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Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study

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Abstract

Background

The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR. Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10–17. CHR participants were children and adolescents aged 10–17, meeting one or more of the CHR criteria assessed at baseline and at 18 months’ follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276–30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293–14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185–64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

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Authors and Affiliations

  1. Child and Adolescent Mental Health Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa, 39-57, Esplugues de Llobregat, Barcelona, 08950, Spain

    Montserrat Dolz, Jordina Tor, Daniel Muñoz-Samons, Marta Pardo, Xavier Alvarez-Subiela, Marta Rodriguez-Pascual, Gisela Sugranyes & Inmaculada Baeza

  2. Child and Adolescent Psychiatry and Psychology Department, Hospital Sant Joan de Déu of Barcelona, Passeig Sant Joan de Déu, 002,Esplugues de Llobregat, Barcelona, 08950, Spain

    Montserrat Dolz, Jordina Tor, Daniel Muñoz-Samons, Marta Pardo, Xavier Alvarez-Subiela, Marta Rodriguez-Pascual & Gisela Sugranyes

  3. Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM-ISCIII, Madrid, Spain

    Olga Puig, Elena de la Serna & Daniel Ilzarbe

  4. Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic Universitari of Barcelona, Barcelona, SGR2021-01319, Spain

    Elena de la Serna & Daniel Ilzarbe

  5. Fundació Clínic per a la Recerca Biomèdica-IDIBAPS, Barcelona, Spain

    Daniel Ilzarbe

  6. Department of Medicine, Institute of Neurosciences, University of Barcelona, Bellaterra, Spain

    Daniel Ilzarbe

  7. Universitat Autonoma de Barcelona, Bellaterra, Spain

    Montserrat Dolz

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Contributions

MD and IB designed the study and wrote the protocol. MD and JT managed the literature search and wrote the first draft. JT performed data analyses. All authors contributed to the planning of the study and the enrolling of participants, and critically reviewed the paper. All authors contributed to and have approved the final manuscript.

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Correspondence to Jordina Tor.

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The authors declare no competing interests.

Author contribution

MD. The author has participated as principal site investigator in a Janssen-Cilag, S.A., clinical trial with the esketamine molecule, and a Janssen-Cilat, S.A. clinical trial with the seltorexant molecule. She is also principal site investigator in a Stanley Medical Research Institute grant. She has received grants as principal investigator from the Spanish Ministry of Health, Instituto de Salud Carlos III (PI11/02684; PI15/00509; PI21/0090) and the Alicia Koplowitz foundation. She has received support to attend conferences or speaker fees from Shire, Janssen, and Osuka-Lundbeck.

JT. The author declares that she has no conflict of interest.

OP has received grants as principal investigator from the Alicia Koplowitz foundation.

EDS. The author declares that she has no conflict of interest.

DMS. The author has received support to attend conferences or speaker fees from Shire, Janssen, and Osuka-Lundbeck.

MR. The author declares that she has no conflict of interest.

XAS. The author declares that she has no conflict of interest.

GS has received speaker fees from Angelini Pharma. She has received funding from the Spanish Ministry of Health, Instituto de Salud Carlos III (PI1800976, PI21/00330) co-funded by the European Union, the Alicia Koplowitz foundation, La Marató TV3 Foundation, and the Fundació Clínic Recerca Biomèdica - Ajut a la Recerca Pons Bartran.

DI. The author declares that she has no conflict of interest.

IB has received honoraria and travel support from Angelini, Otsuka-Lundbeck, and Janssen, and grants from the Spanish Ministry of Health, Instituto de Salud Carlos III (PI18/0242, INT19/00021, and PI21/0391, co-funded by the European Union), the Alicia Koplowitz Foundation, Pons-Bartran legacy (FCRB_IPB2_2023), and National Drugs Plan (2022I053).

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Dolz, M., Tor, J., Puig, O. et al. Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study. Eur Child Adolesc Psychiatry (2024). https://doi.org/10.1007/s00787-024-02436-4

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