Neuroendocrine and neuroimmune markers in PTSD: pre-, peri- and post-trauma glucocorticoid and inflammatory dysregulation

Current Opinion in Psychology

Volumn 14, Issue , 2017, Pages 132-137

  Olff, Miranda ^a,b   van Zuiden, Mirjam ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b ARQ PSYCHOTRAUMA EXPERT GROUP   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85012008452     PISSN: 2352250X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.copsyc.2017.01.001     Document Type: Review

References (53)

1. 1 Olff, M., Langeland, W., Gersons, B.P., Effects of appraisal and coping on the neuroendocrine response to extreme stress. Neurosci Biobehav Rev 29 (2005), 457–467.
2. 2 American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 5th ed., 2013, American Psychiatric Association, Arlington, VA.
3. 3 de Vries, G.J., Olff, M., The lifetime prevalence of traumatic events and posttraumatic stress disorder in the Netherlands. J Trauma Stress 22 (2009), 259–267.
4. 4 Kessler, R.C., Petukhova, M., Sampson, N.A., Zaslavsky, A.M., Wittchen, H.U., Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 21 (2012), 169–184.
5. 5 Olff, M., Brosschot, J.F., Godaert, G., Benschop, R.J., Ballieux, R.E., Heijnen, C.J., de Smet, M.B., Ursin, H., Modulatory effects of defense and coping on stress-induced changes in endocrine and immune parameters. Int J Behav Med 2 (1995), 85–103.
6. 6 Yehuda, R., Giller, E.L., Southwick, S.M., Lowy, M.T., Mason, J.W., Hypothalamic–pituitary–adrenal dysfunction in posttraumatic-stress-disorder. Biol Psychiatry 30 (1991), 1031–1048.
7. 7 Olff, M., Guzelcan, Y., de Vries, G.J., Assies, J., Gersons, B.P., HPA- and HPT-axis alterations in chronic posttraumatic stress disorder. Psychoneuroendocrinology 31 (2006), 1220–1230.
8. 8 Morris, M.C., Compas, B.E., Garber, J., Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: a systematic review and meta-analysis. Clin Psychol Rev 32 (2012), 301–315.
9. 9 Rohleder, N., Joksimovic, L., Wolf, J.M., Kirschbaum, C., Hypocortisolism and increased glucocorticoid sensitivity of pro-inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder. Biol Psychiatry 55 (2004), 745–751.
10. 10 Yehuda, R., Golier, J.A., Yang, R.K., Tischler, L., Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder. Biol Psychiatry 55 (2004), 1110–1116.
11. 11 Labonte, B., Azoulay, N., Yerko, V., Turecki, G., Brunet, A., Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder. Transl Psychiatry, 4, 2014.
12. 12 Logue, M.W., Smith, A.K., Baldwin, C., Wolf, E.J., Guffanti, G., Ratanatharathorn, A., Stone, A., Schichman, S.A., Humphries, D., Binder, E.B., et al. An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress. Psychoneuroendocrinology 57 (2015), 1–13.
13. 13 Pitts, K.P., Joksimovic, L., Steudte-Schmiedgen, S., Rohleder, N., Wolf, J.M., Determinants of altered intracellular endocrine-immune interplay in Bosnian war refugees suffering from PTSD. Biol Psychol 118 (2016), 1–7.
14. 14 Mehta, D., Gonik, M., Klengel, T., Rex-Haffner, M., Menke, A., Rubel, J., Mercer, K.B., Putz, B., Bradley, B., Holsboer, F., et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Arch Gen Psychiatry 68 (2011), 901–910.
15. 15 Binder, E.B., Bradley, R.G., Liu, W., Epstein, M.P., Deveau, T.C., Mercer, K.B., Tang, Y., Gillespie, C.F., Heim, C.M., Nemeroff, C.B., et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. J Am Med Assoc 299 (2008), 1291–1305.
16. 16 van Zuiden, M., Geuze, E., Willemen, H., Vermetten, E., Maas, M., Amarouchi, K., Kavelaars, A., Heijnen, C.J., Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study. Biol Psychiatry 71 (2012), 309–316.
