Exploring purinergic and inflammatory pathways in bipolar disorder: evidence for diagnostic utility of UA, IL-6, NACHT, P2X7, ADA, XDH, ADO

Bipolar affective disorder (BD) is a chronic psychiatric illness characterized by alternating manic and depressive episodes. Despite extensive research, its underlying mechanisms remain unclear. Recent studies suggest that purinergic signaling and inflammation may play key roles in BD pathophysiology. This study aimed to explore biomarkers related to these systems to improve understanding of BD and identify potential diagnostic and prognostic indicators.

The study included 76 BD patients and 20 healthy controls from the Department of Adult Psychiatry, Poznan University of Medical Sciences. Blood samples were collected during acute episodes and after symptom remission. Biomarkers analyzed included uric acid (UA), interleukin-6 (IL-6), NACHT, P2X7 receptor, adenosine deaminase (ADA), xanthine dehydrogenase (XDH), and adenosine (ADO), measured by ELISA.

NACHT (p = 0.004) and P2X7 (p = 0.001) were significantly higher post-treatment. Age positively correlated with NACHT, and BMI with UA. P2X7 levels negatively correlated with depressive symptom improvement. Gender differences revealed higher pre-treatment ADA levels in women and greater post-treatment increases in NACHT, ADA, and XDH in men. IL-6 was elevated during depressive episodes, while NACHT and XDH were higher in manic states. ROC analysis indicated strong diagnostic potential for XDH (AUC=0.917) and ADA (AUC=0.903). Logistic regression identified post-treatment NACHT and P2X7 as significant BD predictors.

The study highlights the involvement of purinergic and inflammatory pathways in BD pathophysiology. Biomarkers such as NACHT, P2X7, ADA, and XDH may aid in diagnosing BD and monitoring treatment responses, offering potential for biologically informed therapies.