Journal article
Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder
Neuropsychopharmacology (New York, N.Y.), Vol.48(6), pp.954-962
05/2023
DOI: 10.1038/s41386-023-01557-9
PMCID: PMC10156727
PMID: 36878995
Abstract
Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.
Details
- Title: Subtitle
- Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder
- Creators
- Camila N C Lima - The University of Texas Health Science Center at HoustonEmese H C Kovács - University of IowaSalahudeen Mirza - The University of Texas Health Science Center at HoustonAlexandra Del Favero-Campbell - The University of Texas Health Science Center at HoustonAlexandre Paim Diaz - University of Rochester Medical CenterJoao Quevedo - The University of Texas Health Science Center at HoustonBenney M R Argue - University of IowaJenny Gringer Richards - University of Iowa, RadiologyAislinn Williams - University of Iowa, Iowa Neuroscience InstituteJohn A Wemmie - University of Iowa, Iowa Neuroscience InstituteVincent A Magnotta - University of Iowa, Iowa Neuroscience InstituteJess G Fiedorowicz - University of Iowa, PsychiatryJair C SoaresMarie E Gaine - University of Iowa, Iowa Neuroscience InstituteGabriel R Fries - The University of Texas Health Science Center at Houston
- Resource Type
- Journal article
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), Vol.48(6), pp.954-962
- DOI
- 10.1038/s41386-023-01557-9
- PMID
- 36878995
- PMCID
- PMC10156727
- NLM abbreviation
- Neuropsychopharmacology
- eISSN
- 1740-634X
- Grant note
- K01MH121580 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH125838 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) NARSAD YI / Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) YIG-0-066-20 / American Foundation for Suicide Prevention (AFSP)
- Language
- English
- Electronic publication date
- 03/06/2023
- Date published
- 05/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Psychiatry; Epidemiology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neurosurgery
- Record Identifier
- 9984375458902771
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