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The Complex Role of Oxytocin in Major Depressive Disorder

Year 2022, , 462 - 471, 30.06.2022
https://doi.org/10.33808/clinexphealthsci.975706

Abstract

Objective: One proposed mechanism to subclassify depressive illness relates oxytocinergic dysregulation, via its effect on social behavior and Hypothalamic-pituitary-adrenal (HPA) axis inhibition. To further investigate the role of oxytocin in Major Depressive Disorder (MDD), we compared plasma oxytocin levels in patients with MDD to healthy controls.
Methods: Plasma samples from 12 healthy controls and 33 MDD patients were collected at baseline, 8 weeks, and 12 weeks of treatment and oxytocin was measured by enzyme-immunoassay. Depression and anxiety scales were administered at screening, baseline, and at weeks 2, 4, 8, and 12 of treatment. Additionally, we investigated possible associations between blood concentrations of inflammatory biomarkers and oxytocin.
Results: The average baseline oxytocin level was 429 pg/ml in MDD patients and 392 pg/ml in healthy control subjects. A significant negative correlation was found between baseline oxytocin and BMI. Treatment responders had significantly lower baseline oxytocin levels than non-responders. After stratifying patients into low and high oxytocin groups based on a median split, within the high oxytocin group, patients with no prior depressive episodes had significantly higher baseline oxytocin levels. A Chi-square distribution test revealed that African American patients were more likely to belong to the high baseline oxytocin group while Caucasian and Hispanic patients were more likely to belong to the low baseline oxytocin group. We found significant correlations between oxytocin and Von-Willebrand Factor (VWF) and Epidermal Growth Factor (EGF), only within the high oxytocin subgroup. There were no other significant correlations between baseline oxytocin and any other biomarkers.
Conclusion: Within our limited patient cohort, our data adds to the mixed literature regarding the role of oxytocin in MDD. Oxytocinergic dysregulation and confounding factors may play a role for a subset of depressed patients.

References

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Year 2022, , 462 - 471, 30.06.2022
https://doi.org/10.33808/clinexphealthsci.975706

