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Associations of trauma exposure and post-traumatic stress disorder with the activity of the renin–angiotensin–aldosterone-system in the general population

Published online by Cambridge University Press:  18 June 2018

Jan Terock*
Affiliation:
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany Department of Psychiatry and Psychotherapy, HELIOS Hanseklinikum Stralsund, Stralsund, Germany
Anke Hannemann
Affiliation:
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
Deborah Janowitz
Affiliation:
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
Harald J. Freyberger
Affiliation:
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany Department of Psychiatry and Psychotherapy, HELIOS Hanseklinikum Stralsund, Stralsund, Germany
Stephan B. Felix
Affiliation:
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
Marcus Dörr
Affiliation:
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
Matthias Nauck
Affiliation:
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
Henry Völzke
Affiliation:
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
Hans J. Grabe
Affiliation:
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany German Center for Neurodegenerative Diseases DZNE, Site Rostock/Greifswald, Germany
*
Author for correspondence: Jan Terock, E-mail: [email protected]

Abstract

Background

Previous studies suggested that exposure to traumatic events during childhood and adulthood and post-traumatic stress disorder (PTSD) are associated with a dysregulation of different neuroendocrine systems. However, the activity of the renin–angiotensin–aldosterone-system (RAAS) in relation to trauma/PTSD has been largely neglected.

Methods

Traumatization, PTSD, and plasma concentrations of renin and aldosterone were measured in 3092 individuals from the general population. Subgroups according to the status of traumatization (‘without trauma’; ‘trauma, without PTSD’, ‘PTSD’) were formed and compared regarding renin and aldosterone concentrations. Additionally, we calculated the associations between the number of traumata, renin, and aldosterone concentrations. Finally, associations of PTSD with renin/aldosterone levels were controlled for the number of traumata (‘trauma load’).

Results

Levels of renin, but not aldosterone, were increased in traumatized persons without PTSD (p = 0.02) and, even stronger, with PTSD (p < 0.01). Moreover, we found a dose–response relation between the number of traumata and renin levels (β = 0.065; p < 0.001). Regression analyses showed PTSD as a significant predictor of renin (β = 0.38; p < 0.01). This effect was only slightly attenuated when controlled for trauma load (β = 0.32; p < 0.01).

Conclusions

Our results suggest that traumatization has lasting and cumulative effects on RAAS activity. Finding elevated renin levels in PTSD independent from trauma load supports the concept of PTSD as a disorder with specific neuroendocrine characteristics. Alternatively, elevated renin levels in traumatized persons may increase the risk for developing PTSD. Our findings contribute to explain the relationship between traumatic stress/PTSD and physical disorders.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Contributed equally.

