Elsevier

Biological Psychiatry

Volume 66, Issue 7, 1 October 2009, Pages 708-711
Biological Psychiatry

Brief Report
Gene Expression Patterns Associated with Posttraumatic Stress Disorder Following Exposure to the World Trade Center Attacks

https://doi.org/10.1016/j.biopsych.2009.02.034Get rights and content

Background

Although genetic risk factors for posttraumatic stress disorder (PTSD) in similarly traumatized cohorts can be confounded with risk for type of exposure, the primary risk for exposure to the 9/11 attack on New York City was proximity, allowing study of PTSD risk in a sample that is not confounded by exposure-related risk.

Methods

Thirty-five Caucasians (15 with PTSD, stratified for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the attack from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained.

Results

Seventeen probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal (HPA) axis, signal transduction, or brain and immune cell function. FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity, showed reduced expression in PTSD, consistent with enhanced GR responsiveness. FKBP5 expression was predicted by cortisol when entered with PTSD severity in regression analysis. Quantitative polymerase chain reaction confirmed significant reductions in FKBP5. Also less expressed in PTSD were STAT5B, a direct inhibitor of GR, and major histocompatibility complex (MHC) Class II.

Conclusions

Consistent with observations of HPA axis dysfunction in PTSD, several genes involved in glucocorticoid signaling are differentially expressed among those with current PTSD.

Section snippets

Participants

A random sample of 20 Caucasians with high-magnitude exposure to 9/11 who met criteria for PTSD in at least two of four waves in a previously described longitudinal study (7) were recruited. Subjects were then stratified by age and gender to 20 similarly exposed Caucasians without PTSD. The study was approved by the Institutional Review Board (IRB) at the Mount Sinai School of Medicine. All participants provided written, informed consent. Participants were excluded if they had psychosis,

Results

Table 1 shows clinical characteristics of the sample. Differences were observed in childhood traumatization, number of lifetime traumas, and severity of PTSD symptoms.

Analysis of expression profiles revealed 17 probe sets, corresponding to 16 genes, differentially expressed between those with and without PTSD (Table 2). All genes showed present call rates of >90% in cases and control subjects, with the exception of probe set 238900_at, which showed a present call rate of 60% in control subjects

Discussion

Several of the identified regulated genes are involved in GR regulation, signal transduction, and brain and immune cell function. FKBP5 acts as an inhibitor of GR (via its function as a co-chaperone of the central heat-shock protein 90 [Hsp90]) (14) and has been associated with recurrence of depression and impaired recovery of the stress response (15, 16, 17). Here, FKBP5 expression was significantly lower in PTSD than in control subjects. Similarly, STAT5B is a direct inhibitor of the nuclear

References (20)

There are more references available in the full text version of this article.

Cited by (251)

View all citing articles on Scopus
View full text