Association of Prospective Risk for Chronic PTSD Symptoms With Low TNFα and IFNγ Concentrations in the Immediate Aftermath of Trauma Exposure
Publication: American Journal of Psychiatry
Abstract
Objective:
Although several reports have documented heightened systemic inflammation in posttraumatic stress disorder (PTSD), few studies have assessed whether inflammatory markers serve as prospective biomarkers for PTSD risk. The present study aimed to characterize whether peripheral immune factors measured in blood samples collected in an emergency department immediately after trauma exposure would predict later chronic development of PTSD.
Methods:
Participants (N=505) were recruited from a hospital emergency department and underwent a 1.5-hour assessment. Blood samples were drawn, on average, about 3 hours after trauma exposure. Follow-up assessments were conducted 1, 3, 6, and 12 months after trauma exposure. Latent growth mixture modeling was used to identify classes of PTSD symptom trajectories.
Results:
Three distinct classes of PTSD symptom trajectories were identified: chronic (N=28), resilient (N=160), and recovery (N=85). Multivariate analyses of covariance revealed a significant multivariate main effect of PTSD symptom trajectory class membership on proinflammatory cytokines. Univariate analyses showed a significant main effect of trajectory class membership on plasma concentrations of proinflammatory tumor necrosis factor α (TNFα) and interferon-γ (IFNγ). Concentrations of proinflammatory TNFα and IFNγ were significantly lower in individuals in the chronic PTSD class compared with those in the recovery and resilient classes. There were no significant differences in interleukin (IL) 1β and IL-6 concentrations by PTSD symptom trajectory class. Anti-inflammatory and other cytokines, as well as chemokines and growth factor concentrations, were not associated with development of chronic PTSD.
Conclusions:
Overall, the study findings suggest that assessing the proinflammatory immune response to trauma exposure immediately after trauma exposure, in the emergency department, may help identify individuals most at risk for developing chronic PTSD in the aftermath of trauma.
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History
Received: 14 January 2019
Revision received: 4 April 2019
Revision received: 1 May 2019
Accepted: 6 May 2019
Published online: 29 July 2019
Published in print: January 01, 2020
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Funding Information
Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659: SCHU 3259/1-1
Eunice Kennedy Shriver National Institute of Child Health and Human Developmenthttp://dx.doi.org/10.13039/100009633: HD085850
National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: MH094757, MH094759
Supported by the Howard Hughes Medical Institute, NIH (grant R01 MH094757 to Dr. Ressler; grant R01 MH094759 to Dr. Nemeroff), the National Institute of Child Health and Human Development (grant K12 HD085850 to Dr. Michopoulos), the National Center for Advancing Translational Sciences (grant UL1 TR000424), the German Research Foundation (grant SCHU 3259/1-1 to Dr. Schultebraucks), and the Brain and Behavior Research Foundation.Dr. Galatzer-Levy receives a salary from AiCure. Dr. Rothbaum has received funding from the Wounded Warrior Project, the Department of Defense (clinical trial grant W81XWH-10-1-1045), NIMH (grant 1R01MH094757-01), and the McCormick Foundation; she has served on advisory boards for Aptinyx, Genentech, Jazz Pharmaceuticals, Neuronetics, Nobilis Therapeutics, and Sandoz; and she receives royalties from Oxford University Press, Guilford Publications, American Psychiatric Association Publishing, and Emory University. Dr. Ressler has received research funding from the Burroughs Wellcome Foundation, the Howard Hughes Medical Institute, NARSAD, and NIMH; he has served as a consultant for Alkermes, Biogen, and Resilience Therapeutics; and he holds patents for a number of targets related to improving extinction of fear (he has received no equity or income within the past 3 years related to these). Dr. Nemeroff has received research support from NIH and the Stanley Medical Research Institute; he has served a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Prismic Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceutical, Takeda, TC MSO, Total Pain Solutions, and Xhale; he is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; he has served on scientific advisory boards for the American Foundation for Suicide Prevention (AFSP), the Anxiety Disorders Association of America (ADAA), Bracket (Clintara), the Brain and Behavior Research Foundation, the Laureate Institute for Brain Research, Skyland Trail, and Xhale; he has served on boards of directors for ADAA, AFSP, and Gratitude America; he has income sources or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), CME Outfitters, Intra-Cellular Therapies, Magstim, Takeda, and Xhale; and he has patents on a method and devices for transdermal delivery of lithium (US 6,375,990B1) and on a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2). The other authors report no financial relationships with commercial interests.Metrics & Citations
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