SuPAR levels are increased in sera of euthymic patients with bipolar disorder and correlate with executive functions...

Bipolar disorder (BD) is a major psychiatric disorder in which neuroinflammation-induced axonal degeneration is thought to contribute to cognitive impairment and functional disability. This study aimed to compare serum biomarkers reflecting potential axonal degeneration and cognitive dysfunction among individuals with BD-1, first-degree relatives of patients diagnosed with BD-1 (FDR), and healthy controls (HC).

This cross-sectional comparative study included 50 BD patients, 42 FDR, and 53 HC aged 18-50 years. Serum levels of chitinase-3-like protein 1 (YKL-40), soluble urokinase plasminogen activator receptor (suPAR), growth-associated protein 43 (GAP-43), and drebrin were quantified. Comprehensive neurocognitive assessments were performed across multiple cognitive domains.

YKL-40 and suPAR levels were significantly elevated in BD patients compared to both FDR (p = 0.036, p < 0.001) and HC (p = 0.020, p < 0.001). While no relationship was found between YKL-40 and cognitive tests, suPAR was significantly associated with executive function, as well as verbal (immediate recall p = 0.001, total recall p = 0.012) and visual memory (immediate recall p = 0.045, delayed recall p = 0.019) domains. SuPAR levels were also associated with age, illness duration, and psychotropic medication exposure, and group differences were attenuated after adjustment for these factors.

Elevated levels of YKL-40 and suPAR may indicate peripheral inflammatory alterations in BD. However, the association of suPAR with cognitive impairment and clinical symptoms suggests that it reflects the overall burden of the illness and the effects of treatment rather than being specific to the disorder itself. Further longitudinal research is needed to determine how this marker could be used clinically.