Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors

Ziv Ben-Zion, Yoav Zeevi, Nimrod Jackob Keynan, Roee Admon, Tal Kozlovski, Haggai Sharon, Pinchas Halpern, Israel Liberzon, Arieh Y. Shalev, Yoav Benjamini, Talma Hendler

Research output: Contribution to journalArticlepeer-review


Contemporary symptom-based diagnosis of post-traumatic stress disorder (PTSD) largely overlooks related neurobehavioral mechanisms and relies entirely on subjective interpersonal reporting. Previous studies associating biomarkers with PTSD have mostly used symptom-based diagnosis as the main outcome measure, disregarding the wide variability and richness of PTSD phenotypical features. Here, we aimed to computationally derive potential biomarkers that could efficiently differentiate PTSD subtypes among recent trauma survivors. A three-staged semi-unsupervised method (“3C”) was used to firstly categorize individuals by current PTSD symptom severity, then derive clusters based on clinical features related to PTSD (e.g. anxiety and depression), and finally to classify participants’ cluster membership using objective multi-domain features. A total of 256 features were extracted from psychometrics, cognitive functioning, and both structural and functional MRI data, obtained from 101 adult civilians (age = 34.80 ± 11.95; 51 females) evaluated within 1 month of trauma exposure. The features that best differentiated cluster membership were assessed by importance analysis, classification tree, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural MRI domain), in-task amygdala’s functional connectivity with the insula and thalamus (functional MRI domain), executive function and cognitive flexibility (cognitive testing domain) best differentiated between two clusters associated with PTSD severity. Cross-validation established the results’ robustness and consistency within this sample. The neural and cognitive potential biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral mechanisms associated with PTSD and demonstrate the usefulness of standardized and objective measurements as differentiating clinical sub-classes shortly after trauma.

Original languageEnglish
Article number208
JournalTranslational Psychiatry
Issue number1
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
This work was supported by award number R01-MH-103287 from the National Institute of Mental Health (NIMH) given to A. Y.S. (PI), I.L. and T.H. (co-Investigators, subcontractors), and had undergone critical review by the NIMH Adult Psychopathology and Disorders of Aging study section. This work was also supported by funding to the Human Brain Project from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no. 604102 (HBP). Sagol School of Neuroscience at Tel-Aviv University and the HBP supported Z.B.Z. and Y.Z. fellowships, and Sagol Brain Institute at Tel-Aviv Sourasky Medical Center supported NK and HS fellowships. 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 major contribution in carrying out this research, including subjects’ recruitment and screening, and performing clinical, cognitive, and neural assessments. We also want to thank 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. An initial version of this work was published as a preprint on bioRxiv: 721068v1.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


Dive into the research topics of 'Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors'. Together they form a unique fingerprint.

Cite this