17. 17 Steudte-Schmiedgen, S., Kirschbaum, C., Alexander, N., Stalder, T., An integrative model linking traumatization, cortisol dysregulation and posttraumatic stress disorder: insight from recent hair cortisol findings. Neurosci Biobehav Rev 69 (2016), 124–135.
18. 18•• Passos, I.C., Vasconcelos-Moreno, M.P., Costa, L.G., Kunz, M., Brietzke, E., Quevedo, J., Salum, G., Magalhaes, P.V., Kapczinski, F., Kauer-Sant'Anna, M., Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2 (2015), 1002–1012 This comprehensive systematic review, meta-analysis and meta-regression aimed to summarize the mixed results on inflammatory markers in PTSD, and observed that several pro-inflammatory cytokines were significantly higher in PTSD patients than healthy controls. Several important moderators explaining previous inconsistent findings were identified.
19. 19 Lohr, J.B., Palmer, B.W., Eidt, C.A., Aailaboyina, S., Mausbach, B.T., Wolkowitz, O.M., Thorp, S.R., Jeste, D.V., Is post-traumatic stress disorder associated with premature senescence? A review of the literature. Am J Geriatr Psychiatry 23 (2015), 709–725.
20. 20 Guardado, P., Olivera, A., Rusch, H.L., Roy, M., Martin, C., Lejbman, N., Lee, H., Gill, J.M., Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-kappaB) systems is associated with posttraumatic stress disorder in military personnel. J Anxiety Disord 38 (2016), 9–20.
21. 21 Nievergelt, C.M., Maihofer, A.X., Mustapic, M., Yurgil, K.A., Schork, N.J., Miller, M.W., Logue, M.W., Geyer, M.A., Risbrough, V.B., O'Connor, D.T., et al. Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: a genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene. Psychoneuroendocrinology 51 (2015), 459–471.
22. 22 Michopoulos, V., Rothbaum, A.O., Jovanovic, T., Almli, L.M., Bradley, B., Rothbaum, B.O., Gillespie, C.F., Ressler, K.J., Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma. Am J Psychiatry 172 (2015), 353–362.
23. 23• Steudte-Schmiedgen, S., Stalder, T., Schonfeld, S., Wittchen, H.U., Trautmann, S., Alexander, N., Miller, R., Kirschbaum, C., Hair cortisol concentrations and cortisol stress reactivity predict PTSD symptom increase after trauma exposure during military deployment. Psychoneuroendocrinology 59 (2015), 123–133 This is the first prospective study investigating whether hair cortisol and experimental cortisol stress reactivity measured prior to trauma predict development of PTSD symptoms. In deployed soldiers, pre-deployment hair cortisol and cortisol stress reactivity were inversely related with PTSD symptoms after return from deployment, but only in soldiers who had experienced traumatic events during deployment.
24. 24 van Zuiden, M., Kavelaars, A., Geuze, E., Olff, M., Heijnen, C.J., Predicting PTSD: pre-existing vulnerabilities in glucocorticoid-signaling and implications for preventive interventions. Brain Behav Immun 30 (2013), 12–21.
25. 25 van Zuiden, M., Heijnen, C.J., Maas, M., Amarouchi, K., Vermetten, E., Geuze, E., Kavelaars, A., Glucocorticoid sensitivity of leukocytes predicts PTSD, depressive and fatigue symptoms after military deployment: a prospective study. Psychoneuroendocrinology 37 (2012), 1822–1836.
26. 26 Eraly, S.A., Nievergelt, C.M., Maihofer, A.X., Barkauskas, D.A., Biswas, N., Agorastos, A., O'Connor, D.T., Baker, D.G., Marine Resiliency Study Team, Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry 71 (2014), 423–431.
