Advertisement

Oxytocin and Anxiety Disorders

  • Michael G. Gottschalk
  • Katharina Domschke
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 35)

Abstract

In the present chapter, we review the literature focusing on oxytocin (OT)-centered research in anxiety spectrum conditions, comprising separation anxiety disorder, specific phobias, social anxiety disorder (SAD), panic disorder, generalized anxiety disorder, and anxiety-related endophenotypes (e.g., trust behavior, behavioral inhibition, neuroticism, and state/trait anxiety). OT receptor gene (OXTR) polymorphisms have been implicated in gene–environment interactions with attachment style and childhood maltreatment and to influence clinical outcomes, including SAD intensity and limbic responsiveness. Epigenetic OXTR DNA methylation patterns have emerged as a link between categorical, dimensional, neuroendocrinological, and neuroimaging SAD correlates, highlighting them as potential peripheral surrogates of the central oxytocinergic tone. A pathophysiological framework of OT integrating the dynamic nature of epigenetic biomarkers and the summarized genetic and peripheral evidence is proposed. Finally, we emphasize opportunities and challenges of OT as a key network node of social interaction and fear learning in social contexts. In conjunction with multi-level investigations incorporating a dimensional understanding of social affiliation and avoidance in anxiety spectrum disorders, these concepts will help to promote research for diagnostic, state, and treatment response biomarkers of the OT system, advancing towards indicated preventive interventions and personalized treatment approaches.

Keywords

Amygdala Anxiety disorder Epigenetic Fear extinction Generalized anxiety disorder Genetic Imaging genetics Intranasal oxytocin Neuroticism OXT OXTR Oxytocin Oxytocin receptor Panic disorder Separation anxiety disorder Social anxiety disorder Social phobia Specific phobia Therapy genetics Trait anxiety Treatment response 

Abbreviations

5-HTTLPR

Serotonin transporter gene length polymorphic region

CCK-4

Cholecystokinin tetrapeptide

CpG

Cytosine-phosphate-guanine

CTQ

Childhood Trauma Questionnaire

DASS

Depression Anxiety and Stress Scale

fMRI

Functional magnetic resonance imaging

HA

Harm avoidance

KSP

Karolinska Scales of Personality

MDD

Major depressive disorder

OT

Oxytocin

OXT

Oxytocin/neurophysin I prepropeptide gene

OXTR

Oxytocin receptor gene

SAD

Social anxiety disorder

SLC6A4

Solute carrier family 6 member 4 (serotonin transporter) gene

STAI-S/T

State-Trait Anxiety Inventory

TSST

Trier Social Stress Test

Notes

Acknowledgments

This work was supported by the German Research Foundation (DFG) (SFB-TRR-58, projects C02 and Z02 to KD) and the Federal Ministry of Education and Research (BMBF, 01EE1402A, PROTECT-AD, P5 to KD).

