Methylation profile scores of environmental exposures and risk of relapse after a first episode of schizophrenia
Both genetic and environmental factors have been found to play a significant role in psychosis relapse, either independently or through their synergistic interaction. Recently, DNA methylation (DNAm) has been proposed through the calculation of methylation profile scores (MPS). The aim of the present study is to evaluate the association of MPS as a surrogate marker of the biological impact of early stressful life events (including stressful intrauterine conditions and obstetric complications, childhood adversity and toxic habits), with the risk of schizophrenia (SCZ) relapse. 91 participants from a cohort of first-episode schizophrenia (FES) patients with less than five years of evolution were classified as non-relapse (patients who had not experienced a relapse after 3 years of enrollment) or relapse (patients who relapsed during the 3-year follow-up). As inclusion criteria, patients fulfilled Andreasen's criteria of symptomatic remission. Genome-wide DNA methylation (DNAm) was profiled and fourteen MPS reflecting environmental exposure were constructed including both early stressful life events (including stressful intrauterine conditions and delivery issues, childhood adversity) and toxic habits. Increased levels of MPS reflecting gestational diabetes (p = 0.009), hypertensive disorders during pregnancy (p = 0.004), pre-eclampsia (p = 0.049), early preterm birth (p = 0.030), childhood adversity abuse (p = 0.021) and all childhood adversity (p = 0.030) were significantly associated with an increased risk of relapse. Our study suggests that changes in specific methylation patterns may represent one of the biological mechanisms linking early stressful life events to an increased risk of relapse.
Authors
- Edith Pomarol‐Clotet (ORCID: https://orcid.org/0000-0002-8159-8563)
- Ángela Ibáñez (ORCID: https://orcid.org/0000-0003-2751-0150)
- L. Prohens (ORCID: https://orcid.org/0000-0003-1039-8027)
- Clemente García‐Rizo (ORCID: https://orcid.org/0000-0002-4855-1608)
- Estela Jiménez‐López (ORCID: https://orcid.org/0000-0001-8553-7701)
- Rubio-Abadal Elena (ORCID: https://orcid.org/0000-0003-2538-842X)
- Lorea Mar‐Barrutia (ORCID: https://orcid.org/0000-0002-7531-0316)
- Salvador Sarró (ORCID: https://orcid.org/0000-0003-1835-2189)
- Laura Julià (ORCID: https://orcid.org/0000-0001-5161-2267)
- Raymond Salvador (ORCID: https://orcid.org/0000-0001-5557-1562)
- Anna Mané (ORCID: https://orcid.org/0000-0003-2127-349X)
- Roberto Rodríguez–Jiménez (ORCID: https://orcid.org/0000-0003-2251-7249)
- Javier González‐Peñas (ORCID: https://orcid.org/0000-0002-3850-3012)
- Miquel Bernardo (ORCID: https://orcid.org/0000-0001-8748-6717)
- Mara Parellada (ORCID: https://orcid.org/0000-0001-7977-3601)
- Lucía Moreno-Izco
- Sergi Mas (ORCID: https://orcid.org/0000-0003-3336-6298)
- Ana M. Sánchez-Torres (ORCID: https://orcid.org/0000-0002-9505-2406)
- Leticia González-Blanco
- Alexandra Roldán (ORCID: https://orcid.org/0000-0001-9905-3943)
- Esther Pousa (ORCID: https://orcid.org/0000-0003-4423-6739)
- Sílvia Amoretti (ORCID: https://orcid.org/0000-0001-6017-2734)
- Anna Butjosa (ORCID: https://orcid.org/0000-0001-5317-9508)
- S. Salmerón (ORCID: https://orcid.org/0000-0002-0212-4491)
- Àlex G. Segura (ORCID: https://orcid.org/0000-0002-9398-2183)
- Olga Rivero (ORCID: https://orcid.org/0000-0002-2664-4053)
- Amira Trabsa (ORCID: https://orcid.org/0000-0002-8669-0676)
- Esther Berrocoso (ORCID: https://orcid.org/0000-0003-0208-7472)
- Leticia León-Quismondo (ORCID: https://orcid.org/0000-0001-5082-8381)
- Concepción De‐la‐Cámara
- Ángeles Sánchez-Cabezudo
- Xaquín Gurriarán
- António Lobo (ORCID: https://orcid.org/0000-0002-9098-655X)
- Anaid Pérez‐Ramos (ORCID: https://orcid.org/0000-0001-6515-2425)
- Eric P. Zorrilla (ORCID: https://orcid.org/0000-0001-6444-8208)
- Natalia Rodríguez
- M.L. Ribero
- Manuel J Cuesta
- Laura Martínez (ORCID: https://orcid.org/0000-0001-5033-7312)
- Ana González-Pinto
- Judith Usall
- Adriana Farré (ORCID: https://orcid.org/0000-0001-6396-1771)
- Jerónimo Saíz
- Laura Pino-Camacho
- Guillermo Cano-Escalera
Institutions
- Instituto de Salud Pública de Navarra (ES)
- Research Institute Hospital 12 de Octubre (ES)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Navarre Institute of Health Research (ES)
- Hospital Clínic de Barcelona (ES)
- Biomedical Research and Innovation Institute of Cadiz (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Parc Sanitari Sant Joan de Déu (ES)
- Hospital Mare de Déu de la Mercè (ES)
- Instituto de Investigación Sanitaria Aragón (ES)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- INCLIVA Health Research Institute (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Instituto de Investigación Sanitaria del Principado de Asturias (ES)
- Institut de Recerca Sant Joan de Déu
- Universitat de Barcelona (ES)
Publication Details
- Journal
- European Neuropsychopharmacology
- Published
- 2025-02-15
- DOI
- https://doi.org/10.1016/j.euroneuro.2025.02.003
- Citations
- 2
- Primary Topic
- Schizophrenia research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.94
Funders
- Universitat de Barcelona