Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment

David A Slattery, Inga D Neumann, David A Slattery, Inga D Neumann

Abstract

Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain neuropeptides, characterized by discrete synthesis sites and multiple receptors, represent likely research candidates for novel therapeutic targets. The present review summarises the available preclinical and human evidence regarding the neuropeptide, oxytocin, and its implications in the aetiology and treatment of MDD. While the evidence is not conclusive at present additional studies are warranted to determine whether OXT may be of therapeutic benefit in subsets of MDD patients such as those with comorbid anxiety symptoms and low levels of social attachment.

Keywords: depression; early-life; neuropeptide; oxytocin; social attachment.

References

    1. Kessler R.C., Berglund P., Demler O., Jin R., Koretz D., Merikangas K.R., Rush A.J., Walters E.E., Wang P.S. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) JAMA. 2003;289:3095–3105.
    1. Licinio J., Wong M.L. Depression, antidepressants and suicidality: a critical appraisal. Nat. Rev. Drug Discov. 2005;4:165–171.
    1. Murray C.J., Lopez A.D. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997;349:1498–1504.
    1. Cryan J.F., Slattery D.A. Animal models of mood disorders: Recent developments. Curr.Opini. Psychiat. 2007;20:1–7.
    1. Nemeroff C.B., Vale W.W. The neurobiology of depression: inroads to treatment and new drug discovery. J. Clin. Psychiat. 2005;66:5–13.
    1. Slattery D.A., Hudson A.L., Nutt D.J. Invited review: the evolution of antidepressant mechanisms. Fundam. Clin. Pharm. 2004;18:1–21.
    1. Nutt D., Wilson S., Paterson L. Sleep disorders as core symptoms of depression. Dialogues Clin. Neurosci. 2008;10:329–336.
    1. Kennedy S.H. Core symptoms of major depressive disorder: relevance to diagnosis and treatment. Dialogues Clin. Neurosci. 2008;10:271–277.
    1. Matthews K., Christmas D., Swan J., Sorrell E. Animal models of depression: navigating through the clinical fog. Neurosci. Biobehav. Rev. 2005;29:503–513.
    1. Holsboer F., Ising M. Central CRH system in depression and anxiety -- Evidence from clinical studies with CRH1 receptor antagonists. Eur. Pharm. 2008;583:350–357.
    1. Nemeroff C.B. The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol. Psychiat. 1996;1:336–342.
    1. Frank E., Landgraf R. The vasopressin system—From antidiuresis to psychopathology. Eur. J. Pharmacol. 2008;583:226–242.
    1. Landgraf R., Kessler M.S., Bunck M., Murgatroyd C., Spengler D., Zimbelmann M., Nussbaumer M., Czibere L., Turck C.W., Singewald N., Rujescu D., Frank E. Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: focus on vasopressin and glyoxalase-I. Neurosci. Biobehav. Rev. 2007;31:89–102.
    1. Neumann I.D. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J. Neuroendocrinol. 2008;20:858–865.
    1. Gimpl G., Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 2001;81:629–683.
    1. Neumann I.D. Stimuli and consequences of dendritic release of oxytocin within the brain. Biochem. Soc. Trans. 2007;35:1252–1257.
    1. Bale T.L., Davis A.M., Auger A.P., Dorsa D.M., McCarthy M.M. CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J. Neurosci. 2001;21:2546–2552.
    1. Neumann I.D., Torner L., Wigger A. Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats. Neuroscience. 2000;95:567–575.
    1. Ring R.H., Malberg J.E., Potestio L., Ping J., Boikess S., Luo B., Schechter L.E., Rizzo S., Rahman Z., Rosenzweig-Lipson S. Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. PsychoPharmacology. 2006;185:218–225.
    1. Slattery D.A., Neumann I.D. Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats. Neuropharmacology. 2010;58:56–61.
    1. Windle R.J., Shanks N., Lightman S.L., Ingram C.D. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology. 1997;138:2829–2834.
    1. Arletti R., Bertolini A. Oxytocin acts as an antidepressant in two animal models of depression. Life Sci. 1987;41:1725–1730.
    1. Arletti R., Benelli A., Poggioli R., Luppi P., Menozzi B., Bertolini A. Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin. Neuropeptides. 1995;29:177–182.