References

  1. Acheson D, Feifel D, de Wilde S, McKinney R, Lohr J, Risbrough V (2013) The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample. Psychopharmacology 229(1):199–208. doi: 10.1007/s00213-013-3099-4CrossRefPubMedPubMedCentralGoogle Scholar
  2. Acheson DT, Feifel D, Kamenski M, McKinney R, Risbrough VB (2015) Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response. Depress Anxiety 32(6):400–407. doi: 10.1002/da.22362CrossRefPubMedGoogle Scholar
  3. Alvares GA, Hickie IB, Guastella AJ (2010) Acute effects of intranasal oxytocin on subjective and behavioral responses to social rejection. Exp Clin Psychopharmacol 18(4):316–321. doi: 10.1037/a0019719CrossRefPubMedGoogle Scholar
  4. Alvares GA, Chen NT, Balleine BW, Hickie IB, Guastella AJ (2012) Oxytocin selectively moderates negative cognitive appraisals in high trait anxious males. Psychoneuroendocrinology 37(12):2022–2031. doi: 10.1016/j.psyneuen.2012.04.018CrossRefPubMedGoogle Scholar
  5. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, ArlingtonCrossRefGoogle Scholar
  6. Apps MA, Lockwood PL, Balsters JH (2013) The role of the midcingulate cortex in monitoring others’ decisions. Front Neurosci 7:251. doi: 10.3389/fnins.2013.00251CrossRefPubMedPubMedCentralGoogle Scholar
  7. Apter-Levy Y, Feldman M, Vakart A, Ebstein RP, Feldman R (2013) Impact of maternal depression across the first 6 years of life on the child’s mental health, social engagement, and empathy: the moderating role of oxytocin. Am J Psychiatry 170(10):1161–1168. doi: 10.1176/appi.ajp.2013.12121597CrossRefPubMedGoogle Scholar
  8. Bailey JE, Kendrick A, Diaper A, Potokar JP, Nutt DJ (2007) A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers. J Psychopharmacol 21(1):42–49. doi: 10.1177/0269881106063889CrossRefPubMedGoogle Scholar
  9. Bakermans-Kranenburg MJ, van Ijzendoorn MH (2008) Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cogn Affect Neurosci 3(2):128–134. doi: 10.1093/scan/nsn004CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bale TL, Davis AM, Auger AP, Dorsa DM, McCarthy MM (2001) CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J Neurosci 21(7):2546–2552CrossRefGoogle Scholar
  11. Bartz JA, Zaki J, Bolger N, Hollander E, Ludwig NN, Kolevzon A, Ochsner KN (2010a) Oxytocin selectively improves empathic accuracy. Psychol Sci 21(10):1426–1428. doi: 10.1177/0956797610383439CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bartz JA, Zaki J, Ochsner KN, Bolger N, Kolevzon A, Ludwig N, Lydon JE (2010b) Effects of oxytocin on recollections of maternal care and closeness. Proc Natl Acad Sci U S A 107(50):21371–21375. doi: 10.1073/pnas.1012669107CrossRefPubMedPubMedCentralGoogle Scholar
  13. Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes? Mol Psychiatry 14(8):746–754. doi: 10.1038/mp.2009.44CrossRefPubMedPubMedCentralGoogle Scholar
  14. Bendix M, Uvnas-Moberg K, Petersson M, Gustavsson P, Svanborg P, Asberg M, Jokinen J (2015) Plasma oxytocin and personality traits in psychiatric outpatients. Psychoneuroendocrinology 57:102–110. doi: 10.1016/j.psyneuen.2015.04.003CrossRefPubMedGoogle Scholar
  15. Bos PA, Panksepp J, Bluthe RM, van Honk J (2012) Acute effects of steroid hormones and neuropeptides on human social-emotional behavior: a review of single administration studies. Front Neuroendocrinol 33(1):17–35. doi: 10.1016/j.yfrne.2011.01.002CrossRefPubMedGoogle Scholar
  16. Bradley B, Davis TA, Wingo AP, Mercer KB, Ressler KJ (2013) Family environment and adult resilience: contributions of positive parenting and the oxytocin receptor gene. Eur J Psychotraumatol 4. doi: 10.3402/ejpt.v4i0.21659CrossRefGoogle Scholar
  17. Buchheim A, Heinrichs M, George C, Pokorny D, Koops E, Henningsen P, O'Connor MF, Gundel H (2009) Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology 34(9):1417–1422. doi: 10.1016/j.psyneuen.2009.04.002CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cardoso C, Ellenbogen MA, Serravalle L, Linnen AM (2013) Stress-induced negative mood moderates the relation between oxytocin administration and trust: evidence for the tend-and-befriend response to stress? Psychoneuroendocrinology 38(11):2800–2804. doi: 10.1016/j.psyneuen.2013.05.006CrossRefPubMedGoogle Scholar
  19. Carson DS, Berquist SW, Trujillo TH, Garner JP, Hannah SL, Hyde SA, Sumiyoshi RD, Jackson LP, Moss JK, Strehlow MC, Cheshier SH, Partap S, Hardan AY, Parker KJ (2015) Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Mol Psychiatry 20(9):1085–1090. doi: 10.1038/mp.2014.132CrossRefPubMedGoogle Scholar
  20. Chagnon YC, Potvin O, Hudon C, Preville M (2015) DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet 6:230. doi: 10.3389/fgene.2015.00230CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chang WH, Lee IH, Chen KC, Chi MH, Chiu NT, Yao WJ, Lu RB, Yang YK, Chen PS (2014) Oxytocin receptor gene rs53576 polymorphism modulates oxytocin-dopamine interaction and neuroticism traits – a SPECT study. Psychoneuroendocrinology 47:212–220. doi: 10.1016/j.psyneuen.2014.05.020CrossRefPubMedGoogle Scholar
  22. Chen FS, Kumsta R, von Dawans B, Monakhov M, Ebstein RP, Heinrichs M (2011) Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proc Natl Acad Sci U S A 108(50):19937–19942. doi: 10.1073/pnas.1113079108CrossRefPubMedPubMedCentralGoogle Scholar
  23. Chen FS, Kumsta R, Dvorak F, Domes G, Yim OS, Ebstein RP, Heinrichs M (2015) Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach. Transl Psychiatry 5:e664. doi: 10.1038/tp.2015.163CrossRefPubMedPubMedCentralGoogle Scholar
