Genotype-controlled analysis of serum dopamine β-hydroxylase activity in civilian Post-traumatic Stress Disorder

• Type of Material: Article
• Authors: Yilang Tang, Emory University; Wenbiao Li, Emory University; Kristina Mercer, Howard Hughes Medical Institute; Bekh Bradley-Davino, Emory University; Charles Gillespie, Emory University; Robert Bonsall, Emory University; Kerry Ressler, Emory University; Joseph F Cubells, Emory University
• Language: English
• Date: 2010-12-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pnpbp.2010.07.002
• Title of Journal or Parent Work: Progress in Neuro-Psychopharmacology and Biological Psychiatry
• ISSN: 0278-5846
• Volume: 34
• Issue: 8
• Start Page: 1396
• End Page: 1401
• Grant/Funding Information: This work was supported by National Institutes of Mental Health (MH071537).; Support was also received from NIMH(MH069884 to KJR), National Institute of Drug Abuse (DA015766 to JFC), and the Burroughs Wellcome Fund (KJR).; This work was also supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.
• Keywords: post-traumatic stress disorder; association; genotype; depression; serum dopamine β-hydroxylase; civilian trauma
• Research Categories: Psychology, Psychobiology; Biology, Genetics; Biology, Neuroscience

Abstract

Background: Norepinephrine (NE) plays a central role in post-traumatic stress disorder (PTSD). Dopamine β-hydroxylase (DβH) converts dopamine (DA) to NE and its activity varies widely across individuals. Mustapic et al. (2007) reported a PTSD-associated deficit in serum DβH activity (sDβH) in a genotype-controlled analysis of combat veterans. We tested whether such a deficit would occur in a sample of civilians. Methods: The severity of current adult PTSD symptoms and current DSM-IV diagnosis of PTSD were determined by the PTSD Symptom Scale (PSS). Adulthood trauma exposure was assessed using the Traumatic Experience Inventory (TEI). sDβH was assayed by HPLC with electrochemical detection and genotypes were determined using the Taqman® platform. Results: Two hundred and twenty seven African American (AA) subjects were enrolled in this study, with a mean age (± SD) of 42.9 (±12.9) years. We found a strong association between rs1611115 genotype and sDβH (p<0.0001). After controlling for adulthood trauma exposure, there were no significant differences of sDβH between subjects who met a PTSD diagnosis and those who did not (p>0.05) in any genotype group. No significant correlations were found between sDβH and PTSD severity, but sDβH significantly associated with the status of comorbid depression based on the cutoff of HAMD (p=0.014) in subjects with PTSD. Conclusions: We have replicated in this sample the prior finding that DBH rs1611115 genotype strongly associates with sDβH. No associations between sDβH and PTSD diagnosis or symptom severity in this civilian sample.