Abstract

References

  • REFERENCES Romano A, Tempesta B, Micioni Di Bonaventura MV, Gaetani S. From Autism to Eating Disorders and More: The Role of Oxytocin in Neuropsychiatric Disorders. Front Neurosci [Internet]. 2016 Jan 12;9. Available from: http://journal.frontiersin.org/Article/10.3389/fnins.2015.00497/abstract
  • Scantamburlo G, Ansseau M, Geenen V, Legros J-J. Oxytocin: From milk ejection to maladaptation in stress response and psychiatric disorders. A psychoneuroendocrine perspective. Ann Endocrinol (Paris) [Internet]. 2009 Dec;70(6):449–54. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0003426609002649
  • Slattery DA, Neumann ID. Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment. Pharmaceuticals [Internet]. 2010 Mar 16;3(3):702–24. Available from: http://www.mdpi.com/1424-8247/3/3/702
  • Cochran DM, Fallon D, Hill M, Frazier JA. The Role of Oxytocin in Psychiatric Disorders. Harv Rev Psychiatry [Internet]. 2013;21(5):219–47. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00023727-201309000-00001
  • Keating C, Dawood T, Barton DA, Lambert GW, Tilbrook AJ. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder. BMC Psychiatry [Internet]. 2013 Dec 29;13(1):124. Available from: http://bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-13-124
  • Lien Y-J, Chang HH, Tsai H-C, Kuang Yang Y, Lu R-B, See Chen P. Plasma oxytocin levels in major depressive and bipolar II disorders. Psychiatry Res [Internet]. 2017 Dec;258:402–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0165178117301014
  • Carter CS. The oxytocin-vasopressin pathway in the context of love and fear. Front Endocrinol (Lausanne). 2017;8(DEC):1–12.
  • Neumann ID, Landgraf R. Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci [Internet]. 2012 Nov;35(11):649–59. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016622361200152X
  • Lang UE, Borgwardt S. Molecular mechanisms of depression: Perspectives on new treatment strategies. Cell Physiol Biochem. 2013;31(6):761–77.
  • Halaris A, Hage B, Carter CS, Nazarloo HP, Singh J. Does Arginine Vasopressin Reflect HPA-axis Activation in Major Depressive Disorder? Clin Exp Investig [Internet]. 2020 Mar 30;1–8. Available from: https://www.sciencerepository.org/does-arginine-vasopressin-reflect_CEI-2020-2-101
  • Ozden A, Michelle M, Edwin M, Angelos H. Efficacy and Tolerability of Quetiapine Extended Release (XR) as Monotherapy in the Treatment of Major Depressive Disorder. Int J Depress Anxiety [Internet]. 2019 Nov 25;2(2). Available from: https://www.clinmedjournals.org/articles/ijda/international-journal-of-depression-and-anxiety-ijda-2-017.php?jid=ijda
  • Sue Carter C, Pournajafi-Nazarloo H, Kramer KM, Ziegler TE, White-Traut R, Bello D, et al. Oxytocin: Behavioral Associations and Potential as a Salivary Biomarker. Ann N Y Acad Sci [Internet]. 2007 Mar 1;1098(1):312–22. Available from: http://doi.wiley.com/10.1196/annals.1384.006
  • MacLean EL, Wilson SR, Martin WL, Davis JM, Nazarloo HP, Carter CS. Challenges for measuring oxytocin: The blind men and the elephant? Psychoneuroendocrinology [Internet]. 2019 Sep;107:225–31. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0306453019302380
  • Chu C, Hammock EA., Joiner TE. Unextracted plasma oxytocin levels decrease following in-laboratory social exclusion in young adults with a suicide attempt history. J Psychiatr Res [Internet]. 2020 Feb;121:173–81. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022395619308726
  • Saxbe D, Khaled M, Horton KT, Mendez AJ. Maternal prenatal plasma oxytocin is positively associated with prenatal psychological symptoms, but method of immunoassay extraction may affect results. Biol Psychol [Internet]. 2019 Oct;147:107718. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0301051118301017
  • Ellis BJ, Horn AJ, Carter CS, van IJzendoorn MH, Bakermans-Kranenburg MJ. Developmental programming of oxytocin through variation in early-life stress: Four meta-analyses and a theoretical reinterpretation. Clin Psychol Rev [Internet]. 2021 Jun;86:101985. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0272735821000283
  • Ozsoy S, Esel E, Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res [Internet]. 2009 Oct;169(3):249–52. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0165178108002023
  • Parker KJ, Kenna HA, Zeitzer JM, Keller J, Blasey CM, Amico JA, et al. Preliminary evidence that plasma oxytocin levels are elevated in major depression. Psychiatry Res [Internet]. 2010 Jul;178(2):359–62. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016517810900362X
  • Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Pinto E, Reggers J, et al. AVP- and OT-neurophysins response to apomorphine and clonidine in major depression. Psychoneuroendocrinology [Internet]. 2005 Oct;30(9):839–45. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0306453005000818
  • Van Londen L, Goekoop JG, Van Kempen GMJ, Frankhuijzen-Sierevogel AC, Wiegant VM, Van Der Velde EA, et al. Plasma levels of arginine vasopressin elevated in patients with major depression. Neuropsychopharmacology [Internet]. 1997 Oct;17(4):284–92. Available from: http://www.nature.com/doifinder/10.1016/S0893-133X(97)00054-7
  • Cyranowski JM, Hofkens TL, Frank E, Seltman H, Cai H-M, Amico JA. Evidence of Dysregulated Peripheral Oxytocin Release Among Depressed Women. Psychosom Med [Internet]. 2008 Nov;70(9):967–75. Available from: https://journals.lww.com/00006842-200811000-00003
  • Massey SH, Backes KA, Schuette SA. Plasma Oxytocin Concentration and Depressive Symptoms: A Review of Current Evidence and Directions for Future Research. Depress Anxiety [Internet]. 2016 Apr;33(4):316–22. Available from: http://doi.wiley.com/10.1002/da.22467
  • Rutigliano G, Rocchetti M, Paloyelis Y, Gilleen J, Sardella A, Cappucciati M, et al. Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis. Psychiatry Res. 2016;241:207–20.
  • Yuen KW, Garner JP, Carson DS, Keller J, Lembke A, Hyde SA, et al. Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol. J Psychiatr Res [Internet]. 2014 Apr;51:30–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022395613003877
  • Meynen G, Unmehopa UA, Hofman MA, Swaab DF, Hoogendijk WJG. Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry [Internet]. 2007 Feb 25;12(2):118–9. Available from: http://www.nature.com/articles/4001911
  • Sue Carter C, Kenkel WM, Maclean EL, Wilson SR, Perkeybile AM, Yee JR, et al. Is oxytocin “nature’s medicine”? Pharmacol Rev. 2020;72(4):829–61.
  • Tsai TY, Tseng HH, Chi MH, Chang HH, Wu CK, Yang YK, et al. The interaction of oxytocin and social support, loneliness, and cortisol level in major depression. Clin Psychopharmacol Neurosci. 2019;17(4):487–94.
  • Massey SH, Schuette SA, Pournajafi-Nazarloo H, Wisner KL, Carter CS. Interaction of oxytocin level and past depression may predict postpartum depressive symptom severity. Arch Womens Ment Health [Internet]. 2016 Oct 8;19(5):799–808. Available from: http://link.springer.com/10.1007/s00737-016-0616-6
  • Holt-Lunstad J, Birmingham W, Light KC. The influence of depressive symptomatology and perceived stress on plasma and salivary oxytocin before, during and after a support enhancement intervention. Psychoneuroendocrinology [Internet]. 2011 Sep;36(8):1249–56. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0306453011000965
  • Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clin Psychol Rev [Internet]. 1988 Jan;8(1):77–100. Available from: https://linkinghub.elsevier.com/retrieve/pii/0272735888900505
  • Seay JS, Lattie E, Schneiderman N, Antoni MH, Fekete EM, Mendez AJ, et al. Linear and Quadratic Associations of Plasma Oxytocin With Depressive Symptoms in Ethnic Minority Women Living With HIV. J Appl Biobehav Res [Internet]. 2014 Mar;19(1):70–8. Available from: http://doi.wiley.com/10.1111/jabr.12016
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There are 55 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Angelos Halaris 0000-0002-2855-1811