    1. Nowakowska E., Kus K., Bobkiewicz-Kozlowska T., Hertmanowska H. Role of neuropeptides in antidepressant and memory improving effects of venlafaxine. Pol. J. Pharm. 2002;54:605–613.
    1. Cryan J.F., Markou A., Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol. Sci. 2002;23:238–245.
    1. Ermisch A., Ruhle H.J., Landgraf R., Hess J. Blood-brain barrier and peptides. J. Cereb. Blood Flow Metab. 1985;5:350–357.
    1. Jones P.M., Robinson I.C. Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs. Neuroendocrinology. 1982;34:297–302.
    1. de Wied D., Diamant M., Fodor M. Central nervous system effects of the neurohypophyseal hormones and related peptides. Front. Neuroendocrinology. 1993;14:251–302.
    1. Petersson M., Alster P., Lundeberg T., Uvnas-Moberg K. Oxytocin causes a long-term decrease of blood pressure in female and male rats. Physiol. Behav. 1996;60:1311–1315.
    1. Ring R.H., Schechter L.E., Leonard S.K., Dwyer J.M., Platt B.J., Graf R., Grauer S., Pulicicchio C., Resnick L., Rahman Z., Sukoff Rizzo S.J., Luo B., Beyer C.E., Logue S.F., Marquis K.L., Hughes Z.A., Rosenzweig-Lipson S. Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist. Neuropharmacology. 2010;58:69–77. doi: 10.1016/j.neuropharm.2009.07.016.
    1. Ebner K., Bosch O.J., Kromer S.A., Singewald N., Neumann I.D. Release of oxytocin in the rat central amygdala modulates stress-coping behavior and the release of excitatory amino acids. Neuropsychopharmacology. 2005;30:223–230.
    1. Lancel M., Kromer S., Neumann I.D. Intracerebral oxytocin modulates sleep-wake behaviour in male rats. Regul. Pept. 2003;114:145–152.
    1. Landgraf R., Wigger A. High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety. Behav. Genet. 2002;32:301–314.
    1. Liberzon I., Trujillo K.A., Akil H., Young E.A. Motivational properties of oxytocin in the conditioned place preference paradigm. Neuropsychopharmacology. 1997;17:353–359.
    1. Qi J., Yang J.Y., Wang F., Zhao Y.N., Song M., Wu C.F. Effects of oxytocin on methamphetamine-induced conditioned place preference and the possible role of glutamatergic neurotransmission in the medial prefrontal cortex of mice in reinstatement. Neuropharmacology. 2009;56:856–865.
    1. Melis M.R., Melis T., Cocco C., Succu S., Sanna F., Pillolla G., Boi A., Ferri G.L., Argiolas A. Oxytocin injected into the ventral tegmental area induces penile erection and increases extracellular dopamine in the nucleus accumbens and paraventricular nucleus of the hypothalamus of male rats. Eur. Neurosci. 2007;26:1026–1035.
    1. Melis M.R., Succu S., Sanna F., Boi A., Argiolas A. Oxytocin injected into the ventral subiculum or the posteromedial cortical nucleus of the amygdala induces penile erection and increases extracellular dopamine levels in the nucleus accumbens of male rats. Eur. J. Neurosci. 2009;30:1349–1357.
    1. Wise R.A. Brain reward circuitry: insights from unsensed incentives. Neuron. 2002;36:229–240.
    1. Neumann I., Ludwig M., Engelmann M., Pittman Q.J., Landgraf R. Simultaneous microdialysis in blood and brain: oxytocin and vasopressin release in response to central and peripheral osmotic stimulation and suckling in the rat. Neuroendocrinology. 1993;58:637–645.
    1. Slattery D.A., Neumann I.D. No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain. J. Physiol. 2008;586:377–385.
    1. Febo M., Numan M., Ferris C.F. Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling. J. Neurosci. 2005;25:11637–11644.
    1. Seip K.M., Morrell J.I. Increasing the incentive salience of cocaine challenges preference for pup- over cocaine-associated stimuli during early postpartum: place preference and locomotor analyses in the lactating female rat. Psychopharmacology. 2007;194:309–319.
    1. Seip K.M., Pereira M., Wansaw M.P., Reiss J.I., Dziopa E.I., Morrell J.I. Incentive salience of cocaine across the postpartum period of the female rat. Psychopharmacology. 2008;199:119–130.
