Neuropsychiatric systemic lupus erythematosus (NPSLE) includes a broad spectrum of central and peripheral nervous system disorders that significantly impact morbidity and quality of life. Identifying clinical and immunological factors associated with neuropsychiatric symptoms is essential to improve diagnostic accuracy and guide targeted interventions.

A cross-sectional study was conducted in patients with SLE, recording clinical and serological data. Neuropsychiatric manifestations and disease activity (SLEDAI) were evaluated. Mann-Whitney U tests and binary logistic regression (95% OR, p < 0.05) were applied.

Among 161 patients with SLE, 87% (n = 140) were female, with a mean age of 44 ± 12.35 years. Neuropsychiatric symptoms were present in 55.9% (n = 90), mainly anxiety (26.7%), insomnia (21.1%), headache (20.5%) and depression (19.9%). Higher SLEDAI scores were associated with anxiety (Exp(B)=1.10; p<0.001), depression (Exp(B)=1.08; p=0.004), seizures (Exp(B)=1.12; p=0.001), headache (Exp(B)=1.12; p<0.001), insomnia (Exp(B)=1.07; p=0.004), neuropathy (Exp(B)=1.13; p=0.003), and cognitive impairment (Exp(B)=1.21; p=0.005). ANA antibodies were protective against anxiety (Exp(B)=0.18; p=0.004) but associated with cognitive impairment (Exp(B)=25.86; p=0.040). ANCA antibodies showed a protective effect against headache (Exp(B)=0.26; p=0.029). Neuralgia, encephalitis, and myelitis showed no significant associations. Disease duration was not related to neuropsychiatric manifestations (p=0.067). Twelve patients (7.5%) died, with no significant association with NPSLE (p=0.860).