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. 2025 Aug 1;8(8):e2525644.
doi: 10.1001/jamanetworkopen.2025.25644.

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

Johanna Seitz-Holland  1 , Grace R Jacobs  1 , Jenna Reinen  2 , Daniel Mathalon  3   4 , Cheryl Corcoran  5   6 , Abraham Reichenberg  5   7   8 , Mark Vangel  1 , Robert J Glynn  9 , Nora Penzel  1 , Kang-Ik K Cho  1 , Eduardo Castro  2 , Anastasia Haidar  1 , Jean M Addington  10 , Tina Kapur  11 , Sylvain Bouix  1   12 , Carrie E Bearden  13 , John M Kane  14   15 , Patrick D McGorry  16   17 , Scott W Woods  18   19 , Barnaby Nelson  16   17 , René S Kahn  5 , Martha E Shenton  1   11 , Guillermo A Cecchi  2 , Ofer Pasternak  1   11
Affiliations

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

Johanna Seitz-Holland et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Glynn reported receiving grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work. Dr Bouix reported receiving grants from the National Institute of Mental Health, Natural Sciences and Engineering Research Council of Canada, and Communications Research Centre Canada outside the submitted work. Dr Bearden reported receiving grants from the Shear Family Foundation, Simons Foundation, and Levin Trust outside the submitted work. Dr Kane reported receiving personal fees from AbbVie, Alkermes, Allergan, Boehringer-Ingelheim, Bristol Meyers-Squibb, Cerevel, Dainippon Sumitomo, H. Lundbeck, HealthRhythms, HLS Therapeutics, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Mapi, Maplight, Merck, Minerva, Neurocrine, Newron, Novartis, NW PharmaTech, Otsuka, Roche, Saladax, Sunovion, Teva, Terran, and Click Therapeutics; grants from Sunovion, H. Lundbeck, Janssen Pharmaceutical, and Otsuka; having stock options with HealthRhythms, LB Pharmaceuticals, North Shore Therpeutics, NW PharmaTech, Saladax, Terran, and MedinCell; holding equity in Vanguard Research Group; and receiving royalties from UpToDate outside the submitted work. Dr McGorry reported being a founding director, patron, and former founding board member of Headspace and being the executive director of Orygen, Australia’s National Centre of Excellence in Youth Mental Health and lead agency for 5 Headspace centres across northwest Melbourne, outside the submitted work. Dr Woods reported receiving personal fees from the American Psychiatric Association and Medscape Features, being a consulting partner with stock options for NW Pharmatech, and holding a patent (No. 8492418 B2) outside the submitted work. Dr Cecchi reported being a full time employee of the IBM Corporation outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Incidence and Prevalence of Remission at Each Follow-Up Visit
A, Incidence of first remission based on who was eligible to achieve first remission at this visit. B, The probability of first remission based on everyone with available data for this visit (including converters). C, The prevalence of remission based on the available data for this visit. Individuals who converted at or before a visit were included in the analyses as nonremitters. Panels A and B report measures standardized by a 2-month follow-up time. For unstandardized measures, see eFigure 2 in Supplement 1. To see absolute counts, percentage of individuals remitted relative to the individuals with data available, and 95% CIs for these percentages, see eTable 3, eTable 4, and eTable 6 in Supplement 1.
Figure 2.
Figure 2.. Stability of Remission at Each Visit
A stable remitter was defined as someone who did not meet clinical high risk (CHR) criteria again or transitioned to psychosis after a previous remission. An unstable remitter was defined as someone who met CHR criteria again or transitioned to psychosis after a previous remission. For absolute counts, the percentage of individuals who were first time, stable, and unstable remitters relative to all who had remitted up to that follow-up visit, and 95% CIs for these percentages, see eTable 7 in Supplement 1.
Figure 3.
Figure 3.. Prevalence of Remission at Each Visit, Depending on Previous Remission Visits
For absolute counts, the percentage of individuals remitted relative to the individuals with data available, and 95% CIs for these percentages, see eTable 8 and eTable 9 in Supplement 1.
See this image and copyright information in PMC

References

    1. Yung AR, Phillips LJ, McGorry PD, et al. Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppl. 1998;172(33):14-20. doi: 10.1192/S0007125000297602 - DOI - PubMed
    1. Fusar-Poli P, Borgwardt S, Bechdolf A, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013;70(1):107-120. doi: 10.1001/jamapsychiatry.2013.269 - DOI - PMC - PubMed
    1. Nelson B, Yuen HP, Wood SJ, et al. Long-term follow-up of a group at ultra high risk (“prodromal”) for psychosis: the PACE 400 study. JAMA Psychiatry. 2013;70(8):793-802. doi: 10.1001/jamapsychiatry.2013.1270 - DOI - PubMed
    1. Hartmann JA, Yuen HP, McGorry PD, et al. Declining transition rates to psychotic disorder in “ultra-high risk” clients: investigation of a dilution effect. Schizophr Res. 2016;170(1):130-136. doi: 10.1016/j.schres.2015.11.026 - DOI - PubMed
    1. Beck K, Andreou C, Studerus E, et al. Clinical and functional long-term outcome of patients at clinical high risk (CHR) for psychosis without transition to psychosis: a systematic review. Schizophr Res. 2019;210:39-47. doi: 10.1016/j.schres.2018.12.047 - DOI - PubMed

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