  24. Clark-Elford R, Nathan PJ, Auyeung B, Voon V, Sule A, Muller U, Dudas R, Sahakian BJ, Phan KL, Baron-Cohen S (2014) The effects of oxytocin on social reward learning in humans. Int J Neuropsychopharmacol 17(2):199–209. doi: 10.1017/S1461145713001120CrossRefPubMedPubMedCentralGoogle Scholar
  25. Clark-Elford R, Nathan PJ, Auyeung B, Mogg K, Bradley BP, Sule A, Muller U, Dudas RB, Sahakian BJ, Baron-Cohen S (2015) Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males. Int J Neuropsychopharmacol 18(2). doi: 10.1093/ijnp/pyu012
  26. 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 GB, Martini C (2009a) Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology 34(10):1506–1514. doi: 10.1016/j.psyneuen.2009.05.006CrossRefPubMedGoogle Scholar
  27. Costa B, Pini S, Martini C, Abelli M, Gabelloni P, Ciampi O, Muti M, Gesi C, Lari L, Cardini A, Mucci A, Bucci P, Lucacchini A, Cassano GB (2009b) Mutation analysis of oxytocin gene in individuals with adult separation anxiety. Psychiatry Res 168(2):87–93. doi: 10.1016/j.psychres.2008.04.009CrossRefPubMedGoogle Scholar
  28. Cyranowski JM, Hofkens TL, Frank E, Seltman H, Cai HM, Amico JA (2008) Evidence of dysregulated peripheral oxytocin release among depressed women. Psychosom Med 70(9):967–975. doi: 10.1097/PSY.0b013e318188ade4CrossRefPubMedPubMedCentralGoogle Scholar
  29. Dadds MR, Moul C, Cauchi A, Dobson-Stone C, Hawes DJ, Brennan J, Ebstein RE (2014) Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy. Dev Psychopathol 26(1):33–40. doi: 10.1017/S0954579413000497CrossRefPubMedPubMedCentralGoogle Scholar
  30. Dannlowski U, Kugel H, Grotegerd D, Redlich R, Opel N, Dohm K, Zaremba D, Grogler A, Schwieren J, Suslow T, Ohrmann P, Bauer J, Krug A, Kircher T, Jansen A, Domschke K, Hohoff C, Zwitserlood P, Heinrichs M, Arolt V, Heindel W, Baune BT (2015) Disadvantage of social sensitivity: interaction of oxytocin receptor genotype and child maltreatment on brain structure. Biol Psychiatry 80(5):398–405. doi: 10.1016/j.biopsych.2015.12.010CrossRefPubMedGoogle Scholar
  31. de Oliveira DC, Chagas MH, Garcia LV, Crippa JA, Zuardi AW (2012a) Oxytocin interference in the effects induced by inhalation of 7.5% CO(2) in healthy volunteers. Hum Psychopharmacol 27(4):378–385. doi: 10.1002/hup.2237CrossRefPubMedGoogle Scholar
  32. de Oliveira DC, Zuardi AW, Graeff FG, Queiroz RH, Crippa JA (2012b) Anxiolytic-like effect of oxytocin in the simulated public speaking test. J Psychopharmacol 26(4):497–504. doi: 10.1177/0269881111400642CrossRefPubMedPubMedCentralGoogle Scholar
  33. Declerck CH, Boone C, Kiyonari T (2010) Oxytocin and cooperation under conditions of uncertainty: the modulating role of incentives and social information. Horm Behav 57(3):368–374. doi: 10.1016/j.yhbeh.2010.01.006CrossRefPubMedGoogle Scholar
  34. Di Simplicio M, Massey-Chase R, Cowen PJ, Harmer CJ (2009) Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol 23(3):241–248. doi: 10.1177/0269881108095705CrossRefPubMedPubMedCentralGoogle Scholar
  35. Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M (2009) Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 65(9):728–731. doi: 10.1016/j.biopsych.2008.10.011CrossRefPubMedPubMedCentralGoogle Scholar
  36. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood AG, Nathan PJ, Phan KL (2014) Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology 39(9):2061–2069. doi: 10.1038/npp.2014.53CrossRefPubMedPubMedCentralGoogle Scholar
  37. Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC (2007a) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62(10):1187–1190. doi: 10.1016/j.biopsych.2007.03.025CrossRefGoogle Scholar
  38. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007b) Oxytocin improves “mind-reading” in humans. Biol Psychiatry 61(6):731–733. doi: 10.1016/j.biopsych.2006.07.015CrossRefPubMedPubMedCentralGoogle Scholar
  39. Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC (2010) Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology 35(1):83–93. doi: 10.1016/j.psyneuen.2009.06.016CrossRefGoogle Scholar
  40. Domes G, Sibold M, Schulze L, Lischke A, Herpertz SC, Heinrichs M (2013) Intranasal oxytocin increases covert attention to positive social cues. Psychol Med 43(8):1747–1753. doi: 10.1017/S0033291712002565CrossRefGoogle Scholar
  41. Domschke K, Dannlowski U (2010) Imaging genetics of anxiety disorders. Neuroimage 53(3):822–831. doi: 10.1016/j.neuroimage.2009.11.042CrossRefPubMedGoogle Scholar
  42. Domschke K, Deckert J (2010) Genetics. Curr Top Behav Neurosci 2:63–75CrossRefGoogle Scholar
  43. Domschke K, Deckert J (2012) Genetics of anxiety disorders – status quo and quo vadis. Curr Pharm Des 18(35):5691–5698CrossRefGoogle Scholar
  44. Domschke K, Maron E (2013) Genetic factors in anxiety disorders. Mod Trends Pharmacopsychiatry 29:24–46. doi: 10.1159/000351932CrossRefPubMedGoogle Scholar
  45. Domschke K, Reif A (2012) Behavioral genetics of affective and anxiety disorders. Curr Top Behav Neurosci 12:463–502. doi: 10.1007/7854_2011_185CrossRefPubMedGoogle Scholar
  46. Domschke K, Stevens S, Pfleiderer B, Gerlach AL (2010) Interoceptive sensitivity in anxiety and anxiety disorders: an overview and integration of neurobiological findings. Clin Psychol Rev 30(1):1–11. doi: 10.1016/j.cpr.2009.08.008CrossRefPubMedGoogle Scholar
  47. Drevets WC, Savitz J, Trimble M (2008) The subgenual anterior cingulate cortex in mood disorders. CNS Spectr 13(8):663–681CrossRefGoogle Scholar
  48. Eapen V, Dadds M, Barnett B, Kohlhoff J, Khan F, Radom N, Silove DM (2014) Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period. PLoS One 9(9):e107745. doi: 10.1371/journal.pone.0107745CrossRefPubMedPubMedCentralGoogle Scholar
