Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy

M J Bakermans-Kranenburg, M H van I Jzendoorn, M J Bakermans-Kranenburg, M H van I Jzendoorn

Abstract

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

Figures

Figure 1
Figure 1
Effects of oxytocin administration on face recognition, trust to in-group and trust to out-group in healthy participants: combined effect sizes (d) and 95% confidence intervals. The combined effect size for distrust to out-group is not significant.
Figure 2
Figure 2
Randomized controlled trials with oxytocin administration in clinical groups: effect sizes (Cohen's d, 95% confidence interval) and significance.
Figure 3
Figure 3
A contextual psychoneurobiological model of oxytocin (OT) treatment: moderation by childhood experiences.

References

    1. Guastella AJ, Howard AL, Dadds MR, Mtchell P, Carson DS. A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology. 2009b;34:917–923.
    1. Striepens N, Kendrick KM, Maier W, Hurlemann R. Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Front Neuroendocrinol. 2011;32:426–450.
    1. Yamasue H, Yee JR, Hurlemann R, Rilling JK, Chen FS, Meyer-Lindenberg A, et al. Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci. 2012;32:14109–14117.
    1. Feldman R. Oxytocin and social affiliation in humans. Horm Behav. 2012;61:380–391.
    1. Churchland PS, Winkielman P. Modulating social behavior with oxytocin: How does it work? What does it mean. Horm Behav. 2012;61:392–399.
    1. Guastella AJ, MacLeod C. A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions. Horm Behav. 2012;61:410–418.
    1. Landgraf R, Neumann ID. Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrin. 2004;25:150–176.
    1. MacDonald K, MacDonald TM. The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harvard Rev Psychiat. 2010;18:1–21.
    1. Carter CS. Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology. 1998;23:779–818.
    1. Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010;65:768–779.
    1. Galbally M, Lewis A, Van IJzendoorn MH, Permezel M. The role of oxytocin in maternal–infant relationships: a systematic review of human studies. Harvard Rev Psychiat. 2011;19:1–14.
    1. Feldman R, Weller A, Zagoori-Sharon O, Levine A. Evidence for a neuroendrocrinological foundation of human affiliation. Psychol Sci. 2007;18:965–970.
    1. Skrundz M, Bolten M, Nast I, Hellhammer DH, Meinlschmidt G. Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology. 2011;36:1886–1893.
    1. Frasch A, Zetzsche T, Steiger A, Jirikowski GF. Reduction of plasma oxytocin levels in patients suffering from major depression. Adv Exp Med Biol. 1995;395:257–258.
    1. Gordon I, Zagoory-Sharon O, Schneiderman I, Leckman JF, Weller A, Feldman R. ‘Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress'. Dev Psychobiol. 2008;50:728.
    1. Cyranowski JM, Hofkens BA, Frank E, Seltman H, Cai H, Amico J. Evidence of dysregulated peripheral oxytocin release among depressed women. Psychosom Med. 2008;70:967–975.
    1. Keri S, Kiss I, Kelemen O. Sharing secrets: oxytocin and trust in schizophrenia. Soc Neurosci. 2009;4:287–293.
    1. Rubin LH, Carter CS, Drogos L, Pournajafi-Nazarloo H, Sweeney JA, Maki PM. Peripheral oxytocin is associated with reduced symptom severity inschizophrenia. Schizophr Res. 2010;124:13–21.
    1. Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader–Willi syndrome: a study of five cases. J Clin Endocrinol Metab. 1995;80:573–579.
    1. Bruins J, Hijman R, Van Ree JM. Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects. Peptides. 1992;13:461–468.
    1. Perry A, Bentin S, Shalev I, Israel S, Uzefovsky F, Bar-On D, et al. Intranasal oxytocin modulates EEG mu/alpha and beta rhythms during perception of biological motion. Psychoneuroendocrinology. 2010;35:1446–1453.
    1. Riem MME, Bakermans-Kranenburg MJ, Pieper S, Tops M, Boksem MA, Vermeiren RR, et al. Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial. Biol Psychiatry. 2011;70:291–297.
    1. Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ. Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav. 2009;56:128–132.
    1. Naber F, Van IJzendoorn MH, Deschamps P, Van Engeland H, Bakermans-Kranenburg MJ. Intranasal oxytocin increases fathers' observed responsiveness during play with their children: a double-blind within-subject experiment. Psychoneuroendocrinology. 2010;35:1583–1586.
