The associations between glucose, inflammation, cognitive functions, and white matter structural connectivity in euthymic bipolar patients

Background: Previous studies have shown that human white matter structural connectivity is independently associated with glucose metabolism, inflammation, and cognitive function. However, an integrative understanding of these relationships in bipolar disorder (BD) remains unclear. Methods: This study included 44 euthymic patients with BD and 59 healthy controls (HCs). White matter structural connectivity was assessed using diffusion tensor imaging (DTI). Metabolic parameters, including fasting glucose and high-sensitivity C-reactive protein (hsCRP), were measured. Cognitive function was evaluated using the Wisconsin Card Sorting Test (WCST). Results: DTI analysis revealed that BD patients had significantly higher gamma (46.52 ± 2.89 vs. 45.21 ± 2.95, p = 0.026) and sigma (41.73 ± 2.30 vs. 40.58 ± 2.40, p = 0.016) metrics compared to HCs after adjusting for age, years of education, and body mass index. In the BD group, the gamma and sigma metrics of DTI showed significantly negative correlations with the total number of categories completed in the WCST. Furthermore, in BD patients, both gamma and sigma metrics were positively correlated with fasting glucose and hsCRP levels. Conclusions: Cognitive deficits in patients with BD may be linked to over-segregated neuronal activities, as indicated by elevated gamma DTI metrics. These abnormalities appear to be associated with higher levels of inflammation and glucose metabolism.