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Role of Oxytocin in Post-traumatic Stress Disorder: A Systematic Review

외상 후 스트레스 장애에 대한 옥시토신의 역할: 체계적 문헌 고찰

  • Oh, Jaeuk (College of Nursing, Yonsei University) ;
  • Kim, Minsu (College of Nursing, Yonsei University) ;
  • Chu, Sang Hui (College of Nursing, Yonsei University)
  • Received : 2022.01.21
  • Accepted : 2022.02.21
  • Published : 2022.02.28

Abstract

Purpose: Recently, oxytocin has been introduced experimentally as a pharmacological treatment for post-traumatic stress disorder (PTSD). This study attempted to investigate the possibility of oxytocin as a treatment option for patients with PTSD by examining its dose, interval, and effectiveness in patients with PTSD. Methods: A systematic review was done on articles published from 1967 to 2020 using the PubMed, PsycINFO, and Cochrane databases. Our inclusion criteria were 1) subjects 18 years of age or older diagnosed with PTSD or exposed to a traumatic event that met criterion A of the Diagnostic and Statistical Manual of Mental Disorders (DSM) for PTSD, 2) oxytocin was administered at least once, 3) clinical trials, and 4) studies published in Korean or English. Two independent researchers reviewed 22 articles and recorded the contents. The risk of bias was evaluated to determine the quality of the reviewed article. Results: The parameters for evaluating the effectiveness of oxytocin were identified as socio-behavioral measures in 11 articles, neuronal imaging in 9, and biomarkers in 4. In 5 papers, oxytocin was administered multiple times. Socio-behavioral measures were improved in 3 out of 5 studies in which oxytocin was administered multiple times. In 2 studies in which prolonged exposure treatment and nasal oxytocin administration were combined for 10 weeks, patient symptoms were decreased compared to the control group. Conclusion: The possibility of oxytocin as an adjuvant treatment for PTSD psychotherapy was confirmed. Further studies are necessary to evaluate the long term effectiveness of administering oxytocin multiple times combined with psychotherapy.

Keywords

Acknowledgement

이 논문은 2019년도 정부(교육부)의 재원으로 한국연구재단의 지원을 받아 수행된 기초연구사업임(No. 2019R1I1A2A01058746).

