You are currently viewing Methylation of the AIM2 Gene: An Epigenetic Mediator of PTSD-Related Inflammation and Neuropathology Plasma Biomarkers

Methylation of the AIM2 Gene: An Epigenetic Mediator of PTSD-Related Inflammation and Neuropathology Plasma Biomarkers

Hawn, S. E., Neale, Z., Wolf, E. J., Zhao, X., Pierce, M., Fein Schaffer, D., … & Miller, M. W. (2022). Methylation of the AIM2 Gene: An Epigenetic Mediator of PTSD Related Inflammation and Neuropathology Plasma Biomarkers. Depression and Anxiety.

Abstract

Background

Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood.

Method

We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology.

Results

Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018–0.023, all p-values adjusted for multiple testing [padj] < 0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß = −0.018, padj = 0.02) via AIM2methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = −0.018, padj = 0.04) controlling for baseline IL-10.

Conclusions

Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.

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