Elevated Serum Purine Levels in Schizophrenia: A Reverse Translational Study to Identify Novel Inflammatory Biomarkers

Background Immunological markers and related signaling molecules in the blood are altered in schizophrenia mouse models, in acutely relapsed patients with schizophrenia, and in persons at a clinically high risk for subsequently developing psychosis, highlighting their potential as prognostic and theranostic biomarkers. Therefore, we herein aimed to identify novel potential biomarkers in the serum that are associated with purinergic signaling. Methods To our knowledge, this is the first study to assess the correlations among the levels of human serum adenine nucleotides (ATP, ADP), adenosine, P2X7 receptor, and disease activity in patients hospitalized due to an acute relapse of schizophrenia (n=53) and healthy controls (n=47). In addition, to validate these findings using a reverse translational approach, we examined the same parameters in an acute phencyclidine (PCP)-induced schizophrenia mouse model. Results We found consistently elevated levels of ATP, ADP, IL-6, and IL-10 in both schizophrenia groups compared to the controls. The levels of adenosine, IL-1β, IL-12, and C-reactive protein (CRP) were also increased in the human patient samples. Moreover, ATP and ADP were significantly positively correlated with the Positive and Negative Symptom Scale (PANSS) item ‘lack of judgment and insight’; IL-1β, IL-12 and TNF-α were significantly positively correlated with ‘tension’ and ‘depression’; and ‘disorientation’ and ‘poor attention’ were correlated significantly with IL-6 and IL-8. Conclusions Our study suggests the promising potential of blood purines and inflammatory markers as future prognostic tools.