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The Relationship between Plasma Oxytocin Levels and Social Anxiety Symptoms

  • Oh, Kang-Seob (Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kim, Eun-Jin (Workplace Mental Health Institute, Kangbuk Samsung Hospital) ;
  • Ha, Ju-Won (Yonsei Forest Mental Health Clinic) ;
  • Woo, Hee-Yeon (Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kwon, Min-Jung (Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Shin, Dong-Won (Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Shin, Young-Chul (Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Lim, Se-Won (Department of Psychiatry, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine)
  • 투고 : 2017.06.23
  • 심사 : 2018.08.31
  • 발행 : 2018.11.30

초록

Objective The pathophysiology of social anxiety disorder (SAD) is not yet well understood, but previous research has suggested that oxytocin is associated with social behavior and may play a role in human anxiety states and anxiety-related traits. The aim of this study was to investigate the possible relationship between social anxiety symptoms and plasma oxytocin levels. Methods Twenty-three male patients with SAD and 28 healthy male controls participated in this study. All participants were assessed using the Mini International Neuropsychiatric Interview (MINI) and the Liebowitz Social Anxiety Scale (LSAS). Multivariate regression analysis was performed to identify associations between plasma oxytocin levels and SAD. Results In multiple regression models, after controlling for age and years of education, we found that higher oxytocin levels were significantly associated with higher total LSAS scores ($R^2=0.157$, coefficient=0.145, 95% CI=-0.0005-0.291, p=0.051) and fear subscale scores ($R^2=0.134$, coefficient=0.083, 95% CI=0.007-0.159, p=0.034) in the SAD group. Conclusion In this study, increased plasma oxytocin levels were associated with higher social anxiety symptoms among SAD patients, but not among controls. This might be because among SAD patients, higher oxytocin (OT) secretion is an insufficient compensatory attempt to reduce social anxiety symptoms.