  49. Eckstein M, Scheele D, Weber K, Stoffel-Wagner B, Maier W, Hurlemann R (2014) Oxytocin facilitates the sensation of social stress. Hum Brain Mapp 35(9):4741–4750. doi: 10.1002/hbm.22508CrossRefPubMedPubMedCentralGoogle Scholar
  50. Eckstein M, Becker B, Scheele D, Scholz C, Preckel K, Schlaepfer TE, Grinevich V, Kendrick KM, Maier W, Hurlemann R (2015) Oxytocin facilitates the extinction of conditioned fear in humans. Biol Psychiatry 78(3):194–202. doi: 10.1016/j.biopsych.2014.10.015CrossRefPubMedPubMedCentralGoogle Scholar
  51. Eckstein M, Scheele D, Patin A, Preckel K, Becker B, Walter A, Domschke K, Grinevich V, Maier W, Hurlemann R (2016) Oxytocin facilitates Pavlovian fear learning in males. Neuropsychopharmacology 41(4):932–939. doi: 10.1038/npp.2015.245CrossRefGoogle Scholar
  52. Eng W, Heimberg RG, Hart TA, Schneier FR, Liebowitz MR (2001) Attachment in individuals with social anxiety disorder: the relationship among adult attachment styles, social anxiety, and depression. Emotion 1(4):365–380CrossRefGoogle Scholar
  53. Evans S, Shergill SS, Averbeck BB (2010) Oxytocin decreases aversion to angry faces in an associative learning task. Neuropsychopharmacology 35(13):2502–2509. doi: 10.1038/npp.2010.110CrossRefPubMedPubMedCentralGoogle Scholar
  54. Fang A, Hoge EA, Heinrichs M, Hofmann SG (2014) Attachment style moderates the effects of oxytocin on social behaviors and cognitions during social rejection: applying an RDoC framework to social anxiety. Clin Psychol Sci 2(6):740–747. doi: 10.1177/2167702614527948CrossRefPubMedPubMedCentralGoogle Scholar
  55. Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y (2010) The effect of intranasal administration of oxytocin on fear recognition. Neuropsychologia 48(1):179–184. doi: 10.1016/j.neuropsychologia.2009.09.003CrossRefPubMedPubMedCentralGoogle Scholar
  56. Gamer M, Zurowski B, Buchel C (2010) Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Proc Natl Acad Sci U S A 107(20):9400–9405. doi: 10.1073/pnas.1000985107CrossRefPubMedPubMedCentralGoogle Scholar
  57. Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81(2):629–683CrossRefGoogle Scholar
  58. Goldman D, Domschke K (2014) Making sense of deep sequencing. Int J Neuropsychopharmacol 17(10):1717–1725. doi: 10.1017/S1461145714000789CrossRefPubMedPubMedCentralGoogle Scholar
  59. Goodin BR, Anderson AJ, Freeman EL, Bulls HW, Robbins MT, Ness TJ (2014) Intranasal oxytocin administration is associated with enhanced endogenous pain inhibition and reduced negative mood states. Clin J Pain. doi: 10.1097/AJP.0000000000000166
  60. Gorka SM, Fitzgerald DA, Labuschagne I, Hosanagar A, Wood AG, Nathan PJ, Phan KL (2015) Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder. Neuropsychopharmacology 40(2):278–286. doi: 10.1038/npp.2014.168CrossRefPubMedGoogle Scholar
  61. Gottschalk MG, Domschke K (2016) Novel developments in genetic and epigenetic mechanisms of anxiety. Curr Opin Psychiatry 29(1):32–38. doi: 10.1097/YCO.0000000000000219CrossRefPubMedGoogle Scholar
  62. Guastella AJ, Mitchell PB, Mathews F (2008) Oxytocin enhances the encoding of positive social memories in humans. Biol Psychiatry 64(3):256–258. doi: 10.1016/j.biopsych.2008.02.008CrossRefPubMedPubMedCentralGoogle Scholar
  63. Guastella AJ, Carson DS, Dadds MR, Mitchell PB, Cox RE (2009a) Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology 34(2):220–225. doi: 10.1016/j.psyneuen.2008.09.001CrossRefPubMedGoogle Scholar
  64. Guastella AJ, Howard AL, Dadds MR, Mitchell P, Carson DS (2009b) A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology 34(6):917–923. doi: 10.1016/j.psyneuen.2009.01.005CrossRefPubMedGoogle Scholar
  65. Heim C, Young LJ, Newport DJ, Mletzko T, Miller AH, Nemeroff CB (2009) Lower CSF oxytocin concentrations in women with a history of childhood abuse. Mol Psychiatry 14(10):954–958. doi: 10.1038/mp.2008.112CrossRefPubMedPubMedCentralGoogle Scholar
  66. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54(12):1389–1398CrossRefGoogle Scholar
  67. Hettema JM, Prescott CA, Myers JM, Neale MC, Kendler KS (2005) The structure of genetic and environmental risk factors for anxiety disorders in men and women. Arch Gen Psychiatry 62(2):182–189. doi: 10.1001/archpsyc.62.2.182CrossRefPubMedGoogle Scholar
  68. Hoge EA, Pollack MH, Kaufman RE, Zak PJ, Simon NM (2008) Oxytocin levels in social anxiety disorder. CNS Neurosci Ther 14(3):165–170. doi: 10.1111/j.1755-5949.2008.00051.xCrossRefPubMedPubMedCentralGoogle Scholar
  69. Hoge EA, Lawson EA, Metcalf CA, Keshaviah A, Zak PJ, Pollack MH, Simon NM (2012) Plasma oxytocin immunoreactive products and response to trust in patients with social anxiety disorder. Depress Anxiety 29(11):924–930. doi: 10.1002/da.21973CrossRefPubMedPubMedCentralGoogle Scholar
  70. Hommers LG, Domschke K, Deckert J (2015) Heterogeneity and individuality: microRNAs in mental disorders. J Neural Transm (Vienna) 122(1):79–97. doi: 10.1007/s00702-014-1338-4CrossRefGoogle Scholar
  71. Hostinar CE, Cicchetti D, Rogosch FA (2014) Oxytocin receptor gene polymorphism, perceived social support, and psychological symptoms in maltreated adolescents. Dev Psychopathol 26(2):465–477. doi: 10.1017/S0954579414000066CrossRefPubMedPubMedCentralGoogle Scholar
  72. Hu J, Qi S, Becker B, Luo L, Gao S, Gong Q, Hurlemann R, Kendrick KM (2015) Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions. Hum Brain Mapp 36(6):2132–2146. doi: 10.1002/hbm.22760CrossRefPubMedGoogle Scholar
  73. Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM (2010) Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J Neurosci 30(14):4999–5007. doi: 10.1523/JNEUROSCI.5538-09.2010CrossRefPubMedPubMedCentralGoogle Scholar
