Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

R. H. Segman*, N. Shefi, T. Goltser-Dubner, N. Friedman, N. Kaminski, A. Y. Shalev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

244 Scopus citations

Abstract

Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results.

Original languageAmerican English
Pages (from-to)500-513
Number of pages14
JournalMolecular Psychiatry
Volume10
Issue number5
DOIs
StatePublished - May 2005

Bibliographical note

Funding Information:
This work was supported by a Horowitz foundation grant from the Hadassah Hebrew University Medical Center – Hadassit Research and Development Division to RHS and AYS. NS and NF were supported in part by a German-Israeli Foundation (GIF) grant. NS was supported in part by the Sudarsky center for computational biology. NF was also supported by an Alon Fellowship and by the Harry and Abe Sherman Senior Lectureship in Computer Science. AYS was supported in part by a PHS Research Grant No. MH50379. NK is the Dorothy P and Richards P Simmons Chair for Interstitial Lung Diseases in the University of Pittsburgh. We thank Nelly Glusman and Jasmine Jacob-Hirsch, staff of the Functional Genomics Unit, The Chaim Sheba Medical Center, Israel, for their help in the preparation of samples and hybridization; to Yair Banet, Neta Bargai, Ruth Boker, Sara Freedman and Rivka Tuval of the Center for Traumatic Stress at Hadassah University Hospital for recruitment and clinical assessments; to Laura Canetti of the Department of Psychiatry at Hadassah University Hospital for help in statistical analyses; and to Derek Angus, Michael Donahoe, Laura Garwin, Aviv Regev and Zohar Yakhini for helpful comments during manuscript preparation. We are named inventors on a patent to use gene expression technology to ascertain PTSD prognosis.

Keywords

  • Gene expression
  • Microarray
  • Mononuclear
  • Post-traumatic stress disorder

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