Sex-specific associations between serum uric acid, psychopathology, and cognition in deficit schizophrenia

Deficit schizophrenia (DS) is a distinct subtype characterized by persistent negative symptoms. Uric acid (UA), a major endogenous antioxidant, shows marked sex differences, but its associations with psychopathology and cognition in DS remain unclear. This study examined sex-specific associations of serum UA with clinical symptoms and cognition in DS.

A total of 76 DS patients (47 men, 46.23 ± 12.51 years; 29 women, 50.86 ± 10.51 years) and 210 non-deficit schizophrenia (NDS) patients (88 men, 46.56 ± 12.03 years; 122 women, 45.49 ± 12.35 years) were enrolled. Psychopathology and cognition were assessed using the Positive and Negative Syndrome Scale and the Repeatable Battery for the Assessment of Neuropsychological Status. Serum UA was measured by enzymatic colorimetric assay. Sex and diagnosis effects were examined using two-way analysis of variance. Pearson correlation and multivariable linear regression analyses were performed within sex- and diagnosis-defined subgroups.

A showed a significant main effect of sex (F = 40.82, p < 0.001), with higher levels in men than women in both DS and NDS. Distinct sex-specific associations were observed only in DS: in men, higher UA levels were independently associated with more severe positive symptoms (β = 0.301, p = 0.040), whereas in women, higher UA levels were associated with better delayed memory (β = 0.421, p = 0.009) and RBANS total score (β = 0.465, p = 0.006). No significant associations were observed in NDS.

Serum UA shows distinct sex-specific associations with symptom and cognitive profiles in DS.