The role of neural derived extracellular vesicles micro-ribonucleic acid cargo in white matter integrity in early-onset and late-onset bipolar disorder

Bipolar disorder (BD) shows different clinical manifestations according to illness onset (early vs late onset). Its etiology is multifaceted and no reliable biomarkers are available. However, clinical manifestations of BD may stem from disruption in white matter (WM) integrity within brain networks or selective epigenetic alterations, including plasma neural derived extracellular vesicles (NDEVs). In this context, this study further explores the existence of similar epigenetic expression patterns in NDVEs, such as micro-ribonucleic acid (miRNA), and seeks to correlate them with biological markers obtained through Diffusion Tensor Imaging and with clinical data. 23 early onset BD (35% males) (EOBD), 15 late-onset BD (47% males) (LOBD), and 18 healthy controls (44% males) (HC) were recruited. Fractional anisotropy (FA) was investigated through Tract-Based Spatial Statistics. NDEVs were isolated from plasma, and their miRNA content was profiled using real-time polymerase chain reaction. Compared to HC, miR-20a and miR-299-5p were upregulated in EOBD, while miR-323-3p expression was reduced in both EOBD and LOBD patients relative to HC. Moreover, compared to HC, EOBD and LOBD showed decreased FA in the left posterior thalamic radiation and the left anterior corona radiata, respectively. Finally, after Bonferroni correction, EOBD patients showed a negative correlation between miR-323-3p and FA in the left tapetum. Our results shed light on a possible interaction between miRNA expression and WM modifications in BD. However, further research is needed to better characterize the role of miRNA by FA interaction in BD pathophysiology.