Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder

BMC Psychiatry

Alan J Tilbrook³  Gavin W Lambert²  David A Barton⁵  Tye Dawood¹  Charlotte Keating⁴ 

[1] Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Australia;South Australian Research and Development Institute, The University of Adelaide, Adelaide, Australia;Brain and Psychological Sciences Research Centre, Swinburne University of Technology, Hawthorn, Australia;Mental Health Program, Southern Health, Melbourne, Australia

关键词: SSRI;    Hypothalamopuitary adrenal axis;    Cortisol;    Oxytocin;    Major depressive disorder;   

Others  :  1124069
DOI  :  10.1186/1471-244X-13-124

 received in 2012-11-21, accepted in 2013-04-23,  发布年份 2013

【 摘 要 】

Background

Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI.

Method

We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493).

Results

Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment.

Conclusions

These outcomes demonstrate that symptoms of MDD were reduced following effective treatment with an SSRI, and further, stress physiology was unlikely to be a key factor in this outcome. Further research is required to discriminate potential differences in underlying stress physiology for individuals with MDD who respond to antidepressant treatment, relative to those who experience treatment resistance.

【 授权许可】

   
2013 Keating et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Gimpl G, Fahrenholz F: The oxytocin receptor system: structure, function, and regulation. Physiol Rev 2001, 81(2):629-683.
• [2]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.
• [3]Witt DM, Winslow JT, Insel TR: Enhanced social interactions in rats following chronic, centrally infused oxytocin. Pharmacol Biochem Behav 1992, 43(3):855-861.
• [4]Lim MM, Young LJ: Neuropeptidergic regulation of affiliative behavior and social bonding in animals. Horm Behav 2006, 50(4):506-517.
• [5]Parker KJ, Buckmaster CL, Schatzberg AF, Lyons DM: Intranasal oxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology 2005, 30(9):924-929.
• [6]Landgraf R, Neumann ID: Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol 2004, 25(3–4):150-176.
• [7]Onaka T: Neural pathways controlling central and peripheral oxytocin release during stress. J Neuroendocrinol 2004, 16(4):308-312.
• [8]Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M: Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 2009, 65(9):728-731.
• [9]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(12):1389-1398.
• [10]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):917-923.
• [11]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(12):2974-2982.
• [12]Gold PW, Chrousos GP: Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002, 7(3):254-275.
• [13]Ising M, Kunzel HE, Binder EB, Nickel T, Modell S, Holsboer F: The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog Neuropsychopharmacol Biol Psychiatry 2005, 29(6):1085-1093.
• [14]Keck ME: Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety. Amino Acids 2006, 31(3):241-250.
• [15]Schule C: Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol 2007, 19(3):213-226.
• [16]Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF: Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 1996, 53(2):137-143.
• [17]Meynen G, Unmehopa UA, Hofman MA, Swaab DF, Hoogendijk WJ: Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry 2007, 12(2):118-119.
• [18]Parker KJ, Kenna HA, Zeitzer JM, Keller J, Blasey CM, Amico JA, Schatzberg AF: Preliminary evidence that plasma oxytocin levels are elevated in major depression. Psychiatry Res 2010, 178(2):359-362.
• [19]Bell CJ, Nicholson H, Mulder RT, Luty SE, Joyce PR: Plasma oxytocin levels in depression and their correlation with the temperament dimension of reward dependence. J Psychopharmacol 2006, 20(5):656-660.
• [20]Van Londen L, Goekoop JG, Zwinderman AH, Lanser JB, Wiegant VM, De Wied D: Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression. Psychol Med 1998, 28(2):275-284.
• [21]Swedo SE, Leonard HL, Kruesi MJ, Rettew DC, Listwak SJ, Berrettini W, Stipetic M, Hamburger S, Gold PW, Potter WZ: Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. Arch Gen Psychiatry 1992, 49(1):29-36.
• [22]Anderberg UM, Uvnas-Moberg K: Plasma oxytocin levels in female fibromyalgia syndrome patients. Z Rheumatol 2000, 59(6):373-379.
• [23]Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Marechal P, Pequeux C, Ansseau M, Legros JJ: Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology 2007, 32(4):407-410.
• [24]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(9):967-975.
• [25]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(3):249-252.
• [26]Pitts AF, Samuelson SD, Meller WH, Bissette G, Nemeroff CB, Kathol RG: Cerebrospinal fluid corticotropin-releasing hormone, vasopressin, and oxytocin concentrations in treated patients with major depression and controls. Biol Psychiatry 1995, 38(5):330-335.
• [27]Slattery DA, Neumann ID: Oxytocin and major depressive disorder: experimental and clinical evidence for links to aetiology and possible treatment. Pharmaceuticals 2010, 3:702-724.
• [28]Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T, Nishimori K: Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci 2009, 29(7):2259-2271.
• [29]Emiliano AB, Cruz T, Pannoni V, Fudge JL: The interface of oxytocin-labeled cells and serotonin transporter-containing fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects? Neuropsychopharmacology 2007, 32(5):977-988.
• [30]Fava M: Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003, 53(8):649-659.
• [31]Fava GA, Fabbri S, Sonino N: Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry 2002, 26(6):1019-1027.
• [32]Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C, Socratous F, Hastings J, Guo L, Wiesner G: Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry 2008, 65(1):38-46.
• [33]Marazziti D, Dell’Osso B, Baroni S, Mungai F, Catena M, Rucci P: A relationship between oxytocin and anxiety of romantic attachment. ClinPractEpidemolMentHealth 2006, 2(28):1-6.
• [34]Bocking AD, McMillen IC, Harding R, Thorburn GD: Effect of reduced uterine blood flow on fetal and maternal cortisol. J Dev Physiol 1986, 8(4):237-245.
• [35]Uvnas-Moberg K, Bjokstrand E, Hillegaart V, Ahlenius S: Oxytocin as a possible mediator of SSRI-induced antidepressant effects. Psychopharmacology (Berl) 1999, 142(1):95-101.
• [36]Jorgensen H, Kjaer A, Knigge U, Moller M, Warberg J: Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides. J Neuroendocrinol 2003, 15(6):564-571.
• [37]Binder EB, Kunzel HE, Nickel T, Kern N, Pfennig A, Majer M, Uhr M, Ising M, Holsboer F: HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients. Psychoneuroendocrinology 2009, 34(1):99-109.
• [38]Juruena MF, Pariante CM, Papadopoulos AS, Poon L, Lightman S, Cleare AJ: Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance. Br J Psychiatry 2009, 194(4):342-349.
• [39]Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A: Measuring cortisol in human psychobiological studies. Physiol Behav 2007, 90(1):43-53.
• [40]Burke HM, Davis MC, Otte C, Mohr DC: Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 2005, 30(9):846-856.
• [41]Lopez-Duran NL, Kovacs M, George CJ: Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis. Psychoneuroendocrinology 2009, 34(9):1272-1283.
• [42]Weisman O, Zagoory-Sharon O, Schneiderman I, Gordon I, Feldman R: Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety. Psychoneuroendocrinology 38(5):694-701.