Introduction

Immune dysregulation has been increasingly recognized as a key factor in the pathophysiology of psychotic disorders: research suggests that alterations in the immune system, including altered cytokine levels, chronic low-grade inflammation, and dysregulation of immune cell populations, may contribute to the onset and progression of psychosis. Immune-brain interactions have been observed in psychotic disorders, with alterations in white matter integrity and neuronal function. Diffusion tensor imaging (DTI) is a non-invasive magnetic resonance imaging (MRI) technique, which allows the study of white matter integrity.

Methods

In this work, we considered 39 first-episode psychosis (FEP) patients (mean age 25.7 ± 8.2 years, 17 M/22 F) and 48 healthy controls (HC, mean age 33.2 ± 9.9 years, 35 M/13 F). DTI images were acquired on a 3T Siemens Allegra scanner, along 35 non-collinear directions (TR=5s, TE=0.14s, B0=1000mm/s², matrix size 2x2x6mm). Expression of 33 genes forming the immune signature of the FEP patients was quantified via qPCR from peripheral blood. Gene-fractional anisotropy (FA interaction was analyzed using tract-based spatial statistics (TBSS).

Results

Gene-FA interaction analysis identified significant group-specific associations for five immune markers (CXCR3, CD4, CD27, CD38, IL12a; p < 0.001, TFCE-corrected). Notably, CXCR3, CD4, and CD27 exhibited opposing trends between FEP and HC, suggesting distinct immune-driven influences on white matter integrity. Affected tracts were widespread in the brain. including the corpus callosum, cingulum, and superior longitudinal fasciculus.

Conclusion

This study underscores specific immune system-FA interactions in FEP, investigated with DTI, providing insight into the immune-related contributions to white matter alterations in early psychosis.