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

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. Molecular Psychiatry (2005) 10, 500-513.

The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder

“…33,34 Furthermore, higher FKBP5 mRNA expression in peripheral blood hours after the traumatic experience predicted PTSD symptom development in survivors 4 months later. 63 …”

Gene expression analysis in combat veterans with and without post-traumatic stress disorder

“…Differentially expressed genes identified in previous GEA studies of PTSD (23)(24)(25)(26), consistent with case-control candidate gene association studies, have a role in regulating the HPA axis, the ANS and CNS, and more specifically in immune activation, inflammation, signal transduction and apoptosis, similar to biological systems implicated by non-gene biological studies of PTSD (27). The present study reports preliminary data that shows the importance of quality control methods in GEA studies and the possible differential expression of genes regulating pathways between the HPA, ANS and inflammation in PTSD.…”

Differential gene expression in peripheral blood of patients suffering from post-traumatic stress disorder

“…Recently, similar experiments have been carried out in patients suffering from acute traumatic events, using Affymetrix chips. 1 In our study, considerable efforts have been made to accurately standardize any condition possibly interfering with measurements. Whole blood was used and, very importantly, the group of PTSD patients was homogeneous in that all of them experienced the same traumatic event (Ramstein air show catastrophe, 1989).…”