    1. Paterson N.E., Markou A. Animal models and treatments for addiction and depression co-morbidity. Neurotox. Res. 2007;11:1–32.
    1. McGregor I.S., Callaghan P.D., Hunt G.E. From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? Br. J. Pharm. 2008;154:358–368.
    1. Kovacs G.L., Sarnyai Z., Szabo G. Oxytocin and addiction: a review. Psychoneuroendocrinology. 1998;23:945–962.
    1. Kovacs G.L., Sarnyai Z., Barbarczi E., Szabo G., Telegdy G. The role of oxytocin-dopamine interactions in cocaine-induced locomotor hyperactivity. Neuropharmacology. 1990;29:365–368.
    1. Kovacs G.L., Sarnyai Z., Izbeki F., Szabo G., Telegdy G., Barth T., Jost K., Brtnik F. Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists. J. Pharm. Exp. Therap. 1987;241:569–574.
    1. Qi J., Yang J.Y., Song M., Li Y., Wang F., Wu C.F. Inhibition by oxytocin of methamphetamine-induced hyperactivity related to dopamine turnover in the mesolimbic region in mice. Naunyn-Schmiedeberg's Arch. Pharm. 2008;376:441–448. doi: 10.1007/s00210-007-0245-8.
    1. Succu S., Sanna F., Melis T., Boi A., Argiolas A., Melis M.R. Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: Involvement of central oxytocin. Neuropharmacology. 2007;52:1034–1043.
    1. Butovsky E., Juknat A., Elbaz J., Shabat-Simon M., Eilam R., Zangen A., Altstein M., Vogel Z. Chronic exposure to Delta9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas. Mol. Cell. Neurosci. 2006;31:795–804.
    1. You Z.D., Li J.H., Song C.Y., Wang C.H., Lu C.L. Chronic morphine treatment inhibits oxytocin synthesis in rats. Neuroreport. 2000;11:3113–3116.
    1. Brown C.H., Russell J.A. Cellular mechanisms underlying neuronal excitability during morphine withdrawal in physical dependence: lessons from the magnocellular oxytocin system. Stress (Amsterdam, Netherlands) 2004;7:97–107.
    1. Cui S.S., Bowen R.C., Gu G.B., Hannesson D.K., Yu P.H., Zhang X. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J. Neurosci. 2001;21:9867–9876.
    1. Slattery D.A., Markou A., Froestl W., Cryan J.F. The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat. Neuropsychopharmacology. 2005;30:2065–2072.
    1. Carter C.S., Grippo A.J., Pournajafi-Nazarloo H., Ruscio M.G., Porges S.W. Oxytocin, vasopressin and sociality. Prog. Brain Res. 2008;170:331–336.
    1. Donaldson Z.R., Young L.J. Oxytocin, vasopressin, and the neurogenetics of sociality. Science. 2008;322:900–904. doi: 10.1126/science.1158668.
    1. Goodson J.L. Nonapeptides and the evolutionary patterning of sociality. Prog. Brain Res. 2008;170:3–15.
    1. Young L.J., Wang Z. The neurobiology of pair bonding. Nat. Neurosci. 2004;7:1048–1054.
    1. Ferguson J.N., Aldag J.M., Insel T.R., Young L.J. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J. Neurosci. 2001;21:8278–8285.
    1. Grippo A.J., Cushing B.S., Carter C.S. Depression-Like Behavior and Stressor-Induced Neuroendocrine Activation in Female Prairie Voles Exposed to Chronic Social Isolation. Psychosom. Med. 2007;69:149–157.
    1. Grippo A.J., Gerena D., Huang J., Kumar N., Shah M., Ughreja R., Sue Carter C. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles. Psychoneuroendocrinology. 2009;32:966–980.
    1. Krishnan V., Han M.H., Graham D.L., Berton O., Renthal W., Russo S.J., Laplant Q., Graham A., Lutter M., Lagace D.C., Ghose S., Reister R., Tannous P., Green T.A., Neve R.L., Chakravarty S., Kumar A., Eisch A.J., Self D.W., Lee F.S., Tamminga C.A., Cooper D.C., Gershenfeld H.K., Nestler E.J. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007;131:391–404.
