Oxytocin and Psychiatric Disorders

Abstract

Oxytocin is a neuropeptide that plays critical role in mother-infant bonding, pair bonding and prosocial behaviors. Several neuropsychiatric disorders such as autism, schizophrenia, affective disorders, anxiety disorders, attention deficit/hyperactivity disorder, alcohol/substance addiction, aggression, suicide, eating disorders and personality disorders show abnormalities of oxytocin system. These findings have given rise to the studies searching therapeutic use of oxytocin for psychiatric disorders. The studies of oxytocin interventions in psychiatric disorders yielded potentially promising findings. This paper reviews the role of oxytocin in emotions, behavior and its effects in psychiatric disorders.

Keywords

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Oksitosin ve Psikiyatrik Bozukluklar

Öz

Oksitosin anne ve bebeğin bağlanması, çiftlerin bağlanması ve sosyal davranışlarda rol oynayan bir nöropeptiddir. Otizm, şizofreni, duygudurum bozuklukları, anksiyete bozuklukları, dikkat eksikliği/hiperaktivite bozukluğu, alkol/madde bağımlılığı, agresyon, intihar, yeme bozuklukları ve kişilik bozuklukları gibi pek çok psikiyatrik bozuklukta oksitosin sistemine ait anormallikler tespit edilmiştir. Bu bulgular oksitosinin psikiyatrik bozuklukların tedavisinde kullanımının araştırıldığı çalışmalara öncülük etmiştir. Çalışmaların sonuçları incelendiğinde oksitosinin psikiyatrik bozukluklar üzerindeki etkisi umut vericidir. Bu derlemede oksitosinin duygu ve davranışlardaki rolü ve psikiyatrik bozukluklar üzerine etkileri ele alınmıştır.

Anahtar Kelimeler

• Oksitosin, psikiyatrik bozukluklar, sosyal davranış, otizm

Kaynakça

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. Psychopharmacol, 229:199-208.
2. Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S et al. (2012)Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism, 3:16.
3. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A (2010) Promoting socialbehavior with oxytocin in high- functioning autism spectrum disorders. Proc Natl Acad Sci USA, 107: 4389-4394.
4. Atzil S, Hendler T, Feldman R (2011) Specifying the neurobiological basis of human attachment: brain, hormones, and behavior in synchronous and intrusive mothers. Neuropsychopharmacology, 36:2603-2615.
5. Bartz JA, McInnes LA. (2007) CD38 regulates oxytocin secretion and complex social behavior. Bioessays, 29:837–841.
6. Beitchman JH, Zai CC, Muir K, Berall L, Nowrouzi B, Choi E et al. (2012) Childhood aggression, callous-unemotional traits and oxytocin genes. Eur Child Adolesc Psychiatry, 21:125-132.
7. Bertsch K, Gamer M, Schmidt B, Schmidinger I, Walther S, Kästel T et al. (2013) Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. Am J Psychiatry, 170:1169-1177.
8. Broadbear JH, Tunstall B, Beringer K (2011) Examining the role of oxytocin in the interoceptive effects of 3,4- methylenedioxymethamphetamine (MDMA, ‘ecstasy’) using a drug discrimination paradigm in the rat. Addict Biol, 16:202– 14.

