Symptoms Associated with Abnormal Epinephrine Levels

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Affective Disorders and Mood[edit]

Panic disorder and phobias. Epinephrine-induced activation of β receptors has been suggested as a mechanism for the onset of spontaneous panic attacks in those with panic disorder and social phobia.[1] Several studies have shown that infusing epinephrine leads to anxiety-like symptoms.[1][2][3] More recent data show that those who panic in response to epinephrine are more likely to have a greater cardiovascular response to epinephrine and a greater fall in transcutaneous carbon dioxide pressure than those who do not panic in response to epinephrine.[1] However, research also suggest that increasing plasma epinephrine levels is not sufficient for causing social anxiety.[4]

Anxiety and depression. Epinephrine is related to anxiety, with several clinical implications beyond psychiatric health. For instance, epinephrine and resulting anxiety can impact the duration of labor and the well-being of the baby.[5]

Cognition[edit]

Cognitive functioning. Epinephrine is implicated in a number of areas of cognition. One study has found that older men with higher levels of urinary epinephrine are more likely to suffer cognitive decline based on assessments of spatial recognition and construction, abstraction, language, and memory.[6]

Memory. When humans are injected with epinephrine, their memory appears to be enhanced in a dose-dependent manner.[7] Studies on the impact of epinephrine on memory suggest that the impact of epinephrine on memory is not mediated by changes in attention but rather through improved memory consolidation. The evidence for the role of epinephrine in memory consolidation versus attention comes from observations that epinephrine achieves its effects on memory when it is administered after learning.

Behavior[edit]

According to preclinical data, epinephrine appears to increase avoidance behavior.[8] Similarly, epinephrine injections lead to exaggerations in submissive behavior.[9]

Physical Symptoms[edit]

Hypertension. Epinephrine may contribute to hypertension pathogenesis.[10][11][12] Though circulating epinephrine has little direct effect on blood pressure control, epinephrine may lead to hypertension indirectly if enough accumulates in sympathetic nerve endings and is re-released via the stimulation of sympathetic nerves.[10] It has been suggested that this mechanism for hypertension could occur only in a subset of people who have a genetic predisposition that heightens their propensity for high blood pressure.[13] On the other hand, epinephrine is said to protect against hypertension in the long-term by preventing stress and improving glucose tolerance.[14]

Epinephrine catalyzes the fight or flight response by increases the supply of both oxygen and glucose to the brain and muscle but also by increasing vasodilation and cardiac output.[15] Normally, low concentrations of epinephrine lead to vasodilation through activation of β2 receptors, while high concentrations of epinephrine lead to vasoconstriction and increased heart rate through activation of β1 receptors, as well as α1 and α2 receptors.

Obesity. Epinephrine appears to play a role in weight, with baseline excretion rates of epinephrine correlating negatively with changes in the ratio of waist-to-thigh circumference.[16] Chronic stimulation of β2 receptors with epinephrine leads to increases in protein synthesis and muscle mass as well as decreases in fat mass. Though these changes are not necessarily accompanied by overall weight changes, the reduction in visceral fat may have health benefits. Consistent with this idea, lower BMI is associated with increased excretion of epinephrine.[17]

  • Insulin resistance. Data suggest that acute epinephrine impairs the sensitivity of tissue to increases in plasma insulin levels and that this effect occurs through its action on β-adrenergic receptors.[14][18][19][20]
  • Metabolic syndrome. Endogenous epinephrine counteracts metabolic syndrome in the long-term by lowering blood glucose and blood pressure and increasing HDL cholesterol.[14] At the same time, low glucose levels stimulate epinephrine.[17]

Fatigue. Epinephrine is implicated in fatigue. Research has shown that people with chronic fatigue syndrome have both lower baseline levels of epinephrine as well as reduced responses to epinephrine.[21]

Headaches. Epinephrine has been implicated in headaches. For example, in those who have headaches induced by head-down-tilted bed rest, epinephrine levels in platelets are higher than normal.[22]

Sweating. When epinephrine is injected intradermally, it induces eccrine sweating.[23] This effect appears to occur due to an increase in active sweat secretion.

Vagal tone. Research has shown that higher levels of epinephrine are observed in the plasma of IBS patients with low vagal tone.[24]

Immunity. Epinephrine appears to play a role in immunity. For example, there is evidence that epinephrine suppresses cell-mediated immunity in preclinical models of leukemia, promoting disease progression.[25] Researchers therefore suggest that extended blockade of β receptors could improve hematological malignancies. It has also been shown that inducing epinephrine release in humans leads to suppression of innate immune responses.[26]

Tissue damage. Research on trauma has shown that patients with higher levels of epinephrine are more likely to not survive their traumas.[27] These epinephrine levels are thought to be related to tissue and endothelial damage.