    1. Moos F., Richard P. Serotonergic control of oxytocin release during suckling in the rat: opposite effects in conscious and anesthetized rats. Neuroendocrinology. 1983;36:300–306.
    1. Javed A., Kamradt M.C., Van de Kar L.D., Gray T.S. D-Fenfluramine induces serotonin-mediated Fos expression in corticotropin-releasing factor and oxytocin neurons of the hypothalamus, and serotonin-independent Fos expression in enkephalin and neurotensin neurons of the amygdala. Neuroscience. 1999;90:851–858.
    1. Bagdy G., Kalogeras K.T. Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat. Brain Res. 1993;611:330–332.
    1. Uvnas-Moberg K., Hillegaart V., Alster P., Ahlenius S. Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat. Neuropharmacology. 1996;35:1635–1640.
    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;15:564–571.
    1. Saphier D. Paraventricular nucleus magnocellular neuronal responses following electrical stimulation of the midbrain dorsal raphe. Experim. Brain Res. 1991;85:359–363.
    1. Van de Kar L.D., Rittenhouse P.A., Li Q., Levy A.D., Brownfield M.S. Hypothalamic paraventricular, but not supraoptic neurons, mediate the serotonergic stimulation of oxytocin secretion. Brain Res. Bull. 1995;36:45–50.
    1. Uvnas-Moberg K., Bjokstrand E., Hillegaart V., Ahlenius S. Oxytocin as a possible mediator of SSRI-induced antidepressant effects. Psychopharmacology. 1999;142:95–101.
    1. Emiliano A.B., Cruz T., Pannoni V., Fudge J.L. The interface of oxytocin-labeled cells and serotonin transporter-containing fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects? Neuropsychopharmacology. 2007;32:977–988. doi: 10.1038/sj.npp.1301206.
    1. Carmichael M.S., Warburton V.L., Dixen J., Davidson J.M. Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity. Arch. Sex. Behav. 1994;23:59–79. doi: 10.1007/BF01541618.
    1. Murphy M.R., Seckl J.R., Burton S., Checkley S.A., Lightman S.L. Changes in oxytocin and vasopressin secretion during sexual activity in men. J. Clin. Endocrinol. Metab. 1987;65:738–741.
    1. Argiolas A., Collu M., D'Aquila P., Gessa G.L., Melis M.R., Serra G. Apomorphine stimulation of male copulatory behavior is prevented by the oxytocin antagonist d(CH2)5 Tyr(Me)-Orn8-vasotocin in rats. Pharmacol. Biochem. Behav. 1989;33:81–83.
    1. Waldherr M., Neumann I.D. Centrally released oxytocin mediates mating-induced anxiolysis in male rats. Proc. Natl. Acad. Sci. USA. 2007;104:16681–16684.
    1. Cantor J.M., Binik Y.M., Pfaus J.G. Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin. Psychopharmacology. 1999;144:355–362.
    1. Li Q., Brownfield M.S., Battaglia G., Cabrera T.M., Levy A.D., Rittenhouse P.A., van de Kar L.D. Long-term treatment with the antidepressants fluoxetine and desipramine potentiates endocrine responses to the serotonin agonists 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) and (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) J. Pharm. Experim. Therap. 1993;266:836–844.
    1. Li Q., Levy A.D., Cabrera T.M., Brownfield M.S., Battaglia G., Van de Kar L.D. Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats. Brain Res. 1993;630:148–156. doi: 10.1016/0006-8993(93)90652-4.
    1. Li Q., Muma N.A., van de Kar L.D. Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1A agonist. J. Pharm. Experim. Therap. 1996;279:1035–1042.
    1. Yoshida M., Takayanagi Y., Inoue K., Kimura T., Young L.J., Onaka T., Nishimori K. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J. Neurosci. 2009;29:2259–2271.
    1. Bosch O.J., Meddle S.L., Beiderbeck D.I., Douglas A.J., Neumann I.D. Brain oxytocin correlates with maternal aggression: link to anxiety. J. Neurosci. 2005;25:6807–6815.
    1. Ebner K., Wotjak C.T., Landgraf R., Engelmann M. A single social defeat experience selectively stimulates the release of oxytocin, but not vasopressin, within the septal brain area of male rats. Brain Res. 2000;872:87–92. doi: 10.1016/S0006-8993(00)02464-1.
