Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Assessment of early neurocognitive functioning increases the accuracy of predicting chronic PTSD risk

Molecular Psychiatry volume 27, pages 2247–2254 (2022)Cite this article

Subjects

Abstract

Post-traumatic stress disorder (PTSD) is a protracted and debilitating consequence of traumatic events. Identifying early predictors of PTSD can inform the disorder’s risk stratification and prevention. We used advanced computational models to evaluate the contribution of early neurocognitive performance measures to the accuracy of predicting chronic PTSD from demographics and early clinical features. We consecutively enrolled adult trauma survivors seen in a general hospital emergency department (ED) to a 14-month long prospective panel study. Extreme Gradient Boosting algorithm evaluated the incremental contribution to 14 months PTSD risk of demographic variables, 1-month clinical variables, and concurrent neurocognitive performance. The main outcome variable was PTSD diagnosis, 14 months after ED admission, obtained by trained clinicians using the Clinician-Administered PTSD Scale (CAPS). N = 138 trauma survivors (mean age = 34.25 ± 11.73, range = 18–64; n = 73 [53%] women) were evaluated 1 month after ED admission and followed for 14 months, at which time n = 33 (24%) met PTSD diagnosis. Demographics and clinical variables yielded a discriminatory accuracy of AUC = 0.68 in classifying PTSD diagnostic status. Adding neurocognitive functioning improved the discriminatory accuracy (AUC = 0.88); the largest contribution emanating from poorer cognitive flexibility, processing speed, motor coordination, controlled and sustained attention, emotional bias, and higher response inhibition, and recall memory. Impaired cognitive functioning 1-month after trauma exposure is a significant and independent risk factor for PTSD. Evaluating cognitive performance could improve early screening and prevention.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Consort diagram.
Fig. 2: Discriminatory accuracy for classifying PTSD diagnosis.
Fig. 3: Variable importance.
Fig. 4: Variable importance for the subset of participants who met 1-month PTSD symptom criteria.

Similar content being viewed by others

References

  1. Galatzer-Levy IR, Ankri Y, Freedman S, Israeli-Shalev Y, Roitman P, Gilad M, et al. Early PTSD symptom trajectories: persistence, recovery, and response to treatment: results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS). PLoS ONE. 2013;8:e70084. https://doi.org/10.1371/journal.pone.0070084. Erratum in: PLoS ONE. 2013;8. https://doi.org/10.1371/annotation/0af0b6c6-ac23-4fe9-a692-f5c30a3a30b3.

  2. Lowe SR, Ratanatharathorn A, Lai BS, van der Mei W, Barbano AC, Bryant RA, et al. Posttraumatic stress disorder symptom trajectories within the first year following emergency department admissions: pooled results from the International Consortium to predict PTSD. Psychol Med. 2021;51:1129–39. https://doi.org/10.1017/S0033291719004008. Epub 2020 Feb 3.

  3. Schultebraucks K, Chang BP. The opportunities and challenges of machine learning in the acute care setting for precision prevention of posttraumatic stress sequelae. Exp Neurol. 2021;336:113526. https://doi.org/10.1016/j.expneurol.2020.113526. Epub 2020 Nov 4.

  4. Heim C, Schultebraucks K, Marmar CR, Nemeroff CB. Neurobiological Pathways Involved in Fear, Stress, and PTSD. In: Nemeroff CB, Marmar C (editors) Post‐traumatic stress disorder. Oxford University Press; 2018. pp. 331–351.

  5. Galatzer-Levy IR, Huang SH, Bonanno GA. Trajectories of resilience and dysfunction following potential trauma: a review and statistical evaluation. Clin Psychol Rev. 2018;63:41–55.

  6. Shalev A, Liberzon I, Marmar C. Post-traumatic stress disorder. N Engl J Med. 2017;376:2459–69.

    Article  PubMed  Google Scholar 

  7. Schultebraucks K, Shalev A, Michopoulos V, Grudzen C, Shin S, Stevens J, et al. A validated predictive algorithm of posttraumatic stress course following emergency department admission after a traumatic stressor. Nat Med. 2020;26:1084–8.

