Evaluation of serum oxytocin levels in patients with depression, generalized anxiety disorder, panic disorder, and social anxiety disorder: A case-control study

Taha Can Tuman; Osman Yıldırım; Ali Evren Tufan

doi:10.28982/josam.922612

Authors

Taha Can Tuman https://orcid.org/0000-0001-8401-4992
Osman Yıldırım https://orcid.org/0000-0001-9712-2909
Ali Evren Tufan https://orcid.org/0000-0001-5207-6240

DOI:

https://doi.org/10.28982/josam.922612

Keywords:

Oxytocin, Depression, Generalized anxiety, Social anxiety, Panic disorder

Abstract

Background/Aim: Oxytocin, an endogenous anti-stress, antidepressant, and anxiolytic hormone, is reported to increase in stressful situations to reduce the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and amygdala for coping with stress and improving social functioning. This study aimed to compare serum oxytocin levels of patients with depression, generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD) with that of healthy controls. Methods: The study included 50 patients (25 male, 25 female) with major depression, 26 patients (9 male, 17 female) with GAD, 31 patients (14 male, 17 female) with SAD, and 40 patients (17 male, 23 female) with PD and 30 healthy volunteers. Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Perceived Stress Scale (PSS), and Anxiety Sensitivity Index-3 (ASI-3) were applied to all groups. In addition, Generalized Anxiety Disorder-7 (GAD-7), Panic Disorder Severity Scale (PDSS), and Liebowitz Social Phobia Scale were applied to patients with GAD, panic disorder, and social anxiety disorder, respectively. Serum oxytocin levels were measured by ELISA. Results: Serum oxytocin levels of patients with depression were significantly lower, and those of patients with generalized anxiety disorder, social anxiety disorder, and panic disorder with agoraphobia were significantly higher compared to the control group (2.46 (2.8) vs. 2.86 (0.72), P=0.004, 11.49 (11.35) vs. 2.86 (0.72), P=0.001, 10.67 (11.32) vs. 2.86 (0.72), P=0.001, and 6.97 (5.01) vs. 2.86 (0.72), P=0.001, respectively). Conclusion: Lower oxytocin levels in depressed patients and higher oxytocin levels in patients with GAD, and PD with agoraphobia suggest that oxytocin has a role in psychiatric disorders. Further studies are needed to better understand the relationship between depression, anxiety disorders, oxytocin, and the underlying mechanisms.

Downloads

Download data is not yet available.

References

Insel TR, Young LJ. The neurobiology of attachment. Nat Rev Neurosci. 2001;2(2):129-36.

Macdonald K, Macdonald TM. The peptide that binds: A systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry. 2010;18(1):1–21.

Hollander E, Bartz J, Chaplin W. Oxytocin increases retention in social cognition in autism. Biol Psychiatry. 2007;61(4):498-503.

Heinrichs M, Baumgartner T, Kirschbaum C, Ulrike E. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54(12):1389–98.

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. J Neurosci. 2005;25(49):11489–93.

Parker KJ, Buckmaster CL, Schatzberg AF, Lyons DM. Intranasal oxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology. 2005;30:924-29.

Neumann ID, Krömer SA, Toschi N, Ebner K. Brain oxytocin inhibits the (re) activity of the hypothalamo–pituitary–adrenal axis in male rats: involvement of hypothalamic and limbic brain regions. Regul Pept. 2000;96:31-8.

Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD. Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci. 2005;102:17237-40.

Heim C, Young LJ, Newport DJ. Lower CSF oxytocin concentrations in women with a history of childhood abuse. Mol Psychiatry. 2009;14:954-8.

Rault JL, Carter CS, Garner JP, Marchant-Forde JN, Richert BT, Lay Jr DJ. Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior. Physiol Behav. 2013;112-113:40-8.

Lee R, Ferris C, Van de Kar LD, Coccaro EF. Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinology. 2009;34(10):1567–73.

