This study investigated cortical morphological changes in systemic lupus erythematosus (SLE) patients diagnosed with anxiety and/or depression, all of whom exhibited no major neuropsychiatric symptoms and had normal conventional magnetic resonance imaging (MRI) findings. We also further examined the correlation between these morphological alterations and clinical characteristics.

Employing advanced structural MRI (sMRI) techniques, we implemented a dual analytical approach combining voxel-based morphometry (VBM) and surface-based morphometry (SBM) to assess structural differences across three cohorts comprising 59 SLE patients with anxiety and/or depression (SLE-AD), 35 SLE patients with no anxiety and/or depression (SLE-NAD), and 48 age-matched healthy controls (HCs). Within the SBM-based analysis framework, we set a minimum clustering threshold of 50 vertices to secure robust outcomes and delineate significant brain regions. The study focused on whole-brain gray matter volume (GMV), cortical thickness (CT), depth of the sulci (SD), cortical gyrification index (GI), and fractal dimension (FD).

Quantitative analyses revealed significant GMV reductions in the SLE-AD group compared with HCs and the SLE-NAD groups (gaussian random field (GRF) correction: p_voxel < 0.0005, p_cluster < 0.0005). Additionally, we observed widespread decreases in the CT and SD, as well as reduced GIs across multiple regions (p_uncorr < 0.001, cluster size >50 vertices). The most prominent alterations were in the left temporal lobe, bilateral thalamus, prefrontal cortex cingulate gyrus, insula, postcentral gyrus, and fusiform gyrus. GMV in the left middle temporal gyrus (r = –0.288, p = 0.027) and CT in the left fusiform gyrus (r = –0.337, p = 0.009), along with CT in the right middle frontal sulcus (r = –0.306, p = 0.018) and right middle frontal gyrus (r = –0.356, p = 0.006), were inversely associated with SLE disease activity index (SLEDAI). However, neither GMV, CT, nor cortical complexity exhibited significant associations with Hamilton Anxiety Scale (HAMA) or Hamilton Depression Scale (HAMD) scores. Multivariate linear regression analysis indicated that the CT of left hemisphere-related brain areas—including the superior occipital gyrus, parieto-occipital sulcus, cuneus and opercular part of the inferior frontal gyrus—and the GI of the superior frontal gyrus significantly influenced HAMD/HAMA scores. CT of the left hemisphere’s intraparietal sulcus and transverse parietal sulci, along with SD of the right hemisphere’s central sulcus, were predictors of HAMA scores.

Our findings demonstrate that SLE patients presenting with anxiety and/or depression exhibit distinct neuroanatomical alterations, even without prominent neuropsychiatric manifestations. These morphological changes may represent the neurobiological substrate underlying the heterogeneous clinical spectrum of neuropsychiatric SLE (NPSLE), potentially serving as early neuroimaging biomarkers. Furthermore, these findings provide a structural framework for future studies investigating the causal relationships between these anatomical changes and the neurophysiological mechanisms underlying NPSLE.