Background and hypothesis: The early phase of psychosis is critical for interventions to modify long-term outcomes. It is unclear what proportion of individuals' exhibit early persistent psychosis and the long-term implications.
Study design: An epidemiologic sample of individuals with acute psychosis was recruited at first admission and followed for 25 years. Early persistent psychosis was defined as presence of active psychosis for ≥90% of the days of the 4 years after first hospitalization for psychosis. Multivariable regression analyses were conducted, testing the association between baseline predictors and persistent psychosis, and between persistent psychosis and 25-year outcomes.
Study results: Out of 526 individuals (age = 27.4 ± 9.4 years, males = 56.8%, baseline schizophrenia/schizoaffective disorder = 30.0%), 101 (19.2%) had early persistent psychosis. At baseline, low premorbid cognitive performance (odds ratio (OR) = 2.08, 95% CI, 1.05-4.12), lower Global Assessment of Functioning (OR = 1.59, 95% CI, 1.16-2.13), low role function (OR = 1.49, 95% CI, 1.03-2.16) and worse social function (OR = 1.52, 95% CI, 1.03-2.22) were predictive of persistent psychosis. At 25-year follow-up (n = 307, 58.9%), early persistent psychosis was associated with worse avolition ($\beta$=0.25, 95% CI, 0.14-0.35), more severe reality distortion ($\beta$=0.19, 95% CI, 0.07-0.31), disorganization ($\beta$=0.21, 95% CI, 0.09-0.32), worse social ($\beta$=-0.18, 95% CI, -0.06 to -0.30), role ($\beta$=-0.22, 95% CI, -0.09 to -0.34), and global function ($\beta$=-0.28, 95% CI, -0.17 to -0.38), greater odds of being on public assistance (OR = 2.13, 95% CI, 1.15-3.95), lower odds of living independently (OR = 0.43, 95% CI, 0.23-0.80) or recovery (OR = 0.09, 95% CI, 0.02-0.38).
Conclusions: One in 5 individuals with first-episode psychosis had early persistent psychosis without clearly modifiable premorbid factors, and with strong associations with adverse long-term outcomes. Individuals experiencing early persistent psychosis require focused long-term interventions.
Keywords: early intervention services; longitudinal course of illness; treatment resistance.
© The Author(s) 2026. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.