    1. Engelmann M., Landgraf R., Wotjak C.T. The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: an old concept revisited. Front. Neuroendocrinol. 2004;25:132–149.
    1. Landgraf R., Neumann I.D. Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front. Neuroendocrinol. 2004;25:150–176.
    1. Wotjak C.T., Ganster J., Kohl G., Holsboer F., Landgraf R., Engelmann M. Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience. 1998;85:1209–1222. doi: 10.1016/S0306-4522(97)00683-0.
    1. Neumann I.D., Toschi N., Ohl F., Torner L., Kromer S.A. Maternal defence as an emotional stressor in female rats: correlation of neuroendocrine and behavioural parameters and involvement of brain oxytocin. Eur. J. Neurosci. 2001;13:1016–1024.
    1. Nomura M., Saito J., Ueta Y., Muglia L.J., Pfaff D.W., Ogawa S. Enhanced up-regulation of corticotropin-releasing hormone gene expression in response to restraint stress in the hypothalamic paraventricular nucleus of oxytocin gene-deficient male mice. J. Neuroendocrinol. 2003;15:1054–1061.
    1. Amico J.A., Miedlar J.A., Cai H.M., Vollmer R.R. Oxytocin knockout mice: a model for studying stress-related and ingestive behaviours. Prog. Brain Res. 2008;170:53–64.
    1. Caldwell H.K., Stephens S.L., Young W.S., 3rd Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice. Mol. Psychiat. 2009;14:190–196.
    1. Windle R.J., Kershaw Y.M., Shanks N., Wood S.A., Lightman S.L., Ingram C.D. Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. J. Neurosci. 2004;24:2974–2982.
    1. Kiss A., Aguilera G. Regulation of the hypothalamic pituitary adrenal axis during chronic stress: responses to repeated intraperitoneal hypertonic saline injection. Brain Res. 1993;630:262–270.
    1. Herman J.P., Flak J., Jankord R. Chronic stress plasticity in the hypothalamic paraventricular nucleus. Prog. Brain Res. 2008;170:353–364.
    1. Reber S.O., Neumann I.D. Defensive behavioral strategies and enhanced state anxiety during chronic subordinate colony housing are accompanied by reduced hypothalamic vasopressin, but not oxytocin, expression. Ann. NY Acad. Sci. 1148:184–195.
    1. Ising M., Kunzel H.E., Binder E.B., Nickel T., Modell S., Holsboer F. The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog. Neuro-psychopharmacol. Biol. Psychiat. 2005;29:1085–1093. doi: 10.1016/j.pnpbp.2005.03.014.
    1. Heinrichs M., Meinlschmidt G., Neumann I., Wagner S., Kirschbaum C., Ehlert U., Hellhammer D.H. Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women. J. Clin. Endocrinol. Metab. 2001;86:4798–4804.
    1. Chiodera P., Salvarani C., Bacchi-Modena A., Spallanzani R., Cigarini C., Alboni A., Gardini E., Coiro V. Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women. Horm. Res. 1991;35:119–123.
    1. Nissen E., Uvnas-Moberg K., Svensson K., Stock S., Widstrom A.M., Winberg J. Different patterns of oxytocin, prolactin but not cortisol release during breastfeeding in women delivered by caesarean section or by the vaginal route. Early Human Develop. 1996;45:103–118.
    1. Neumann I., Landgraf R. Septal and Hippocampal Release of Oxytocin, but not Vasopressin, in the Conscious Lactating Rat During Suckling. J. Neuroendocrinol. 1989;1:305–308. doi: 10.1111/j.1365-2826.1989.tb00120.x.
    1. Strathearn L., Fonagy P., Amico J., Montague P.R. Adult Attachment Predicts Maternal Brain and Oxytocin Response to Infant Cues. Neuropsychopharmacology. 2009;34:2655–2666. doi: 10.1038/npp.2009.103.
    1. Light K.C., Grewen K.M., Amico J.A., Boccia M., Brownley K.A., Johns J.M. Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy. Addict. Behav. 2004;29:1541–1564. doi: 10.1016/j.addbeh.2004.02.062.
    1. Pryce C.R., Ruedi-Bettschen D., Dettling A.C., Weston A., Russig H., Ferger B., Feldon J. Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research. Neurosci. Biobehav. Rev. 2005;29:649–674.
