Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks.

Abstract:

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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Yehuda R,Cai G,Golier JA,Sarapas C,Galea S,Ising M,Rein T,Schmeidler J,Müller-Myhsok B,Holsboer F,Buxbaum JD

doi

10.1016/j.biopsych.2009.02.034

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

708-11

issue

7

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(09)00394-1

journal_volume

66

pub_type

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