    1. Van IJzendoorn MH, Bakermans-Kranenburg MJ. A sniff of trust: meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group. Psychoneuroendocrinology. 2012;37:438–443.
    1. Huffmeijer R, Alink LRA, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, et al. Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration. Neuroendocrinol Lett. 2012;33:21–25.
    1. Weisman O, Zagoory-Sharon O, Feldman R. Intranasal oxytocin administration is reflected in human saliva. Psychoneuroendocrinology. 2012;37:1582–1586.
    1. Van IJzendoorn MH, Bhandari R, Van der Veen R, Grewen KM, Bakermans-Kranenburg MJ. Elevated salivary levels of oxytocin persist more than 7 h after intranasal administration. Front Neurosci. 2012;6:1–6.
    1. Guastella AJ, Hickie JB, McGuiness MM, Otis M, Woods EA, Disinger HM, et al. Recommendations for the standardization of oxytocin nasal administration and guidelines for its reporting in human research. Psychoneuroendocrinology. 2013;38:612–625.
    1. Bartz JA, Zaki J, Bolger N, Hollander E, Ludwig NN, Kolevzon A, et al. Oxytocin selectively improves empathic accuracy. Psychol Sci. 2010;21:1426–1428.
    1. Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, et al. Oxytocin enhances amygdale-dependent, socially reinforces learning and emotional empathy in humans. J Neurosci. 2010;30:4999–5007.
    1. 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;25:11489–11493.
    1. Marsh AA, Yu HH, Pine DS, Blair RJR. Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology. 2010;209:225–232.
    1. De Dreu CKW, Greer LL, Handgraaf MJJ, Shalvi S, Van Kleef GA, Baas M, et al. The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science. 2010;328:1408–1411.
    1. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocinincreases trust in humans. Nature. 2005;435:673–676.
    1. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychological stress. Biol Psychiatry. 2003;54:1389–1398.
    1. Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test'—a tool for nvestigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28:76–81.
    1. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184.
    1. Morrison SE, Salzman CD. Re-valuing the amygdale. Curr Opin Neurobiol. 2010;20:221–230.
    1. Riem MM, van IJzendoorn MH, Tops M, Boksem MA, Rombouts SA, Bakermans-Kranenburg MJ. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter. Neuropsychopharmacology. 2012;37:1257–1266.
    1. Berridge KC. The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology. 2007;191:391–431.
    1. Berridge KC, Kringelbach ML. Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology. 2008;199:457–480.
    1. Bos PA, Panksepp J, Bluthé RM, Honk JV. Acute effects of steroid hormones and neuropeptides on human social-emotional behavior: A review of single administration studies. Front Neuroendocrinol. 2012;33:17–35.
    1. Haber SN, Knutson B. The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35:4–26.
    1. Kringelbach ML. The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci. 2005;6:691–702.
    1. Gamer M, Zurowski B, Büchel C. Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Natl Acad Sci USA. 2010;107:9400–9405.
    1. Skuse DH, Gallagher L. Dopaminergic-neuropeptide interactions in the social brain. Trends in cognitive sciences. 2009;13:27–35.
    1. Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, et al. Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology. 2010;35:83–93.
    1. Lischke A, Gamer M, Berger C, Grossmann A, Hauenstein K, Heinrichs M, et al. Oxytocin increases amygdala reactivity to threatening scenes in females. Psychoneuroendocrinology. 2012;37:1431–1438.
    1. Strathearn L, Fonagy P, Amico J, Montague PR. Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychofarmacology. 2009;34:2655–2666.
    1. Leitman DI, Wolf DH, Ragland JD, Laukka P, Loughead J, Valdez JN, et al. ‘It's not what you say, but how you say it': a reciprocal temporo-frontal network for affective prosody. Front Hum Neurosc. 2010;4:1–13.
    1. Gondoli DM, Silverberg SB. Maternal emotional distress and diminished responsiveness: the mediating role of parenting efficacy and parental perspective taking. Dev Psychol. 1997;33:861–868.
    1. Leerkes EM. Predictors of maternal sensitivity to infant distress. Parent Sci Pract. 2010;10:219–239.
    1. Feldman R. On the origins of background emotions: From affect synchrony to symbolic expression. Emotion. 2007;7:601–611.
