Impact of immune function and white matter integrity on cognitive function in patients with bipolar disorder

Cognitive impairment significantly impacts social function in Bipolar disorder (BD). This study explores the link between immune markers, white matter microstructure, and cognitive function in depressed BD patients enhance early diagnosis and treatment.

The study included 52 depressed BD patients and 40 healthy controls(HC), collecting data on inflammation, lymphocyte subpopulations, MRI scans, and cognitive tests, using Spearman correlation and machine learning for comparison.

This study found that the CD4+ T cell count (P = 0.002) and the percentage of regulatory T cells (P = 0.003) in depressed BD patients were significantly higher than those in the HC. Additionally, the expression levels of IL-6, IL-8, and TNF-α in the BD group were significantly higher than those in the HC (P values of 0.020, 0.012, and 0.029). Analysis of the fractional anisotropy (FA) and mean diffusivity (MD) of white matter revealed that depressed BD patients had significantly lower FA values in multiple brain regions compared to HC, including the right posterior limb of the internal capsule (P = 0.009), right medial thalamic tract (P = 0.017), right posterior thalamic radiation (P = 0.046), right sagittal stratum (P = 0.041), and left sagittal stratum (P = 0.038). Additionally, cognitive function test results indicated that the Go/No-Go accuracy of depressed BD patients was significantly lower than that of HC (P = 0.027); the ODD reaction time of depressed BD patients was significantly longer than that of HC (P = 0.04). Correlation analysis showed that IL-6 was weakly correlated with the Go/No-Go accuracy difference (r=-0.044, P = 0.027). the MD values of the left superior corona radiata and left superior frontal occipital tract were negatively correlated with the difference in Go/No-Go accuracy (r=-0.220 and r=-0.517). Results from the support vector machine (SVM) model indicated that the Stroop task (β=1.155 ± 0.056), the inflammatory factors IL-6 (β=1.073 ± 0.069) and TNF-α (β=1.071 ± 0.062) demonstrated the highest discriminative power in distinguishing BD depression.

This study suggests that neuroinflammation and white matter structure play pivotal roles in the pathogenesis of BD with a depressive episode. These findings advance the understanding of the immunological and neuroimaging underlying mechanisms in BD with a depressive episode and highlight potential drivers of cognitive impairment.