Cyranowski JM, Hofkens TL, Frank E, Seltman H, Cai HM, Amico JA. Evidence of dysregulated peripheral oxytocin release among depressed women. Psychosom. Med. 2008;70:967-75.

Özsoy S, Eşel E, Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Research. 2009;169(3):249-52.

Turan T, Uysal C, Asdemir A, Kılıç E. May oxytocin be a trait marker for bipolar disorder? Psychoneuroendocrinology. 2013;38(12):2890-6.

Aydın O, Lysaker PH, Balıkçı K, Ünal-Aydın P, Esen-Danacı A. Associations of oxytocin and vasopressin plasma levels with neurocognitive, social cognitive and meta cognitive function in schizophrenia. Psychiatry Res. 2018;270:1010-6.

Marazziti D, DellOsso MC. The role of oxytocin in neuropsychiatric disorders. Curr Med Chem. 2008;15:698-704.

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Washington DC, American Psychiatric Association, 2013.

Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-61.

Akdemir A, Örsel S, Dağ İ, Türkçapar H, İşcan N, Özbay H. Clinical use and the reliability and validity of the Turkish version of the Hamilton Depression Rating Scale (HDRS). Psikiyatri Psikoloji Psikofarmakoloji Dergisi. 1996;4(4):251-59.

Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50-5.

Yazıcı MK, Demir B, Tanrıverdi N, Karaağaoğlu E, Yolaç P. Hamilton Anksiyete Değerlendirme Ölçeği, değerlendiriciler arası güvenirlik ve geçerlilik çalışması. Turk Psikiyatri Derg. 1998;9:114-7.

Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Archives of internal medicine. 2006;166(10):1092-7.

Konkan R, Şenormancı Ö, Güçlü O, Aydın E, Sungur MZ. Yaygın Anksiyete Bozukluğu-7 (YAB-7) Testi Türkçe uyarlaması, geçerlik ve güvenirliği. Nöropsikiyatri Arşivi. 2013;50(1):53-9.

Shear MK, Brown TA, Barlow DH. Multicenter collaborative panic disorder severity scale. Am J Psychiatry. 1997;154:1571-5.

Monkul ES, Tural U, Onur E, Panic disorder severity scale: reliability and validity of the Turkish version. Depress Anxiety. 2004;20:8-16.

Heimberg G, Hornerk J, Justerh R, Safrens A, Browne J, Scheiırf R, et al. Psychometric properties of the Liebowitz Social Anxiety Scale. Psychological Medicine. 1999;29:199-212.

Soykan C, Ozguven HD, Gencoz T. Liebowitz Social Anxiety Scale: the Turkish version. Psychol Rep. 2003;93:1059-69.

Taylor S, Zvolensky MJ, Cox BJ, Deacon B, Heimberg RG, Ledley DR, et al. Robust dimensions of anxiety sensitivity: development and initial validation of the Anxiety Sensitivity Index-3. Psychol Assess. 2007;19:176-88.

Mantar A, Yemez B, Alkın T. Anksiyete Duyarlılığı İndexi-3’ün Türkçe formunun geçerlik ve güvenilirlik çalışması. Türk Psikiyatri Dergisi. 2010;21:225-34.

Nielsen MG, Ørnbøl E, Vestergaard M, Bech P, Larsen FB, Lasgaard M, et al. The construct validity of the Perceived Stress Scale. J Psychosom Res. 2016;84:22–30.

Eskin M, Harlak H, Demirkıran F, Dereboy Ç. Algılanan Stres Ölçeğinin Türkçeye Uyarlanması: Güvenirlik ve Geçerlik Analizi. Yeni Symposium. 2013;51:132–40.

Striepens N, Kendrick KM, Maier W, Hurlemann R. Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Frontiers in Neuroendocrinology. 2011;32:426-50.

Frasch A, Zetzsche T, Steiger A, Jirikowski GF. Reduction of plasma oxytocin levels in patients suffering from major depression. Adv Exp Med Biol. 1995;395:257-8.

