Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia

BACKGROUND: Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. METHODS: A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. RESULTS: A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, p(Bonferroni) = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, p(Bonferroni) = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all p(Bonferroni) < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = − 0.07, p = 0.02). CONCLUSION: Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.