    Article  CAS  PubMed  Google Scholar 

  8. Koren D, Arnon I, Klein E. Long term course of chronic posttraumatic stress disorder in traffic accident victims: a three-year prospective follow-up study. Behav Res Ther. 2001;39:1449–58.

    Article  CAS  PubMed  Google Scholar 

  9. Perkonigg A, Pfister H, Stein MB, Höfler M, Lieb R, Maercker A, et al. Longitudinal course of posttraumatic stress disorder and posttraumatic stress disorder symptoms in a community sample of adolescents and young adults. Am J Psychiatry. 2005;162:1320–7.

    Article  PubMed  Google Scholar 

  10. Stein DJ, Karam EG, Shahly V, Hill ED, King A, Petukhova M, et al. Post-traumatic stress disorder associated with life-threatening motor vehicle collisions in the WHO World Mental Health Surveys. BMC Psychiatry. 2016;16:1–14.

    Article  Google Scholar 

  11. Schultebraucks K, Qian M, Abu-Amara D, Dean K, Laska E, Siegel C, et al. Pre-deployment risk factors for PTSD in active-duty personnel deployed to Afghanistan: a machine-learning approach for analyzing multivariate predictors. Mol Psychiatry. 2020;26:5011–22.

  12. Samuelson KW, Newman J, Abu Amara D, Qian M, Li M, Schultebraucks K, et al. Predeployment neurocognitive functioning predicts postdeployment posttraumatic stress in Army personnel. Neuropsychology. 2020;34:276.

    Article  PubMed  Google Scholar 

  13. Scott JC, Matt GE, Wrocklage KM, Crnich C, Jordan J, Southwick SM, et al. A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychological Bull. 2015;141:105.

    Article  Google Scholar 

  14. Johnsen GE, Asbjørnsen AE. Consistent impaired verbal memory in PTSD: a meta-analysis. J Affect Disord. 2008;111:74–82.

    Article  PubMed  Google Scholar 

  15. Samuelson KW. Post-traumatic stress disorder and declarative memory functioning: a review. Dialogues Clin Neurosci. 2011;13:346.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Aupperle RL, Melrose AJ, Stein MB, Paulus MP. Executive function and PTSD: disengaging from trauma. Neuropharmacology. 2012;62:686–94.

    Article  CAS  PubMed  Google Scholar 

  17. Polak AR, Witteveen AB, Reitsma JB, Olff M. The role of executive function in posttraumatic stress disorder: a systematic review. J Affect Disord. 2012;141:11–21.

    Article  PubMed  Google Scholar 

  18. Casada JH, Roache JD. Behavioral inhibition and activation in posttraumatic stress disorder. J Nerv Ment Dis. 2005;193:102–9.

    Article  PubMed  Google Scholar 

  19. Hart RP, Bagrodia R, Rahman N, Bryant RA, Titcombe-Parekh R, Marmar CR, et al. Neuropsychological predictors of trauma centrality in OIF/OEF veterans. Front Psychol. 2017;8:1120.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Koenen KC, Driver KL, Oscar-Berman M, Wolfe J, Folsom S, Huang MT, et al. Measures of prefrontal system dysfunction in posttraumatic stress disorder. Brain Cogn. 2001;45:64–78.

    Article  CAS  PubMed  Google Scholar 

  21. Ben-Zion Z, Fine NB, Keynan NJ, Admon R, Green N, Halevi M, et al. Cognitive flexibility predicts PTSD symptoms: observational and interventional studies. Front Psychiatry. 2018;9:477.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ben-Zion Z, Zeevi Y, Keynan NJ, Admon R, Kozlovski T, Sharon H, et al. Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors. Transl Psychiatry. 2020;10:1–11.

    Article  Google Scholar 

  23. Hastie T, Tibshirani R, Friedman J. The elements of statistical learning: data mining, inference, and prediction. New York: Springer Science & Business Media, 2009.

  24. Chen T, Guestrin C. XGBoost: a scalable tree boosting system. Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. San Francisco, California, USA: ACM; 2016, p. 785–94.

  25. Shalev AY, Ankri YL, Peleg T, Israeli-Shalev Y, Freedman S. Barriers to receiving early care for PTSD: results from the Jerusalem trauma outreach and prevention study. Psychiatr Serv. 2011;62:765–73.

