Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-05T05:13:41.810Z Has data issue: false hasContentIssue false
  • English
  • Français

Oxytocin and vasopressin levels are decreased in the plasma of male schizophrenia patients

Published online by Cambridge University Press:  07 October 2013

Andrea Jobst ,
Sandra Dehning ,
Simone Ruf ,
Tobias Notz ,
Anna Buchheim ,
Kristina Henning-Fast ,
Dominik Meißner ,
Sebastian Meyer ,
Brigitta Bondy  and
Norbert Müller
...Show all authors
Andrea Jobst*
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Sandra Dehning
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Simone Ruf
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Tobias Notz
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Anna Buchheim
Affiliation:
Department of Psychology, Clinical Psychology, University of Innsbruck, Innsbruck, Austria
Kristina Henning-Fast
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Dominik Meißner
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Sebastian Meyer
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Brigitta Bondy
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Norbert Müller
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
Peter Zill
Affiliation:
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
*
Andrea Jobst, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany.Tel: +49 89 44005 5331; Fax: +49 89 44005 4548; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Impaired social functioning and autistic symptoms are characteristics of schizophrenia. The social hormones oxytocin (OT) and arginine-vasopressin (AVP) both modulate social interaction and therefore may be involved in the pathogenesis of schizophrenia. We investigated whether men with schizophrenia show altered OT and AVP levels compared with healthy controls (HC) and whether autism symptoms are associated with OT levels.

Methods

Forty-one men with non-acute schizophrenia and 45 matched HC were enroled. Schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Blood samples were collected on 2 days, and plasma OT and AVP levels were measured by ELISA immunoassay.

Results

The schizophrenia patients had significantly lower plasma OT levels than the HC; a similar trend was found for AVP. Plasma OT levels were associated with severe life events, fewer important attached persons, and a higher score on the PANSS negative scale; the most dominant PANSS items were ‘preoccupation’, ‘emotional withdrawal’, and ‘passive/apathetic social withdrawal’.

Conclusion

These findings support an association between the social hormones OT and AVP and schizophrenia. We suggest that OT metabolism may be altered in schizophrenia, but other possible causes for decreased plasma OT levels in schizophrenia patients include decreased OT synthesis, mRNA expression, and translation. Especially the ‘autistic’ symptoms of schizophrenia seem to be closely linked to an altered metabolism of OT, the ‘attachment’ hormone.

Keywords

attachmentoxytocinschizophreniasocial deficitsvasopressin
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 6 , December 2014 , pp. 347 - 355
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