27. 27•• Breen, M.S., Maihofer, A.X., Glatt, S.J., Tylee, D.S., Chandler, S.D., Tsuang, M.T., Risbrough, V.B., Baker, D.G., O'Connor, D.T., Nievergelt, C.M., et al. Gene networks specific for innate immunity define post-traumatic stress disorder. Mol Psychiatry 20 (2015), 1538–1545 In this first transcriptome wide study with a prospective design it was observed that Marines with PTSD upon return from deployment showed overexpression of genes associated with innate immune function and interferon signaling prior to deployment. Gene-expression alterations as a consequence of trauma exposure were also observed.
28. 28 van Zuiden, M., Heijnen, C.J., van de Schoot, R., Amarouchi, K., Maas, M., Vermetten, E., Geuze, E., Kavelaars, A., Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone: a prospective, longitudinal study. PLoS One, 6, 2011.
29. 29 Mouthaan, J., Sijbrandij, M., Luitse, J.S., Goslings, J.C., Gersons, B.P., Olff, M., The role of acute cortisol and DHEAS in predicting acute and chronic PTSD symptoms. Psychoneuroendocrinology 45 (2014), 179–186.
30. 30 Walsh, K., Nugent, N.R., Kotte, A., Amstadter, A.B., Wang, S., Guille, C., Acierno, R., Kilpatrick, D.G., Resnick, H.S., Cortisol at the emergency room rape visit as a predictor of PTSD and depression symptoms over time. Psychoneuroendocrinology 38 (2013), 2520–2528.
31. 31 McFarlane, A.C., Barton, C.A., Yehuda, R., Wittert, G., Cortisol response to acute trauma and risk of posttraumatic stress disorder. Psychoneuroendocrinology 36 (2011), 720–727.
32. 32 Pervanidou, P., Kolaitis, G., Charitaki, S., Margeli, A., Ferentinos, S., Bakoula, C., Lazaropoulou, C., Papassotiriou, I., Tsiantis, J., Chrousos, G.P., Elevated morning serum interleukin (IL)-6 or evening salivary cortisol concentrations predict posttraumatic stress disorder in children and adolescents six months after a motor vehicle accident. Psychoneuroendocrinology 32 (2007), 991–999.
33. 33• Smid, G.E., van Zuiden, M., Geuze, E., Kavelaars, A., Heijnen, C.J., Vermetten, E., Cytokine production as a putative biological mechanism underlying stress sensitization in high combat exposed soldiers. Psychoneuroendocrinology 51 (2015), 534–546 In this study neurobiological mechanisms associated with stress sensitization and increasing PTSD severity were investigated using a prospective design. It was observed that increases in PTSD symptom severity over the course of one year in formerly deployed soldiers was associated with baseline stimulated cytokine production, but only in soldiers exposed to subsequent stressful events, suggesting immune function may contribute to stress sensitization.
34. 34 Olff, M., de Vries, G.J., Guzelcan, Y., Assies, J., Gersons, B.P., Changes in cortisol and DHEA plasma levels after psychotherapy for PTSD. Psychoneuroendocrinology 32 (2007), 619–626.
35. 35 Yehuda, R., Daskalakis, N.P., Desarnaud, F., Makotkine, I., Lehrner, A.L., Koch, E., Flory, J.D., Buxbaum, J.D., Meaney, M.J., Bierer, L.M., Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Front Psychiatry, 4, 2013, 118.
36. 36 Yehuda, R., Pratchett, L.C., Elmes, M.W., Lehrner, A., Daskalakis, N.P., Koch, E., Makotkine, I., Flory, J.D., Bierer, L.M., Glucocorticoid-related predictors and correlates of post-traumatic stress disorder treatment response in combat veterans. Interface Focus, 4, 2014.
37. 37 Rauch, S.A., King, A.P., Abelson, J., Tuerk, P.W., Smith, E., Rothbaum, B.O., Clifton, E., Defever, A., Liberzon, I., Biological and symptom changes in posttraumatic stress disorder treatment: a randomized clinical trial. Depress Anxiety 32 (2015), 204–212.
38. 38 Gill, J.M., Saligan, L., Lee, H., Rotolo, S., Szanton, S., Women in recovery from PTSD have similar inflammation and quality of life as non-traumatized controls. J Psychosom Res 74 (2013), 301–306.
