Duration of untreated psychosis and cognitive function in first-episode antipsychotic-naïve schizophrenia: Evidence from auditory P300.

Objective: The relationship between the duration of untreated psychosis (DUP) and cognitive function in schizophrenia (SZ) patients remains debated, with no empirical evidence from event-related potential (ERP) studies supporting their association. This study aims to investigate the relationship between DUP and cognitive functions, as well as psychiatric symptoms, in first-episode antipsychotic-naïve SZ (FEAN-SZ) patients using ERP.

Methods: The study included 321 Chinese FEAN-SZ patients and 146 healthy controls. The DUP and sociodemographic characteristics of all participants were collected, and psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale. The P300 (P3) components, including P3a, P3b and N100, were recorded from all participants using auditory oddball paradigm.

Results: 25.5 % of patients did not receive timely treatment for over four years, and those with lower educational levels or more severe negative symptoms had longer DUP (p = 0.027, p = 0.020). Compared to healthy controls, FEAN-SZ patients exhibited longer latencies and lower amplitudes in the P3 components (all p_s < 0.001). Significant differences in the P3 components were observed among three groups of DUP (< 8 months, 8 to 48 months, and ≥ 48 months) (all p_s < 0.001). In the 8 ≤ DUP < 48 months group, the N1 amplitude and P3a latency predicted positive symptom scores and general psychopathology scores, respectively (β = -0.165, p = 0.037; β = 0.541, p < 0.001); P3b latency predicted negative symptom scores in the DUP < 8 months group (β = 0.391, p < 0.001). N1 amplitude predicted general psychopathology scores only in the DUP > 48 months group (β = -0.228, p = 0.040). Multiple linear regression analysis indicated that the latency and amplitude of P3a were independently associated with DUP (B = 0.124, p < 0.001; B = -1.161, p = 0.012).

Conclusions: SZ patients who have a longer DUP exhibit more severe P3 deficits, and the P3 components may be indicative of different psychiatric symptom severity in DUPs of different lengths, as well as the P3a component may serve as an electrophysiologic marker to assess the length of DUP.