Methylation profile scores of environmental exposures and risk of relapse after a first episode of schizophrenia


Por: Segura, AG, Prohens, L, Julià, L, Amoretti, S, Ribero, M, Pino-Camacho, L, Cano-Escalera, G, Mane, A, Rodriguez-Jimenez, R, Roldan, A, Sarró, S, Ibañez, A, Usall, J, Lobo, A, Garcia-Rizo, C, Cuesta, MJ, Parellada, M, González-Pinto, A, Berrocoso, E, Mas, S, Rodriguez, N, Perez-Ramos, A, Salmeron, S, González-Peñas, J, Gurriarán, X, Farré, A, Pousa, E, Zorrilla, I, Mar-Barrutia, L, Trabsa, A, Martinez, L, Sánchez-Cabezudo, A, Jiménez-López, E, Pomarol-Clotet, E, Salvador, R, Butjosa, A, Elena, RA, Moreno-Izco, L, Torres, AMS, Saiz, J, León-Quismondo, L, Rivero, O, González-Blanco, L, De-la-Camára, C, Bernardo, M

Publicada: 1 may 2025 Ahead of Print: 1 feb 2025
Resumen:
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.

Filiaciones:
Segura, AG:
 Hosp Clin Barcelona, Bipolar & Depress Disorders Unit, Barcelona, Spain

Prohens, L:
 Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain

Julià, L:
 Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain

Amoretti, S:
 Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain

 Univ Barcelona UB, Hosp Clin Barcelona, Inst Neurociencies UBNeuro, Dept Med,Barcelona Clin Schizophrenia Unit, Barcelona, Spain

 Vall dHebron Res Inst VHIR, Grp Psychiat, Mental Hlth & Addict, Barcelona, Spain

 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Univ Navarra, Dept Psychiat, Pamplona, Spain

Ribero, M:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Univ Navarra, Dept Psychiat, Pamplona, Spain

 Navarra Inst Hlth Res IdiSNA, Pamplona, Spain

Pino-Camacho, L:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Complutense, Hosp Gen Univ Gregorio Maranon IiSGM, Dept Child & Adolescent Psychiat,Inst Psychiat & M, Sch Med, Madrid, Spain

Cano-Escalera, G:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Basque Country, Hosp Univ Alava, Dept Psychiat, BIOARABA, Vitoria, Spain

Mane, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp del Mar Medicar Res Inst IMIM, Barcelona, Spain

 Inst Recerca Sant Joan Parc Sanit St Joan Deu, Sant Boi Llobregat, Spain

Rodriguez-Jimenez, R:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Complutense Madrid UCM, Madrid, Spain

 Inst Invest Sanitaria Hosp 12 Octubre Imas12, Madrid, Spain

Roldan, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Santa Creu & Sant Pau, Pharm Dept, IIB Sant Pau, Barcelona 08025, Spain

Sarró, S:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 FIDMAG Germanes Hosp Res Fdn, Barcelona, Spain

Ibañez, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Alcala, Hosp Univ Ramo & Cajal, Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain

Usall, J:
 Inst Recerca Sant Joan Parc Sanit St Joan Deu, Sant Boi Llobregat, Spain

Lobo, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Zaragoza, Dept Med & Psychiat, Inst Invest Sanitaria Arago IIS Aragon, Zaragoza, Spain

Garcia-Rizo, C:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Cuesta, MJ:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Parellada, M:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Complutense, Hosp Gen Univ Gregorio Maranon IiSGM, Dept Child & Adolescent Psychiat,Inst Psychiat & M, Sch Med, Madrid, Spain

González-Pinto, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Berrocoso, E:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Cadiz, Dept Neurosci, Neuropsychopharmacol & Psychobiol Res Grp, Cdiz, Spain

Mas, S:
 Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain

 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Rodriguez, N:
 Univ Barcelona, Dept Clin Fdn, Pharmacol Unit, Barcelona, Spain

 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Perez-Ramos, A:
 Univ Barcelona UB, Hosp Clin Barcelona, Inst Neurociencies UBNeuro, Dept Med,Barcelona Clin Schizophrenia Unit, Barcelona, Spain

Salmeron, S:
 Univ Barcelona UB, Hosp Clin Barcelona, Inst Neurociencies UBNeuro, Dept Med,Barcelona Clin Schizophrenia Unit, Barcelona, Spain

González-Peñas, J:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Complutense, Hosp Gen Univ Gregorio Maranon IiSGM, Dept Child & Adolescent Psychiat,Inst Psychiat & M, Sch Med, Madrid, Spain

Gurriarán, X:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Complutense, Hosp Gen Univ Gregorio Maranon IiSGM, Dept Child & Adolescent Psychiat,Inst Psychiat & M, Sch Med, Madrid, Spain

Farré, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Santa Creu & Sant Pau, Pharm Dept, IIB Sant Pau, Barcelona 08025, Spain

Pousa, E:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Santa Creu & Sant Pau, Pharm Dept, IIB Sant Pau, Barcelona 08025, Spain

Zorrilla, I:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Mar-Barrutia, L:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Trabsa, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Martinez, L:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Sánchez-Cabezudo, A:
 Inst Invest Sanitaria Hosp 12 Octubre Imas12, Madrid, Spain

Jiménez-López, E:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Univ Puerta Mar, Inst Invest & Innovacio Biom, INiBICA, Cadiz, Spain

Pomarol-Clotet, E:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 FIDMAG Germanes Hosp Res Fdn, Barcelona, Spain

Salvador, R:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 FIDMAG Germanes Hosp Res Fdn, Barcelona, Spain

Butjosa, A:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Inst Recerca Sant Joan Parc Sanit St Joan Deu, Sant Boi Llobregat, Spain

Elena, RA:
 Inst Recerca Sant Joan Parc Sanit St Joan Deu, Sant Boi Llobregat, Spain

Moreno-Izco, L:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Torres, AMS:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

Saiz, J:
 Univ Alcala, Hosp Univ Ramo & Cajal, Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain

León-Quismondo, L:
 Univ Alcala, Hosp Univ Ramo & Cajal, Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain

Rivero, O:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Castilla La Mancha, Hlth & Social Res Ctr, Cuenca, Spain

 Fdn Invest Hosp Clin Valencia, INCLIVA Biomed Res Inst, Valencia, Spain

González-Blanco, L:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Univ Oviedo, Dept Psychiat, Mental Hlth Serv Principal Asturias SESPA, Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain

De-la-Camára, C:
 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Clin Univ Inst Invest Sanitaria IIS Aragon, Zaragoza, Spain

Bernardo, M:
 Univ Barcelona UB, Hosp Clin Barcelona, Inst Neurociencies UBNeuro, Dept Med,Barcelona Clin Schizophrenia Unit, Barcelona, Spain

 Inst Salud Carlos III, Ctr Invest Biome Red Salud Mental CIBERSAM, Madrid, Spain

 Hosp Clin Barcelona, Neurosci Inst, Barcelona Clin Schizophrenia Unit BCSU, Barcelona, Spain

 Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain

 Ctr Invest Biomed salud Mental CIBERSAM, Barcelona, Spain

 Univ Barcelona, Dept Med, Barcelona, Spain
ISSN: 0924977X





EUROPEAN NEUROPSYCHOPHARMACOLOGY
Editorial
ELSEVIER, RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 94 Número:
Páginas: 4-15
WOS Id: 001429224500001
ID de PubMed: 39956014
imagen Green Submitted, hybrid

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