Anderberg UM, Uvnäs-Moberg K. Plasma oxytocin levels levels in female fibromyalgia syndrome patients. Z Rheumatol. 2000;59(6):373-79.

Özsoy S, Eşel E, Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Research. 2009;169:249-52.

Scantamburlo G, Hansenne M, Fuchs S. Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology. 2007;32:407-10.

Apter-Levy Y, Feldman M, Vakart A, Ebstein RP, Feldman R. Impact of maternal depression across the first 6 years of life on the childs mental health, socal engagement and empathy: the moderating role of oxytocin. Am J Psychiatry. 2013;170(10):1161-68.

Van Londen L, Goekoop JG, Van Kempen GM. Plasma levels of arginine vasopressin elevated in patients with major depression. Biol Psychiatry. 1998;43(3):196-204.

Legros JJ. Inhibitory effect of oxytocin on corticotrope function in humans: are vasopressin and oxytocin ying-yang neurohormones? Psychoneuroendocrinology. 2001;26(7):649–55.

Bealer SL, Crowley WR. Noradrenergic control of central oxytocin release during lactation in rats. Am. J. Physiol. 1998;274:453-58.

Insel TR, Shapiro LE. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc Natl Acad Sci. 1992;89:5981–5.

Matsuzaki M, Matsushita H, Tomizawa K, Matsui H. Oxytocin: a therapeutic target for mental disorders. J Physiol Sci. 2012;62:441-4.

Clodi M, Vila G, Geyeregger R, Riedl M, Stulnig TM, Struck J, et al. Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men. Am J Physiol Endocrinol. Metab. 2008;295:686-91.

Hoge E, Pollack MH, Kaufman RE, Zak PJ, Simon NM. Oxytocin Levels in Social Anxiety Disorder. CNS Neuroscience & Therapeutics. 2008;145:165-70.

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):2403-13.

Hoge EA, Lawson EA, Metcalf CA, Keshaviah A, Zak PJ, Pollack MH, et al. Plasma oxytocin immunoreactive products and responce to trust in patients with social anxiety disorder. Depress Anxiety. 2012;29(11):924-30.

Keck ME, Welt T, Müller MB, Landgraf R, Holsboer F. The high-affinity non-peptide CRH1 receptor antagonist R121919 attenuates stress-induced alterations in plasma oxytocin, prolactin, and testosterone secretion in rats. Pharmacopsychiatry. 2003;36:27–31.

Bruhn TO, Sutton SW, Plotsky PM, Vale WW. Central administration of corticotropin-releasing factor modulates oxytocin secretion in the rat. Endocrinology. 1986;119:1558-63.

Walker CD, Deschamps S, Proulx K, Tu M, Salzman C, Woodside B, et al. Mother to infant or infant to mother? Reciprocal regulation of responsiveness to stress in rodents and the implications for humans. J Psychiatry Neurosci. 2004;29:364–82.

Amico JA, Cai HM, Vollmer RR. Corticosterone release in oxytocin gene deletion mice following exposure to psychogenic versus non-psychogenic stress. Neurosci Lett. 2008;442:262–66.

Danevova V, Kvetnansky R, Jezova D. Kinetics of oxytocin response to repeated restraint stress and/or chronic cold exposure. Horm Metab Res. 2013;45:845–48.

Amico JA, Mantella RC, Vollmer RR, Li X. Anxiety and stress responses in female oxytocin deficient mice. Journal of Neuroendocrinology. 2004;16:319–24.

Flak JN, Jankord R, Solomon MB, Krause EG, Herman JP. Opposing effects of chronic stress and weight restriction on cardiovascular, neuroendocrine and metabolic function. Physiol Behav. 2011;104:228-34.

Taşdelen Y, Yağcı İ. Anxiety, depression, type D personality, somatosensory amplification levels and childhood traumas in patients with panic disorders. J Surg Med. 2019;3(5):366-70.