39. 39 Yehuda, R., Bierer, L.M., Sarapas, C., Makotkine, I., Andrew, R., Seckl, J.R., Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001. Psychoneuroendocrinology 34 (2009), 1304–1313.
40. 40 Yehuda, R., Bierer, L.M., Pratchett, L.C., Lehrner, A., Koch, E.C., Van Manen, J.A., Flory, J.D., Makotkine, I., Hildebrandt, T., Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: randomized trial showing improved treatment retention and outcome. Psychoneuroendocrinology 51 (2015), 589–597.
41. 41 Yehuda, R., Bierer, L.M., Pratchett, L.C., Pelcovitz, M., Using biological markers to inform a clinically meaningful treatment response. Barchas, J.D., Difede, J., (eds.) Psychiatric and Neurologic Aspects of War, vol. 1208, 2010, Annals of the New York Academy of Sciences, 158–163.
42. 42 Nijdam, M.J., van Amsterdam, J.G., Gersons, B.P., Olff, M., Dexamethasone-suppressed cortisol awakening response predicts treatment outcome in posttraumatic stress disorder. J Affect Disord 184 (2015), 205–208.
43. 43 Levy-Gigi, E., Szabo, C., Kelemen, O., Keri, S., Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biol Psychiatry 74 (2013), 793–800.
44. 44 Wilker, S., Pfeiffer, A., Kolassa, S., Elbert, T., Lingenfelder, B., Ovuga, E., Papassotiropoulos, A., de Quervain, D., Kolassa, I.T., The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder. Transl Psychiatry, 4, 2014, e403.
45. 45 Lehrner, A., Yehuda, R., Biomarkers of PTSD: military applications and considerations. Eur J Psychotraumatol, 5, 2014.
46. 46 Hendriks, G.J., De Kleine, R., Van Minnen, A., Optimizing the efficacy of exposure in PTSD treatment. Eur J Psychotraumatol, 6, 2015.
47. 47 Kelmendi, B., Adams, T., Yarnell, S., Southwick, S., Abdallah, C., Krystal, J., PTSD: from neurobiology to pharmacological treatments. Eur J Psychotraumatol, 7, 2016.
48. 48•• Sijbrandij, M., Kleiboer, A., Bisson, J.I., Barbui, C., Cuijpers, P., Pharmacological prevention of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis. Lancet Psychiatry 2 (2015), 413–421 This is the first systematic review and meta-analysis investigating efficacy of early pharmacotherapy in preventing PTSD or Acute Stress Disorder. Results show that specifically hydrocortisone seems to reduce the risk of developing PTSD.
49. 49 van Zuiden, M., Frijling, J.L., Nawijn, L., Koch, S.B., Goslings, J.C., Luitse, J.S., Biesheuvel, T.H., Honig, A., Veltman, D.J., Olff, M., Intranasal oxytocin to prevent PTSD symptoms: a randomized controlled trial in emergency department patients. Biol Psychiatry, 2017 (in press).
50. 50 Yehuda, R., Bierer, L.M., Pratchett, L., Malowney, M., Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report. Eur J Psychotraumatol, 1, 2010.
51. 51 Ludascher, P., Schmahl, C., Feldmann, R.E. Jr., Kleindienst, N., Schneider, M., Bohus, M., No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder—a randomized, double-blind, placebo-controlled, crossover study. J Psychopharmacol 29 (2015), 1077–1084.
52. 52 Golier, J.A., Caramanica, K., Michaelides, A.C., Makotkine, I., Schmeidler, J., Harvey, P.D., Yehuda, R., A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness. Psychoneuroendocrinology 64 (2016), 22–30.
53. 53 Koch, S.B., van Zuiden, M., Nawijn, L., Frijling, J.L., Veltman, D.J., Olff, M., Intranasal oxytocin normalizes amygdala functional connectivity in posttraumatic stress disorder. Neuropsychopharmacology 41 (2016), 2041–2051.