Correlates of C-reactive protein with neural reward circuitry in adolescents with psychiatric symptoms

Introduction: Increased inflammation has been implicated in many psychiatric conditions across ages. We previously reported relationships between blood cytokine levels and anhedonia, the decreased capacity to experience pleasure, as well as with reward-related brain activation in adolescents with psychiatric symptoms. Here, we sought to extend this work in a larger cohort of adolescents with psychiatric symptoms and assess the relationships of C-Reactive Protein (CRP, inflammation biomarker) with clinical symptoms and reward-related brain activation. Methods: Subjects were 64 psychotropic-medication-free adolescents with psychiatric symptoms (ages: 15.17 ​± ​2.10, 44 female). All had psychiatric evaluations and dimensional assessments for anxiety, depression, anhedonia, and suicidality. Neuroimaging included the Reward Flanker fMRI Task examining brain activation during reward anticipation, attainment, and positive prediction error. Both whole-brain and ROI analyses focusing on reward circuitry were performed. All analyses were controlled for BMI, age, and sex at p_FWE < 0.05. Results: No relationships were identified between CRP and clinical symptom severity. CRP was positively associated with brain activation during reward attainment in regions of the visual and dorsal attention networks, as well as during positive prediction error in the cerebellum. In ROI analyses, CRP was negatively correlated with brain activation during reward anticipation in the dorsal anterior cingulate cortex. When one subject with high CRP was excluded, CRP was also positively correlated with positive predication error activation in the nucleus accumbens. Conclusion: Despite the lack of association between CRP and clinical symptomatology, our fMRI findings suggest a relationship between inflammation and brain function early course of psychiatric conditions.