md-medicaldata


Go to content

Main menu:

 

 

 

 

 

 

 

CIP -  Каталогизација у публикацији
Народна библиотека Србије, Београд
61
MD : Medical Data : medicinska revija = medical review / glavni i odgovorni urednik Dušan Lalošević. - Vol. 1, no. 1 (2009)- . - Zemun : Udruženje za kulturu povezivanja Most Art Jugoslavija ; Novi Sad : Pasterovo društvo, 2009- (Beograd : Scripta Internacional). - 30 cm

Dostupno i na: http://www.md-medicaldata.com. - Tri puta godišnje.

ISSN 1821-1585 = MD. Medical Data
COBISS.SR-ID 158558988


THERAPEUTIC POTENTIAL OF NEUROPEPTIDE OXYTOCIN IN THE TREATMENT OF PSYCHIATRIC DISORDERS /

TERAPIJSKI POTENCIJAL NEUROPEPTIDA OKSITOCINA U TRETMANU PSIHIJATRIJSKIH POREMEĆAJA

Authors

 

Dušanka Stanić1, Bojan Batinić1, Marin Jukić1, Vesna Pešić1

1Katedra za fiziologiju, Farmaceutski fakultet, Univerzitet u Beogradu / Department of Physiology, Faculty of Pharmacy, University of Belgrade

 

UDK: 615.357:577.175.3
616.89-085


The paper was received / Rad primljen: 26.08.2020.

Accepted / Rad prihvaćen: 28.08.2020.

 


Correspondence to:


Dušanka Stanić
Katedra za fiziologiju, Farmaceutski fakultet, Univerzitet u Beogradu/
Department of Physiology, Faculty of Pharmacy, University of Belgrade
Vojvode Stepe 450, 11 221 Beograd
Tel: +381 63 361 774
e-mail: dstanic@pharmacy.bg.ac.rs

 

 

Sažetak

 

Poremećaji raspoloženja se smatraju jednim od najvećih zdravstvenih problema današnjice, zbog njihove visoke prevalence, hroničnog toka bolesti, kao i značajnog negativnog uticaja koji imaju na sam kvalitet života pojedinca. Postojeći tretmani ovih bolesti često nisu efikasni, ne obezbeđuju potpunu remisiju simptoma, niti mogu sprečiti pojavu relapsa. Ni jedan novi lek već dugo nije uveden u terapiju poremećaja raspoloženja, što jasno ukazuje na potrebu za pronalaženjem neke dodatne terapije navedenih poremećaja, koja će povećati stopu pozitivnog odgovora pacijenata na terapiju prvog izbora i omogućiti bolju kontrolu simptoma bolesti. Oksitocin je hormone peptidne strukture, uglavnom najbolje poznat po svojim efektima nakon traktilnost uterusailaktaciju. Danas je jako dobro poznato da su receptori za oksitocin široko rasprostranjeni i u mozgu, tačnije u regionima uključenim u regulaciju reproduktivnog i majčinskog ponašanja, učenja i pamćenja, kao i u delovima mozga koji učestvuju u regulaciji odgovora organizma na stress i kontroli anksioznosti. Navedena saznanja postavila su temelje značajno obimnijih istraživanja koja su podrazumevala ispitivanje uticaja oksitocina na centralni nervni sistem, pre svega na ponašanje.
Ovaj rad obuhvata dosadašnje znanje o uticaju oksitocina na aktivnost osovine hipotalamus-hipofiza-nadbubrežna žlezda, socijalno i emocionalno ponašanje, kao i o ulozi koju ovaj hormone ima u modulaciji ponašanja, kako iz studija na životinjama, tako i iz studija na humanoj populaciji. Takođe, rad pruža naučno potvrđene kliničke implikacije koje dovode u razmatranjeu potrebu oksitocina kao dodatne terapije u tretmanu velikog broja psihijatrijskih poremećaja koje karakteriše prisustvo socijalne i emocionalne disfunkcije, kao što su anksiozni i depresivni poremećaji, post-traumatski stresni sindrom, autizam, šizofrenija i zavisnost. Međutim, sve ove studije još uvek su na samom početku, i veliki broj pitanja i dalje zahteva odgovore kako bi tretman oksitocinom kod navedenih poremećaja bio ne samo efikasan, već i bezbedan.