The authors A.J. and S.D. contributed equally to this paper

References

1.Bleuler, E. Dementia Praecox oder Gruppe der Schizophrenien. Handbuch der Psychiatrie. Leipzig: Deuticke ed, 1911.Google Scholar
2.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276. PubMed PMID: 3616518. Epub 1987/01/01. eng.Google Scholar
3.White, L, Harvey, PD, Opler, L, Lindenmayer, JP. Empirical assessment of the factorial structure of clinical symptoms in schizophrenia. A multisite, multimodel evaluation of the factorial structure of the Positive and Negative Syndrome Scale. The PANSS Study Group. Psychopathology 1997;30:263–274. PubMed PMID: 9353855. Epub 1997/01/01. eng.CrossRefGoogle ScholarPubMed
4.Couture, SM, Penn, DL, Roberts, DL. The functional significance of social cognition in schizophrenia: a review. Schizophr Bull 2006;32(Suppl. 1):S44–S63. PubMed PMID: 16916889. Pubmed Central PMCID: PMC2632537. Epub 2006/08/19. eng.Google Scholar
5.Tremeau, F. A review of emotion deficits in schizophrenia. Dialogues Clin Neurosci 2006;8:59–70. PubMed PMID: 16640115. Pubmed Central PMCID: PMC3181757. Epub 2006/04/28. eng.Google Scholar
6.Brune, M. ‘Theory of mind’ in schizophrenia: a review of the literature. Schizophr Bull 2005;31:21–42. PubMed PMID: 15888423. Epub 2005/05/13. eng.Google Scholar
7.Leifker, FR, Bowie, CR, Harvey, PD. Determinants of everyday outcomes in schizophrenia: the influences of cognitive impairment, functional capacity, and symptoms. Schizophr Res 2009;115:82–87. PubMed PMID: 19775869. Epub 2009/09/25. eng.Google Scholar
8.Donaldson, ZR, Young, LJ. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 2008;322:900–904. PubMed PMID: 18988842. Epub 2008/11/08. eng.Google Scholar
9.Kosfeld, M, Heinrichs, M, Zak, PJ, Fischbacher, U, Fehr, E. Oxytocin increases trust in humans. Nature 2005;435:673–676. PubMed PMID: 15931222. Epub 2005/06/03. eng.Google Scholar
10.Domes, G, Heinrichs, M, Michel, A, Berger, C, Herpertz, SC. Oxytocin improves ‘mind-reading’ in humans. Biol Psychiatr 2007;61:731–733. PubMed PMID: 17137561. Epub 2006/12/02. eng.Google Scholar
11.de Vries, GJ. Sex differences in vasopressin and oxytocin innervation of the brain. Prog Brain Res 2008;170:17–27. PubMed PMID: 18655868. Epub 2008/07/29. eng.Google Scholar
12.Ludwig, M, Leng, G. Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 2006;7:126–136. PubMed PMID: 16429122. Epub 2006/01/24. eng.CrossRefGoogle ScholarPubMed
13.Beckmann, H, Lang, RE, Gattaz, WF. Vasopressin – oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls. Psychoneuroendocrinology 1985;10:187–191. PubMed PMID: 4034849. Epub 1985/01/01. eng.Google Scholar
14.Legros, JJ, Gazzotti, C, Carvelli, Tet al. Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics. Psychoneuroendocrinology 1992;17:611–617. PubMed PMID: 1287681. Epub 1992/11/01. eng.Google Scholar
15.Glovinsky, D, Kalogeras, KT, Kirch, DG, Suddath, R, Wyatt, RJ. Cerebrospinal fluid oxytocin concentration in schizophrenic patients does not differ from control subjects and is not changed by neuroleptic medication. Schizophr Res 1994;11:273–276. PubMed PMID: 7910756. Epub 1994/02/01. eng.Google Scholar
16.Sasayama, D, Hattori, K, Teraishi, Tet al. Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia. Schizophr Res 2012;139:201–206. PubMed PMID: 22742979. Epub 2012/06/30. eng.Google Scholar
17.Goldman, M, Marlow-O'Connor, M, Torres, I, Carter, CS. Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. Schizophr Res 2008;98:247–255. PubMed PMID: 17961988. Pubmed Central PMCID: 2277481. Epub 2007/10/27. eng.CrossRefGoogle ScholarPubMed
18.Keri, S, Kiss, I, Kelemen, O. Sharing secrets: oxytocin and trust in schizophrenia. Soc Neurosci 2009;4:287–293. PubMed PMID: 18671168. Epub 2008/08/02. eng.Google Scholar
19.Rubin, LH, Carter, CS, Drogos, L, Pournajafi-Nazarloo, H, Sweeney, JA, Maki, PM. Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophr Res 2010;124:13–21. PubMed PMID: 20947304. Pubmed Central PMCID: PMC2981685. Epub 2010/10/16. eng.Google Scholar
20.Rubin, LH, Carter, CS, Bishop, JRet al. Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. Schizophr Bull 2014; 1–11. PubMed PMID: 24619535. Epub 2014/03/13. Eng.Google Scholar
21.Rubin, LH, Carter, CS, Bishop, JRet al. Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis. Schizophr Res 2013;146:138–143. PubMed PMID: 23465965. Pubmed Central PMCID: PMC3622845. Epub 2013/03/08. eng.CrossRefGoogle Scholar
22.Caldwell, HK, Stephens, SL, Young, WS 3rd. Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice. Mol Psychiatry 2009;14:190–196. PubMed PMID: 18227836. Epub 2008/01/30. eng.CrossRefGoogle ScholarPubMed
23.Feifel, D, Reza, T. Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating. Psychopharmacology 1999;141:93–98. PubMed PMID: 9952070. Epub 1999/02/10. eng.Google Scholar
24.Lee, PR, Brady, DL, Shapiro, RA, Dorsa, DM, Koenig, JI. Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology 2005;30:1883–1894. PubMed PMID: 15798779. Epub 2005/03/31. eng.Google Scholar
25.Bujanow, W. Letter: is oxytocin an anti-schizophrenic hormone? Can Psychiatr Assoc J 1974;19:323 PubMed PMID: 4841051. Epub 1974/06/01. eng.CrossRefGoogle ScholarPubMed
