11.6 Correlations Between Anhedonia and Adrenergic Attenuation of Immune Activation in Adolescents With Diverse Mood and Anxiety Symptoms

Abstract

While the link between peripheral immune activation and mental health symptoms has been supported, the role of immune-modulating processes by the adrenergic nervous system in psychopathology remains unclear. Here, we sought to investigate the β2-agonist clenbuterol (CBL) as a promising agent to model adrenergic-driven immune attenuation following ex vivo immune activation with lipopolysaccharide (LPS). Further, we explored the relationships between CBL-modulated cytokine levels and mental health measures in our adolescent sample. Depression, anxiety, and anhedonia levels were measured with the Beck Depression Inventory (BDI), the Multidimensional Anxiety School for Children (MASC), and the Temporal Experience of Pleasure Scale (TEPS) questionnaires. Fasting whole-blood samples were acquired and stimulated with LPS (0.1 μg/mL) in the presence and absence of CBL (10-6 M) for 6 hours. Supernatants were collected and subjected to Luminex multiplex assay for 41 cytokines. Cytokine levels were compared between 3 conditions: control, LPS, and LPS+CBL. Then, an exploratory factor analysis (EFA) was utilized to dimensionally reduce cytokine data from the 3 conditions and the differences between them. Correlations between each latent factor and mental health symptoms were examined. The statistical significance of all associations was assessed after Bonferroni correction for multiple comparisons. Ten cytokines were significantly affected by CBL treatment compared to LPS alone. In each of the 6 examined conditions, EFA reduced 41 cytokines into 5 orthogonal factors. Only factor 3 of the LPS+CBL condition was found to be significantly correlated with both anticipatory anhedonia (rho = –0.39; p = 6.25 × 10-5) and consummatory anhedonia (rho = –0.36; p = 3.21 × 10-4). No significant correlation was found between any cytokine factor alone and depression or anxiety. Post hoc analysis revealed differences in intercytokine correlation structures between LPS+CBL and LPS conditions, possibly explaining CBL’s effects on the relationships between peripheral immune response and anhedonia subcomponents. Findings support our hypothesis that CBL attenuates inflammatory effects thought to underlie mental health conditions in youth. Following data-driven analyses, distinctive associations between CBL-affected immune response and dimensional anhedonia were identified.