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

Charlotte Keating, Tye Dawood, David A Barton, Gavin W Lambert, Alan J Tilbrook, Charlotte Keating, Tye Dawood, David A Barton, Gavin W Lambert, Alan J Tilbrook

Abstract

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.

Figures

Figure 1
Figure 1
HAM-D scores in patients with MDD, untreated and following SSRI treatment.
Figure 2
Figure 2
Arterial oxytocin concentrations in patients with MDD untreated and following SSRI treatment (p > .05).

References

    1. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629–683.
    1. 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. doi: 10.1111/j.1749-6632.1992.tb34346.x.
    1. Witt DM, Winslow JT, Insel TR. Enhanced social interactions in rats following chronic, centrally infused oxytocin. Pharmacol Biochem Behav. 1992;43(3):855–861. doi: 10.1016/0091-3057(92)90418-F.
    1. Lim MM, Young LJ. Neuropeptidergic regulation of affiliative behavior and social bonding in animals. Horm Behav. 2006;50(4):506–517. doi: 10.1016/j.yhbeh.2006.06.028.
    1. Parker KJ, Buckmaster CL, Schatzberg AF, Lyons DM. Intranasal oxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology. 2005;30(9):924–929. doi: 10.1016/j.psyneuen.2005.04.002.
    1. 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.
    1. Onaka T. Neural pathways controlling central and peripheral oxytocin release during stress. J Neuroendocrinol. 2004;16(4):308–312. doi: 10.1111/j.0953-8194.2004.01186.x.
    1. 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. doi: 10.1016/j.biopsych.2008.10.011.
    1. 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. doi: 10.1016/S0006-3223(03)00465-7.
    1. 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. doi: 10.1016/j.psyneuen.2009.01.005.
    1. 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. doi: 10.1523/JNEUROSCI.3432-03.2004.
    1. 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. doi: 10.1038/sj.mp.4001032.
    1. 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. doi: 10.1016/j.pnpbp.2005.03.014.
    1. Keck ME. Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety. Amino Acids. 2006;31(3):241–250. doi: 10.1007/s00726-006-0333-y.
    1. Schule C. Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol. 2007;19(3):213–226. doi: 10.1111/j.1365-2826.2006.01516.x.
    1. 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. doi: 10.1001/archpsyc.1996.01830020055007.
    1. Meynen G, Unmehopa UA, Hofman MA, Swaab DF, Hoogendijk WJ. Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry. 2007;12(2):118–119. doi: 10.1038/sj.mp.4001911.
    1. 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. doi: 10.1016/j.psychres.2009.09.017.
    1. 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. doi: 10.1177/0269881106060512.
    1. 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. doi: 10.1017/S0033291797006284.
    1. 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. doi: 10.1001/archpsyc.1992.01820010029004.
    1. Anderberg UM, Uvnas-Moberg K. Plasma oxytocin levels in female fibromyalgia syndrome patients. Z Rheumatol. 2000;59(6):373–379. doi: 10.1007/s003930070045.
    1. 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. doi: 10.1016/j.psyneuen.2007.01.009.
    1. 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. doi: 10.1097/PSY.0b013e318188ade4.
    1. 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. doi: 10.1016/j.psychres.2008.06.034.
    1. 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. doi: 10.1016/0006-3223(95)00229-A.
    1. 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. doi: 10.3390/ph3030702.
    1. 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. doi: 10.1523/JNEUROSCI.5593-08.2009.
    1. 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. doi: 10.1038/sj.npp.1301206.
    1. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53(8):649–659. doi: 10.1016/S0006-3223(03)00231-2.
    1. Fava GA, Fabbri S, Sonino N. Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(6):1019–1027. doi: 10.1016/S0278-5846(02)00226-9.
    1. 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. doi: 10.1001/archgenpsychiatry.2007.11.
    1. 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.
    1. 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.
    1. 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. doi: 10.1007/s002130050867.
    1. 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. doi: 10.1046/j.1365-2826.2003.01032.x.
    1. 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. doi: 10.1016/j.psyneuen.2008.08.018.
    1. 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. doi: 10.1192/bjp.bp.108.050278.
    1. Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A. Measuring cortisol in human psychobiological studies. Physiol Behav. 2007;90(1):43–53. doi: 10.1016/j.physbeh.2006.08.025.
    1. Burke HM, Davis MC, Otte C, Mohr DC. Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology. 2005;30(9):846–856. doi: 10.1016/j.psyneuen.2005.02.010.
    1. 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. doi: 10.1016/j.psyneuen.2009.03.016.
    1. 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. pp. 694–701.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다