References[edit]

  1. ↑ 1.0 1.1 1.2 Zijderveld, G.a.van; Veltman, D.J; Dyck, R.van; Doornen, L.J.P.van (1999). "Epinephrine-induced panic attacks and hyperventilation". Journal of Psychiatric Research. 33 (1): 73–78. doi:10.1016/S0022-3956(98)00051-X. PDF
  2. ↑ Guttmacher, Laurence B.; Murphy, Dennis L.; Insel, Thomas R. (1983). "Pharmacologic models of anxiety". Comprehensive Psychiatry. 24 (4): 312–326. doi:10.1016/0010-440X(83)90059-7. PDF
  3. ↑ Breggin, Peter Roger (1964). "THE PSYCHOPHYSIOLOGY OF ANXIETY: WITH A REVIEW OF THE LITERATURE CONCERNING ADRENALINE". The Journal of Nervous and Mental Disease. 139 (6): 558–568. doi:10.1097/00005053-196412000-00009. ISSN 0022-3018. PDF
  4. ↑ Papp LA, Gorman JM, Liebowitz MR, Fyer AJ, Cohen B, Klein DF. (1988) Epinephrine infusions in patients with social phobia. Am J Psychiatry. 145(6):733-736. doi:10.1176/AJP.145.6.733. https://doi.org/10.1176/ajp.145.6.733
  5. ↑ Lederman, Regina P.; Lederman, Edward; Bruce, Work; McCann, Daisy S. (1985). "Anxiety and epinephrine in multiparous women in labor: Relationship to duration of labor and fetal heart rate pattern". American Journal of Obstetrics and Gynecology. 153 (8): 870–877. doi:10.1016/0002-9378(85)90692-1.
  6. ↑ Karlamangla, Arun S; Singer, Burton H; Greendale, Gail A; Seeman, Teresa E (2005). "Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging". Psychoneuroendocrinology. 30 (5): 453–460. doi:10.1016/j.psyneuen.2004.11.004. PDF
  7. ↑ Cahill, Larry; Alkire, Michael T. (2003). "Epinephrine enhancement of human memory consolidation: Interaction with arousal at encoding". Neurobiology of Learning and Memory. 79 (2): 194–198. doi:10.1016/S1074-7427(02)00036-9. PDF
  8. ↑ Carley, John W.; Haynes, Jack R. (1969). "Epinephrine and Nor-Epinephrine Effects on Approach-Avoidance Behavior". Psychological Reports. 24 (1): 100–102. doi:10.2466/pr0.1969.24.1.100. ISSN 0033-2941. PDF
  9. ↑ Lawrence, Carl W.; Haynes, Jack R. (1970). "Epinephrine and Nor-Epinephrine Effects on Social Dominance Behavior". Psychological Reports. 27 (2): 195–198. doi:10.2466/pr0.1970.27.2.195. ISSN 0033-2941. PDF
  10. ↑ 10.0 10.1 Brown, M. J.; Dollery, C. T. (1984). "Adrenaline and Hypertension". Clinical and Experimental Hypertension. Part A: Theory and Practice. 6 (1–2): 539–549. doi:10.3109/10641968409062582. ISSN 0730-0077. PDF
  11. ↑ Weidmann, Peter; de Courten, Maximilian; Boehlen, Lorenz; Shaw, Sidney (1993). "The Pathogenesis of Hypertension in Obese Subjects:". Drugs. 46 (Supplement 2): 197–209. doi:10.2165/00003495-199300462-00030. ISSN 0012-6667. PDF
  12. ↑ Innes KE, Vincent HK, Taylor AG. (2007) Chronic stress and insulin resistance-related indices of cardiovascular disease risk, part 2: A potential role for mind-body therapies. Alternative Therapies in Health and Medicine. 13(5):44-51.
  13. ↑ Floras, J S (1992). "Epinephrine and the genesis of hypertension". Hypertension. 19 (1): 1–18. doi:10.1161/01.HYP.19.1.1. ISSN 0194-911X. PDF
  14. ↑ 14.0 14.1 14.2 Ziegler, Michael G.; Elayan, Hamzeh; Milic, Milos; Sun, Ping; Gharaibeh, Munir (2012). "Epinephrine and the Metabolic Syndrome". Current Hypertension Reports. 14 (1): 1–7. doi:10.1007/s11906-011-0243-6. ISSN 1522-6417. PDF
  15. ↑ Gordan, Richard; Gwathmey, Judith K; Xie, Lai-Hua (2015). "Autonomic and endocrine control of cardiovascular function". World Journal of Cardiology. 7 (4): 204. doi:10.4330/wjc.v7.i4.204. ISSN 1949-8462. PMC 4404375. PMID 25914789.CS1 maint: PMC format (link) PDF
  16. ↑ Tataranni, P. Antonio; Young, James B.; Bogardus, Clifton; Ravussin, Eric (1997). "A Low Sympathoadrenal Activity is Associated with Body Weight Gain and Development of Central Adiposity in Pima Indian Men". Obesity Research. 5 (4): 341–347. doi:10.1002/j.1550-8528.1997.tb00562.x. PDF
  17. ↑ 17.0 17.1 Paine, Nicola J.; Watkins, Lana L.; Blumenthal, James A.; Kuhn, Cynthia M.; Sherwood, Andrew (2015). "Association of Depressive and Anxiety Symptoms With 24-Hour Urinary Catecholamines in Individuals With Untreated High Blood Pressure". Psychosomatic Medicine. 77 (2): 136–144. doi:10.1097/PSY.0000000000000144. ISSN 0033-3174. PMC 5119914. PMID 25647750.CS1 maint: PMC format (link) PDF
  18. ↑ Deibert, David C.; Defronzo, Ralph A. (1980). "Epinephrine-induced Insulin Resistance in Man". Journal of Clinical Investigation. 65 (3): 717–721. doi:10.1172/JCI109718. ISSN 0021-9738. PMC 371414. PMID 6243677.CS1 maint: PMC format (link) PDF
  19. ↑ Zhang, Jianping; Niaura, Raymond; Dyer, Joshua R.; Shen, Biing-Jiun; Todaro, John F.; McCaffery, Jeanne M.; Spiro, Avron; Ward, Kenneth D. (2006). "Hostility and Urine Norepinephrine Interact to Predict Insulin Resistance: The VA Normative Aging Study". Psychosomatic Medicine. 68 (5): 718–726. doi:10.1097/01.psy.0000228343.89466.11. ISSN 0033-3174. PDF
  20. ↑ Seematter, G.; Binnert, C.; Tappy, L. (2005). "Stress and Metabolism". Metabolic Syndrome and Related Disorders. 3 (1): 8–13. doi:10.1089/met.2005.3.8. ISSN 1540-4196. PDF
  21. ↑ Strahler, Jana; Fischer, Susanne; Nater, Urs M.; Ehlert, Ulrike; Gaab, Jens (2013). "Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome". Biological Psychology. 94 (1): 160–166. doi:10.1016/j.biopsycho.2013.06.002. PDF
  22. ↑ Feuerecker, Matthias; van Oosterhout, Willebrordus P.J.; Feuerecker, Benedikt; Matzel, Sandra; Schelling, Gustav; Rehm, Markus; Vein, Alla A.; Choukèr, Alexander (2016). "Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes". Pain. 157 (5): 1072–1078. doi:10.1097/j.pain.0000000000000481. ISSN 0304-3959. PDF
  23. ↑ Hurley, Harry J.; Witkowski, Joseph A. (1961). "Mechanism of epinephrine-induced eccrine sweating in human skin". Journal of Applied Physiology. 16 (4): 652–654. doi:10.1152/jappl.1961.16.4.652. ISSN 8750-7587. PDF
  24. ↑ Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno (2014). Boone, David L. (ed.). "Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn's Disease and Irritable Bowel Syndrome". PLoS ONE. 9 (9): e105328. doi:10.1371/journal.pone.0105328. ISSN 1932-6203. PMC 4160179. PMID 25207649.CS1 maint: PMC format (link) PDF
  25. ↑ Inbar, Shelly; Neeman, Elad; Avraham, Roi; Benish, Marganit; Rosenne, Ella; Ben-Eliyahu, Shamgar (2011). Subbiah, Elankumaran (ed.). "Do Stress Responses Promote Leukemia Progression? An Animal Study Suggesting a Role for Epinephrine and Prostaglandin-E2 through Reduced NK Activity". PLoS ONE. 6 (4): e19246. doi:10.1371/journal.pone.0019246. ISSN 1932-6203. PMC 3084788. PMID 21559428.CS1 maint: PMC format (link) PDF
  26. ↑ Kox, Matthijs; van Eijk, Lucas T.; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C. G. J.; van der Hoeven, Johannes G.; Pickkers, Peter (2014). "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans". Proceedings of the National Academy of Sciences. 111 (20): 7379–7384. doi:10.1073/pnas.1322174111. ISSN 0027-8424. PMC 4034215. PMID 24799686.CS1 maint: PMC format (link) PDF
  27. ↑ Johansson, Pär Ingemar; Stensballe, Jakob; Rasmussen, Lars Simon; Ostrowski, Sisse Rye (2012). "High circulating adrenaline levels at admission predict increased mortality after trauma". Journal of Trauma and Acute Care Surgery. 72 (2): 428–436. doi:10.1097/TA.0b013e31821e0f93. ISSN 0022-5282. PDF
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