Influence of sex and systemic lupus erythematosus disease status on cerebral cortex structure.

OBJECTIVE

To investigate the main and interactive effects of sex and disease diagnosis on cortical morphology in systemic lupus erythematosus (SLE), providing neuroimaging evidence for sex-by-disease interactive mechanisms underlying structural brain alterations.

METHODS

A cross-sectional study design was used to recruit participants. Structural MRI scans were acquired and processed using surface-based morphometry (SBM) to extract cortical thickness (CT), gyrification index (GI), fractal dimension (FD) and sulcal depth (SD) within predefined regions of interest. Two-way analysis of variance assessed main effects and 'sex×diagnosis' interactions (Holm-Bonferroni corrected). Correlation analyses were performed between these structural metrics and SLE disease activity/psychological assessment scores in areas showing significant interactions.

RESULTS

196 individuals participated in this study: 30 male SLE patients, 66 female SLE patients, 33 male healthy controls (HC) and 67 female HC. Significant sex-by-disease interactions were detected: SD in left orbital (H-shaped) sulci (S_orbital-H_Shaped) (F=14.8458, p=0.0150), with male HC >male SLE (p=0.0039) and male HC>female HC (p<0.0001), and GI in left middle frontal sulcus (S_front_middle) (F=14.1650, p=0.0313), with female SLE>male SLE (p<0.0001) and male HC>male SLE (p=0.0003). Diagnostic main effects (HC>SLE) were observed extensively for CT across both hemispheres. No significant correlations emerged between disease activity/psychological assessment scores and structural parameters in interaction-significant regions.

CONCLUSION

This study provides novel evidence for sex-by-diagnosis interactive effects in the neuropathological mechanisms of SLE. Sex and SLE disease status have both independent and interacting impacts on cerebral cortical structure.

TRIAL REGISTRATION NUMBER: NCT00703742.