The relationship between Urokinase-Plasminogen Activator Receptor (UPAR) and bipolar disorder: a case–control study, Egypt

Abstract Background Bipolar disorder (BD)- a leading cause of disability in young adults- lacks reliable biomarkers. This case–control study investigates soluble urokinase plasminogen activator receptor (suPAR), a protein bridging inflammation and neural repair, as a novel biomarker candidate among Egyptian patients with BD. Methods We compared 48 BD patients (DSM-5- diagnosis, confirmed via SCID-5-CV) and 48 age-/sex-matched controls. Sociodemographic data were collected from all participants using a standardized questionnaire, with additional clinical variables assessed exclusively in the bipolar disorder group. Symptom severity was assessed using Arabic-validated Hamilton Depression (HDRS-17) and Young Mania Rating Scale (YMRS). Fasting serum suPAR levels were quantified via ELISA. Results BD patients showed significantly lower suPAR versus controls, without significant associations with key clinical characteristics (as hospitalization, suicidality). ROC analysis identified suPAR ≤ 110.113 ng/ml with an optimal diagnostic cutoff (AUC = 0.758), with 83.3% sensitivity, 60.4% specificity, and 71.9% accuracy. Conclusions Reduced suPAR represents a potential trait biomarker in BD, reflecting impaired neural regeneration rather than episodic symptoms. It may have a clinical utility for early detection, while its role in axonal repair highlights new therapeutic targets.