    1. Iacoboni M. Imitation, empathy and mirror neurons. Annu Rev Psychol. 2009;60:653–670.
    1. Gallese V, Keysers C, Rizzolatti G. A unifying view of the basis of social cognition. Trends Cogn Sci. 2004;8:396–403.
    1. Chakrabarti B, Bullmore E, Baron-Cohen S. Empathizing with basic emotions: common and discrete neural substrates. Soc Neurosci. 2006;1:364–384.
    1. Decety J, Jackson PL. The functional architecture of human empathy. Behav Cogn Neurosci Rev. 2004;3:71–100.
    1. Jabbi M, Swart M, Keysers C. Empathy for positive and negative emotions in the gustatory cortex. Neuroimage. 2007;34:1744–1753.
    1. Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, et al. 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. Heinrichs M, Neumann I, Ehlert U. Lactation and stress: protective effects of breast-feeding in humans. Stress. 2002;5:195–203.
    1. Wilson DB, Lipsey MW. Practical Meta-Analysis. Sage Publications: Newbury Park, CA, USA; 2000.
    1. Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci. 2011;15:301–309.
    1. Declerk CH, Boone C, Kiyonari T. Oxytocin and cooperation under conditions of uncertainty: the modulating role of incentives and social information. Horm Behav. 2010;57:368–374.
    1. Micolajczak M, Gross JJ, Lane A, Corneille O, De Timary PH., Luminet O. Oxytocin makes people trusting, not gullible. Psych Sci. 2010;21:1072–1075.
    1. Schulze L, Lischke A, Greif J, Herpertz SC, Heinrichs M, Domes G. Oxytocin increases recognition of masked emotional faces. Psychoneuroendocrinology. 2011;36:1378–1382.
    1. Unkelbach C, Graustella AJ, Forgas J. Oxytocin selectively facilitates recognition of positive sex and relationship words. Psychol Sci. 2008;19:102–104.
    1. De Dreu CKW, Greer LL, Shalvi S, Handgraaf MJJ, Van Kleef GA. Oxytocin modulates the selection of allies in intergroup conflict. Proc R Soc Ser B. 2012;279:1150–1154.
    1. Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The Autism-Spectrum Quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord. 2001;31:5–17.
    1. Huffmeijer R, Alink LRA, Tops M, Bakermans-Kranenburg MJ, Van IJzendoorn MH. Asymmetric frontal brain activity and parental rejection predict altruistic behavior: moderation of oxytocin effects. Cogn Affect Behav Neurosci. 2012;12:382–392.
    1. Fraley RC, Waller NG, Brennan KA. An item-response theory analysis of self-report measures of adult attachment. J Person Soc Psychol. 2000;78:350–365.
    1. Roisman GI, Holland A, Fortuna K, Fraley RC, Clausell E, Clarke A. The adult attachment interview and self-reports of attachment style: an empirical rapprochement. J Person Soc Psychol. 2007;92:678–697.
    1. Noftle EE, Shaver PR. Attachment dimensions and the big five personality traits: associations and comparative ability to predict relationship quality. J Res Person. 2006;40:179–208.
    1. Van IJzendoorn MH, Bakermans–Kranenburg MJ. Stretched until it snaps: attachment and close relationships. Child Dev Perspect. 2010;4:109–111.
    1. Riem MME, Bakermans-Kranenburg MJ, Huffmeijer R, Van IJzendoorn MH.Does intranasal oxytocin promote prosocial behavior to an excluded fellow player? A randomized controlled trial with Cyberball Psychoneuroendocrinology 2013(in press).
    1. Crowley MJ, Wu J, McCarty ER, David DH, Bailey CA, Mayes LC. Exclusion and micro-rejection: event-related potential response predicts mitigated distress. NeuroReport. 2009;20:1518–1522.
    1. Williams KD, Jarvis B. Cyberball: a program for use in research on ostracism and interpersonal acceptance. Behav Res Methods Instr Comput. 2006;38:174–180.
    1. Van IJzendoorn MH, Huffmeijer R, Alink LRA, Bakermans-Kranenburg MJ, Tops M. The impact of oxytocin administration on charitable donating is moderated by experiences of parental love-withdrawal. Front Psychol. 2012;2:1–8.
