Comparing the proteome profiling of plasma-derived extracellular vesicles in individuals with schizophrenia and healthy controls: a pilot study

Background

Studying extracellular vesicles (EVs)—tiny intercellular communicators with a diverse molecular cargo—may provide insight into the poorly understood neuropathology and pathophysiology of schizophrenia (SCZ). Here, we focused on the protein profile of plasma-derived EVs with the aim to detect differences between individuals with SCZ and healthy controls (HCs).

Methods

EVs were isolated from blood plasma of 73 individuals with SCZ and 77 HCs and evaluated by nanoparticle tracking analysis, electron microscopy, and Western blot analysis. EV proteins were identified by liquid chromatography coupled with mass spectrometry. Proteomic data were analyzed using logistic regression analyses.

Results

A total of 1659 proteins were identified, and analyses were performed with the 1021 proteins with quantitative data available for more than 50 % of the participants in each group (SCZ and HC). Comparing these proteins between the two groups showed no significant differences. An enrichment analysis based on the proteins with a noncorrected significant p value revealed a significant enrichment of pathways connected to complement system. Although comparison of complement components between the two groups did not show significant differences, but it demonstrated that antipsychotics and duration of illness may affect EV protein levels.

Conclusion

Overall, even as our findings highlight the importance of medication use and duration of illness on EV protein levels, they suggest that the complement system may be involved in the etiopathology of SCZ. Although, the results of this pilot study need to be replicated in larger research, they may help elucidate the mechanisms involved in the pathophysiology of SCZ.