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참고문헌

  1. Toth I, Neumann ID. Animal models of social avoidance and social fear. Cell Tissue Res 2013;354:107-118. https://doi.org/10.1007/s00441-013-1636-4
  2. Aderka IM, McLean CP, Huppert JD, Davidson JR, Foa EB. Fear, avoidance and physiological symptoms during cognitive-behavioral therapy for social anxiety disorder. Behav Res Ther 2013;51:352-358. https://doi.org/10.1016/j.brat.2013.03.007
  3. Marazziti D, Abelli M, Baroni S, Carpita B, Ramacciotti CE, Dell'Osso L. Neurobiological correlates of social anxiety disorder: an update. CNS Spectr 2015;20:100-111. https://doi.org/10.1017/S109285291400008X
  4. Stevens FL, Weisman O, Feldman R, Hurley RA, Taber KH. Oxytocin and behavior: evidence for effects in the brain. J Neuropsychiatry Clin Neurosci 2013;25:96-102. https://doi.org/10.1176/appi.neuropsych.13030061
  5. Sofroniew MV. Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res 1983;60:101-114.
  6. Ozsoy S, Esel E, Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res 2009;169:249-252. https://doi.org/10.1016/j.psychres.2008.06.034
  7. Uvnas-Moberg K. Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology 1998;23:819-835. https://doi.org/10.1016/S0306-4530(98)00056-0
  8. Ross HE, Young LJ. Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 2009;30:534-547. https://doi.org/10.1016/j.yfrne.2009.05.004
  9. Pedersen CA, Caldwell JD, Peterson G, Walker CH, Mason GA. Oxytocin activation of maternal behavior in the rat. Ann N Y Acad Sci 1992;652:58-69. https://doi.org/10.1111/j.1749-6632.1992.tb34346.x
  10. Huber D, Veinante P, Stoop R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 2005;308:245-248. https://doi.org/10.1126/science.1105636
  11. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev 2001;81:629-683. https://doi.org/10.1152/physrev.2001.81.2.629
  12. Evans KC, Wright CI, Wedig MM, Gold AL, Pollack MH, Rauch SL. A functional MRI study of amygdala responses to angry schematic faces in social anxiety disorder. Depress Anxiety 2008;25:496-505. https://doi.org/10.1002/da.20347
  13. Goldin PR, Manber T, Hakimi S, Canli T, Gross JJ. Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. Arch Gen Psychiatry 2009;66:170-180. https://doi.org/10.1001/archgenpsychiatry.2008.525
  14. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, et al. Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. Int J Neuropsychopharmacol 2012;15:883-896. https://doi.org/10.1017/S1461145711001489
  15. 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;39:2061-2069. https://doi.org/10.1038/npp.2014.53
  16. 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;35:2403-2413. https://doi.org/10.1038/npp.2010.123
  17. Amico JA, Mantella RC, Vollmer RR, Li X. Anxiety and stress responses in female oxytocin deficient mice. J Neuroendocrinol 2004;16:319-324. https://doi.org/10.1111/j.0953-8194.2004.01161.x
  18. Neumann ID. Involvement of the brain oxytocin system in stress coping: interactions with the hypothalamo-pituitary-adrenal axis. Prog Brain Res 2002;139:147-162.
  19. Miller MW, McKinney AE, Kanter FS, Korte KJ, Lovallo WR. Hydrocortisone suppression of the fear-potentiated startle response and posttraumatic stress disorder. Psychoneuroendocrinology 2011;36:970-980. https://doi.org/10.1016/j.psyneuen.2010.12.009
  20. Wojciak P, Remlinger-Molenda A, Rybakowski J. The role of oxytocin and vasopressin in central nervous system activity and mental disorders. Psychiatr Pol 2012;46:1043-1052.
  21. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 2003;54:1389-1398. https://doi.org/10.1016/S0006-3223(03)00465-7
  22. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature 2005;435:673-676. https://doi.org/10.1038/nature03701
  23. Rimmele U, Hediger K, Heinrichs M, Klaver P. Oxytocin makes a face in memory familiar. J Neurosci 2009;29:38-42. https://doi.org/10.1523/JNEUROSCI.4260-08.2009
  24. Evans SL, Dal Monte O, Noble P, Averbeck BB. Intranasal oxytocin effects on social cognition: a critique. Brain Res 2014;1580:69-77. https://doi.org/10.1016/j.brainres.2013.11.008
  25. Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Marechal P, Pequeux C, et al. Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology 2007;32:407-410. https://doi.org/10.1016/j.psyneuen.2007.01.009
  26. Hoge EA, Lawson EA, Metcalf CA, Keshaviah A, Zak PJ, Pollack MH, et al. Plasma oxytocin immunoreactive products and response to trust in patients with social anxiety disorder. Depress Anxiety 2012;29:924-930. https://doi.org/10.1002/da.21973
  27. Hoge EA, Pollack MH, Kaufman RE, Zak PJ, Simon NM. Oxytocin levels in social anxiety disorder. CNS Neurosci Ther 2008;14:165-170. https://doi.org/10.1111/j.1755-5949.2008.00051.x
  28. Leckman JF, Goodman WK, North WG, Chappell PB, Price LH, Pauls DL, et al. Elevated cerebrospinal fluid levels of oxytocin in obsessivecompulsive disorder. Comparison with Tourette's syndrome and healthy controls. Arch Gen Psychiatry 1994;51:782-792. https://doi.org/10.1001/archpsyc.1994.03950100030003
