2.57 ASSOCIATIONS BETWEEN INFLAMMATORY MARKERS AND ANHEDONIA IN YOUTH

Objectives: Inflammation is implicated across a wide range of psychiatric disorders. Emerging data point to the role of inflammatory processes in neural reward circuitry disturbances, which are manifested clinically as anhedonia, the reduced capacity to experience pleasure. Adolescence is an ideal stage for examining this association, as it is a time when many disorders emerge and when reward function can be most disrupted. Further, anhedonia is prevalent among adolescents across disorders, exists on a continuum of severity, and predicts adult psychopathology. We present data from an ongoing research domain criteria (RDoC) study where we examine immunological markers in relation to anhedonia. Methods: Participants included 35 psychotropic medication-free youth (51 percent female; ages 12-20 years), with diverse psychiatric symptoms, who were recruited from the Icahn School of Medicine at Mount Sinai (ISMMS) and advertisements in the New York metropolitan area. The study was approved by the institutional review board of ISMMS. Participants completed the Snaith-Hamilton Pleasure Scale (SHAPS), a dimensional measure of anhedonia, and the Children's Depression Rating Scale (CDRS-R), a measure of depressive symptom severity. Cytokine levels [e.g., interleukin (IL)-1β; IL-6; IL-8; interferon (IFN)-α; IFN-γ tumor necrosis factor (TNF)-α; TNF-β; regulated on activation, normal T cell expressed and secreted (RANTES)] were measured in blood, both before and after in vitro stimulation with lipopolysaccharide (LPS), an immune trigger. Results: Partial correlation analyses (controlling for CDRS-R) revealed that SHAPS score was not associated with any cytokines prior to LPS. After LPS stimulation, the following cytokines showed partial correlations with anhedonia: IL-1b (r = 0.37, P = 0.03), IL-8 (r = 0.35, P = 0.045), RANTES (r=-0.37, P = 0.03), and IFN-α (r = -0.33, P = 0.07). Conclusions: Findings implicate inflammatory processes in reward circuitry deficits in adolescents. Specific associations between immunological markers and anhedonia underscore the importance of examining dimensional symptom indicators. Methodologically, our results suggest the importance of an immune trigger. Replication in our full sample group (by October 2016) will confirm these findings.