    1. Bakermans-Kranenburg MJ, Van IJzendoorn MH, Riem MME, Tops M, Alink LRA. Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences. Soc Cogn Affect Neurosci. 2012;7:951–957.
    1. Riem MME, Van IJzendoorn MH, Tops M, Boksem M, Rombouts SARB, Bakermans-Kranenburg MJ.Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal Eur Neuropsychopharmacology 2013(in press).
    1. Tomasi D, Volkow ND. Association between functional connectivity hubs and brain networks. Cereb cortex. 2011;21:2003–2013.
    1. Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006;129:564–583.
    1. Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex. 2009;19:2485–2497.
    1. Hua QP, Zeng XZ, Liu JY, Wang JY, Guo JY, Luo F. Dynamic changes in brain activations and functional connectivity during affectively different tactile stimuli. Cell Mol Neurobiol. 2008;28:57–70.
    1. McCabe C, Rolls ET, Bilderbeck A, McGlone F. Cognitive influences on the affective representation of touch and the sight of touch in the human brain. Soc Cogn Affect Neurosci. 2008;3:97–108.
    1. Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 2010;20:236–260.
    1. Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012;11:352–365.
    1. Alalade E, Denny K, Potter G, Steffens D, Wang L. Altered cerebellar–cerebral functional connectivity in geriatric depression. PLoS One. 2011;6:e20035.
    1. Giedd JN, Schmitt JE, Neale MC. Structural brain magnetic resonance imaging of pediatric twins. Hum Brain Mapp. 2007;28:474–481.
    1. Bauer PM, Hanson JL, Pierson RK, Davidson RJ, Pollak SD. Cerebellar volume and cognitive functioning in children who experienced early deprivation. Biol Psychiatry. 2009;66:1100–1106.
    1. Meinlschmidt G, Heim C. Sensitivity to intranasal oxytocin in adult men with early parental separation. Biol Psychiatry. 2007;61:1109–1111.
    1. Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, et al. Oxytocin infusion reduces repetitive behaviours in adults with autistic and Asperger's disorders. Neuropsychopharmacology. 2003;28:193–198.
    1. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61:498–503.
    1. Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I. The ‘Reading the Mind in the Eyes' Test, revised version: a study with normal adults, and adults with Asperger's syndrome or high-functioning autism. J Child Psychol Psychiatry. 2001;42:241–251.
    1. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010;67:692–694.
    1. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behaviour with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci USA. 2010;107:4389–4394.
    1. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011;1380:42–77.
    1. Hogart A, Wu D, LaSalle JM, Schanen NC. The comorbidity of autism with the genomic disorders of chromosome 15q11.2–q13. Neurobiol Dis. 2010;38:181–191.
    1. Tauber M, Mantoulan C, Copet P, Jauregui J, Demeer G, Diene G, et al. Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader–Willi syndrome: a randomised placebo-controlled trial in 24 patients. J Rare Dis. 2011;6:47.
    1. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 2010;35:2403–2413.
    1. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, et al. Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. Int J Neuropsychopharmacol. 2012;15:883–896.
    1. Hall SS, Lightbody AA, McCarthy BE, Parker KJ, Reiss AL. Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology. 2012;37:509–518.
    1. Pitman RK, Orr SP, Lasko NB. Effects of intranasal vasopressin and oxytocinon physiologic responding during personal combat imagery in Vietnam veterans with post-traumatic stress disorders. PsychiatryRes. 1993;48:107–117.
    1. Yatzkar U, Klein E. Intranasal oxytocin in patients with post traumatic stress disorder: a single dose pilot double blind crossover study. Clin Neuropsychopharmacol. 2009;32:S84.
    1. Pincus D, Kose S, Arana A, Johnson K, Chua P, Morgan, Borckhardt J, et al. Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: a double-blind placebo controlled FMRI study. Front Psychiatry. 2010;1:134.
    1. Mah BL, Van IJzendoorn MH, Smith R, Bakermans-Kranenburg MJ. Oxytocin in postnatally depressed mothers: its influence on mood and expressed emotion. Progr Neuro-Psychopharmacol Biol Psychiatry. 2013;40:267–272.
    1. Caldwell HK, Stephens SL, Young WS. Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice. Mol Psychiatry. 2009;14:190–196.