  74. Insel TR, Young LJ (2001) The neurobiology of attachment. Nat Rev Neurosci 2(2):129–136. doi: 10.1038/35053579CrossRefGoogle Scholar
  75. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE (2005a) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62(6):593–602. doi: 10.1001/archpsyc.62.6.593CrossRefPubMedGoogle Scholar
  76. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005b) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62(6):617–627. doi: 10.1001/archpsyc.62.6.617CrossRefPubMedPubMedCentralGoogle Scholar
  77. Kim HS, Sherman DK, Sasaki JY, Xu J, Chu TQ, Ryu C, Suh EM, Graham K, Taylor SE (2010) Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking. Proc Natl Acad Sci U S A 107(36):15717–15721. doi: 10.1073/pnas.1010830107CrossRefPubMedPubMedCentralGoogle Scholar
  78. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25(49):11489–11493. doi: 10.1523/JNEUROSCI.3984-05.2005CrossRefPubMedPubMedCentralGoogle Scholar
  79. Klackl J, Pfundmair M, Agroskin D, Jonas E (2013) Who is to blame? Oxytocin promotes nonpersonalistic attributions in response to a trust betrayal. Biol Psychol 92(2):387–394. doi: 10.1016/j.biopsycho.2012.11.010CrossRefPubMedGoogle Scholar
  80. Klahr AM, Klump K, Burt SA (2015) A constructive replication of the association between the oxytocin receptor genotype and parenting. J Fam Psychol 29(1):91–99. doi: 10.1037/fam0000034CrossRefPubMedGoogle Scholar
  81. Klauke B, Deckert J, Reif A, Pauli P, Domschke K (2010) Life events in panic disorder-an update on “candidate stressors”. Depress Anxiety 27(8):716–730. doi: 10.1002/da.20667CrossRefPubMedGoogle Scholar
  82. Knobloch HS, Charlet A, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, Osten P, Schwarz MK, Seeburg PH, Stoop R, Grinevich V (2012) Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73(3):553–566. doi: 10.1016/j.neuron.2011.11.030CrossRefPubMedPubMedCentralGoogle Scholar
  83. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435(7042):673–676. doi: 10.1038/nature03701CrossRefPubMedPubMedCentralGoogle Scholar
  84. Kossowsky J, Pfaltz MC, Schneider S, Taeymans J, Locher C, Gaab J (2013) The separation anxiety hypothesis of panic disorder revisited: a meta-analysis. Am J Psychiatry 170(7):768–781. doi: 10.1176/appi.ajp.2012.12070893CrossRefPubMedGoogle Scholar
  85. Kumsta R, Heinrichs M (2013) Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system. Curr Opin Neurobiol 23(1):11–16. doi: 10.1016/j.conb.2012.09.004CrossRefPubMedPubMedCentralGoogle Scholar
  86. Kumsta R, Hummel E, Chen FS, Heinrichs M (2013) Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience. Front Neurosci 7:83. doi: 10.3389/fnins.2013.00083CrossRefPubMedPubMedCentralGoogle Scholar
  87. Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, Azuma C, Murata Y (2001) DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochem Biophys Res Commun 289(3):681–686. doi: 10.1006/bbrc.2001.6024CrossRefPubMedGoogle Scholar
  88. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout JC, Nathan PJ (2010) Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 35(12):2403–2413. doi: 10.1038/npp.2010.123CrossRefPubMedPubMedCentralGoogle Scholar
  89. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout JC, Nathan PJ (2011) Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. Int J Neuropsychopharmacol 1–14 doi: 10.1017/S1461145711001489CrossRefPubMedGoogle Scholar
  90. Landgraf R, Neumann ID (2004) Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol 25(3–4):150–176. doi: 10.1016/j.yfrne.2004.05.001CrossRefPubMedPubMedCentralGoogle Scholar
  91. Le Melledo JM, Bradwejn J, Koszycki D, Bellavance F, Bichet D (2001) Arginine-vasopressin and oxytocin response to cholecystokinin-tetrapeptide. Peptides 22(8):1349–1357CrossRefGoogle Scholar
  92. Lebowitz ER, Leckman JF, Feldman R, Zagoory-Sharon O, McDonald N, Silverman WK (2016a) Salivary oxytocin in clinically anxious youth: associations with separation anxiety and family accommodation. Psychoneuroendocrinology 65:35–43. doi: 10.1016/j.psyneuen.2015.12.007CrossRefPubMedGoogle Scholar
  93. Lebowitz ER, Leckman JF, Silverman WK, Feldman R (2016b) Cross-generational influences on childhood anxiety disorders: pathways and mechanisms. J Neural Transm (Vienna) 123(9):1053–1067. doi: 10.1007/s00702-016-1565-yCrossRefGoogle Scholar
  94. Leng G, Ludwig M (2016) Intranasal oxytocin: myths and delusions. Biol Psychiatry 79(3):243–250. doi: 10.1016/j.biopsych.2015.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  95. Linnen AM, Ellenbogen MA, Cardoso C, Joober R (2012) Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students. Stress 15(4):393–402. doi: 10.3109/10253890.2011.631154CrossRefPubMedGoogle Scholar
  96. Lischke A, Gamer M, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC, Domes G (2012) Oxytocin increases amygdala reactivity to threatening scenes in females. Psychoneuroendocrinology 37(9):1431–1438. doi: 10.1016/j.psyneuen.2012.01.011CrossRefPubMedPubMedCentralGoogle Scholar
  97. Lissek S, Levenson J, Biggs AL, Johnson LL, Ameli R, Pine DS, Grillon C (2008) Elevated fear conditioning to socially relevant unconditioned stimuli in social anxiety disorder. Am J Psychiatry 165(1):124–132. doi: 10.1176/appi.ajp.2007.06091513CrossRefPubMedGoogle Scholar
  98. Love TM, Enoch MA, Hodgkinson CA, Pecina M, Mickey B, Koeppe RA, Stohler CS, Goldman D, Zubieta JK (2012) Oxytocin gene polymorphisms influence human dopaminergic function in a sex-dependent manner. Biol Psychiatry 72(3):198–206. doi: 10.1016/j.biopsych.2012.01.033CrossRefPubMedPubMedCentralGoogle Scholar