Jasleen Singh 0000-0001-9992-0939

C. Sue Carter 0000-0001-5056-7740

Hossein Nazarloo This is me 0000-0001-5562-7407

Brandon Hage This is me 0000-0002-4119-5452

Publication Date June 30, 2022
Submission Date August 11, 2021
Published in Issue Year 2022

Cite

APA Halaris, A., Singh, J., Carter, C. S., Nazarloo, H., et al. (2022). The Complex Role of Oxytocin in Major Depressive Disorder. Clinical and Experimental Health Sciences, 12(2), 462-471. https://doi.org/10.33808/clinexphealthsci.975706
AMA Halaris A, Singh J, Carter CS, Nazarloo H, Hage B. The Complex Role of Oxytocin in Major Depressive Disorder. Clinical and Experimental Health Sciences. June 2022;12(2):462-471. doi:10.33808/clinexphealthsci.975706
Chicago Halaris, Angelos, Jasleen Singh, C. Sue Carter, Hossein Nazarloo, and Brandon Hage. “The Complex Role of Oxytocin in Major Depressive Disorder”. Clinical and Experimental Health Sciences 12, no. 2 (June 2022): 462-71. https://doi.org/10.33808/clinexphealthsci.975706.
EndNote Halaris A, Singh J, Carter CS, Nazarloo H, Hage B (June 1, 2022) The Complex Role of Oxytocin in Major Depressive Disorder. Clinical and Experimental Health Sciences 12 2 462–471.
IEEE A. Halaris, J. Singh, C. S. Carter, H. Nazarloo, and B. Hage, “The Complex Role of Oxytocin in Major Depressive Disorder”, Clinical and Experimental Health Sciences, vol. 12, no. 2, pp. 462–471, 2022, doi: 10.33808/clinexphealthsci.975706.
ISNAD Halaris, Angelos et al. “The Complex Role of Oxytocin in Major Depressive Disorder”. Clinical and Experimental Health Sciences 12/2 (June 2022), 462-471. https://doi.org/10.33808/clinexphealthsci.975706.
JAMA Halaris A, Singh J, Carter CS, Nazarloo H, Hage B. The Complex Role of Oxytocin in Major Depressive Disorder. Clinical and Experimental Health Sciences. 2022;12:462–471.
MLA Halaris, Angelos et al. “The Complex Role of Oxytocin in Major Depressive Disorder”. Clinical and Experimental Health Sciences, vol. 12, no. 2, 2022, pp. 462-71, doi:10.33808/clinexphealthsci.975706.
Vancouver Halaris A, Singh J, Carter CS, Nazarloo H, Hage B. The Complex Role of Oxytocin in Major Depressive Disorder. Clinical and Experimental Health Sciences. 2022;12(2):462-71.

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