Clinical high risk for psychosis (CHR-P)


What is CHR-P?

The clinical high risk for psychosis (CHR-P) paradigm identifies individuals who show early, subthreshold signs of psychosis before a full psychotic disorder develops, with the goal of enabling early intervention to prevent or delay transition to psychosis.

History in a nutshell

The CHR-P paradigm emerged in the early 1990s through parallel developments across several research groups. Alison Yung and Patrick McGorry in Melbourne established the first dedicated at-risk clinic (PACE, 1994) and formalized the Ultra High Risk (UHR) criteria based on attenuated psychotic symptoms and functional decline. Around the same time, Thomas McGlashan and Scott Woods at Yale developed overlapping criteria and structured assessment tools, which became widely adopted in North American research. Concurrently, the basic symptoms approach was further developed by Joachim Klosterkötter, Anita Riecher-Rössler and colleagues in the German-speaking world, focusing on subtle, self-experienced neuropsychological disturbances as early indicators of psychotic vulnerability. These traditions have since been (sort-of) integrated and exported worldwide into the modern CHR-P framework. For a fairly recent overview see this study by Raballo et al. (2024).

Pros and cons

The CHR-P paradigm has been transformative in shifting psychiatry toward earlier identification and intervention, instead of a more reactive approach to established psychotic conditions. It has generated a substantial evidence base and led to the development of dedicated early intervention services that have helped many young people receive support before full psychotic breakdown. At the same time, the paradigm is not without flaws: the majority of those labeled CHR-P never develop psychosis, raising serious concerns about stigma, unnecessary anxiety, and potential overmedicalization of what may be transient distress. Critics have argued that the binary focus on "conversion" as the primary outcome reflects a narrow, disease-centered view that neglects broader functional and personal recovery outcomes, and that categorical risk labeling sits uneasily with the dimensional, continuous nature of psychotic experiences in the general population.

Personal contributions

My personal research contributions stem from my PhD project in Utrecht (2005-2010), which was focused on young CHR-P adolescents (12-18y). Interesting findings were, for example, evidence for early changes in cortical thickness and sensorimotor gating in those at risk, particularly for those later developing psychosis. On the other hand, the conversion rate in young adolescents appeared to be even lower than at a later age, further scrutinising the potential benefits of the paradigm in younger populations. Later on, our work was included in some large-scale collaborations to meta-analyse conversion rates and to optimize prediction models, e.g. most recently by Bonnet et al. (2025) The final prediction model in that study included disorders of thought content, disorganised speech and general functioning, which had fairly good predictive ability. Furthermore, two recent studies in the NICOTINE project showed that smoking was NOT related to structural (grey matter) or functional (resting-state) brain alterations in CHR-P youth.

Although I am currently not involved in new research projects including CHR-P individuals, my aim is to continue to contribute to the finetuning of screenings for psychosis-risk in the future, in particular for autism.

Publications


Resting-state connectivity and tobacco smoking in clinical high-risk for psychosis (NAPLS-3)


M. Koster, M. van der Pluijm, R. Veelers, E. van de Giessen, L. de Haan, G. van Wingen, T. Ziermans, J. Vermeulen

General Psychiatry, vol. 39, 2026 Feb


Tobacco Smoking and Gray Matter Volume in Individuals at Clinical High Risk for Psychosis: A Longitudinal Magnetic Resonance Imaging Study


M. Koster, M. van der Pluijm, M. Fraikin, G. van Wingen, E. van de Giessen, L. de Haan, J. Vermeulen, T. Ziermans

Biological Psychiatry: Global Open Science, vol. 5, 2025 Sep


Clinical prediction model for transition to psychosis in individuals meeting At Risk Mental State criteria


L. J. Bonnett, A. Hunt, A. Flores, C. Tudur Smith, F. Varese, R. Byrne, H. Law, M. Milicevic, R. Carney, S. Parker, A. R. Yung, IPPACT Study Group

Schizophrenia, vol. 11, 2025 Feb


A Meta-Analysis of Autism and Clinical High-Risk for Psychosis is Too Premature. Comment on: Vaquerizo-Serrano, Salazar de Pablo, Singh & Santosh (2021)


T. Ziermans, A. Groenman, R. Schalbroeck

Journal of autism and developmental disorders, vol. 52, 2022 Nov, pp. 5079-5082


The Attenuated Psychosis Syndrome and Facial Affect Processing in Adolescents With and Without Autism


A. Maat, S. Therman, H. Swaab, T. Ziermans

Frontiers in Psychiatry, vol. 11, 2020 Aug


Individualized Prediction of Transition to Psychosis in 1,676 Individuals at Clinical High Risk: Development and Validation of a Multivariable Prediction Model Based on Individual Patient Data Meta-Analysis


A. Malda, N. Boonstra, H. Barf, S. de Jong, A. Aleman, J. Addington, M. Pruessner, D. Nieman, L. de Haan, A. Morrison, A. Riecher-Rössler, E. Studerus, S. Ruhrmann, F. Schultze-Lutter, S. K. An, S. Koike, K. Kasai, B. Nelson, P. McGorry, S. Wood, A. Lin, A.Y. Yung, M. Kotlicka-Antczak, M. Armando, S. Vicari, M. Katsura, K. Matsumoto, S. Durston, T. Ziermans, L. Wunderink, H. Ising, M. van der Gaag, P. Fusar-Poli, G. H. M. Pijnenborg

Frontiers in Psychiatry, vol. 10, 2019 May


Individual prediction of long-term outcome in adolescents at ultra-high risk for psychosis: Applying machine learning techniques to brain imaging data


S. de Wit, T. B. Ziermans, M. Nieuwenhuis, P. F. Schothorst, H. van Engeland, R. S. Kahn, S. Durston, H. G. Schnack

Human Brain Mapping, vol. 38, 2017 Feb, pp. 704-714


Brain development in adolescents at ultra-high risk for psychosis: Longitudinal changes related to resilience


S. de Wit, L. M. Wierenga, B. Oranje, T. B. Ziermans, P. F. Schothorst, H. van Engeland, R. S. Kahn, S. Durston

NeuroImage: Clinical, vol. 12, 2016 Sep, pp. 542-549


Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification


P. Fusar-Poli, M. Cappucciati, S. Borgwardt, S. W. Woods, J. Addington, B. Nelson, D. H. Nieman, D. R. Stahl, G. Rutigliano, A. Riecher-Rössler, A. E. Simon, M. Mizuno, T. Y. Lee, J. S. Kwon, M. M. L. Lam, J. Perez, S. Keri, P. Amminger, S. Metzler, W. Kawohl, W. Rössler, J. Lee, J. Labad, T. Ziermans, S. K. An, C.-C. Liu, K. A. Woodberry, A. Braham, C. Corcoran, P. McGorry, A. R. Yung, P. K. McGuire

JAMA Psychiatry, vol. 73, 2016 Feb, pp. 113-120


Neurocognitive and clinical predictors of long-term outcome in adolescents at ultra-high risk for psychosis: a 6-year follow-up


T. Ziermans, S. de Wit, P. Schothorst, M. Sprong, H. van Engeland, R. Kahn, S. Durston

PLoS ONE, vol. 9, 2014, pp. e93994


Adolescents at ultra-high risk for psychosis: long-term outcome of individuals who recover from their at-risk state


S. de Wit, P. F. Schothorst, B. Oranje, T. B. Ziermans, S. Durston, R. S. Kahn

European Neuropsychopharmacology, vol. 24, 2014 Jun, pp. 865-73


Quantitative and qualitative symptomatic differences in individuals at Ultra-High Risk for psychosis and healthy controls


E. Velthorst, E. M. Derks, P. Schothorst, H. Becker, S. Durston, T. Ziermans, D. H. Nieman, L. de Haan

Psychiatry Research, vol. 210, 2013 Dec, pp. 432-437


Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence


T. B. Ziermans, P. F. Schothorst, M. Sprong, M. J. C. M. Magnée, H. van Engeland, C. Kemner

Schizophrenia Research, vol. 134, 2012 Jan, pp. 10-15


Neuroendocrine markers of high risk for psychosis: salivary testosterone in adolescent boys with prodromal symptoms


S. van Rijn, A. Aleman, L. de Sonneville, M. Sprong, T. Ziermans, P. Schothorst, H. van Engeland, H. Swaab

Psychological Medicine, vol. 41, 2011 Sep, pp. 1815-1822


Affective dysfunctions in adolescents at risk for psychosis: emotion awareness and social functioning


S. van Rijn, P. Schothorst, M. van 't Wout, M. Sprong, T. Ziermans, H. van Engeland, A. Aleman, H. Swaab

Psychiatry Research, vol. 187, 2011 May, pp. 100-105


Misattribution of facial expressions of emotion in adolescents at increased risk of psychosis: the role of inhibitory control


S. van Rijn, A. Aleman, L. de Sonneville, M. Sprong, T. Ziermans, P. Schothorst, H. van Engeland, H. Swaab

Psychological Medicine, vol. 41, 2011 Mar, pp. 499-508


Transition and remission in adolescents at ultra-high risk for psychosis


T. B. Ziermans, P. F. Schothorst, M. Sprong, H. van Engeland

Schizophrenia Research, vol. 126, 2011 Mar, pp. 58-64


Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study


T. Ziermans, P. Schothorst, M. Magnée, H. van Engeland, C. Kemner

Journal of Psychiatry & Neuroscience, vol. 36, 2011 Mar, pp. 127-134


No evidence for structural brain changes in young adolescents at ultra high risk for psychosis


T. B. Ziermans, S. Durston, M. Sprong, H. Nederveen, N. E. M. van Haren, H. G. Schnack, B. E. Lahuis, P. F. Schothorst, H. van Engeland

Schizophrenia Research, vol. 112, 2009 Jul, pp. 1-6


Pathways to psychosis: a comparison of the pervasive developmental disorder subtype Multiple Complex Developmental Disorder and the "At Risk Mental State"


M. Sprong, H. E. Becker, P. F. Schothorst, H. Swaab, T. B. Ziermans, P. M. Dingemans, D. Linszen, H. van Engeland

Schizophrenia Research, vol. 99, 2008 Feb, pp. 38-47