References

  1. Donadon MF, Martin-Santos R, Osorio FL. The associations between oxytocin and trauma in humans: systematic review. Frontiers in Pharmacology. 2018;9:154. http://doi.org/10.3389/fphar.2018.00154
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: American Psychiatric Publishing; 2013.
  3. Miao XR, Chen QB, Wei K, Tao KM, Lu ZJ. Posttraumatic stress disorder: from diagnosis to prevention. Military Medical Research.2018;5(1):32. http://doi.org/10.1186/s40779-018-0179-0
  4. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the world mental health surveys. Psychology Medicine. 2017;47(13):2260-2274. http://doi.org/10.1017/s0033291717000708
  5. Cho MJ, Seong SJ, Park JE, Chung IW, Lee YM, Bae A, et al. Prevalence and correlates of DSM-IV mental disorders in south korean adults: the Korean epidemiologic catchment area study 2011. Psychiatry Investigation. 2015;12(2):164-170. http://doi.org/10.4306/pi.2015.12.2.164
  6. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry. 2005;62(6):593-602. http://doi.org/10.1001/archpsyc.62.6.593
  7. Van Ameringen M, Mancini C, Patterson B, Boyle MH. Post-traumatic stress disorder in Canada. CNS Neuroscience & Therapeautics. 2008;14(3):171-181. http://doi.org/10.1111/j.1755-5949.2008.00049.x
  8. van Minnen A, Zoellner LA, Harned MS, Mills K. Changes in comorbid conditions after prolonged exposure for PTSD: a literature review. Current Psychiatry Reports. 2015;17(3):549. http://doi.org/10.1007/s11920-015-0549-1
  9. Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron. 2008;58(4):639-650. http://doi.org/10.1016/j.neuron.2008.04.009
  10. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood AG, Nathan PJ, et al. Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology. 2014;39(9):2061-2069. http://doi.org/10.1038/npp.2014.53
  11. Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biological Psychiatry. 2007;62(10):1187-1190. http://doi.org/10.1016/j.biopsych.2007.03.025
  12. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, et al. Oxytocin modulates neural circuitry for social cognition and fear in humans. Journal of Neuroscience. 2005;25(49):11489-11493. http://doi.org/10.1523/jneurosci.3984-05.2005
  13. Kumar J, Vollm B, Palaniyappan L. Oxytocin affects the connectivity of the precuneus and the amygdala: a randomized, double-blinded, placebo-controlled neuroimaging trial. International Journal of Neuropsychopharmacology. 2015;18(5):pyu051. http://doi.org/10.1093/ijnp/pyu051
  14. Cardoso C, Kingdon D, Ellenbogen MA. A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: moderation by method and mental health. Psychoneuroendocrinology. 2014;49:161-170. http://doi.org/10.1016/j.psyneuen.2014.07.014
  15. Gulpinar M, Yegen B. The physiology of learning and memory: role of peptides and stress. Current Protein and Peptide Science. 2004;5(6):457-473. http://doi.org/10.2174/1389203043379341
  16. Feeser M, Fan Y, Weigand A, Hahn A, Gartner M, Boker H, et al. Oxytocin improves mentalizing - pronounced effects for individuals with attenuated ability to empathize. Psychoneuroendocrinology. 2015;53:223-232. http://doi.org/10.1016/j.psyneuen.2014.12.015
  17. Radke S, de Bruijn ER. Does oxytocin affect mind-reading? A replication study. Psychoneuroendocrinology. 2015;60:75-81. http://doi.org/10.1016/j.psyneuen.2015.06.006
  18. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 2010;35(12):2403-2413. http://doi.org/10.1038/npp.2010.123
  19. Petrovic P, Kalisch R, Singer T, Dolan RJ. Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. Journal of Neuroscience. 2008;28(26):6607-6615. http://doi.org/10.1523/jneurosci.4572-07.2008
  20. Brondino N, Fusar-Poli L, Politi P. Something to talk about: gossip increases oxytocin levels in a near real-life situation. Psychoneuroendocrinology. 2017;77:218-224. http://doi.org/10.1016/j.psyneuen.2016.12.014
  21. Gonzalez A, Jenkins JM, Steiner M, Fleming AS. The relation between early life adversity, cortisol awakening response and diurnal salivary cortisol levels in postpartum women. Psychoneuroendocrinology. 2009;34(1):76-86. http://doi.org/10.1016/j.psyneuen.2008.08.012
  22. Ozbay F, Fitterling H, Charney D, Southwick S. Social support and resilience to stress across the life span: a neurobiologic framework. Current Psychiatry Reports. 2008;10(4):304-310. http://doi.org/10.1007/s11920-008-0049-7
  23. Frijling JL, van Zuiden M, Nawijn L, Koch SB, Neumann ID, Veltman DJ, et al. Salivary oxytocin and vasopressin levels in police officers with and without post-traumatic stress disorder. Journal of Neuroendocrinology. 2015;27(10):743-751. http://doi.org/10.1111/jne.12300
  24. Opacka-Juffry J, Mohiyeddini C. Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men. Stress. 2012;15(1):1-10. http://doi.org/10.3109/10253890.2011.560309
  25. Cardoso C, Ellenbogen MA, Orlando MA, Bacon SL, Joober R. Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study. Psychoneuroendocrinology. 2013;38(3):399-407. http://doi.org/10.1016/j.psyneuen.2012.07.013
  26. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Review. 2006;2006(1):Cd002795. http://doi.org/10.1002/14651858.CD002795.pub2
  27. Foa EB, Keane TM, Friedman MJ, Cohen JA. Effective treatments for PTSD: practice guidelines from the international society for traumatic stress studies. New York: Guilford press; 2010. p.15-16.
  28. Jonas DE, Cusack K, Forneris CA, Wilkins TM, Sonis J, Middleton JC, et al. Psychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD). Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Apr. Report No.: 13-EHC011-EF.