    1. Veenema A.H., Reber S.O., Selch S., Obermeier F., Neumann I.D. Early life stress enhances the vulnerability to chronic psychosocial stress and experimental colitis in adult mice. Endocrinology. 2008;149:2727–2736.
    1. Champagne F.A., Meaney M.J. Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol. Psychiat. 2006;59:1227–1235.
    1. Heim C., Newport D.J., Mletzko T., Miller A.H., Nemeroff C.B. The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology. 2008;33:693–710.
    1. House J.S., Landis K.R., Umberson D. Social relationships and health. Science (New York) 1988;241:540–545.
    1. Neumann I.D. The advantage of social living: brain neuropeptides mediate the beneficial consequences of sex and motherhood. Front. Neuroendocrinol. 2009;30:483–496.
    1. Kendler K.S., Neale M.C., Kessler R.C., Heath A.C., Eaves L.J. Childhood parental loss and adult psychopathology in women. A twin study perspective. Arch. Gen. Psychiat. 1992;49:109–116.
    1. Meinlschmidt G., Heim C. Sensitivity to Intranasal Oxytocin in Adult Men with Early Parental Separation. Biol. Psychiat. 2007;61:1109–1111.
    1. Born J., Lange T., Kern W., McGregor G.P., Bickel U., Fehm H.L. Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci. 2002;5:514–516.
    1. Buchheim A., Heinrichs M., George C., Pokorny D., Koops E., Henningsen P., O'Connor M.F., Gundel H. Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology. 2009;34:1417–1422.
    1. Sloman L., Gilbert P., Hasey G. Evolved mechanisms in depression: the role and interaction of attachment and social rank in depression. J. Affect. Disord. 2003;74:107–121.
    1. Costa B., Pini S., Gabelloni P., Abelli M., Lari L., Cardini A., Muti M., Gesi C., Landi S., Galderisi S., Mucci A., Lucacchini A., Cassano G.B., Martini C. Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology. 2009;34:1506–1514.
    1. Heim C., Young L.J., Newport D.J., Mletzko T., Miller A.H., Nemeroff C.B. Lower CSF oxytocin concentrations in women with a history of childhood abuse. Mol. Psychiat. 2009;14:954–958.
    1. Kirschbaum C., Klauer T., Filipp S.H., Hellhammer D.H. Sex-specific effects of social support on cortisol and subjective responses to acute psychological stress. Psychosom. Med. 1995;57:23–31.
    1. Heinrichs M., Baumgartner T., Kirschbaum C., Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol. Psychiat. 2003;54:1389–1398.
    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. Psychiat. 2009;65:728–731.
    1. Kirsch P., Esslinger C., Chen Q., Mier D., Lis S., Siddhanti S., Gruppe H., Mattay V.S., Gallhofer B., Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J. Neurosci. 2005;25:11489–11493.
    1. Domes G., Heinrichs M., Glascher J., Buchel C., Braus D.F., Herpertz S.C. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol. Psychiat. 2007;62:1187–1190.
    1. Domes G., Lischke A., Berger C., Grossmann A., Hauenstein K., Heinrichs M., Herpertz S.C. Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology. 2009
    1. Di Simplicio M., Massey-Chase R., Cowen P.J., Harmer C.J. Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J. Psychopharmacol. (Oxford, England) 2009;23:241–248. doi: 10.1177/0269881108095705.
    1. Harmer C.J., Bhagwagar Z., Perrett D.I., Vollm B.A., Cowen P.J., Goodwin G.M. Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology. 2003;28:148–152.
    1. Harmer C.J., Mackay C.E., Reid C.B., Cowen P.J., Goodwin G.M. Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol. Psychiat. 2006;59:816–820.
    1. Norbury R., Mackay C.E., Cowen P.J., Goodwin G.M., Harmer C.J. Short-term antidepressant treatment and facial processing. Functional magnetic resonance imaging study. Br. J. Psychiat. 2007;190:531–532. doi: 10.1192/bjp.bp.106.031393.
    1. Frasch A., Zetzsche T., Steiger A., Jirikowski G.F. Reduction of plasma oxytocin levels in patients suffering from major depression. Adv. Experim. Med. Biol. 1995;395:257–258.
    1. Zetzsche T., Frasch A., Jirikowski G.F., Murck H., Steiger A. Nocturnal oxytocin secretion is reduced in major depression. Biol. Psychiat. 1996;39:584.
