Serum FGF21 and GDF15 levels and their association with cognitive function in bipolar disorder

Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor 15 (GDF15) are mitochondrial stress-related biomarkers increasingly studied in psychiatric disorders. Their potential associations with cognitive dysfunction in bipolar disorder (BD) remain underexplored.

This study aimed to compare serum FGF21 and GDF15 levels between euthymic BD patients and healthy controls, and investigate the relationship between these biomarkers and cognitive performance in individuals with BD.

A total of 174 participants (87 euthymic BD patients and 87 matched healthy controls) were enrolled. Cognitive functions were assessed using the Wisconsin Card Sorting Test (WCST), Stroop Test (ST), and Trail Making Test (TMT). Serum FGF21 and GDF15 levels were measured using ELISA. Clinical, sociodemographic, and neuropsychological data were analyzed using correlation and multiple regression analyses.

BD patients exhibited significantly elevated serum levels of FGF21 and GDF15 compared to controls (p < 0.001 and p = 0.017, respectively). They also performed worse on cognitive tasks assessing executive function, attention, and processing speed. FGF21 levels negatively correlated with TMT completion times and Stroop interference scores, suggesting a potential link to better cognitive performance. GDF15 levels correlated with age, illness duration, and number of depressive episodes but not directly with cognitive test scores. Regression analyses indicated that age, education level, number of depressive episodes, and FGF21 levels were significantly associated with cognitive performance.

FGF21 and GDF15 may serve as biomarkers reflecting mitochondrial dysfunction and disease burden in BD. Particularly, FGF21 appears to be associated with executive functioning and cognitive flexibility. These findings suggest a potential role for FGF21 in the neurobiological mechanisms underlying cognitive impairment in bipolar disorder.