Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes

Laura Campbell-Sills; Xiaoying Sun; Karmel W Choi; Feng He; Robert J Ursano; Ronald C Kessler; Daniel F Levey; Jordan W Smoller; Joel Gelernter; Sonia Jain; Murray B Stein

doi:10.1017/S0033291721000428

Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes

Psychol Med. 2021 May 5;52(15):1-9. doi: 10.1017/S0033291721000428. Online ahead of print.

Authors

Laura Campbell-Sills¹, Xiaoying Sun², Karmel W Choi^{3

4

5

6}, Feng He², Robert J Ursano⁷, Ronald C Kessler⁸, Daniel F Levey^{9

10}, Jordan W Smoller^{3

4

5

6}, Joel Gelernter^{9

10}, Sonia Jain², Murray B Stein^{1

11

12}

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
² Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
³ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA.
⁷ Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁸ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
⁹ Department of Psychiatry, Genetics, and Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
¹⁰ Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
¹¹ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
¹² Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Abstract

Background: Definition of disorder subtypes may facilitate precision treatment for posttraumatic stress disorder (PTSD). We aimed to identify PTSD subtypes and evaluate their associations with genetic risk factors, types of stress exposures, comorbidity, and course of PTSD.

Methods: Data came from a prospective study of three U.S. Army Brigade Combat Teams that deployed to Afghanistan in 2012. Soldiers with probable PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ≥31) at three months postdeployment comprised the sample (N = 423) for latent profile analysis using Gaussian mixture modeling and PTSD symptom ratings as indicators. PTSD profiles were compared on polygenic risk scores (derived from external genomewide association study summary statistics), experiences during deployment, comorbidity at three months postdeployment, and persistence of PTSD at nine months postdeployment.

Results: Latent profile analysis revealed profiles characterized by prominent intrusions, avoidance, and hyperarousal (threat-reactivity profile; n = 129), anhedonia and negative affect (dysphoric profile; n = 195), and high levels of all PTSD symptoms (high-symptom profile; n = 99). The threat-reactivity profile had the most combat exposure and the least comorbidity. The dysphoric profile had the highest polygenic risk for major depression, and more personal life stress and co-occurring major depression than the threat-reactivity profile. The high-symptom profile had the highest rates of concurrent mental disorders and persistence of PTSD.

Conclusions: Genetic and trauma-related factors likely contribute to PTSD heterogeneity, which can be parsed into subtypes that differ in symptom expression, comorbidity, and course. Future studies should evaluate whether PTSD typology modifies treatment response and should clarify distinctions between the dysphoric profile and depressive disorders.

Keywords: Posttraumatic stress disorder; latent class analysis; military personnel; polygenic risk scores; typology.