  29. Cusack K, Jonas DE, Forneris CA, Wines C, Sonis J, Middleton JC, et al. Psychological treatments for adults with posttraumatic stress disorder: a systematic review and meta-analysis. Clinical psychology review. 2016;43:128-141. http://doi.org/10.1016/j.cpr.2015.10.003
  30. Lee DJ, Schnitzlein CW, Wolf JP, Vythilingam M, Rasmusson AM, Hoge CW. Psychotherapy versus pharmacotherapy for posttraumatic stress disorder: systemic review and meta-analyses to determine first-line treatments. Depression and anxiety. 2016;33(9):792-806. http://doi.org/10.1002/da.22511
  31. Courtois CA, Sonis JH, Brown LS, Cook JM, Fairbank JA, Friedman MJ, et al. Summary of the clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD) in adults. The American psychologist. 2019;74(5):596-607. http://doi.org/10.1037/amp0000473
  32. Bradley R, Greene J, Russ E, Dutra L, Westen D. A multidimensional meta-analysis of psychotherapy for PTSD. American Journal of Psychiatry. 2005;162(2):214-227. http://doi.org/10.1176/appi.ajp.162.2.214
  33. Choi YK. Evidence-based treatment of posttraumatic stress disorder. Korean Journal of Clinical Psychology. 2017;36(4):526-549. http://doi.org/10.15842/kjcp.2017.36.4.006
  34. Dunlop BW, Mansson E, Gerardi M. Pharmacological innovations for posttraumatic stress disorder and medication- enhanced psychotherapy. Current Pharmaceutical Design. 2012;18(35):5645-5658. http://doi.org/10.2174/138161212803530899
  35. Giovanna G, Damiani S, Fusar-Poli L, Rocchetti M, Brondino N, de Cagna F, et al. Intranasal oxytocin as a potential therapeutic strategy in post-traumatic stress disorder: a systematic review. Psychoneuroendocrinology. 2020;115:104605. http://doi.org/10.1016/j.psyneuen.2020.104605
  36. Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, et al. The clinician-administered PTSD scale for DSM-5 (CAPS-5): development and initial psychometric evaluation in military veterans. Psychological Assessment. 2018;30(3):383-395. http://doi.org/10.1037/pas0000486
  37. Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. The PTSD checklist for DSM-5 (PCL-5) [Internet].U.S: National Center for PTSD. 2013 [cited 2021 Oct 12]. Available from: https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp#obtain
  38. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane collaboration's tool for assessing risk of bias in randomised trials. 2011;343:d5928.https://doi.org/10.1136/bmj.d5928
  39. Janezic EM, Uppalapati S, Nagl S, Contreras M, French ED, Fellous JM. Beneficial effects of chronic oxytocin administration and social co-housing in a rodent model of post-traumatic stress disorder. Behavioural Pharmacology. 2016;27(8):704-717. http://doi.org/10.1097/fbp.0000000000000270
  40. Rauch SAM, Kim HM, Powell C, Tuerk PW, Simon NM, Acierno R, et al. Efficacy of prolonged exposure therapy, sertraline hydrochloride, and their combination among combat veterans with posttraumatic stress disorder: a randomized clinical trial. Journal of American Medical Association Psychiatry. 2019;76(2):117-126. http://doi.org/10.1001/jamapsychiatry.2018.3412
  41. Hembree EA, Rauch SAM, Foa EB. Beyond the manual: The insider's guide to prolonged exposure therapy for PTSD. Cognitive and Behavioral Practice. 2003;10(1):22-30. https://doi.org/10.1016/S1077-7229(03)80005-6
  42. Flanagan JC, Mitchell JM. Augmenting treatment for posttraumatic stress disorder and co-occurring conditions with oxytocin. Current Treatment Options in Psychiatry. 2019;6(2):132-142. http://doi.org/10.1007/s40501-019-00171-1
  43. Dhuria SV, Hanson LR, Frey II WH. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. Journal of Pharmaceutical Sciences. 2010;99(4):1654-1673. http://doi.org/10.1002/jps.21924
  44. Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opinion on Drug Delivery. 2012;9(1):19-31. http://doi.org/10.1517/17425247.2012.636801
  45. Guastella AJ, Hickie IB, McGuinness MM, Otis M, Woods EA, Disinger HM, et al. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research. Psychoneuroendocrinology. 2013;38(5):612-625. http://doi.org/10.1016/j.psyneuen.2012.11.019
  46. Yoon JS, Kim MS, Chu SH. Trends in brain imaging research on refugees with post-traumatic stress disorder: a scoping review. Journal of Korean Biological Nursing Science. 2021;23(3):159-169. http://doi.org/10.7586/jkbns.2021.23.3.159
  47. Molina PE. Appendix: normal values of metabolic parameters and tests of endocrine function. Endocrine Physiology. 4e. New York, NY: The McGraw-Hill Companies; 2013.
  48. Maestrini S, Mele C, Mai S, Vietti R, Di Blasio A, Castello L, et al. Plasma oxytocin concentration in pre- and postmenopausal women: its relationship with obesity, body composition and metabolic variables. Obesity Facts. 2018;11(5):429-439. http://doi.org/10.1159/000492001
  49. Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, et al. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nature Communications. 2014;5:4082-4082. http://doi.org/10.1038/ncomms5082
  50. Piantadosi S. Clinical Trials: A Methodologic Perspective. 2nd edition. Hoboken: Wiley Blackwell; 2005. p. 684-697.
  51. Cho Y, Kim C, Kang B. Risk of bias assessment of randomised controlled trials referenced in the 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care: a cross-sectional review. British Medical Journal Open. 2019;9(5):e023725-e023725. http://doi.org/10.1136/bmjopen-2018-023725