A pilot investigation of the association of genetic polymorphisms regulating corticotrophin-releasing hormone with posttraumatic stress and depressive symptoms in medical-surgical intensive care unit survivors.
OBJECTIVE
To determine if single nucleotide polymorphisms of the corticotrophin-releasing hormone binding protein (CRHBP, rs10055255) and CRH receptor type 1 (CRHR1, rs1876831) were associated with posttraumatic stress disorder (PTSD) and depressive symptoms following medical-surgical intensive care unit (ICU) hospitalization.


METHODS
We extracted DNA for genotyping from saliva samples of 93 ICU patients enrolled in a prospective cohort investigation. Follow-up interviews conducted 3 and 12-months post-ICU included assessment of PTSD symptoms with the PTSD Checklist-Civilian Version and depressive symptoms with the Patient Health Questionnaire-9.


RESULTS
Homozygosity for the CRHBP rs10055255 T allele was associated with significantly fewer post-ICU PTSD (β = -10.8, 95% confidence interval [95% CI], -17.7 to -3.9; P = .002) and depressive symptoms (β = -3.7, 95% CI, -6.7 to -0.7; P = .02). Carrying a CRHR1 rs1876831 C allele was associated with significantly more post-ICU depressive symptoms compared to T/T homozygotes (C/T heterozygtes: β = 6.9, 95% CI, 1.2-12.6; P = .02; C/C homozygotes: β = 5.8; 95% CI: 0.2-11.3; P = .04). These associations remained significant after adjustment for age, race, illness severity, and in-ICU steroid exposure.


CONCLUSIONS
Despite a small sample size, our findings suggest a potential role for genetic variants of CRHBP and CRHR1 in the development of post-ICU psychiatric morbidity.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Electronic address: ddavydo1@u.washington.edu.
Dimitry S
DS
Davydow
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Ruth
R
Kohen
Department of Medicine, University of Washington, Seattle, WA, USA.
Catherine L
CL
Hough
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Julia Helen
JH
Tracy
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Douglas
D
Zatzick
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Wayne J
WJ
Katon
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D017741:Survivors
D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein
Corticotrophin-releasing hormone binding protein; Corticotrophin-releasing hormone receptor-type 1; Critical care; Depression; Posttraumatic stress disorder