9. Brüne M, Ebert A, Kolb M, Tas C, Edel MA, Roser P (2013) Oxytocin influences avoidant reactions to social threat in adults with borderline personality disorder. Hum Psychopharmacol, 28:552-561.
10. Buisman-Pijlman FT, Sumracki NM, Gordon JJ, Hull PR, Carter CS, Tops M (2014)Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system. Pharmacol Biochem Behav, 119:22-38.
11. Churchland PS, Winkielman P (2012) Modulating social behavior with oxytocin: how does it work? what does it mean? Horm Behav, 61:392-399.
12. Dadds MR, Macdonald E, Cauchi A, Williams K, Levy F, Brennan J (2014) Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial. J Autism Dev Disord, 44:521-531.
13. Davis MC, Lee J, Horan WP, Clarke AD, McGee MR, Green MF et al. (2013)Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr Res,147:393-397.
14. den Boer JA, Westenberg HGM (1992) Oxytocin in obsessive compulsive disorder. Peptides, 13:1083–1085.
15. de Oliveira DC, Zuardi AW, Graeff FG, Queiroz RH, Crippa JA (2012) Anxiolytic-like effect of oxytocin in the simulated public speaking test. J Psychopharmacol, 26:497–504.
16. 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, 65:728-731.
17. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007) Oxytocin improves "mindreading" in humans. Biol Psychiatry, 61:731-733.
18. Domes G, Kumbier E, Heinrichs M, Herpertz SC (2014) Oxytocin promotes facial emotionrecognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology, 39:698-706.
19. Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M et al. (2010) Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology, 35:83-93.
20. Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ et al. (2009) Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4 methylenedioxymethamphetamine) administration. Soc Neurosci, 4: 359–366.
21. Eckstein M, Becker B, Scheele D, Scholz C, Preckel K, Schlaepfer TE et al. (2015) Oxytocin facilitates the extinction of conditioned fear in humans. Biol Psychiatry, 78:194-202.
22. Engelmann M, Landgraf R, Wotjak CT (2004) The hypothalamicneurohypophysial system regulates the hypothalamic- pituitaryadrenal axis under stress: an old concept revisited. Front Neuroendocrinol, 25:132-149.
23. EppersonCN, McDougleCJ, PriceLH (1996) Intranasal oxytocin in obsessive-compulsive disorder. Biol Psychiatry, 40:547-549.
24. Frasch A, Zetzsche T, Steiger A, Jirikowski GF (1995) Reduction of plasma oxytocin levels in patients suffering from major depression. Adv Exp Med Biol, 395:257-258.
25. Freedman D, Brown AS, Shen L, Schaefer CA (2015) Perinatal oxytocin increases the risk of offspring bipolar disorder and childhood cognitive impairment. J Affect Disord, 173:65-72.
26. Green LA, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M (2001) Oxytocin and autistic disorder: alteration in peptide forms. Biol. Psychiatry, 50:609-613.
27. Grewen KM, Light KC, Mechlin B, Girdler SS (2008) Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women. Ethn Health, 13:219-241.
28. Grillon C, Krimsky M, Charney DR, Vytal K, Ernst M, Cornwell B (2013) Oxytocin increases anxiety to unpredictable threat. Mol Psychiatry, 18:958–960.
29. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ et al. (2010) Intranasaloxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry, 67:692-694.
30. Guastella AJ, Mitchell PB, Dadds MR (2008) Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry, 63:3-5.
31. 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, 14:954-958.
32. 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, 54:1389-1398.
33. Heinrichs M, von Dawans B, Domes G (2009) Oxytocin, vasopressin, and human social behavior. Front Neuroendocrinol, 30:548- 557.
34. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L et al. (2007)Oxytocin increases retention of social cognition in autism. Biol Psychiatry, 61:498-503.
35. Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR et al. (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharmacology, 28:193-198.
36. Holt-Lunstad J, Birmingham W, Light KC (2011) The influence of depressive symptomatology and perceived stress on plasma and salivary oxytocin before, during and after a support enhancement intervention. Psychoneuroendocrinol, 36:1249-1256.
