Translational Psychiatry (Oct 2024)
The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis
- Luis Alameda,
- Victoria Rodriguez,
- Marta Di Forti,
- Edoardo Spinazzola,
- Giulia Trotta,
- Celso Arango,
- Manuel Arrojo,
- Miguel Bernardo,
- Julio Bobes,
- Lieuwe de Haan,
- Cristina Marta Del-Ben,
- Charlotte Gayer-Anderson,
- Lucia Sideli,
- Peter B. Jones,
- James B. Kirkbride,
- Caterina La Cascia,
- Giada Tripoli,
- Laura Ferraro,
- Daniele La Barbera,
- Antonio Lasalvia,
- Sarah Tosato,
- Pierre-Michel Llorca,
- Paulo Rossi Menezes,
- Jim van Os,
- Bart P. Rutten,
- Jose Luis Santos,
- Julio Sanjuán,
- Jean-Paul Selten,
- Andrei Szöke,
- Ilaria Tarricone,
- Andrea Tortelli,
- Eva Velthorst,
- Hannah E. Jongsma,
- Evangelos Vassos,
- Diego Quattrone,
- Robin M. Murray,
- Monica Aas
Affiliations
- Luis Alameda
- Service of General Psychiatry, Treatment and Early Intervention in Psychosis Program, Lausanne University Hospital (CHUV)
- Victoria Rodriguez
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London
- Marta Di Forti
- Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Edoardo Spinazzola
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London
- Giulia Trotta
- Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Celso Arango
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM
- Manuel Arrojo
- Department of Psychiatry, Psychiatric Genetic Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago de Compostela
- Miguel Bernardo
- Barcelona Clinic Schizophrenia Unit, Hospital Clinic, Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERSAM, ISCIII
- Julio Bobes
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
- Lieuwe de Haan
- Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam
- Cristina Marta Del-Ben
- Neuroscience and Behaviour Department, Ribeirão Preto Medical School, University of São Paulo
- Charlotte Gayer-Anderson
- ESRC Centre for Society and Mental Health, King’s College London
- Lucia Sideli
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London
- Peter B. Jones
- Department of Psychiatry, University of Cambridge
- James B. Kirkbride
- Psylife Group, Division of Psychiatry, University College London
- Caterina La Cascia
- Section of Psychiatry, Department of Biomedicine, Neuroscience and advanced Diagnostic (BiND), University of Palermo
- Giada Tripoli
- Section of Psychiatry, Department of Biomedicine, Neuroscience and advanced Diagnostic (BiND), University of Palermo
- Laura Ferraro
- Section of Psychiatry, Department of Biomedicine, Neuroscience and advanced Diagnostic (BiND), University of Palermo
- Daniele La Barbera
- Section of Psychiatry, Department of Biomedicine, Neuroscience and advanced Diagnostic (BiND), University of Palermo
- Antonio Lasalvia
- Section of Psychiatry, Department of Neuroscience, Biomedicine and Movement, University of Verona
- Sarah Tosato
- Section of Psychiatry, Department of Neuroscience, Biomedicine and Movement, University of Verona
- Pierre-Michel Llorca
- Université Clermont Auvergne
- Paulo Rossi Menezes
- Department of Preventive Medicine, Faculdade de Medicina, Universidade de São Paulo
- Jim van Os
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London
- Bart P. Rutten
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre
- Jose Luis Santos
- Department of Psychiatry, Servicio de Psiquiatría Hospital “Virgen de la Luz”, C/Hermandad de Donantes de Sangre
- Julio Sanjuán
- Department of Psychiatry, School of Medicine, Universidad de Valencia, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)
- Jean-Paul Selten
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre
- Andrei Szöke
- University of Paris Est Creteil, INSERM, IMRB, AP-HP, Hôpitaux Universitaires, H. Mondor, DMU IMPACT
- Ilaria Tarricone
- Bologna Transcultural Psychosomatic Team (BoTPT), Department of Medical and Surgical Science, Alma Mater Studiorum Università di Bologna
- Andrea Tortelli
- Institut Mondor de recherché biomedicale
- Eva Velthorst
- Department of Research, Community Mental Health Service, GGZ Noord-Holland-Noord
- Hannah E. Jongsma
- Centre for Transcultural Psychiatry ‘Veldzicht’
- Evangelos Vassos
- Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Diego Quattrone
- Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Robin M. Murray
- Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London
- Monica Aas
- Social, Genetics and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- DOI
- https://doi.org/10.1038/s41398-024-03149-7
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 7
Abstract
Abstract Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = −0.34, 95% CI = [−0.660, −0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.