  99. Lucht MJ, Barnow S, Sonnenfeld C, Rosenberger A, Grabe HJ, Schroeder W, Volzke H, Freyberger HJ, Herrmann FH, Kroemer H, Rosskopf D (2009) Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Prog Neuro-Psychopharmacol Biol Psychiatry 33(5):860–866. doi: 10.1016/j.pnpbp.2009.04.004CrossRefGoogle Scholar
  100. Lueken U, Zierhut KC, Hahn T, Straube B, Kircher T, Reif A, Richter J, Hamm A, Wittchen HU, Domschke K (2016) Neurobiological markers predicting treatment response in anxiety disorders: a systematic review and implications for clinical application. Neurosci Biobehav Rev 66:143–162. doi: 10.1016/j.neubiorev.2016.04.005CrossRefPubMedGoogle Scholar
  101. MacDonald K, Feifel D (2014) Oxytocin’s role in anxiety: a critical appraisal. Brain Res 1580:22–56. doi: 10.1016/j.brainres.2014.01.025CrossRefPubMedPubMedCentralGoogle Scholar
  102. Macdonald K, Macdonald TM (2010) The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 18(1):1–21. doi: 10.3109/10673220903523615CrossRefPubMedGoogle Scholar
  103. MacDonald K, MacDonald TM, Brune M, Lamb K, Wilson MP, Golshan S, Feifel D (2013) Oxytocin and psychotherapy: a pilot study of its physiological, behavioral and subjective effects in males with depression. Psychoneuroendocrinology 38(12):2831–2843. doi: 10.1016/j.psyneuen.2013.05.014CrossRefPubMedGoogle Scholar
  104. Marazziti D, Catena Dell’osso M (2008) The role of oxytocin in neuropsychiatric disorders. Curr Med Chem 15(7):698–704CrossRefGoogle Scholar
  105. Marazziti D, Dell’osso B, Baroni S, Mungai F, Catena M, Rucci P, Albanese F, Giannaccini G, Betti L, Fabbrini L, Italiani P, Del Debbio A, Lucacchini A, Dell’osso L (2006) A relationship between oxytocin and anxiety of romantic attachment. Clin Pract Epidemiol Ment Health 2:28. doi: 10.1186/1745-0179-2-28CrossRefPubMedPubMedCentralGoogle Scholar
  106. Marsh AA, Yu HH, Pine DS, Blair RJ (2010) Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology 209(3):225–232. doi: 10.1007/s00213-010-1780-4CrossRefPubMedGoogle Scholar
  107. Marusak HA, Furman DJ, Kuruvadi N, Shattuck DW, Joshi SH, Joshi AA, Etkin A, Thomason ME (2015) Amygdala responses to salient social cues vary with oxytocin receptor genotype in youth. Neuropsychologia 79(Pt A):1–9. doi: 10.1016/j.neuropsychologia.2015.10.015CrossRefPubMedPubMedCentralGoogle Scholar
  108. Mattick JS, Gagen MJ (2001) The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol 18(9):1611–1630CrossRefGoogle Scholar
  109. McQuaid RJ, McInnis OA, Stead JD, Matheson K, Anisman H (2013) A paradoxical association of an oxytocin receptor gene polymorphism: early-life adversity and vulnerability to depression. Front Neurosci 7:128. doi: 10.3389/fnins.2013.00128CrossRefPubMedPubMedCentralGoogle Scholar
  110. Meaburn EL, Schalkwyk LC, Mill J (2010) Allele-specific methylation in the human genome: implications for genetic studies of complex disease. Epigenetics 5(7):578–582. doi: 10.4161/epi.5.7.12960CrossRefPubMedPubMedCentralGoogle Scholar
  111. Meinlschmidt G, Heim C (2007) Sensitivity to intranasal oxytocin in adult men with early parental separation. Biol Psychiatry 61(9):1109–1111. doi: 10.1016/j.biopsych.2006.09.007CrossRefPubMedGoogle Scholar
  112. Mikolajczak M, Pinon N, Lane A, de Timary P, Luminet O (2010) Oxytocin not only increases trust when money is at stake, but also when confidential information is in the balance. Biol Psychol 85(1):182–184. doi: 10.1016/j.biopsycho.2010.05.010CrossRefPubMedPubMedCentralGoogle Scholar
  113. Milrod B, Markowitz JC, Gerber AJ, Cyranowski J, Altemus M, Shapiro T, Hofer M, Glatt C (2014) Childhood separation anxiety and the pathogenesis and treatment of adult anxiety. Am J Psychiatry 171(1):34–43. doi: 10.1176/appi.ajp.2013.13060781CrossRefPubMedGoogle Scholar
  114. Montag C, Fiebach CJ, Kirsch P, Reuter M (2011) Interaction of 5-HTTLPR and a variation on the oxytocin receptor gene influences negative emotionality. Biol Psychiatry 69(6):601–603. doi: 10.1016/j.biopsych.2010.10.026CrossRefPubMedPubMedCentralGoogle Scholar
  115. Moons WG, Way BM, Taylor SE (2014) Oxytocin and vasopressin receptor polymorphisms interact with circulating neuropeptides to predict human emotional reactions to stress. Emotion 14(3):562–572. doi: 10.1037/a0035503CrossRefPubMedPubMedCentralGoogle Scholar
  116. Morris SE, Cuthbert BN (2012) Research domain criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues Clin Neurosci 14(1):29–37PubMedPubMedCentralGoogle Scholar
  117. Myers AJ, Williams L, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR, Nemeroff CB (2014) Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. J Psychiatr Res 59:93–100. doi: 10.1016/j.jpsychires.2014.08.021CrossRefPubMedPubMedCentralGoogle Scholar
  118. Nissen E, Gustavsson P, Widstrom AM, Uvnas-Moberg K (1998) Oxytocin, prolactin, milk production and their relationship with personality traits in women after vaginal delivery or Cesarean section. J Psychosom Obstet Gynaecol 19(1):49–58CrossRefGoogle Scholar
  119. Notzon S, Domschke K, Holitschke K, Ziegler C, Arolt V, Pauli P, Reif A, Deckert J, Zwanzger P (2016) Attachment style and oxytocin receptor gene variation interact in influencing social anxiety. World J Biol Psychiatry 17(1):76–83. doi: 10.3109/15622975.2015.1091502CrossRefPubMedGoogle Scholar
  120. Oettl LL, Ravi N, Schneider M, Scheller MF, Schneider P, Mitre M, da Silva Gouveia M, Froemke RC, Chao MV, Young WS, Meyer-Lindenberg A, Grinevich V, Shusterman R, Kelsch W (2016) Oxytocin enhances social recognition by modulating cortical control of early olfactory processing. Neuron 90(3):609–621. doi: 10.1016/j.neuron.2016.03.033CrossRefPubMedPubMedCentralGoogle Scholar