 

 

 

Ključne reči:

oksitocin, psihijatrijski poremećaji, dodatna terapija, osovina hipotalamus-hipofiza-nadbubrežna žlezda

 

 

Abstract

 

Mood disorders are considered as one of the biggest health problems nowadays, because of their high prevalence, chronic course of illness and significant negative impact on life quality. Conventional treatments are often ineffective, cannot ensure full remission of symptoms nor prevent relapses. In the therapy of mood disorders a new drug has not been introduced for a long period of time, which clearly indicates the urge for finding some additional therapy that would improve patient response to the first line treatment, and ensure better control of the symptoms. Oxytocin is a nonapeptide hormone mostly known by its effects on uterine contractions and lactation. Today, it is well known that oxytocin receptors are widely distributed in the brain regions involved in regulation of reproduction, maternal behavior, learning and memory, as well as stress response and anxiety. Those findings laid the groundwork for significantly larger body of research that involved investigations of oxytocin effects in the central nervous system, especially on behaviour.
This paper summarizes "up to date" knowledge about oxytocin effects on the Hypothalamic-Pituitary-Adrenal axis activity, social and emotional behaviour, as well as its role in the modulation of behaviour from both, animal and human studies. It also provides scientifically proven clinical implications about considering oxytocin as additional therapy in the treatment of a large number of psychiatric disorders characterized by social and emotional dysfunction such as anxiety disorders, depression, post-traumatic stress syndrome, autism, schizophrenia and addiction. However those studies are still at their early beginning, and various issues need to be solved in order to establish oxytocin as effective and safe treatment option.

 

 

Key words:

Oxytocin, Psychiatric disorders, Additional therapy, Hypothalamic-pituitary-Adrenal axis

 

 

References:

