DNA methylation patterns and epigenetic aging associated with suicide attempts in bipolar disorder.
Por:
Mitjans M, Acosta-Díez M, Giménez-Palomo A, Zafrilla-López M, Saiz PA, Barrot-Feixat C, Jiménez E, Papiol S, Defez J, Xifró-Collsamata A, Ortega-Sánchez M, Ruiz V, Gavín P, García-Portilla MP, González-Blanco L, Bobes J, Schulze TG, Vieta E, Benabarre A and Arias B
Publicada:
1 ene 2026
Ahead of Print:
24 ago 2025
Resumen:
BACKGROUND: Suicidal thoughts and behaviors (STBs) are a public health issue highly prevalent in bipolar disorder (BD). Multiple factors contribute to STBs, and new evidence highlights the significant role of epigenetics, specifically DNA methylation (DNAm). Additionally, recent studies found accelerated epigenetic aging (EA) in both BD and STBs. This study aimed to detect epigenetic risk factors for STBs, particularly for suicide attempts (SAs), comparing DNAm patterns and EA between BD patients with (BD/SA) and without (BD/non-SA) a history of SAs. Moreover, EA was calculated to explore age acceleration (AgeAccel) in the BD/SA group. METHODS: Genome-wide DNAm patterns of blood samples from 46 BD/SA and 32 BD/non-SA were assessed using Infinium HumanMethylationEPIC v1.0 BeadChip (Illumina). Differentially methylated positions (DMPs) and regions (DMRs) were compared between groups. Gene network analysis was performed using genes mapped to DMPs and DMRs. Lastly, EA from different epigenetic clocks was estimated and compared between groups. RESULTS: We identified 18 DMPs and 2 DMRs (adjusted p-value < 0.05) between BD/SA and BD/non-SA. Among the 18 genes mapped to DMPs and DMRs, the MAD1L1 gene was previously associated with severe SAs. Trends of AgeAccel using the GrimAge and GrimAge2 clocks (p-value = 0.022; adjusted p-value > 0.05) were found in BD/SA. LIMITATIONS: Relatively small sample size, cross-sectional design, and use of peripheral blood. CONCLUSIONS: Our findings highlight the importance of considering epigenetic markers when studying SAs in mental disorders. These results may contribute to a better understanding of the biological basis of SAs in BD, which could ultimately help identify at-risk individuals for SAs.
Filiaciones:
:
Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
Biomedicine Institute of the University of Barcelona (IBUB), Spain
Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Acosta-Díez M:
Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
Giménez-Palomo A:
Bipolar and Depressive Disorders Unit, Psychiatry and Psychology Service, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
Zafrilla-López M:
Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
Saiz PA:
Department of Psychiatry, School of Medicine, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Barrot-Feixat C:
Forensic Genetic Laboratory, University of Barcelona, Catalonia, Spain
Jiménez E:
Bipolar and Depressive Disorders Unit, Psychiatry and Psychology Service, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
Institut de Neurociències, Department of Medicine, University of Barcelona, Barcelona, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Papiol S:
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany
Max Planck Institute of Psychiatry, Munich, Germany
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Defez J:
Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC), Ciutat de la Justícia, Barcelona, Spain
Xifró-Collsamata A:
Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC), Ciutat de la Justícia, Barcelona, Spain
Ortega-Sánchez M:
Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC), Ciutat de la Justícia, Barcelona, Spain
Ruiz V:
Bipolar and Depressive Disorders Unit, Psychiatry and Psychology Service, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
Gavín P:
Department of Psychiatry, School of Medicine, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
García-Portilla MP:
Department of Psychiatry, School of Medicine, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
González-Blanco L:
Department of Psychiatry, School of Medicine, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Bobes J:
Department of Psychiatry, School of Medicine, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Schulze TG:
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Vieta E:
Bipolar and Depressive Disorders Unit, Psychiatry and Psychology Service, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
Institut de Neurociències, Department of Medicine, University of Barcelona, Barcelona, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Benabarre A:
Bipolar and Depressive Disorders Unit, Psychiatry and Psychology Service, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
Institut de Neurociències, Department of Medicine, University of Barcelona, Barcelona, Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
Arias B:
Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
Biomedicine Institute of the University of Barcelona (IBUB), Spain
CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
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