Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome

Overview

Journal medRxiv

Date 2023 Sep 11

PMID 37693435

Authors

Emily M Hicks

Maria Niarchou

Slavina Goleva

Dia Kabir

Julia Ciarcia

Jordan W Smoller

Lea K Davis

Caroline M Nievergelt

Karestan C Koenen

Laura M Huckins

Karmel W Choi

Affiliations

Soon will be listed here.

Abstract

Background: Prior epidemiological research has linked PTSD with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records (EHR) provide an opportunity to overcome prior clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

Methods: PTSD was defined among biobank participants (total N=123,365) in a major healthcare system using two ICD code-based definitions: broad (1+ PTSD or acute stress codes versus 0; N=14,899) and narrow (2+ PTSD codes versus 0; N=3,026). Using a phenome-wide association (PheWAS) design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified PheWAS analyses including a sex-by-diagnosis interaction term in each logistic regression.

Results: A substantial number of phecodes were significantly associated with PTSD (61%) and PTSD (83%). While top associations were shared between the two definitions, PTSD captured 334 additional phecodes not significantly associated with PTSD and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed, in that PTSD was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients, and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients.

Conclusions: This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using EHR.

References

Giordano N, Richmond T, Farrar J, Trip Buckenmaier Iii C, Gallagher R, Polomano R . Differential Pain Presentations Observed across Post-Traumatic Stress Disorder Symptom Trajectories after Combat Injury. Pain Med. 2021; 22(11):2638-2647. PMC: 8633788. DOI: 10.1093/pm/pnab204. View

Carvalho C, Wendt F, Pathak G, Maihofer A, Stein D, Sumner J . Disentangling sex differences in the shared genetic architecture of posttraumatic stress disorder, traumatic experiences, and social support with body size and composition. Neurobiol Stress. 2021; 15:100400. PMC: 8477211. DOI: 10.1016/j.ynstr.2021.100400. View

Iglesias-Rios L, Harlow S, Reed B . Depression and posttraumatic stress disorder among women with vulvodynia: evidence from the population-based woman to woman health study. J Womens Health (Larchmt). 2015; 24(7):557-62. PMC: 4628213. DOI: 10.1089/jwh.2014.5001. View

Stein M, Levey D, Cheng Z, Wendt F, Harrington K, Pathak G . Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nat Genet. 2021; 53(2):174-184. PMC: 7972521. DOI: 10.1038/s41588-020-00767-x. View

Kohane I, Aronow B, Avillach P, Beaulieu-Jones B, Bellazzi R, Bradford R . What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask. J Med Internet Res. 2021; 23(3):e22219. PMC: 7927948. DOI: 10.2196/22219. View

Lamvu G, Carrillo J, OuYang C, Rapkin A . Chronic Pelvic Pain in Women: A Review. JAMA. 2021; 325(23):2381-2391. DOI: 10.1001/jama.2021.2631. View

Duenas H, Seah C, Johnson J, Huckins L . Implicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data. Hum Mol Genet. 2020; 29(R1):R33-R41. PMC: 7530523. DOI: 10.1093/hmg/ddaa192. View

Pietrzak R, Goldstein R, Southwick S, Grant B . Physical health conditions associated with posttraumatic stress disorder in U.S. older adults: results from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Am Geriatr Soc. 2012; 60(2):296-303. PMC: 3288257. DOI: 10.1111/j.1532-5415.2011.03788.x. View

Asmundson G, Coons M, Taylor S, Katz J . PTSD and the experience of pain: research and clinical implications of shared vulnerability and mutual maintenance models. Can J Psychiatry. 2003; 47(10):930-7. DOI: 10.1177/070674370204701004. View

10.

Sareen J, Cox B, Stein M, Afifi T, Fleet C, Asmundson G . Physical and mental comorbidity, disability, and suicidal behavior associated with posttraumatic stress disorder in a large community sample. Psychosom Med. 2007; 69(3):242-8. DOI: 10.1097/PSY.0b013e31803146d8. View

11.

Ruan Y, Lin Y, Feng Y, Chen C, Lam M, Guo Z . Improving polygenic prediction in ancestrally diverse populations. Nat Genet. 2022; 54(5):573-580. PMC: 9117455. DOI: 10.1038/s41588-022-01054-7. View

12.

Kang B, Xu H, McConnell E . Neurocognitive and psychiatric comorbidities of posttraumatic stress disorder among older veterans: A systematic review. Int J Geriatr Psychiatry. 2018; 34(4):522-538. DOI: 10.1002/gps.5055. View

13.

Flory J, Yehuda R . Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations. Dialogues Clin Neurosci. 2015; 17(2):141-50. PMC: 4518698. View

14.

Kim G, Uddin M . Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood. Biol Sex Differ. 2020; 11(1):13. PMC: 7106761. DOI: 10.1186/s13293-020-00288-6. View

15.

Lopresti A, Drummond P . Obesity and psychiatric disorders: commonalities in dysregulated biological pathways and their implications for treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 45:92-9. DOI: 10.1016/j.pnpbp.2013.05.005. View

16.

Marchese S, Huckins L . Trauma Matters: Integrating Genetic and Environmental Components of PTSD. Adv Genet (Hoboken). 2023; 4(3):2200017. PMC: 10520418. DOI: 10.1002/ggn2.202200017. View

17.

Pacella M, Hruska B, Delahanty D . The physical health consequences of PTSD and PTSD symptoms: a meta-analytic review. J Anxiety Disord. 2012; 27(1):33-46. DOI: 10.1016/j.janxdis.2012.08.004. View

18.

Sharp T, Harvey A . Chronic pain and posttraumatic stress disorder: mutual maintenance?. Clin Psychol Rev. 2001; 21(6):857-77. DOI: 10.1016/s0272-7358(00)00071-4. View

19.

Vezina-Gagnon P, Bergeron S, Hebert M, McDuff P, Guerin V, Daigneault I . Childhood sexual abuse, girls' genitourinary diseases, and psychiatric comorbidity: A matched-cohort study. Health Psychol. 2020; 40(2):104-112. DOI: 10.1037/hea0000994. View

20.

Kucharska J . Sex differences in the appraisal of traumatic events and psychopathology. Psychol Trauma. 2016; 9(5):575-582. DOI: 10.1037/tra0000244. View