  1. Zhao Y, Ma R, Shen J, Su H, Xing D, Du L. A mouse model of depression induced by repeated corticosterone injections. Eur. J. Pharmacol. 2008; 58: 113-20.
  2. Gold PW. The organization of the stress system and its dysregulation in depressive illness. Mol. Psych. 2014; 20: 32-47.
  3. Blanco C, Bragdon LB, Schneier FR, Liebowitz MR. The evidence-based pharmacotherapy of social anxiety disorder. Int. J. Neuropsychopharmacol. 2013; 16(01): 235-49.
  4. Clark SL, Adkins DE, Aberg K, Hettema JM, McClay JL, Souza RP, van den Oord EJ. Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D. Psychol. Med. 2012; 42: 1151–62.
  5. Lee HJ, Macbeth AH, Pagani J, Young WS. Oxytocin: the great facilitator of life. Prog. Neurobiol. 2009; 88: 127-51.
  6. Ott I, Scott JC. The Action of Infundibulum upon Mammary Secretion. Proc. Soc. Exp. Biol. 1910; 8: 48–9.
  7. Du Vigneaud V, Ressler C, Trippett S. The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J. Biol. Chem. 1953; 205: 949–57.
  8. Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H. Structure and expression of a human oxytocin receptor. Nature. 1992; 356: 526–9.
  9. Gimpl G. Oxytocin receptor ligands: a survey of the patent literature. Expert Opinion on Therapeutic Patents. 2008; 18: 1239–51.
  10. Manning M, Cheng LL, Klis WA, Stoev S, Przybzlski J, Bankowski K, Sawyer WH, Barberis C, Chan WY. Advances in the design of selective antagonists, potential tocolytics, and radioiodinated ligands for oxytocin receptors. Adv. Exp. Med. Biol. 1995; 395: 559-83.
  11. Ivell R, Richter D. The gene for the hypothalamic peptide hormone oxytocin is highly expressed in the bovine corpus luteum: biosynthesis, structure and sequence analysis. EMBO J. 1984; 3: 2351–4.
  12. McNeilly AS. The blood levels of oxytocin during suckling and hand-milking in the goat with some observations on the pattern of hormone release. J. Endocrinol. 1972; 52. 177-88.
  13. Pickering BT, Birkett SD, Guldenaar SE, Nicholson HD, Worley RT, Yavachev L. Oxytocin in the testis: what, where, and why? Ann. N.Y. Acad. Sci. 1989; 564. 198-209.
  14. Bodanszky M, Sharaf H, Roy JB, Said SI. Contractile activity of vasotocin, oxytocin, and vasopressin on mammalian prostate. Eur. J. Pharmacol. 1992; 2016: 311-3.
  15. Verbalis JG, Dohanics J. Vasopressin and oxytocin secretion in chronically hyposmolar rats. Am. J. Physiol. Regulatory IntegrativeComp. Physiol.1991; 261: 1028–38.
  16. Petty MA, Lang RE, Unger T, Ganten D. The cardiovascular effects of oxytocin in conscious male rats. Eur. J. Pharmacol.1985; 112: 203–10.
  17. Geenen V, Legros JJ, Franchimont P, Baudrihaye M, Defresne MP, Boniver J. The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus. Science1986; 232: 508–11.
  18. Dunning BE, Moltz JH, Fawcett CP. Modulation of insulin and glucagon secretion from the perfused rat pancreas by the neurohypophysial hormones and by desamino-D-arginine vasopressin (DDAVP). Peptides 1984; 5: 871–5.
  19. Nussey SS, Prysor-Jones RA, Taylor A, Ang VT, Jenkins JS. Arginine vasopressin and oxytocin in the bovine adrenal gland. J. Endocrinol. 1987; 115: 141-9.
  20. Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E and others. REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci. Ther. 2010; 16: 138-156.
  21. Li X, Schwartz P, Rissman E. Distribution of estrogenreceptor-beta-like immunoreactivity in rat forebrain.Neuroendocrinol.1997; 66: 63–7.
  22. Febo M, Shields J, Ferris C, King J. Oxytocin modulatesunconditioned fear response in lactating dams: An fMRIstudy. Brain Res. 2009; 1302: 183–193.
  23. Bethlehem RAI, Lombardo MV, Lai MC, Auyeung B, Crockford SK, Deakin J, Soubramanian S, et al. Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women. Transl. psych. 2017; e1099.
  24. Landgraf R and Neumann ID. Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front. Neuroendocrinol. 2004; 25: 150–76.
  25. Naja WJ and Aoun MP. Oxytocin and anxiety disorders: Translational and therapeutic aspects. Curr. Psych. Rep. 2017; 19: 67-79.
  26. Mottolese R, Redoute J, Costes N, et al. Switching brain serotonin with oxytocin. Proc. Natl. Acad. Sci. U.S.A. 2014; 111 (23): 8637-42.
