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
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