References

Aguilera, G (1993). Factors controlling steroid biosynthesis in the zona glomerulosa of the adrenal. The Journal of Steroid Biochemistry and Molecular Biology 45, 147151.Google Scholar
Aguilera, G, Kiss, A and Sunar-Akbasak, B (1995). Hyperreninemic hypoaldosteronism after chronic stress in the rat. Journal of Clinical Investigation 96, 15121519.Google Scholar
Anda, RF, Felitti, VJ, Bremner, JD, Walker, JD, Whitfield, C, Perry, BD, Dube, SR and Giles, WH (2006). The enduring effects of abuse and related adverse experiences in childhood. European Archives of Psychiatry and Clinical Neuroscience 256, 174186.Google Scholar
Armando, I, Carranza, A, Nishimura, Y, Hoe, K-L, Barontini, M, Terrón, JA, Falcón-Neri, A, Ito, T, Juorio, AV and Saavedra, JM (2001). Peripheral administration of an angiotensin II AT1 receptor antagonist decreases the hypothalamic-pituitary-adrenal response to isolation stress. Endocrinology 142, 38803889.Google Scholar
Baker, CK, Norris, FH, Jones, EC and Murphy, AD (2009). Childhood trauma and adulthood physical health in Mexico. Journal of Behavioral Medicine 32, 255.Google Scholar
Boscarino, JA (1997). Diseases among men 20 years after exposure to severe stress: implications for clinical research and medical care. Psychosomatic Medicine 59, 605614.Google Scholar
Boscarino, JA (2008). A prospective study of PTSD and early-age heart disease mortality among Vietnam veterans: implications for surveillance and prevention. Psychosomatic Medicine 70, 668676.Google Scholar
Cohen, H, Benjamin, J, Geva, AB, Matar, MA, Kaplan, Z and Kotler, M (2000). Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks. Psychiatry Research 96, 113.Google Scholar
Cohen, H, Kotler, M, Matar, MA, Kaplan, Z, Loewenthal, U, Miodownik, H and Cassuto, Y (1998). Analysis of heart rate variability in posttraumatic stress disorder patients in response to a trauma-related reminder. Biological Psychiatry 44, 10541059.Google Scholar
De Kloet, CS, Vermetten, E, Geuze, E, Kavelaars, A, Heijnen, CJ and Westenberg, HGM (2006). Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. Journal of Psychiatric Research 40, 550567.Google Scholar
Edwards, VJ, Anda, RF, Nordenberg, DF, Felitti, VJ, Williamson, DF and Wright, JA (2001). Bias assessment for child abuse survey: factors affecting probability of response to a survey about childhood abuse. Child Abuse & Neglect 25, 307312.Google Scholar
Elhai, JD, Gray, MJ, Kashdan, TB and Franklin, CL (2005). Which instruments are most commonly used to assess traumatic event exposure and posttraumatic effects? A survey of traumatic stress professionals. Journal of Traumatic Stress 18, 541545.Google Scholar
Felitti, VJ, Anda, RF, Nordenberg, D, Williamson, DF, Spitz, AM, Edwards, V, Koss, MP and Marks, JS (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the Adverse Childhood Experiences (ACE) Study. American Journal of Preventive Medicine 14, 245258.Google Scholar
Gallo, LC, Roesch, SC, Fortmann, AL, Carnethon, MR, Penedo, FJ, Perreira, K, Birnbaum-Weitzman, O, Wassertheil-Smoller, S, Castañeda, SF, Talavera, GA, Sotres-Alvarez, D, Daviglus, ML, Schneiderman, N and Isasi, CR (2014). Associations of chronic stress burden, perceived stress, and traumatic stress with cardiovascular disease prevalence and risk factors in the HCHS/SOL Sociocultural Ancillary Study. Psychosomatic Medicine 76, 468475.Google Scholar
Golin, RMA, Gotoh, E, Said, SI and Ganong, WF (1988). Pharmacological evidence that the sympathetic nervous system mediates the increase in renin secretion produced by immobilization and head-up tilt in rats. Neuropharmacology 27, 12091213.Google Scholar
Goodwin, RD and Stein, MB (2004). Association between childhood trauma and physical disorders among adults in the United States. Psychological Medicine 34, 509520.Google Scholar
Groeschel, M and Braam, B (2011). Connecting chronic and recurrent stress to vascular dysfunction: no relaxed role for the renin-angiotensin system. American Journal of Physiology. Renal Physiology 300, F110.Google Scholar
Häfner, S, Baumert, J, Emeny, RT, Lacruz, ME, Bidlingmaier, M, Reincke, M, Kuenzel, H, Holle, R, Rupprecht, R and Ladwig, KH (2012). To live alone and to be depressed, an alarming combination for the renin–angiotensin–aldosterone-system (RAAS). Psychoneuroendocrinology 37, 230237.Google Scholar
Hannemann, A (2012). Populationsbasierte Ergebnisse zum Zusammenhang zwischen Renin-Angiotensin-Aldosteron System und kardiovaskulären sowie metabolischen Phänotypen. Greifswald: Univ., Diss., 2012.Google Scholar
Heim, C, Newport, DJ, Bonsall, R, Miller, AH and Nemeroff, CB (2003). Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. FOCUS 1, 282289.Google Scholar
Heim, C, Newport, DJ, Heit, S, Graham, YP, Wilcox, M, Bonsall, R, Miller, AH and Nemeroff, CB (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 284, 592597.Google Scholar
Heim, C, Newport, DJ, Mletzko, T, Miller, AH and Nemeroff, CB (2008). The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33, 693710.Google Scholar
