Incidence, Prevalence, and Stability of Remission in Individuals With Clinical High Risk for Psychosis

Importance While remission from clinical high risk (CHR) for psychosis is a favorable outcome, it is not well characterized over time. Objective To examine remission incidence, prevalence, and stability, and their association with demographic, clinical, medication, and cognitive variables, comparing 2 commonly used definitions. Design, Setting, and Participants This cohort study examined data from individuals aged 12 to 30 years at CHR in the North American Prodromal Longitudinal Study 3, collected from 9 sites across the US from February 2015 to November 2018. Statistical analyses were conducted between January 2023 and May 2025. Exposure CHR status using 2 definitions: (1) a symptoms-only definition based on the positive symptoms from the Scale of Prodromal Symptoms and (2) a symptoms-and-function definition based on positive symptoms and the modified Global Assessment of Functioning. Main Outcomes and Measures The primary outcomes were remission incidence, prevalence, and stability for 7 follow-up visits over 2 years. Associations of remission with age, sex at birth, race, antipsychotic and antidepressant medication, history of trauma, and cognitive performance were determined using mixed-effects logistic regression. Results The sample included 692 individuals (mean [SD] age, 18.7 [4.1] years; 319 female [46%]) at baseline, with 614 completing at least 1 follow-up. For the symptoms-only definition, 7% (95% CI, 5%-10%) met remission criteria after 2 months, 34% (95% CI, 31%-38%) met remission criteria at least once during the study, and 26% (95% CI, 22%-29%) met criteria at their last visit. The symptoms-and-function definition was associated with a lower remission incidence and prevalence, with 4% (95%CI, 2%-5%) meeting remission criteria after 2 months, 21% (95% CI, 18%-24%) meeting criteria at least once, and 15% (95% CI, 13%-18%) meeting criteria at their last visit. Under the symptoms-only definition, 83 of 153 individuals at CHR with at least 1 follow-up after remission (54%; 95% CI, 46%-62%) were stable remitters. Under the symptoms-and-function definition, 43 of 91 individuals (47%; 95% CI, 37%-58%) were stable remitters. The chance of staying in remission rose drastically once a person had more than 1 previous recorded remission visit. Higher functioning was associated with higher likelihood of remission (current score for symptoms only: OR, 1.04; 95% CI, 1.01-1.08; current score for symptoms and function: OR, 1.08; 95% CI, 1.02-1.14). More symptoms at baseline was associated with a lower likelihood of remission (general symptoms for symptoms only: OR, 0.77; 95% CI, 0.70-0.84; general symptoms for symptoms and function: OR, 0.80; 95% CI, 0.69-0.92). Conclusions and Relevance These findings suggest that CHR status is a dynamic state and that vulnerability can persist even after functional remission. Hence, continued follow-up and facilitated reengagement with clinical services after remission are essential.