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

• Published in: Journal of critical care 2014-02, Vol.29 (1), p.101-106
• Main Authors: Davydow, Dimitry S., MD, MPH, Kohen, Ruth, MD, Hough, Catherine L., MD, MSc, Tracy, Julia Helen, BS, MS, Zatzick, Douglas, MD, Katon, Wayne J., MD
• Format: Article
• Language: English
• Subjects: Adult; Age; Blood products; Carrier Proteins - genetics; Comorbidity; Corticotrophin-releasing hormone binding protein; Corticotrophin-releasing hormone receptor-type 1; Critical Care; Delirium; Depression; Depression - genetics; Female; Hospitalization; Humans; Illnesses; Intensive care; Intensive Care Units; Likert scale; Male; Medical records; Mental depression; Middle Aged; Nursing; Older people; Patients; Pilot Projects; Polymorphism, Single Nucleotide; Posttraumatic stress disorder; Prospective Studies; Real-Time Polymerase Chain Reaction; Receptors, Corticotropin-Releasing Hormone - genetics; Respiratory distress syndrome; Stress Disorders, Post-Traumatic - genetics; Surgery; Survivors; Ventilation
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2013.08.016

Abstract Purpose 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. Materials and 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.