Sex differences in event-related potentials and their clinical predictive value in first-episode antipsychotic-naïve schizophrenia.

This study explored sex differences in cognitive impairments in first-episode antipsychotic-naive schizophrenia (FEAN-SZ) patients using event-related potentials. A total of 321 FEAN-SZ patients and 146 healthy controls (HCs) were enrolled to compare sex differences in the P300 (P3) components elicited by the auditory Oddball paradigm. The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) were used to assess the clinical symptoms. We also examined sex differences in the relationship between P3 components and clinical symptoms. Compared to HCs, FEAN-SZ patients showed reduced P3 amplitude and prolonged latency (all p_s < 0.001). Male patients had significantly lower N100 (N1) amplitude than female patients (F = 5.70, p = 0.018), a difference not observed in HCs. In males, N1 latency correlated with total PANSS (r = 0.361, p < 0.001) and general psychopathology scores (r = 0.354, p < 0.001). Multiple stepwise regression showed that N1 amplitude predicted negative, total PANSS, and HAMD scores in males (β = -0.263, -0.191, -0.289, all p_s < 0.001). In females, P3a latency predicted G, total PANSS, HAMD, and HAMA scores (β = 0.486, 0.600, 0.204, 0.297, all p_s < 0.05). FEAN-SZ patients exhibited reduced P3 amplitude and prolonged latency compared to HCs, with males showing lower N100 amplitude than females. In terms of sex-specific clinical symptom predictors, N1 amplitude in males and P3a latency in females were significantly correlated with PANSS, HAMD, and HAMA scores.