    Article  PubMed  Google Scholar 

  26. Qi W, Ratanatharathorn A, Gevonden M, Bryant R, Delahanty D, Matsuoka Y, et al. Application of data pooling to longitudinal studies of early post-traumatic stress disorder (PTSD): the International Consortium to Predict PTSD (ICPP) project. Eur J Psychotraumatol. 2018;9:1476442.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ben-Zion Z, Fine NB, Keynan NJ, Admon R, Halpern P, Liberzon I, et al. Neurobehavioral moderators of post-traumatic stress disorder (PTSD) trajectories: study protocol of a prospective MRI study of recent trauma survivors. Eur J Psychotraumatol. 2019;10:1683941.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shalev AY, Ankri Y, Israeli-Shalev Y, Peleg T, Adessky R, Freedman S. Prevention of posttraumatic stress disorder by early treatment: results from the Jerusalem Trauma Outreach And Prevention study. Arch Gen Psychiatry. 2012;69:166–76.

    Article  PubMed  Google Scholar 

  29. Roberts NP, Kitchiner NJ, Kenardy J, Bisson JI. Systematic review and meta-analysis of multiple-session early interventions following traumatic events. Am J Psychiatry. 2009;166:293–301.

    Article  PubMed  Google Scholar 

  30. Hoge CW, Riviere LA, Wilk JE, Herrell RK, Weathers FW. The prevalence of post-traumatic stress disorder (PTSD) in US combat soldiers: a head-to-head comparison of DSM-5 versus DSM-IV-TR symptom criteria with the PTSD checklist. Lancet Psychiatry. 2014;1:269–77.

    Article  PubMed  Google Scholar 

  31. Hoge CW, Yehuda R, Castro CA, McFarlane AC, Vermetten E, Jetly R, et al. Unintended consequences of changing the definition of posttraumatic stress disorder in DSM-5: critique and call for action. JAMA Psychiatry. 2016;73:750–2.

    Article  PubMed  Google Scholar 

  32. Stein DJ, McLaughlin KA, Koenen KC, Atwoli L, Friedman MJ, Hill ED, et al. DSM-5 and ICD-11 definitions of posttraumatic stress disorder: investigating “narrow” and “broad” approaches. Depress Anxiety. 2014;31:494–505.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, et al. The development of a clinician-administered PTSD scale. J Trauma Stress. 1995;8:75–90.

    Article  CAS  PubMed  Google Scholar 

  34. Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, et al. The Clinician-Administered PTSD Scale for DSM–5 (CAPS-5): Development and initial psychometric evaluation in military veterans. Psychol Assess. 2018;30:383.

    Article  PubMed  Google Scholar 

  35. Weathers FW, Ruscio AM, Keane TM. Psychometric properties of nine scoring rules for the clinician-administered posttraumatic stress disorder scale. Psychol Assess. 1999;11:124–33.

    Article  Google Scholar 

  36. First M, Spitzer R, Gibbon M, Williams J. Biometrics research. New York State Psychiatric Institute; New York: 2002. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. Clin Trials Version (SCID-CT). 1995;9:92–104.

    Google Scholar 

  37. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873–5.

    Article  CAS  PubMed  Google Scholar 

  38. Rohde P, Lewinsohn PM, Seeley JR. Comparability of telephone and face-to-face interviews in assessing axis I and II disorders. Am J Psychiatry. 1997;154:1593–8.

    Article  CAS  PubMed  Google Scholar 

  39. Weathers FW, Huska JA, Keane TM. PCL-C for DSM-IV. Boston: National Center for PTSD-Behavioral Science Division; 1991.

  40. Beck A, Steer R, Brown G. Beck depression inventory-II. San Antonio. 1996;78:490–8.

    Google Scholar 

  41. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consulting Clin Psychol. 1988;56:893.

    Article  CAS  Google Scholar 

  42. Guy W. Clinical Global Impressions, ECDEU Assessment Manual for Psychopharmacology, revised (DHEW Publ. No. ADM 76-338). National Institute of Mental Health, Rockville; 1976. pp. 218–222.

