Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks.
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.
Yehuda
Rachel
R
Mount Sinai School of Medicine and James J. Peters Veterans Affairs Medical Center, Bronx, New York 10458, USA. rachel.yehuda@va.gov
Cai
Guiqing
G
Golier
Julia A
JA
Sarapas
Casey
C
Galea
Sandro
S
Ising
Marcus
M
Rein
Theo
T
Schmeidler
James
J
Müller-Myhsok
Bertram
B
Holsboer
Florian
F
Buxbaum
Joseph D
JD
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D047851:September 11 Terrorist Attacks; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism* / Q000503:physiopathology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D000949:Histocompatibility Antigens Class II; D011965:Receptors, Glucocorticoid; D050799:STAT5 Transcription Factor; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5