26.Bakharev, VD, Tikhomirov, SM, Lozhkina, TK. Psychotropic properties of oxytocin. Probl endokrinol 1984;30:37–41. PubMed PMID: 6718333. Epub 1984/03/01. Psikhotropnye svoistva oksitotsina. rus.Google ScholarPubMed
27.Feifel, D, Macdonald, K, Nguyen, Aet al. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biological Psychiatry 2010;68:678–680. PubMed PMID: 20615494. Epub 2010/07/10. eng.Google Scholar
28.Feifel, D, Macdonald, K, Cobb, P, Minassian, A. Adjunctive intranasal oxytocin improves verbal memory in people with schizophrenia. Schizophr Res 2012;139:207–210. PubMed PMID: 22682705. Epub 2012/06/12. eng.Google Scholar
29.Modabbernia, A, Rezaei, F, Salehi, Bet al. Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia: an 8-week, randomized, double-blind, placebo-controlled study. CNS Drugs 2013;27:57–65. PubMed PMID: 23233269. Epub 2012/12/13. eng.CrossRefGoogle ScholarPubMed
30.Pedersen, CA, Gibson, CM, Rau, SWet al. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res 2011;132:50–53. PubMed PMID: 21840177. Epub 2011/08/16. eng.Google Scholar
31.Davis, MC, Lee, J, Horan, WPet al. Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr Res 2013;147:393–397. PubMed PMID: 23676253. Epub 2013/05/17. eng.Google Scholar
32.Fischer-Shofty, M, Shamay-Tsoory, SG, Levkovitz, Y. Characterization of the effects of oxytocin on fear recognition in patients with schizophrenia and in healthy controls. Front Neurosci 2013:1–9. PubMed PMID: 23882178. Pubmed Central PMCID: PMC3714571. Epub 2013/07/25. eng.Google Scholar
33.Goldman, MB, Gomes, AM, Carter, CS, Lee, R. Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia. Psychopharmacology 2011;216:101–110. PubMed PMID: 21301811. Epub 2011/02/09. eng.Google Scholar
34.Goldman, MB, Robertson, GL, Hedeker, D. Oropharyngeal regulation of water balance in polydipsic schizophrenics. Clin Endocrinol 1996;44:31–37. PubMed PMID: 8706290. Epub 1996/01/01. eng.Google Scholar
35.Peskind, ER, Raskind, MA, Leake, RD, Ervin, MG, Ross, MG, Dorsa, DM. Clonidine decreases plasma and cerebrospinal fluid arginine vasopressin but not oxytocin in humans. Neuroendocrinology 1987;46:395–400. PubMed PMID: 3431654. Epub 1987/11/01. eng.Google Scholar
36.Raskind, MA, Courtney, N, Murburg, MMet al. Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients. Biol Psychiatry 1987;22:453–462. PubMed PMID: 3567260. Epub 1987/04/01. eng.Google Scholar
37.Brambilla, F, Bondiolotti, GP, Maggioni, Met al. Vasopressin (DDAVP) therapy in chronic schizophrenia: effects on negative symptoms and memory. Neuropsychobiology 1989;20:113–119. PubMed PMID: 2548116. Epub 1989/01/01. eng.Google Scholar
38.Hosseini, SM, Farokhnia, M, Rezaei, Fet al. Intranasal desmopressin as an adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled, clinical trial. Eur Neuropsychopharmacol: J Eur College Neuropsychopharmacol 2014; PubMed PMID: 24636461. Epub 2014/03/19. Eng.Google Scholar
39.Feifel, D, Priebe, K. Vasopressin-deficient rats exhibit sensorimotor gating deficits that are reversed by subchronic haloperidol. Biol Psychiatry 2001;50:425–433. PubMed PMID: 11566159. Epub 2001/09/22. eng.Google Scholar
40.Cilia, J, Gartlon, JE, Shilliam, C, Dawson, LA, Moore, SH, Jones, DN. Further neurochemical and behavioural investigation of Brattleboro rats as a putative model of schizophrenia. J Psychopharmacol (Oxford, England) 2010;24:407–419. PubMed PMID: 19204063. Epub 2009/02/11. eng.CrossRefGoogle ScholarPubMed
41.APA. American Psychiatric Association. Washington, DC: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 1994.Google Scholar
42.Guy, W. ECDEU Assessment Manual for Psychopharmacology — Revised (DHEW Publ No ADM 76-338). Rockville, MD, U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, 1976, pp. 218–222.Google Scholar
43.R-Development-Core-Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2011; ISBN 3-900051-07-0, http://www.R-project.org/Google Scholar
44.Salonia, A, Nappi, RE, Pontillo, Met al. Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women. Horm Behav 2005;47:164–169. PubMed PMID: 15664019. Epub 2005/01/25. eng.Google Scholar
45.Galfi, M, Janaky, T, Toth, Ret al. Effects of dopamine and dopamine-active compounds on oxytocin and vasopressin production in rat neurohypophyseal tissue cultures. Regul Pept 2001;98:49–54. PubMed PMID: 11179778. Epub 2001/02/17. eng.Google Scholar
46.Kiss, A, Soderman, A, Bundzikova, J, Pirnik, Z, Mikkelsen, JD. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat. Brain Res Bull 2006;71:200–207. PubMed PMID: 17113947. Epub 2006/11/23. eng.Google Scholar
47.Uvnas-Moberg, K, Alster, P, Svensson, TH. Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats. Psychopharmacology 1992;109:473–476. PubMed PMID: 1365865. Epub 1992/01/01. eng.Google Scholar
48.Macdonald, K, Feifel, D. Oxytocin in schizophrenia: a review of evidence for its therapeutic effects. Acta neuropsychiatrica 2012;24:130–146. PubMed PMID: 22736892. Pubmed Central PMCID: PMC3378061. Epub 2012/06/28. Eng.Google Scholar