PTSD and epigenetic aging: a longitudinal meta-analysis

Xiang Zhao; Seyma Katrinli; Beth M. McCormick; Mark W. Miller; Nicole R. Nugent; Agaz H. Wani; Anthony S. Zannas; Allison E. Aiello; Dewleen G. Baker; Marco P. Boks; Chia-Yen Chen; Catherine B. Fortier; Joel Gelernter; Elbert Geuze; Karestan C. Koenen; Sarah D. Linnstaedt; Jurjen J. Luykx; Adam X. Maihofer; Samuel A. McLean; William P. Milberg; Andrew Ratanatharathorn; Kerry J. Ressler; Victoria B. Risbrough; Bart P. F. Rutten; Jordan W. Smoller; Murray B. Stein; Robert J. Ursano; Eric Vermetten; Christiaan H. Vinkers; Erin B. Ware; Derek E. Wildman; Ying Zhao; Mark W. Logue; Caroline M. Nievergelt; Alicia K. Smith; Monica Uddin; Erika J. Wolf; PGC PTSD Epigenetics Workgroup

doi:10.1017/S0033291725000558

PTSD and epigenetic aging: a longitudinal meta-analysis

Xiang Zhao, Seyma Katrinli, Beth M. McCormick, Mark W. Miller, Nicole R. Nugent, Agaz H. Wani, Anthony S. Zannas, Allison E. Aiello, Dewleen G. Baker, Marco P. Boks, Chia-Yen Chen, Catherine B. Fortier, Joel Gelernter, Elbert Geuze, Karestan C. Koenen, Sarah D. Linnstaedt, Jurjen J. Luykx, Adam X. Maihofer, Samuel A. McLean, William P. MilbergAndrew Ratanatharathorn, Kerry J. Ressler, Victoria B. Risbrough, Bart P. F. Rutten, Jordan W. Smoller, Murray B. Stein, Robert J. Ursano, Eric Vermetten, Christiaan H. Vinkers, Erin B. Ware, Derek E. Wildman, Ying Zhao, Mark W. Logue, Caroline M. Nievergelt, Alicia K. Smith, Monica Uddin, Erika J. Wolf^*, PGC PTSD Epigenetics Workgroup

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta beta = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta beta = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Original language	English
Article number	e142
Number of pages	13
Journal	Psychological Medicine
Volume	55
DOIs	https://doi.org/10.1017/S0033291725000558
Publication status	Published - 14 May 2025

Keywords

accelerated aging
DNA methylation
meta-analysis
longitudinal
PTSD
POSTTRAUMATIC-STRESS-DISORDER
DNA METHYLATION AGE
TELOMERE LENGTH
TRAUMATIC STRESS
WIDE ASSOCIATION
ASSESS RISK
RESILIENCE
GENES
ARMY

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Zhao, X., Katrinli, S., McCormick, B. M., Miller, M. W., Nugent, N. R., Wani, A. H., Zannas, A. S., Aiello, A. E., Baker, D. G., Boks, M. P., Chen, C.-Y., Fortier, C. B., Gelernter, J., Geuze, E., Koenen, K. C., Linnstaedt, S. D., Luykx, J. J., Maihofer, A. X., McLean, S. A., ... PGC PTSD Epigenetics Workgroup (2025). PTSD and epigenetic aging: a longitudinal meta-analysis. Psychological Medicine, 55, Article e142. https://doi.org/10.1017/S0033291725000558

@article{97c3bbb1a3de47608b59d14160e65a01,

title = "PTSD and epigenetic aging: a longitudinal meta-analysis",

abstract = "Background Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta beta = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta beta = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.",

keywords = "accelerated aging, DNA methylation, meta-analysis, longitudinal, PTSD, POSTTRAUMATIC-STRESS-DISORDER, DNA METHYLATION AGE, TELOMERE LENGTH, TRAUMATIC STRESS, WIDE ASSOCIATION, ASSESS RISK, RESILIENCE, GENES, ARMY",

author = "Xiang Zhao and Seyma Katrinli and McCormick, \{Beth M.\} and Miller, \{Mark W.\} and Nugent, \{Nicole R.\} and Wani, \{Agaz H.\} and Zannas, \{Anthony S.\} and Aiello, \{Allison E.\} and Baker, \{Dewleen G.\} and Boks, \{Marco P.\} and Chia-Yen Chen and Fortier, \{Catherine B.\} and Joel Gelernter and Elbert Geuze and Koenen, \{Karestan C.\} and Linnstaedt, \{Sarah D.\} and Luykx, \{Jurjen J.\} and Maihofer, \{Adam X.\} and McLean, \{Samuel A.\} and Milberg, \{William P.\} and Andrew Ratanatharathorn and Ressler, \{Kerry J.\} and Risbrough, \{Victoria B.\} and Rutten, \{Bart P. F.\} and Smoller, \{Jordan W.\} and Stein, \{Murray B.\} and Ursano, \{Robert J.\} and Eric Vermetten and Vinkers, \{Christiaan H.\} and Ware, \{Erin B.\} and Wildman, \{Derek E.\} and Ying Zhao and Logue, \{Mark W.\} and Nievergelt, \{Caroline M.\} and Smith, \{Alicia K.\} and Monica Uddin and Wolf, \{Erika J.\} and \{PGC PTSD Epigenetics Workgroup\}",

year = "2025",

month = may,

day = "14",

doi = "10.1017/S0033291725000558",

language = "English",

volume = "55",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

Zhao, X, Katrinli, S, McCormick, BM, Miller, MW, Nugent, NR, Wani, AH, Zannas, AS, Aiello, AE, Baker, DG, Boks, MP, Chen, C-Y, Fortier, CB, Gelernter, J, Geuze, E, Koenen, KC, Linnstaedt, SD, Luykx, JJ, Maihofer, AX, McLean, SA, Milberg, WP, Ratanatharathorn, A, Ressler, KJ, Risbrough, VB, Rutten, BPF, Smoller, JW, Stein, MB, Ursano, RJ, Vermetten, E, Vinkers, CH, Ware, EB, Wildman, DE, Zhao, Y, Logue, MW, Nievergelt, CM, Smith, AK, Uddin, M, Wolf, EJ & PGC PTSD Epigenetics Workgroup 2025, 'PTSD and epigenetic aging: a longitudinal meta-analysis', Psychological Medicine, vol. 55, e142. https://doi.org/10.1017/S0033291725000558

TY - JOUR

T1 - PTSD and epigenetic aging

T2 - a longitudinal meta-analysis

AU - Zhao, Xiang

AU - Katrinli, Seyma

AU - McCormick, Beth M.

AU - Miller, Mark W.

AU - Nugent, Nicole R.

AU - Wani, Agaz H.

AU - Zannas, Anthony S.

AU - Aiello, Allison E.

AU - Baker, Dewleen G.

AU - Boks, Marco P.

AU - Chen, Chia-Yen

AU - Fortier, Catherine B.

AU - Gelernter, Joel

AU - Geuze, Elbert

AU - Koenen, Karestan C.

AU - Linnstaedt, Sarah D.

AU - Luykx, Jurjen J.

AU - Maihofer, Adam X.

AU - McLean, Samuel A.

AU - Milberg, William P.

AU - Ratanatharathorn, Andrew

AU - Ressler, Kerry J.

AU - Risbrough, Victoria B.

AU - Rutten, Bart P. F.

AU - Smoller, Jordan W.

AU - Stein, Murray B.

AU - Ursano, Robert J.

AU - Vermetten, Eric

AU - Vinkers, Christiaan H.

AU - Ware, Erin B.

AU - Wildman, Derek E.

AU - Zhao, Ying

AU - Logue, Mark W.

AU - Nievergelt, Caroline M.

AU - Smith, Alicia K.

AU - Uddin, Monica

AU - Wolf, Erika J.

AU - PGC PTSD Epigenetics Workgroup

PY - 2025/5/14

Y1 - 2025/5/14

N2 - Background Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta beta = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta beta = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

AB - Background Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta beta = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta beta = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

KW - accelerated aging

KW - DNA methylation

KW - meta-analysis

KW - longitudinal

KW - PTSD

KW - POSTTRAUMATIC-STRESS-DISORDER

KW - DNA METHYLATION AGE

KW - TELOMERE LENGTH

KW - TRAUMATIC STRESS

KW - WIDE ASSOCIATION

KW - ASSESS RISK

KW - RESILIENCE

KW - GENES

KW - ARMY

U2 - 10.1017/S0033291725000558

DO - 10.1017/S0033291725000558

M3 - Article

SN - 0033-2917

VL - 55

JO - Psychological Medicine

JF - Psychological Medicine

M1 - e142

ER -

PTSD and epigenetic aging: a longitudinal meta-analysis

Abstract

Keywords

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