Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis

Stefania Tognin^#¹, Ana Catalan^#^{1

2}, Claudia Aymerich^{3

4}, Anja Richter¹, Matthew J Kempton^{1

5}, Gemma Modinos^{6

7}, Ryan Hammoud¹, Iñigo Gorostiza⁸, Evangelos Vassos⁹, Mark van der Gaag¹⁰, Lieuwe de Haan¹¹, Barnaby Nelson^{12

13}, Anita Riecher-Rössler¹⁴, Rodrigo Bressan¹⁵, Neus Barrantes-Vidal¹⁶, Marie-Odile Krebs¹⁷, Merete Nordentoft¹⁸, Stephan Ruhrmann¹⁹, Gabriele Sachs²⁰, Bart P F Rutten²¹; EU-GEI High Risk Study; Lucia Valmaggia^{1

12

22}, Philip McGuire²³

Collaborators, Affiliations

Collaborators

EU-GEI High Risk Study:
Philip McGuire, Lucia R Valmaggia, Matthew J Kempton, Maria Calem, Gemma Modinos, Lieuwe de Haan, Mark van der Gaag, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Barnaby Nelson, Patrick McGorry, G Paul Amminger, Christos Pantelis, Athena Politis, Joanne Goodall, Anita Riecher-Rössler, Stefan Borgwardt, Erich Studerus, Rodrigo Bressan, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Neus Barrantes-Vidal, Tecelli Domínguez-Martínez, Anna Racciopi, Thomas R Kwapil, Manel Monsonet, Lídia Hinojosa, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Marie-Odile Krebs, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Glenthøj, Birte Glenthøj, Merete Nordentoft, Stephan Ruhrmann, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Gabriele Sachs, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, Bart P Rutten, Jim van Os

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Basurto University Hospital, OSI Bilbao-Basurto. Biobizkaia Health Research Institute. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barakaldo, Bizkaia, Spain.
³ Basurto University Hospital, OSI Bilbao-Basurto. Biobizkaia Health Research Institute. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barakaldo, Bizkaia, Spain. claudia.aymerich@kcl.ac.uk.
⁴ Department of Children & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. claudia.aymerich@kcl.ac.uk.
⁵ National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), London, UK.
⁶ Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁷ MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
⁸ Research Unit, Basurto University Hospital, REDISSEC, Bilbao, Spain.
⁹ Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁰ VU University, Faculty of Behavioural and Movement Sciences, Department of Clinical Psychology and Parnassia Psychiatric Institute, Department of Psychosis Research, Amsterdam, The Netherlands.
¹¹ AMC, Academic Psychiatric Centre, Department Early Psychosis, Amsterdam, The Netherlands.
¹² Orygen, Parkville, VIC, Australia.
¹³ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
¹⁴ Medical Faculty, University of Basel, Basel, Switzerland.
¹⁵ LiNC-Lab Interdisciplinar Neurociências Clínicas, Depto Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.
¹⁶ Departament de Psicologia Clínica i de la Salut (Universitat Autònoma de Barcelona), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain.
¹⁷ University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Paris, France.
¹⁸ Mental Health Centre Copenhagen and CINS, Mental Health Centre Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
²⁰ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
²¹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
²² Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
²³ Department of Psychiatry, University of Oxford, Oxford, United Kingdom.

^# Contributed equally.

PMID: 39979326
PMCID: PMC11842736
DOI: 10.1038/s41537-025-00562-9

Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis

Stefania Tognin et al. Schizophrenia (Heidelb). 2025.

. 2025 Feb 20;11(1):23.

doi: 10.1038/s41537-025-00562-9.

Authors

Collaborators

EU-GEI High Risk Study:
Philip McGuire, Lucia R Valmaggia, Matthew J Kempton, Maria Calem, Gemma Modinos, Lieuwe de Haan, Mark van der Gaag, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Barnaby Nelson, Patrick McGorry, G Paul Amminger, Christos Pantelis, Athena Politis, Joanne Goodall, Anita Riecher-Rössler, Stefan Borgwardt, Erich Studerus, Rodrigo Bressan, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Neus Barrantes-Vidal, Tecelli Domínguez-Martínez, Anna Racciopi, Thomas R Kwapil, Manel Monsonet, Lídia Hinojosa, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Marie-Odile Krebs, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Glenthøj, Birte Glenthøj, Merete Nordentoft, Stephan Ruhrmann, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Gabriele Sachs, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, Bart P Rutten, Jim van Os