  27. Svanidze M, Bukiya N, Butskhrikidze M. Effect of oxytocin on the emotional state and behavior of rats under stress conditions. Neurophysiol. 2012; 43: 422-5.
  28. Zheng J, Babygirija R, Bulbul M, Cerjak D, Ludwig K, Takahashi T. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 2009; 299: 946-53.
  29. Rash JA and Campbell TS. The effect of intranasal oxytocin administration on acute cold pressor pain: a placebo-controlled, double-blind, within-participants crossover investigation. Psychosom. Med. 2014; 76: 422-9.
  30. Lieberwirth C and Wang Z. Social bonding: regulation by neuropeptides. Front. Neurosci. 2014; 8: 171.
  31. Guzman YF, Tronson NC, Sato K, Mesic I, Guedea AL, Nishimori K, Radulovic J. Role of oxytocin receptors in modulation of fear by social memory. Psychopharmacol. 2014; 231: 2097-105.
  32. Levine A, Zagoory-Sharon O, Feldman R, et al. Oxytocin during pregnancy and early postpartum: individual patterns and maternal-fetal attachment. Peptides 2007; 28: 1162–69.
  33. Gordon I, Zagoory-Sharon O, Schneiderman I, et al. Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress. Psychophysiol. 2008; 45: 349–52.
  34. Nakajima M, Gorlich A, Heintz N. Oxytocin modulates female sociosexualbehavior through a specific class of prefrontal cortical interneurons. Cell 2014; 159: 295-305.
  35. Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V,  et al. Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol. Psych.2015; 69: 875–82.
  36. Plećaš B, Hristić M, Jovović D, Popović A. The response of rat adrenal zona fasciculate and reticularis to oxytocin treatment. Exp. Clin. Endocrinol. 1990; 95: 192-6.
  37. Plećaš B, Ugrešić N, Hristić M, Popović A, Jovović D. The response of rat adrenal medulla to oxytocin. Arch. Int. Physiol. Biochim. 1989; 97: 303-8.
  38. Stanić D, Plećaš-Solarović B, Mirković D, Jovanović P, Dronjak S, Marković B, đorđević T, Ignjatović S, Pešić V. Oxytocin in corticosterone-induced chronic stress model: Focus on adrenal gland function. Psychoneuroendocrinology. 2017; 80: 137-146.
  39. Windle RJ, Kershaw YM, Shanks N, Wood SA, Lightman SL, Ingram CD. Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. J. Neurosci. 2004; 24: 2974-82.
  40. Aspe-Sanchez M, Moreno M, Rivera MI, Rossi A, Ewer J. Oxytocin and vasopressin receptor gene polymorphisms: role in social and psychiatric traits. Front. In Neurosci. 2016; 9: 510.
  41. Meyer-Lindenberg A, Domes G, Kirsch P, et al. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat. Rev. Neurosci. 2011; 12: 524–38.
  42. Wu S, Jia M, Ruan Y, Liu J, Guo Y, Shuang M, et al. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol. Psych.2005; 58: 74–7.
  43. Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook  EHJ. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci. Lett. 2007; 417: 6–9.
  44. Myers AJ, Williams L, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR, Nemeroff CB. Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. J. Psych. Res. 2014; 59: 93-100.
  45. Golimbet V, Alfimova M, Abramova L, Kaleda V, Gritsenko I.  Arginine vasopressin 1a receptor RS3 promoter microsatellites in schizophrenia: a study of the effect of the “risk” allele on clinical symptoms and facial affect recognition.  Psych. Res. 2015;225: 739–40.
  46. Ziegler C, Dannlowski U, Brauer D, Stevens S, Laeger I, Wittmann H, et al. Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety. Neuropsychopharmacol. 2015; 40(6): 1528-38. 
  47. Jones C, Barrera I, Brothers S, Ring R, Wahlestedt C. Oxytocin and social functioning. Dial. Clin. Neurosci. 2017; 19(2): 193-201.
  48. Martinetz S and Neumann I. The potential of oxytocin as a therapeutic target for psychiatric disorders. Expert Opin. Ther. Targets. 2016; 20(5): 515-8.
  49. Leng G and Ludwig M. Intranasal oxytocin: myths and delusions. Biol. Psych. 2015; 79(3): 243-50.
  50. Neumann ID, Maloumby R, Beiderbeck DI, et al. Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology. 2013; 38(10): 1985-93.
  51. Tanaka A, Furubayashi T, Arai M, et al. Delivery of oxytocin to the brain for the treatment of autism spectrum disorder by nasal application. Mol. Pharm. 2018; 15: 1105-11. 
