The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis
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.
Authors
- Celso Arango (ORCID: https://orcid.org/0000-0003-3382-4754)
- Ilaria Tarricone (ORCID: https://orcid.org/0000-0002-5786-2520)
- Daniele La Barbera
- Luis Alameda (ORCID: https://orcid.org/0000-0002-8621-2885)
- Lucia Sideli
- Diego Quattrone (ORCID: https://orcid.org/0000-0002-6051-8309)
- Jim van Os (ORCID: https://orcid.org/0000-0002-7245-1586)
- Miquel Bernardo (ORCID: https://orcid.org/0000-0001-8748-6717)
- Giada Tripoli (ORCID: https://orcid.org/0000-0002-9257-6677)
- Julio Sanjuán
- Robin M. Murray (ORCID: https://orcid.org/0000-0003-0829-0519)
- Bart P. F. Rutten (ORCID: https://orcid.org/0000-0002-9834-6346)
- James B. Kirkbride (ORCID: https://orcid.org/0000-0003-3401-0824)
- Manuel Arrojo (ORCID: https://orcid.org/0000-0002-5609-7134)
- Andreı̈ Szöke (ORCID: https://orcid.org/0000-0003-2973-7981)
- Cristina Marta Del‐Ben (ORCID: https://orcid.org/0000-0003-0145-9975)
- Caterina La Cascia (ORCID: https://orcid.org/0000-0002-2078-0214)
- Eva Velthorst (ORCID: https://orcid.org/0000-0002-9240-2909)
- José Luis Santos (ORCID: https://orcid.org/0000-0003-2895-0369)
- Charlotte Gayer‐Anderson (ORCID: https://orcid.org/0000-0003-1636-889X)
- Peter Brian Jones (ORCID: https://orcid.org/0000-0002-0387-880X)
- Victoria Rodríguez (ORCID: https://orcid.org/0000-0003-0383-0846)
- Evangelos Vassos (ORCID: https://orcid.org/0000-0001-6363-0438)
- Monica Aas (ORCID: https://orcid.org/0000-0002-2338-5826)
- Jean-Paul Selten (ORCID: https://orcid.org/0000-0003-1591-3243)
- Andrea Tortelli (ORCID: https://orcid.org/0000-0003-0437-3018)
- Giulia Trotta (ORCID: https://orcid.org/0000-0003-2801-9718)
- Edoardo Spinazzola (ORCID: https://orcid.org/0000-0002-8070-0618)
- Antonio Lasalvia (ORCID: https://orcid.org/0000-0001-9963-6081)
- Paulo Rossi Menezes (ORCID: https://orcid.org/0000-0001-6330-3314)
- Hannah E. Jongsma (ORCID: https://orcid.org/0000-0001-6346-5903)
- Sarah Tosato (ORCID: https://orcid.org/0000-0002-9665-7538)
- Laura Ferraro (ORCID: https://orcid.org/0000-0002-1205-2356)
- Julio Bobes (ORCID: https://orcid.org/0000-0003-2187-4033)
- Pierre‐Michel Llorca (ORCID: https://orcid.org/0000-0001-7438-8990)
- Marta Di Forti (ORCID: https://orcid.org/0000-0002-3218-6925)
- Lieuwe de Haan
Institutions
- University of Verona (IT)
- Libera Università Maria SS. Assunta (IT)
- Inserm (FR)
- Universitat de València (ES)
- Universidad de Oviedo (ES)
- Universidade de São Paulo (BR)
- King's College London (GB)
- Utrecht University (NL)
- Université Paris-Est Créteil (FR)
- Université Clermont Auvergne (FR)
- University of Cambridge (GB)
- Maastricht University Medical Centre (NL)
- Paris-Est Sup (FR)
- Hospital General Universitario Gregorio Marañón (ES)
- University Medical Center Utrecht (NL)
- GGZ Noord-Holland-Noord (NL)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- Hospital Virgen de la Luz (ES)
- Complejo Hospitalario Universitario de Santiago (ES)
- Assistance Publique – Hôpitaux de Paris (FR)
- GGZ Rivierduinen (NL)
- Hôpitaux Universitaires Henri-Mondor (FR)
- Cambridgeshire and Peterborough NHS Foundation Trust (GB)
- Instituto de Investigación Sanitaria de Santiago (ES)
- Amsterdam University Medical Centers (NL)
- Hospital Universitario Virgen del Rocío (ES)
- Institut Mondor de Recherche Biomédicale (FR)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Instituto de Investigación Sanitaria del Principado de Asturias (ES)
- University College London (GB)
- Universitat de Barcelona (ES)
- University of Amsterdam (NL)
- University of Palermo (IT)
- University of Bologna (IT)
- University of Lausanne (CH)
Publication Details
- Journal
- Translational Psychiatry
- Published
- 2024-10-26
- DOI
- https://doi.org/10.1038/s41398-024-03149-7
- Citations
- 3
- Primary Topic
- Schizophrenia research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Medical Research Council