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Basurto University Hospital, OSI Bilbao-Basurto. Biobizkaia Health Research Institute. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barakaldo, Bizkaia, Spain.
³ Basurto University Hospital, OSI Bilbao-Basurto. Biobizkaia Health Research Institute. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barakaldo, Bizkaia, Spain. claudia.aymerich@kcl.ac.uk.
⁴ Department of Children & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. claudia.aymerich@kcl.ac.uk.
⁵ National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), London, UK.
⁶ Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁷ MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
⁸ Research Unit, Basurto University Hospital, REDISSEC, Bilbao, Spain.
⁹ Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁰ VU University, Faculty of Behavioural and Movement Sciences, Department of Clinical Psychology and Parnassia Psychiatric Institute, Department of Psychosis Research, Amsterdam, The Netherlands.
¹¹ AMC, Academic Psychiatric Centre, Department Early Psychosis, Amsterdam, The Netherlands.
¹² Orygen, Parkville, VIC, Australia.
¹³ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
¹⁴ Medical Faculty, University of Basel, Basel, Switzerland.
¹⁵ LiNC-Lab Interdisciplinar Neurociências Clínicas, Depto Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.
¹⁶ Departament de Psicologia Clínica i de la Salut (Universitat Autònoma de Barcelona), Spanish Mental Health Research Network (CIBERSAM), Barcelona, Spain.
¹⁷ University of Paris, GHU-Paris, Sainte-Anne, C'JAAD, Hospitalo-Universitaire department SHU, Paris, France.
¹⁸ Mental Health Centre Copenhagen and CINS, Mental Health Centre Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
²⁰ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
²¹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
²² Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
²³ Department of Psychiatry, University of Oxford, Oxford, United Kingdom.

^# Contributed equally.

PMID: 39979326
PMCID: PMC11842736
DOI: 10.1038/s41537-025-00562-9

Abstract

Adverse childhood experiences (ACEs) are common in people at clinical high-risk for psychosis (CHR), however, the relationship between ACEs and long-term clinical outcomes is still unclear. This study examined associations between ACEs and clinical outcomes in CHR individuals. 344 CHR individuals and 67 healthy controls (HC) were assessed using the Childhood Trauma Questionnaire (CTQ), the Bullying Questionnaire and the Childhood Experience of Care and Abuse (CECA). CHR were followed up for up to 5 years. Remission from the CHR state, transition to psychosis (both defined with the Comprehensive Assessment of an At Risk Mental State), and level of functioning (assessed with the Global Assessment of Functioning) were assessed. Stepwise and multilevel logistic regression models were used to investigate the relationship between ACEs and outcomes. ACEs were significantly more prevalent in CHR individuals than in HC. Within the CHR cohort, physical abuse was associated with a reduced likelihood of remission (OR = 3.64, p = 0.025). Separation from a parent was linked to an increased likelihood of both remission (OR = 0.32, p = 0.011) and higher level of functioning (OR = 1.77, p = 0.040). Death of a parent (OR = 1.87, p = 0.037) was associated with an increased risk of transitioning to psychosis. Physical abuse and death of a parent are related to adverse long-term outcomes in CHR. The counter-intuitive association between separation from a parent and outcomes may reflect the removal of a child from an adverse environment. Future studies should investigate whether interventions targeting the effect of specific ACEs might help to improve outcomes in this population.

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Conflict of interest statement

Competing interests: A.C. reports personal fees and grants from Janssen-Cilag, ROVI, and Otsuka-Lundbeck outside the submitted work. C.A. reports personal fees and grants from Janssen-Cilag and Neuraxpharm outside the submitted work. The remaining authors have no disclosures to report. Ethical approval: The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Figures

**Fig. 1**
Adjusted odds ratios (adjOR) and 95% confidence intervals (CI) between clinical outcomes and ACEs.

See this image and copyright information in PMC

References

1. Zhang, L. et al. Adverse childhood experiences in patients with schizophrenia: related factors and clinical implications. Front. Psychiatry14, 1247063 (2023). - PMC - PubMed
1. Janssen, I. et al. Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatr. Scand.109, 38–45 (2004). - PubMed
1. Lardinois, M., Lataster, T., Mengelers, R., Van Os, J. & Myin-Germeys, I. Childhood trauma and increased stress sensitivity in psychosis. Acta Psychiatr. Scand.123, 28–35 (2011). - PubMed
1. van Nierop, M. et al. Psychopathological mechanisms linking childhood traumatic experiences to risk of psychotic symptoms: analysis of a large, representative population-based sample. Schizophr. Bull.40, S123–S130 (2014). - PMC - PubMed
1. Varese, F. et al. A meta-analysis of patient- control prospective- andcross-sectional cohort studies. Schizophr. Bull.38, 661–671 (2012). - PMC - PubMed

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Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis

Collaborators

Affiliations

Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources