Renin-angiotensin-aldosterone system activity in a female trauma-exposed sample

Authors

Sinead M. Sinnott, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: smsinnott@mgh.harvard.edu.
Robyn A. Ellis, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA.
Annmarie Khawand, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Paul J. Marvar, George Washington University, WA DC, USA.
Murray B. Stein, Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA.
Kerry J. Ressler, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA.
Jeff C. Huffman, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Antonia V. Seligowski, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Document Type

Journal Article

Publication Date

6-1-2025

Journal

Psychiatry research

Volume

351

DOI

10.1016/j.psychres.2025.116573

Keywords

Estrogen; Posttraumatic stress; Psychophysiology

Abstract

The renin-angiotensin-aldosterone system (RAAS) has been implicated in posttraumatic stress disorder (PTSD) and identified as a prominent neurohormonal system potentially linking PTSD and cardiovascular disease (CVD) and potentially contributing to sex-differences in PTSD. Low estradiol has been implicated as a risk factor for PTSD among women and may down-regulate activity of the RAAS. We aimed to replicate previous work showing higher RAAS activity among those with PTSD. We aimed to characterize associations between RAAS activity, psychophysiological arousal, and estradiol among trauma-exposed females. Cardiovascular measures included heart rate (HR), high frequency HR variability (HF-HRV), and blood pressure (BP) at rest, as well as HR, HF-HRV, and fear potentiated startle (FPS) during fear conditioning. No significant effects of PTSD (n = 37 with PTSD) were found for renin, aldosterone, or the aldosterone-to-renin ratio (ARR). Higher renin and aldosterone levels were associated with higher HR (r's = 0.31-0.41, p's < 0.05); higher renin was associated with larger magnitude FPS (r = 0.49, p = .015); higher ARRs were associated with lower HF-HRV (r = -0.54, p = .003). Differences were found by estradiol level, as higher renin and aldosterone levels were associated with higher HR among those with low estradiol (r's = 0.40-0.63, p's < 0.05). While our findings showed associations between RAAS and previously indicated psychophysiological markers of PTSD, we did not replicate existing work showing a direct relationship between RAAS activity and PTSD. Overall, our results also support the potential protective role of estradiol on the association between the RAAS and cardiovascular function.

APA Citation

Sinnott, Sinead M.; Ellis, Robyn A.; Khawand, Annmarie; Marvar, Paul J.; Stein, Murray B.; Ressler, Kerry J.; Huffman, Jeff C.; and Seligowski, Antonia V., "Renin-angiotensin-aldosterone system activity in a female trauma-exposed sample" (2025). GW Authored Works. Paper 7488.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7488

Department

Pharmacology and Physiology