    1. Ozsoy S., Esel E., Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiat. Res. 2009;169:249–252.
    1. van Londen L., Goekoop J.G., van Kempen G.M., Frankhuijzen-Sierevogel A.C., Wiegant V.M., van der Velde E.A., De Wied D. Plasma levels of arginine vasopressin elevated in patients with major depression. Neuropsychopharmacology. 1997;17:284–292.
    1. Cyranowski J.M., Hofkens T.L., Frank E., Seltman H., Cai H.M., Amico J.A. Evidence of dysregulated peripheral oxytocin release among depressed women. Psychosom. Med. 2008;70:967–975.
    1. Bell C.J., Nicholson H., Mulder R.T., Luty S.E., Joyce P.R. Plasma oxytocin levels in depression and their correlation with the temperament dimension of reward dependence. J. Psychopharmacol. 2006;20:656–660.
    1. Scantamburlo G., Hansenne M., Fuchs S., Pitchot W., Marechal P., Pequeux C., Ansseau M., Legros J.J. Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology. 2007;32:407–410.
    1. Demitrack M.A., Gold P.W. Oxytocin: neurobiologic considerations and their implications for affective illness. Prog. Neuro-psychopharmacol. Biol. Psychiat. 1988;12(Suppl):S23–S51. doi: 10.1016/0278-5846(88)90072-3.
    1. Pitts A.F., Samuelson S.D., Meller W.H., Bissette G., Nemeroff C.B., Kathol R.G. Cerebrospinal fluid corticotropin-releasing hormone, vasopressin, and oxytocin concentrations in treated patients with major depression and controls. Biol. Psychiat. 1995;38:330–335.
    1. Purba J.S., Hoogendijk W.J., Hofman M.A., Swaab D.F. Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch. Gen. Psychiat. 1996;53:137–143.
    1. Meynen G., Unmehopa U.A., Hofman M.A., Swaab D.F., Hoogendijk W.J. Hypothalamic oxytocin mRNA expression and melancholic depression. Mol. Psychiatry. 2007;12:118–119. doi: 10.1038/sj.mp.4001911.
    1. Wang S.S., Kamphuis W., Huitinga I., Zhou J.N., Swaab D.F. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol. Psychiat. 2008;13:786–799.
    1. Scott A.I., Whalley L.J., Bennie J., Bowler G. Oestrogen-stimulated neurophysin and outcome after electroconvulsive therapy. Lancet. 1986;1:1411–1414.
    1. Devanand D.P., Lo E.-S., Sackeim H.A., Ross F., Halbreich U., Prudic J., Cooper T. Specificity of ECT treatment parameters on plasma vasopressin and oxytocin; Annual Meeting of the Society for Biological Psychiatry; Montreal, Canada. 7 May 1988.
    1. Smith J.E., Williams K., Burkett S., Glue P., Nutt D.J. Oxytocin and vasopressin responses to ECT. Psychiat. Res. 1990;32:201–202.
    1. Scott A.I., Shering P.A., Legros J.J., Whalley L.J. Improvement in depressive illness is not associated with altered release of neurophysins over a course of ECT. Psychiat. Res. 1991;36:65–73.
    1. Smith J., Williams K., Birkett S., Nicholson H., Glue P., Nutt D.J. Neuroendocrine and clinical effects of electroconvulsive therapy and their relationship to treatment outcome. Psychol. Med. 1994;24:547–555.
    1. Devanand D.P., Lisanby S., Lo E.-S., Fitzsimons L., Cooper T.B., Halbreich U., Sackeim H.A. Effects of electroconvulsive therapy on plasma vasopressin and oxytocin. Biol. Psychiat. 1998;44:610–616.
    1. Blume A., Bosch O.J., Miklos S., Torner L., Wales L., Waldherr M., Neumann I.D. Oxytocin reduces anxiety via ERK1/2 activation: local effect within the rat hypothalamic paraventricular nucleus. Eur. J. Neurosci. 2008;27:1947–1956.
    1. Tomizawa K., Iga N., Lu Y.F., Moriwaki A., Matsushita M., Li S.T., Miyamoto O., Itano T., Matsui H. Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nat. Neurosci. 2003;6:384–390.

Source: PubMed

Подписаться