  29. American Psychiatric Association. Diagnostic and Stastical Manual of Mental Disorders. Washington DC: American Psychiatric Association; 1994.
  30. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(Suppl 20):22-33; quiz 34-57.
  31. Heimberg RG, Horner KJ, Juster HR, Safren SA, Brown EJ, Schneier FR, et al. Psychometric properties of the Liebowitz Social Anxiety Scale. Psychol Med 1999;29:199-212. https://doi.org/10.1017/S0033291798007879
  32. Liebowitz MR, Gorman JM, Fyer AJ, Klein DF. Social phobia. Review of a neglected anxiety disorder. Arch Gen Psychiatry 1985;42:729-736. https://doi.org/10.1001/archpsyc.1985.01790300097013
  33. Yu ES, Ahn CI, Park KH. Factor structure and diagnostic efficiency of a Korean version of the Liebowitz social anxiety scale. Korean J Clin Psychol 2007;26:251-270. https://doi.org/10.15842/kjcp.2007.26.1.015
  34. Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci 2011;15:301-309.
  35. Van Ijzendoorn MH, Bakermans-Kranenburg MJ. A sniff of trust: metaanalysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group. Psychoneuroendocrinology 2012;37:438-443. https://doi.org/10.1016/j.psyneuen.2011.07.008
  36. MacDonald K, MacDonald TM, Brune M, Lamb K, Wilson MP, Golshan S, et al. Oxytocin and psychotherapy: a pilot study of its physiological, behavioral and subjective effects in males with depression. Psychoneuroendocrinology 2013;38:2831-2843. https://doi.org/10.1016/j.psyneuen.2013.05.014
  37. Marazziti D, Dell'Osso B, Baroni S, Mungai F, Catena M, Rucci P, et al. A relationship between oxytocin and anxiety of romantic attachment. Clin Pract Epidemiol Ment Health 2006;2:28. https://doi.org/10.1186/1745-0179-2-28
  38. Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry 1998;43:270-277. https://doi.org/10.1016/S0006-3223(97)00439-3
  39. Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry 2001;50:609-613. https://doi.org/10.1016/S0006-3223(01)01139-8
  40. Wotjak CT, Ganster J, Kohl G, Holsboer F, Landgraf R, Engelmann M. Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience 1998;85:1209-1222. https://doi.org/10.1016/S0306-4522(97)00683-0
  41. Neumann ID. Stimuli and consequences of dendritic release of oxytocin within the brain. Biochem Soc Trans 2007;35:1252-1257. https://doi.org/10.1042/BST0351252
  42. Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry 2001;6:13-34. https://doi.org/10.1038/sj.mp.4000812
  43. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 2007;164:1476-1488. https://doi.org/10.1176/appi.ajp.2007.07030504
  44. McManus F, Sacadura C, Clark DM. Why social anxiety persists: an experimental investigation of the role of safety behaviours as a maintaining factor. J Behav Ther Exp Psychiatry 2008;39:147-161. https://doi.org/10.1016/j.jbtep.2006.12.002
  45. Goossens L, Sunaert S, Peeters R, Griez EJ, Schruers KR. Amygdala hyperfunction in phobic fear normalizes after exposure. Biol Psychiatry 2007;62:1119-1125. https://doi.org/10.1016/j.biopsych.2007.04.024
  46. Hauner KK, Mineka S, Voss JL, Paller KA. Exposure therapy triggers lasting reorganization of neural fear processing. Proc Natl Acad Sci U S A 2012;109:9203-9208. https://doi.org/10.1073/pnas.1205242109
  47. Vouimba RM, Maroun M. Learning-induced changes in mPFC-BLA connections after fear conditioning, extinction, and reinstatement of fear. Neuropsychopharmacology 2011;36:2276-2285. https://doi.org/10.1038/npp.2011.115
  48. Gouzenes L, Desarmenien MG, Hussy N, Richard P, Moos FC. Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular vasopressin neurons. J Neurosci 1998;18:1879-1885. https://doi.org/10.1523/JNEUROSCI.18-05-01879.1998
  49. Insel TR, Shapiro LE. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc Natl Acad Sci U S A 1992;89:5981-5985. https://doi.org/10.1073/pnas.89.13.5981
  50. Keverne EB, Kendrick KM. Oxytocin facilitation of maternal behavior in sheep. Ann N Y Acad Sci 1992;652:83-101. https://doi.org/10.1111/j.1749-6632.1992.tb34348.x
  51. Amico JA, Levin SC, Cameron JL. Circadian rhythm of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys: effects of castration and adrenalectomy and presence of a caudal-rostral gradient. Neuroendocrinology 1989;50:624-632. https://doi.org/10.1159/000125291
  52. Calza L, Pozza M, Coraddu F, Farci G, Giardino L. Hormonal influences on brain ageing quality: focus on corticotropin releasing hormone-, vasopressin- and oxytocin-immunoreactive neurones in the human brain. J Neural Transm (Vienna) 1997;104:1095-1100. https://doi.org/10.1007/BF01273321
  53. Wierda M, Goudsmit E, Van der Woude PF, Purba JS, Hofman MA, Bogte H, et al. Oxytocin cell number in the human paraventricular nucleus remains constant with aging and in Alzheimer's disease. Neurobiol Aging 1991;12:511-516. https://doi.org/10.1016/0197-4580(91)90081-T

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