  121. Olff M, Frijling JL, Kubzansky LD, Bradley B, Ellenbogen MA, Cardoso C, Bartz JA, Yee JR, van Zuiden M (2013) The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences. Psychoneuroendocrinology 38(9):1883–1894. doi: 10.1016/j.psyneuen.2013.06.019CrossRefGoogle Scholar
  122. Onodera M, Ishitobi Y, Tanaka Y, Aizawa S, Masuda K, Inoue A, Oshita H, Okamoto K, Kawashima C, Nakanishi M, Hirakawa H, Ninomiya T, Maruyama Y, Kanehisa M, Higuma H, Akiyoshi J (2015) Genetic association of the oxytocin receptor genes with panic, major depressive disorder, and social anxiety disorder. Psychiatr Genet 25(5):212. doi: 10.1097/YPG.0000000000000096CrossRefPubMedGoogle Scholar
  123. Opacka-Juffry J, Mohiyeddini C (2012) Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men. Stress 15(1):1–10. doi: 10.3109/10253890.2011.560309CrossRefPubMedGoogle Scholar
  124. Petrovic P, Kalisch R, Singer T, Dolan RJ (2008) Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci 28(26):6607–6615. doi: 10.1523/JNEUROSCI.4572-07.2008CrossRefPubMedPubMedCentralGoogle Scholar
  125. Phaneuf S, Rodriguez Linares B, TambyRaja RL, MacKenzie IZ, Lopez Bernal A (2000) Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour. J Reprod Fertil 120(1):91–97CrossRefGoogle Scholar
  126. Pierrehumbert B, Torrisi R, Laufer D, Halfon O, Ansermet F, Beck Popovic M (2010) Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence. Neuroscience 166(1):168–177. doi: 10.1016/j.neuroscience.2009.12.016CrossRefPubMedGoogle Scholar
  127. Pizzagalli DA (2011) Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 36(1):183–206. doi: 10.1038/npp.2010.166CrossRefPubMedGoogle Scholar
  128. Preckel K, Scheele D, Kendrick KM, Maier W, Hurlemann R (2014) Oxytocin facilitates social approach behavior in women. Front Behav Neurosci 8:191. doi: 10.3389/fnbeh.2014.00191CrossRefPubMedPubMedCentralGoogle Scholar
  129. Puglia MH, Lillard TS, Morris JP, Connelly JJ (2015) Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain. Proc Natl Acad Sci U S A 112(11):3308–3313. doi: 10.1073/pnas.1422096112CrossRefPubMedPubMedCentralGoogle Scholar
  130. Quirin M, Kuhl J, Dusing R (2011) Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities. Psychoneuroendocrinology 36(6):898–904. doi: 10.1016/j.psyneuen.2010.12.005CrossRefPubMedGoogle Scholar
  131. Radke S, Roelofs K, de Bruijn ER (2013) Acting on anger: social anxiety modulates approach-avoidance tendencies after oxytocin administration. Psychol Sci 24(8):1573–1578. doi: 10.1177/0956797612472682CrossRefPubMedGoogle Scholar
  132. Rash JA, Aguirre-Camacho A, Campbell TS (2014) Oxytocin and pain: a systematic review and synthesis of findings. Clin J Pain 30(5):453–462. doi: 10.1097/AJP.0b013e31829f57dfCrossRefPubMedGoogle Scholar
  133. Rimmele U, Hediger K, Heinrichs M, Klaver P (2009) Oxytocin makes a face in memory familiar. J Neurosci 29(1):38–42. doi: 10.1523/JNEUROSCI.4260-08.2009CrossRefGoogle Scholar
  134. Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D (2009) Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci U S A 106(50):21437–21441. doi: 10.1073/pnas.0909579106CrossRefPubMedPubMedCentralGoogle Scholar
  135. Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30(4):534–547. doi: 10.1016/j.yfrne.2009.05.004CrossRefPubMedPubMedCentralGoogle Scholar
  136. Saphire-Bernstein S, Way BM, Kim HS, Sherman DK, Taylor SE (2011) Oxytocin receptor gene (OXTR) is related to psychological resources. Proc Natl Acad Sci U S A 108(37):15118–15122. doi: 10.1073/pnas.1113137108CrossRefPubMedPubMedCentralGoogle Scholar
  137. Savaskan E, Ehrhardt R, Schulz A, Walter M, Schachinger H (2008) Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology 33(3):368–374. doi: 10.1016/j.psyneuen.2007.12.004CrossRefPubMedGoogle Scholar
  138. Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Marechal P, Pequeux C, Ansseau M, Legros JJ (2007) Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology 32(4):407–410. doi: 10.1016/j.psyneuen.2007.01.009CrossRefPubMedGoogle Scholar
  139. Scantamburlo G, Ansseau M, Geenen V, Legros JJ (2009) Oxytocin: from milk ejection to maladaptation in stress response and psychiatric disorders. A psychoneuroendocrine perspective. Ann Endocrinol 70(6):449–454. doi: 10.1016/j.ando.2009.09.002CrossRefGoogle Scholar
  140. Schulze L, Lischke A, Greif J, Herpertz SC, Heinrichs M, Domes G (2011) Oxytocin increases recognition of masked emotional faces. Psychoneuroendocrinology 36(9):1378–1382. doi: 10.1016/j.psyneuen.2011.03.011CrossRefPubMedGoogle Scholar
  141. Shahrestani S, Kemp AH, Guastella AJ (2013) The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis. Neuropsychopharmacology 38(10):1929–1936. doi: 10.1038/npp.2013.86CrossRefPubMedPubMedCentralGoogle Scholar
  142. Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y (2009) Intranasal administration of oxytocin increases envy and schadenfreude (gloating). Biol Psychiatry 66(9):864–870. doi: 10.1016/j.biopsych.2009.06.009CrossRefPubMedPubMedCentralGoogle Scholar
  143. Shear K, Jin R, Ruscio AM, Walters EE, Kessler RC (2006) Prevalence and correlates of estimated DSM-IV child and adult separation anxiety disorder in the National Comorbidity Survey Replication. Am J Psychiatry 163(6):1074–1083. doi: 10.1176/ajp.2006.163.6.1074CrossRefPubMedPubMedCentralGoogle Scholar
  144. Sheng F, Liu Y, Zhou B, Zhou W, Han S (2013) Oxytocin modulates the racial bias in neural responses to others’ suffering. Biol Psychol 92(2):380–386. doi: 10.1016/j.biopsycho.2012.11.018CrossRefPubMedGoogle Scholar
  145. Smearman EL, Almli LM, Conneely KN, Brody GH, Sales JM, Bradley B, Ressler KJ, Smith AK (2016) Oxytocin receptor genetic and epigenetic variations: association with child abuse and adult psychiatric symptoms. Child Dev 87(1):122–134. doi: 10.1111/cdev.12493CrossRefPubMedPubMedCentralGoogle Scholar