  52. Lefevre A, Hurlemann R, Grinevich V. Imaging neuropeptide effects on human brain function. Cell Tiss. Res. 2019; 375: 279-86.
  53. Poisbeau P, Grinevich V, Charlet A. oxytocin signalling in pain: cellular, circuit, system and behavioural levels. Curr. Top. Behav. Neurosci. 2017; 35: 193-211.
  54. Labuschagne I, Phan KL, Wood A. et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 2010; 35(12): 2403-13.
  55. Labuschagne I, Phan KL, Wood A, et al. Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. Int. J. Neuropsychopharmacol. 2012; 15(7): 883-96.
  56. Gorka SM, Fitzgerald DA, Labuschagne I, et al. Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder. Neuropsychopharmacology. 2015; 40(2): 278-86.
  57. Guastella AJ, Howard AL, Dadds MR, Mitchell P, Carson DS. A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology. 2009; 34(6): 917-23.
  58. 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 an mental health. Psychoneuroendocrinology. 2014; 49: 161-70.
  59. Wirth MM, Gaffey AE, Martinez BS. Effects of intranasal oxytocin on steroid hormones in men and women. Neuropsychobiology. 2015; 71(4): 202-11.
  60. Neumann ID and Slattery DA. Oxytocin in general anxiety and social fear: a translational approach. Biol. Psychiatry. 2016; 79(3): 234-42.
  61. ScantamburloG, Hansenne M, Fuchs S, Pitchot W, Marechal P, Pequeux C, Ansseau M, Legros JJ. Plasmaoxytocinlevelsandanxiety in patientswith major depression. Psychoneuroendocrinology. 2007; 32(4): 407-10.
  62. Scantamburlo G, Hansenne M, Geenen V, Legros JJ, Ansseau, M., 2015. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: an open trial. Eur. Psych. 30, 65-68.
  63. Mah BL, Van Ijzendorn MH, Smith R, Bakermans-Krangenburg MJ. Oxytocin in postnatally depressed mothers: its influence on mood and expressed emotion. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2013; 40: 267-72.
  64. Mah BL, Bakermans-Krangenburg MJ, Van IMH, Smith R. Oxytocin promotes protective behavior in depressed mothers: a pilot study with the enthusiastic stranger paradigm. Depress. Anxiety. 2015; 32: 76-81.
  65. Hou Y, Zhao L, Zhang G, Ding L. Effects of oxytocin on the fear memory reconsolidation. Neurosci. Lett. 2015; 594: 1-4.
  66. Acheson D, Feifel D, de Wilde S, Mckinney R, Lohr J, Risbrough V. The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample. Psychopharmacology. 2013; 229(1): 199-208.
  67. Feifel D, MacDonald K, Nguyen A, Cobb P, Warlan H, Galangue B. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol. Psychiatry. 2010; 68(7): 678-80.
  68. Feifel D, Shilling D, MacDonald K. A review of oxytocin’s effects on the positive, negative and cognitive domains of schizophrenia. Biol. Psychiatry. 2015; 79(3): 222-3.
  69. Davis Mc, Lee J, Horan WP, et al. Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr. Res. 2013; 147(2-3): 393-7. 
  70. Preti A, Melis M, Siddi S, Vellante M, Doneddu G, Fadda R. Oxytocin and autism: a systematic review of randomized controlled trials. J. Child. Adolesc. Psychopharmacol. 2014; 24(2): 54-68.
  71. Hollander E, Bartz J, Chaplin W, et al. Oxytocin increases retention of social cognition in autism. Biol. Psychiatry. 2007; 61(4): 498-503.
  72. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci. USA. 2010; 107(9): 4389-94.
  73. Baracz SJ, Everett NA, Cornish JL. The impact of early life stress on the central oxytocin system and susceptibility for drug addiction: Applicability of oxytocin as a pharmacotherapy. Neurosci. Biobehav. Rev. 2020; 110: 114-32.
  74. Pedersen CA. Oxytocin, tolerance and the dark side of addiction. Int. Rev. Neurobiol. 2017; 136: 239-74.
  75. Koob GF. The dark side of emotion: The addiction perspective. Eur. J. Pharmacol. 2015; 753: 73-87.
  76. Kim YR, Kim CH, Cardi V, Eom JS, Seong Y, Treasure J. Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa. Psychoneuroendocrinology. 2014; 44: 133-42.

PDF Stanić D. et al • MD-Medical Data 2020;12(3) 133-138

 

 

 

Naslovna | Revija | Galerija | Dešavanja | Instrukcije | Redakcija | Izdavač | Prijatelji sajta | Saradnja | Kontakt | Site Map


Back to content | Back to main menu