independent research career.
In addition to the well-documented association between inflammation and physical health, emerging evidence suggests that it may play a prominent role in mental health; however, how inflammation may contribute to psychopathology risk remains unclear. Building upon evidence from non-human animal models showing that elevated inflammatory signaling can induce behavioral and neural reward processing deficits that characterize various forms of psychopathology (e.g., depression, schizophrenia, PTSD), this project will examine associations between circulating inflammatory markers and behavioral and neural reward-related phenotypes in humans. Results will guide our understanding of the role of inflammation in psychopathology. Such mechanistic insight may ultimately contribute to advancements in psychopathology-related policy, education, nosology, prevention, and treatment.