    1. Feifel D, Macdonald K, Nguyen A, et al. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry. 2010;68:678–680.
    1. Feifel D, Macdonald K, Cobb P, Minassian A. Adjunctive intranasal oxytocin improves verbal memory in people with schizophrenia. Schizophr Res. 2012;139:207–210.
    1. Pedersen CA, Gibson CM, Rau SW, Salimi K, Smedley KL, Casey RL, et al. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res. 2011;132:50–53.
    1. Averbeck BB, Bobin T, Evans S, Shergill SS. Emotion recognition and oxytocin in patients with schizophrenia. Psychol Med. 2011;41:1–8.
    1. Goldman MB, Gomes AM, Carter CS, Lee R. Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia. Psychopharmacology. 2011;216:101–110.
    1. Den Boer JA, Westenberg HG. Oxytocin in obsessive compulsive disorder. Peptides. 1992;13:1083–1085.
    1. Epperson CN, McDougle CJ, Price LH. Intranasal oxytocin in obsessive-compulsive disorder. Biol Psychiatry. 1996;40:547–549.
    1. Epperson CN, McDougle CJ, Price LH. Intranasal oxytocin in Trichotillomania. Biol Psychiatry. 1996;40:559–561.
    1. Brennan KA, Clark CL, Shaver P.Self-report measures of adult romantic attachmentIn: Simpson JA, Rholes WS (eds).Attachment Theory and Close Relationships Guilford Press: New York, NY, USA; 1998
    1. Simeon D, Bartz J, Hamilton H, Crystal S, Braun A, Ketay S, et al. Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study. Psychoneuroendocrinology. 2011;36:1418–1421.
    1. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Comprehensive Meta-Analysis, Version 2. Biostat: Englewood, NJ, USA; 2005.
    1. Cohen J.Statistical Power Analysis for the Behavioral Sciences2nd ednRoutledge: London, UK; 1988
    1. Rosenthal R. Meta-Analytic Procedures for Social Research. Sage Publications: Newbury Park, CA, USA; 1991.
    1. Duval S, Tweedie R. A nonparametric ‘trim and fill' method for accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000;95:89–98.
    1. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–463.
    1. Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ. 2000;320:1574–1577.
    1. Mullen B. Advanced BASIC Meta-Analysis. Lawrence Erlbaum: Hillsdale, NJ; 1989.
    1. Leckman JF. Variations in maternal behavior—oxytocin and reward pathways—peripheral measures matter?! Neuropsychopharmacology. 2011;36:2587–2588.
    1. Bowles S. Being human: conflict: altruism's midwife. Nature. 2008;456:326–327.
    1. Hrdy SB. Mothers and Others: The Evolutionary Origins of Mutual Understanding. Harvard University Press: Cambridge, MA, USA; 2009.
    1. Bowlby J. Attachment and Loss. Vol 1. Basic Books: , USA; 1969/1982.
    1. Mikulincer M, Shaver PR. Attachment in adulthood. Structure, Dynamics, and Change. Guilford: New York, NY, USA; 2007.
    1. Bakermans-Kranenburg MJ, Steele H, Zeanah CH, Muhamedrahimov RJ, Vorria P, Dobrova-Krol NA, et al. Attachment and emotional development in institutional care: characteristics and catch-up. Monogr Soc Res Child Dev. 2011;76:62–91.
    1. Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, Marmar CR, et al. Trauma and the Vietnam War Generation: Report of Findings From the National Vietnam Veterans Readjustment Study. Bruner/Mazel: New York, NY,USA; 1990.
    1. King DW, King LA, Foy DW, Gudanowski DM. Prewar factors in combat-related posttraumatic stress disorder: structural equation modeling with a national sample of female and male Vietnam veterans. J Consult Clin Psychol. 1996;64:520–531.
    1. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81:629–683.
    1. Marsh AA, Yu HH, Pine DS, Gorodetsky EK, Goldman D, Blair RJR. The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype. Psychopharmacology. 2012;224:469–476.
    1. Chen FS, Kumsta R, Von Dawans R, Monakhov M, Ebstein RP, Heinrichs M. Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proc Natl Acad Sci USA. 2011;108:19937–19942.
    1. Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets and side effects. N Engl J Med. 2003;348:538–549.

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