. 2024 Aug;54(11):2876-2886.

doi: 10.1017/S0033291724000941. Epub 2024 May 22.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study

Stephanie Haering^{1

2}, Antonia V Seligowski³, Sarah D Linnstaedt⁴, Vasiliki Michopoulos⁵, Stacey L House⁶, Francesca L Beaudoin^{7

8}, Xinming An⁴, Thomas C Neylan⁹, Gari D Clifford^{10

11}, Laura T Germine^{12

13

14}, Scott L Rauch^{3

12

14}, John P Haran¹⁵, Alan B Storrow¹⁶, Christopher Lewandowski¹⁷, Paul I Musey Jr¹⁸, Phyllis L Hendry¹⁹, Sophia Sheikh¹⁹, Christopher W Jones²⁰, Brittany E Punches^{21

22}, Robert A Swor²³, Nina T Gentile²⁴, Lauren A Hudak²⁵, Jose L Pascual^{26

27}, Mark J Seamon^{27

28}, Claire Pearson²⁹, David A Peak³⁰, Roland C Merchant³¹, Robert M Domeier³², Niels K Rathlev³³, Brian J O'Neil³⁴, Leon D Sanchez^{31

35}, Steven E Bruce³⁶, Steven E Harte^{37

38}, Samuel A McLean^{39

40}, Ronald C Kessler⁴¹, Karestan C Koenen⁴², Jennifer S Stevens⁵, Abigail Powers⁵

Affiliations

¹ Department of Education and Psychology, Clinical Psychological Intervention, Freie Universität Berlin, Berlin, Germany.
² Charité Center for Health and Human Sciences, Gender in Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
⁴ Department of Anesthesiology, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁷ Department of Epidemiology, Brown University, Providence, RI, USA.
⁸ Department of Emergency Medicine, Brown University, Providence, RI, USA.
⁹ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹¹ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹² Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹³ The Many Brains Project, Belmont, MA, USA.
¹⁴ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁶ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁸ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁹ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
²⁰ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²¹ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²² Ohio State University College of Nursing, Columbus, OH, USA.
²³ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
²⁴ Department of Emergency Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
²⁵ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²⁶ Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁹ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
³⁰ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³¹ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³² Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
³³ Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
³⁴ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³⁵ Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³⁶ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁷ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁸ Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁹ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Department of Psychiatry, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴¹ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
⁴² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

PMID: 38775091
PMCID: PMC11736691
DOI: 10.1017/S0033291724000941

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study

Stephanie Haering et al. Psychol Med. 2024 Aug.

. 2024 Aug;54(11):2876-2886.

doi: 10.1017/S0033291724000941. Epub 2024 May 22.

Authors

Affiliations

¹ Department of Education and Psychology, Clinical Psychological Intervention, Freie Universität Berlin, Berlin, Germany.
² Charité Center for Health and Human Sciences, Gender in Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
⁴ Department of Anesthesiology, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁷ Department of Epidemiology, Brown University, Providence, RI, USA.
⁸ Department of Emergency Medicine, Brown University, Providence, RI, USA.
⁹ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹¹ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹² Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹³ The Many Brains Project, Belmont, MA, USA.
¹⁴ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁶ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁸ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁹ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
²⁰ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²¹ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²² Ohio State University College of Nursing, Columbus, OH, USA.
²³ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
²⁴ Department of Emergency Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
²⁵ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²⁶ Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁹ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
³⁰ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³¹ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³² Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
³³ Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
³⁴ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³⁵ Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³⁶ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁷ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁸ Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁹ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Department of Psychiatry, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴¹ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
⁴² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

PMID: 38775091
PMCID: PMC11736691
DOI: 10.1017/S0033291724000941

Abstract

Background: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

Methods: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Results: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Conclusions: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Keywords: PTSD; risk factors; sex differences; trauma.

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Conflict of interest statement

-Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals.

- In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation, and Samsung Research. Dr Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work.

- Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Dr. Germine’s family also has equity in Intelerad Medical Systems, Inc.

-Dr. Rauch reports grants from NIH during the conduct of the study; personal fees from SOBP (Society of Biological Psychiatry) paid role as secretary, other from Oxford University Press royalties, other from APP (American Psychiatric Publishing Inc.) royalties, other from VA (Veterans Administration) per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers).

- Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex.

- Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Indiana University and Memorial Sloan Kettering Cancer Center.

- Dr. McLean served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations.

- In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences.

- Dr. Koenen’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, the Anonymous Foundation, and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality, and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press.

Figures

**Figure 1. Sex-disaggregated associations with 3-month PTSD severity**
The forest plot depicts the univariable associations of each predictor with PTSD severity at 3-months post-trauma disaggregated by sex. The correlations are depicted in blue for men and in red for women. The equality of coefficients was tested using Fisher’s z tests.

**Figure 2. Subgroup analysis for female sex as a predictor of PTSD severity at 3 months**
The forest plot depicts the parameter estimate and 95% confidence interval associated with female sex (versus male sex as the reference group) within the subgroup specified in a multivariable regression model, including an interaction term between the subgroup variable and sex, adjusting for demographics, baseline mental health and lifetime sexual assault. Continuous variables were standardized, categorical variables were dummy coded.

**Figure 3. Interaction effects of sex and a) pre-traumatic anxiety and b) dissociation at week two post-trauma.**
The scatter plots depict the interaction effect of sex and a) pre-traumatic anxiety symptoms as well as b) dissociative symptoms at two weeks post-trauma, controlling for demographics, baseline mental health, and lifetime sexual assault. All variables were standardized to an overall sample mean of 0 and a standard deviation of 1.

See this image and copyright information in PMC

References

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Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study

Affiliations

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials