Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge (“GrimAge residuals”), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness. Data from two independent trauma-exposed military cohorts (n = 647 [62.9% male, Mage = 52], n = 434 [90% male, Mage = 32]) were evaluated using linear regression models to test associations between GrimAge residuals, psychopathology, and health correlates. Externalizing psychopathology significantly predicted GrimAge residuals in both cohorts (ps < 0.028). PTSD predicted GrimAge residuals in the younger (p = 0.001) but not the older cohort. GrimAge residuals were associated with several neurobiological variables available in the younger cohort, including cognitive disinhibition (padj = 0.021), poorer memory recall (padj = 0.023), cardiometabolic pathology (padj < 0.001), oxidative stress (padj = 0.003), astrocyte damage (padj = 0.021), inflammation (C-reactive protein: padj < 0.001; IL-6: padj < 0.001), and immune functioning (padj < 0.001). A subset of inflammatory and neuropathology analytes were available in the older cohort and showed associations with GrimAge residuals (IL-6: padj < 0.001; TNF-α: padj < 0.001). GrimAge residuals were also associated with reduced cortical thickness in right lateral orbitofrontal cortex (padj = 0.018) and left fusiform gyrus (padj = 0.030), which are related to emotion regulation and facial recognition, respectively. Psychopathology may be a common risk factor for elevated mortality risk. GrimAge could help identify those at risk for adverse health outcomes and allow for early disease identification and treatment.
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Original Publication Citation
Hawn, S. E., Zhao, X., Sullivan, D. R., Logue, M., Fein-Schaffer, D., Milberg, W., McGlinchey, R., Miller, M. W., & Wolf, E. J. (2022). For whom the bell tolls: Psychopathological and neurobiological correlates of a DNA methylation index of time-to-death. Translational Psychiatry, 12(1), 1-10, Article 406. https://doi.org/10.1038/s41398-022-02164-w
Hawn, Sage E.; Zhao, Xiang; Sullivan, Danielle R.; Logue, Mark; Fein-Schaffer, Dana; Milberg, William; McGlinchey, Regina; Miller, Mark W.; and Wolf, Erika J., "For Whom the Bell Tolls: Psychopathological and Neurobiological Correlates of the DNA Methylation Index of Time-To-Death" (2022). Psychology Faculty Publications. 139.