  146. Smoller JW (2014) Psychiatric genetics and the future of personalized treatment. Depress Anxiety 31(11):893–898. doi: 10.1002/da.22322CrossRefPubMedPubMedCentralGoogle Scholar
  147. Stankova T, Eichhammer P, Langguth B, Sand PG (2012) Sexually dimorphic effects of oxytocin receptor gene (OXTR) variants on harm avoidance. Biol Sex Differ 3(1):17. doi: 10.1186/2042-6410-3-17CrossRefPubMedPubMedCentralGoogle Scholar
  148. Striepens N, Scheele D, Kendrick KM, Becker B, Schafer L, Schwalba K, Reul J, Maier W, Hurlemann R (2012) Oxytocin facilitates protective responses to aversive social stimuli in males. Proc Natl Acad Sci U S A 109(44):18144–18149. doi: 10.1073/pnas.1208852109CrossRefPubMedPubMedCentralGoogle Scholar
  149. Stuebe AM, Grewen K, Meltzer-Brody S (2013) Association between maternal mood and oxytocin response to breastfeeding. J Women's Health 22(4):352–361. doi: 10.1089/jwh.2012.3768CrossRefGoogle Scholar
  150. Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9(6):465–476. doi: 10.1038/nrg2341CrossRefPubMedGoogle Scholar
  151. Swaab DF, Pool CW, Nijveldt F (1975) Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. J Neural Transm 36(3–4):195–215CrossRefGoogle Scholar
  152. Tabak BA, McCullough ME, Szeto A, Mendez AJ, McCabe PM (2011) Oxytocin indexes relational distress following interpersonal harms in women. Psychoneuroendocrinology 36(1):115–122. doi: 10.1016/j.psyneuen.2010.07.004CrossRefPubMedGoogle Scholar
  153. Tabak BA, Meyer ML, Dutcher JM, Castle E, Irwin MR, Lieberman MD, Eisenberger NI (2016) Oxytocin, but not vasopressin, impairs social cognitive ability among individuals with higher levels of social anxiety: a randomized controlled trial. Soc Cogn Affect Neurosci. doi: 10.1093/scan/nsw041CrossRefPubMedPubMedCentralGoogle Scholar
  154. Thompson RJ, Parker KJ, Hallmayer JF, Waugh CE, Gotlib IH (2011) Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology 36(1):144–147. doi: 10.1016/j.psyneuen.2010.07.003CrossRefPubMedGoogle Scholar
  155. Tops M, van Peer JM, Korf J, Wijers AA, Tucker DM (2007) Anxiety, cortisol, and attachment predict plasma oxytocin. Psychophysiology 44(3):444–449. doi: 10.1111/j.1469-8986.2007.00510.xCrossRefPubMedGoogle Scholar
  156. Tops M, Huffmeijer R, Linting M, Grewen KM, Light KC, Koole SL, Bakermans-Kranenburg MJ, van Ijzendoorn MH (2013) The role of oxytocin in familiarization-habituation responses to social novelty. Front Psychol 4:761. doi: 10.3389/fpsyg.2013.00761CrossRefPubMedPubMedCentralGoogle Scholar
  157. Tost H, Kolachana B, Hakimi S, Lemaitre H, Verchinski BA, Mattay VS, Weinberger DR, Meyer-Lindenberg A (2010) A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function. Proc Natl Acad Sci U S A 107(31):13936–13941. doi: 10.1073/pnas.1003296107CrossRefPubMedPubMedCentralGoogle Scholar
  158. Turner RA, Altemus M, Enos T, Cooper B, McGuinness T (1999) Preliminary research on plasma oxytocin in normal cycling women: investigating emotion and interpersonal distress. Psychiatry 62(2):97–113CrossRefGoogle Scholar
  159. Unternaehrer E, Luers P, Mill J, Dempster E, Meyer AH, Staehli S, Lieb R, Hellhammer DH, Meinlschmidt G (2012) Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Transl Psychiatry 2:e150. doi: 10.1038/tp.2012.77CrossRefPubMedPubMedCentralGoogle Scholar
  160. Van Bockstaele B, Verschuere B, Tibboel H, De Houwer J, Crombez G, Koster EH (2014) A review of current evidence for the causal impact of attentional bias on fear and anxiety. Psychol Bull 140(3):682–721. doi: 10.1037/a0034834CrossRefPubMedGoogle Scholar
  161. van Roekel E, Verhagen M, Scholte RH, Kleinjan M, Goossens L, Engels RC (2013) The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions. PLoS One 8(11):e77689. doi: 10.1371/journal.pone.0077689CrossRefPubMedPubMedCentralGoogle Scholar
  162. Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E, Dayanithi G (2010) Oxytocin: crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther 16(5):e138–e156. doi: 10.1111/j.1755-5949.2010.00185.x. ReviewCrossRefPubMedPubMedCentralGoogle Scholar
  163. Wang J, Qin W, Liu B, Zhou Y, Wang D, Zhang Y, Jiang T, Yu C (2014) Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament. Brain Struct Funct 219(5):1543–1554. doi: 10.1007/s00429-013-0584-9CrossRefPubMedGoogle Scholar
  164. Weisman O, Zagoory-Sharon O, Schneiderman I, Gordon I, Feldman R (2013) Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety. Psychoneuroendocrinology 38(5):694–701. doi: 10.1016/j.psyneuen.2012.08.011CrossRefGoogle Scholar
  165. Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD (2005) Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci U S A 102(47):17237–17240. doi: 10.1073/pnas.0504767102CrossRefPubMedGoogle Scholar
  166. Zak PJ, Kurzban R, Matzner WT (2005) Oxytocin is associated with human trustworthiness. Horm Behav 48(5):522–527. doi: 10.1016/j.yhbeh.2005.07.009CrossRefPubMedPubMedCentralGoogle Scholar
  167. Ziegler C, Dannlowski U, Brauer D, Stevens S, Laeger I, Wittmann H, Kugel H, Dobel C, Hurlemann R, Reif A, Lesch KP, Heindel W, Kirschbaum C, Arolt V, Gerlach AL, Hoyer J, Deckert J, Zwanzger P, Domschke K (2015) Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety. Neuropsychopharmacology 40(6):1528–1538. doi: 10.1038/npp.2015.2CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental HealthUniversity of WürzburgWürzburgGermany
  2. 2.Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of MedicineUniversity of FreiburgFreiburg im BreisgauGermany

Personalised recommendations