Heim, C, Newport, DJ, Wagner, D, Wilcox, MM, Miller, AH and Nemeroff, CB (2002). The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: a multiple regression analysis. Depression and Anxiety 15, 117125.Google Scholar
Hurt, RC, Garrett, JC, Keifer, OP, Linares, A, Couling, L, Speth, RC, Ressler, KJ and Marvar, PJ (2015). Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear1. Genes, Brain and Behavior 14, 526533.Google Scholar
Jindra, A and Kvetnanskỳ, R (1982). Stress-induced activation of inactive renin. Molecular weight aspects. Journal of Biological Chemistry 257, 59975999.Google Scholar
Khoury, NM, Marvar, PJ, Gillespie, CF, Wingo, A, Schwartz, A, Bradley, B, Kramer, M and Ressler, KJ (2012). The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms. The Journal of Clinical Psychiatry 73, 849855.Google Scholar
Marvar, PJ, Goodman, J, Fuchs, S, Choi, DC, Banerjee, S and Ressler, KJ (2014). Angiotensin type 1 receptor inhibition enhances the extinction of fear memory. Biological Psychiatry 75, 864872.Google Scholar
Meewisse, M-L, Reitsma, JB, Vries, G-JD, Gersons, BPR and Olff, M (2007). Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. The British Journal of Psychiatry 191, 387392.Google Scholar
Miller, GE, Chen, E and Zhou, ES (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin 133, 25.Google Scholar
Nylocks, KM, Michopoulos, V, Rothbaum, AO, Almli, L, Gillespie, CF, Wingo, A, Schwartz, AC, Habib, L, Gamwell, KL, Marvar, PJ, Bradley, B and Ressler, KJ (2015). An angiotensin-converting enzyme (ACE) polymorphism may mitigate the effects of angiotensin-pathway medications on posttraumatic stress symptoms. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 168, 307315.Google Scholar
Pitman, RK, Sanders, KM, Zusman, RM, Healy, AR, Cheema, F, Lasko, NB, Cahill, L and Orr, SP (2002). Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biological Psychiatry 51, 189192.Google Scholar
Plotsky, PM and Meaney, MJ (1993). Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Molecular Brain Research 18, 195200.Google Scholar
Saavedra, JM, Sánchez-Lemus, E and Benicky, J (2011). Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: therapeutic implications. Psychoneuroendocrinology 36, 118.Google Scholar
Spitzer, C, Barnow, S, Völzke, H, John, U, Freyberger, HJ and Grabe, HJ (2009). Trauma, posttraumatic stress disorder, and physical illness: findings from the general population. Psychosomatic Medicine 71, 10121017.Google Scholar
Terock, J, Hannemann, A, Janowitz, D, Völzke, H, Nauck, M, Freyberger, H-J, Wallaschofski, H and Grabe, HJ (2017). Living alone and activation of the renin-angiotensin-aldosterone-system: differential effects depending on alexithymic personality features. Journal of Psychosomatic Research 96, 4248.Google Scholar
Vaiva, G, Ducrocq, F, Jezequel, K, Averland, B, Lestavel, P, Brunet, A and Marmar, CR (2003). Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biological Psychiatry 54, 947949.Google Scholar
Vandenbroucke, JP, Von Elm, E, Altman, DG, Gøtzsche, PC, Mulrow, CD, Pocock, SJ, Poole, C, Schlesselman, JJ, Egger, M and Initiative, S (2007). Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Medicine 4, e297.Google Scholar
Völzke, H, Alte, D, Schmidt, CO, Radke, D, Lorbeer, R, Friedrich, N, Aumann, N, Lau, K, Piontek, M, Born, G, Havemann, C, Ittermann, T, Schipf, S, Haring, R, Baumeister, SE, Wallaschofski, H, Nauck, M, Frick, S, Arnold, A, Jünger, M, Mayerle, J, Kraft, M, Lerch, MM, Dörr, M, Reffelmann, T, Empen, K, Felix, SB, Obst, A, Koch, B, Gläser, S, Ewert, R, Fietze, I, Penzel, T, Dören, M, Rathmann, W, Haerting, J, Hannemann, M, Röpcke, J, Schminke, U, Jürgens, C, Tost, F, Rettig, R, Kors, JA, Ungerer, S, Hegenscheid, K, Kühn, J-P, Kühn, J, Hosten, N, Puls, R, Henke, J, Gloger, O, Teumer, A, Homuth, G, Völker, U, Schwahn, C, Holtfreter, B, Polzer, I, Kohlmann, T, Grabe, HJ, Rosskopf, D, Kroemer, HK, Kocher, T, Biffar, R, John, U and Hoffmann, W (2011). Cohort profile: the study of health in Pomerania. International Journal of Epidemiology 40, 294307.Google Scholar
Williams, LM (1995). Recovered memories of abuse in women with documented child sexual victimization histories. Journal of Traumatic Stress 8, 649673.Google Scholar
Wittchen, H-U, Höfler, M, Gander, F, Pfister, H, Storz, S, Üstün, B, Müller, N and Kessler, Rc (1999). Screening for mental disorders: performance of the Composite International Diagnostic–Screener (CID–S). International Journal of Methods in Psychiatric Research 8, 5970.Google Scholar
Yang, G, Xi, Z-X, Wan, Y, Wang, H and Bi, G (1994). Changes in circulating and tissue angiotensin II during acute and chronic stress. Neurosignals 2, 166172.Google Scholar
Yehuda, R, McFarlane, A and Shalev, A (1998). Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event. Biological Psychiatry 44, 13051313.Google Scholar
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