  43. Silverstein SM, Berten S, Olson P, Paul R, Williams LM, Cooper N, et al. Development and validation of a World-Wide-Web-based neurocognitive assessment battery: WebNeuro. Behav Res Methods. 2007;39:940–9.

    Article  PubMed  Google Scholar 

  44. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, et al. Scikit-learn: machine learning in Python. J Mach Learn Res. 2011;12:2825–30.

    Google Scholar 

  45. Cawley GC, Talbot NL. On over-fitting in model selection and subsequent selection bias in performance evaluation. J Mach Learn Res. 2010;11:2079–107.

    Google Scholar 

  46. Hosmer Jr. DW, Lemeshow S, Sturdivant RX. Applied logistic regression, vol. 398. New York: John Wiley & Sons; 2013.

  47. Carpenter J, Bithell J. Bootstrap confidence intervals: when, which, what? A practical guide for medical statisticians. Stat Med. 2000;19:1141–64.

    Article  CAS  PubMed  Google Scholar 

  48. Pepe MS, Longton G, Janes H. Estimation and comparison of receiver operating characteristic curves. Stata J. 2009;9:1–16.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Lundberg SM, Lee SI. A unified approach to interpreting model predictions. In Proceedings of the 31st international conference on neural information processing systems. 2017; pp. 4768–4777.

  50. Qureshi SU, Long ME, Bradshaw MR, Pyne JM, Magruder KM, Kimbrell T, et al. Does PTSD impair cognition beyond the effect of trauma? J Neuropsychiatry Clin Neurosci. 2011;23:16–28.

    Article  PubMed  Google Scholar 

  51. Dutra SJ, Marx BP, McGlinchey R, DeGutis J, Esterman M. Reward ameliorates posttraumatic stress disorder-related impairment in sustained attention. Chronic Stress. 2018;2:2470547018812400.

    Article  PubMed Central  Google Scholar 

  52. Roitman P, Gilad M, Ankri YL, Shalev AY. Head injury and loss of consciousness raise the likelihood of developing and maintaining PTSD symptoms. J Trauma Stress. 2013;26:727–34.

    Article  PubMed  Google Scholar 

  53. Bryant RA, Creamer M, O’Donnell M, Silove D, Clark CR, McFarlane AC. Post-traumatic amnesia and the nature of post-traumatic stress disorder after mild traumatic brain injury. J Int Neuropsychological Soc. 2009;15:862–7.

    Article  Google Scholar 

  54. Liberzon I, Abelson JL. Context processing and the neurobiology of post-traumatic stress disorder. Neuron. 2016;92:14–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ben-Zion Z, Artzi M, Niry D, Keynan NJ, Zeevi Y, Admon R, et al. Neuroanatomical risk factors for posttraumatic stress disorder in recent trauma survivors. Biol Psychiatry: Cogn Neurosci Neuroimaging. 2020;5:311–9.

    Google Scholar 

  56. Falconer E, Allen A, Felmingham KL, Williams LM, Bryant RA. Inhibitory neural activity predicts response to cognitive-behavioral therapy for posttraumatic stress disorder. J Clin Psychiatry. 2013;74:895–901.

    Article  PubMed  Google Scholar 

  57. Nijdam MJ, de Vries G-J, Gersons BP, Olff M. Response to psychotherapy for posttraumatic stress disorder: The role of pretreatment verbal memory performance. J Clin Psychiatry. 2015;76:1023–8.

    Article  Google Scholar 

  58. Wild J, Gur RC. Verbal memory and treatment response in post-traumatic stress disorder. Br J Psychiatry. 2008;193:254–5.

    Article  PubMed  Google Scholar 

  59. Fine NB, Achituv M, Etkin A, Merin O, Shalev AY. Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol. Eur J Psychotraumatol. 2018;9:1442602.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Fonzo GA, Fine NB, Wright RN, Achituv M, Zaiko YV, Merin O, et al. Internet-delivered computerized cognitive & affective remediation training for the treatment of acute and chronic posttraumatic stress disorder: two randomized clinical trials. J Psychiatr Res. 2019;115:82–9.

    Article  PubMed  Google Scholar 

  61. Nijdam MJ, Martens IJ, Reitsma JB, Gersons BP, Olff M. Neurocognitive functioning over the course of trauma‐focused psychotherapy for PTSD: Changes in verbal memory and executive functioning. Br J Clin Psychol. 2018;57:436–52.

    Article  PubMed  Google Scholar 

  62. Schultebraucks K, Yadav V, Galatzer-Levy IR. Utilization of machine learning-based computer vision and voice analysis to derive digital biomarkers of cognitive functioning in trauma survivors. Digital Biomark. 2021;5:16–23.

    Article  Google Scholar 

  63. Zoellner LA, Bedard-Gilligan MA, Jun JJ, Marks LH, Garcia NM. The evolving construct of posttraumatic stress disorder (PTSD): DSM-5 criteria changes and legal implications. Psychological Inj Law. 2013;6:277–89.

    Article  Google Scholar 

  64. Galatzer-Levy IR, Bryant RA. 636,120 ways to have posttraumatic stress disorder. Perspect Psychological Sci. 2013;8:651–62.

    Article  Google Scholar 

  65. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048–60.

    Article  CAS  PubMed  Google Scholar 

  66. Shalev AY, Freedman S. PTSD following terrorist attacks: a prospective evaluation. Am J Psychiatry. 2005;162:1188–91.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the research team at Tel-Aviv Sourasky Medical Center—including Nili Green, Mor Halevi, Sheli Luvton, Yael Shavit, Olga Nevenchannaya, Iris Rashap, Efrat Routledge, and Ophir Leshets for their significant contributions to participants, screening, enrollment, assessments, and follow-up and to Naomi Fine and Michal Achituv for setting up the clinical aspect of the research. Last but not least, we extend our gratitude to all the participants of this study, who completed all the assessments at three different time-points after experiencing a traumatic event. The work was supported by award number R01-MH-103287 from the National Institute of Mental Health (NIMH) given to AYS (PI), IL, and TH (co-Investigators, subcontractors), and had undergone critical review by the NIMH Adult Psychopathology and Disorders of Aging study section.

Author information

Author notes

  1. These authors contributed equally: Katharina Schultebraucks, Ziv Ben-Zion.

Authors and Affiliations

  1. Department of Emergency Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Katharina Schultebraucks

  2. Department of Psychiatry, Columbia University, New York, NY, USA

    Katharina Schultebraucks

  3. Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, USA

    Katharina Schultebraucks & Arieh Y. Shalev

  4. Sagol Brain Institute Tel-Aviv, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel

    Ziv Ben-Zion, Jackob Nimrod Keynan & Talma Hendler

  5. Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel

    Ziv Ben-Zion, Jackob Nimrod Keynan & Talma Hendler

  6. Departments of Comparative Medicine and Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, USA

    Ziv Ben-Zion

  7. United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, The Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA

    Ziv Ben-Zion

  8. School of Psychological Sciences, University of Haifa, Haifa, Israel

    Roee Admon

  9. Texas A&M Health, Bryan, TX, USA

    Israel Liberzon

Authors
  1. Katharina Schultebraucks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziv Ben-Zion
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roee Admon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jackob Nimrod Keynan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Israel Liberzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Talma Hendler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arieh Y. Shalev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KS, ZB-Z, RA, JNK, IL, TH, and AYS substantially contributed to the design of the study and developed the study concept. ZB-Z, TH, and AYS were involved in the data collection process. KS, ZB-Z, and AYS developed the data analytical plan and performed data analysis. KS wrote the first draft of the manuscript and all co-authors reviewed and revised the manuscript critically for important intellectual content. All co-authors approved the version of the manuscript to be published.

Corresponding author

Correspondence to Katharina Schultebraucks.

Ethics declarations

Competing interests

TH is the chief medical officer of GrayMatters Health Co Haifa Israel. All other authors have no potential conflicts of interest to declare.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schultebraucks, K., Ben-Zion, Z., Admon, R. et al. Assessment of early neurocognitive functioning increases the accuracy of predicting chronic PTSD risk. Mol Psychiatry 27, 2247–2254 (2022). https://doi.org/10.1038/s41380-022-01445-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-022-01445-6

This article is cited by

Search

Advanced search

Quick links