37. Insel TR (2010) The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron, 65:768-779.
38. Ishak WW, Kahloon M, Fakhry H (2011) Oxytocin role in enhancing well-being: a literature review. J Affect Disord, 130:1-9.
39. Kim S, Soeken TA, Cromer SJ, Martinez SR, Hardy LR, Strathearn L (2014) Oxytocin and postpartum depression: delivering on what's known and what's not. Brain Res, 1580:219-232.
40. Kim YR, Kim CH, Cardi V, Eom JS, Seong Y, Treasure J (2014) Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa. Psychoneuroendocrinol, 44:133-142.
41. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S et al. (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci, 25: 11489–11493.
42. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature, 435:673-676.
43. Kurth L, Haussmann R (2011) Perinatal Pitocin as an early ADHD biomarker: neurodevelopmental risk? J Atten Disord, 15:423-431.
44. Jokinen J, Chatzittofis A, Hellström C, Nordström P, Uvnäs-Moberg K, Asberg M (2012) Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinol, 37:482-490.
45. Landry SH, McGrath SK, Kennel JH (1998) The effects of doula support during labor on mother–infant interaction at 2 months. Pediatr Res, 42:13.
46. Lawson EA, Holsen LM, Santin M, DeSanti R, Meenaghan E, Eddy KT et al. (2013) Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa. J Clin Psychiatry, 74:e451-e457.
47. Lee R, Ferris C, Van de Kar LD, Coccaro EF (2009) Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinol, 34:1567-1573.
48. Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP (2008) Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry, 13:980-988.
49. Li X, Zou H, Brown WT (2012) Genes associated with autism spectrum disorder. Brain Res Bull, 88:543-552.
50. Linkowski P, Geenen V, Kerkhofs M, Mendlewicz J, Legros JJ (1984) Cerebrospinal fluid neurophysins in affective illness and in schizophrenia. Eur Arch Psychiatry Neurol Sci, 234:162-165.
51. Liu X, Kawamura Y, Shimada T, Otowa T, Koishi S, Sugiyama T et al. (2010) Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. J Hum Genet, 55:137-141.
52. Lucht MJ, Barnow S, Sonnenfeld C, Rosenberger A, Grabe HJ, Schroeder W et al. (2009) Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry, 33:860-866.
53. McGregor IS, Bowen MT (2012) Breaking the loop: oxytocin as a potential treatment for drug addiction. Horm Behav, 61:331– 339.
54. McRae-Clark AL, Baker NL, Maria MM, Brady KT (2013) Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study. Psychopharmacol, 228:623-631.
55. Miller M, Bales KL, Taylor SL, Yoon J, Hostetler CM, Carter CS (2013) Oxytocin and vasopressin in children and adolescents with autism spectrum disorders: sex differences and associations with symptoms. Autism Res, 6:91-102.
56. Myers AJ, Williams L, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR et al. (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.
57. Neumann ID (2007) Stimuli and consequences of dendritic release of oxytocin within the brain. Biochem Soc Trans, 35:1252-1257.
58. Neumann ID, Landgraf R (2012) Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci, 35:649-659.
59. Ozsoy S, Esel E, Kula M (2009) Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res, 169:249-252.
60. Parker KJ, Kenna HA, Zeitzer JM, Keller J, Blasey CM, Amico JA, Schatzberg AF (2010) Preliminary evidence that plasma oxytocin levels are elevated in major depression. Psychiatry Res, 178:359-362.
61. Pedersen CA (2014) Schizophrenia and alcohol dependence: diverse clinical effects of oxytocin and their evolutionary origins. Brain Res, 1580:102-123.
62. Pedersen CA, Gibson CM, Rau SW, Salimi K, Smedley KL, Casey RL et al. (2011) Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res, 132:50-53.
63. Petersson M, Lundeberg T, Sohlström A, Wiberg U, Uvnäs-Moberg K (1998) Oxytocin increases the survival of musculocutaneous flaps. Naunyn Schmiedeberg's Arch Pharmacol, 357:701-704.
64. Pierrehumbert B, Torrisi R, Glatz N, Dimitrova N, Heinrichs M, Halfon O (2009) The influence of attachment on perceived stress and cortisol response to acute stres in women sexually abused in childhood or adolescence. Psychoneuroendocrinology, 34:924- 938.
65. Pitman RK, Orr SP, Lasko NB (1993) Effects of intranasal vasopressin and oxytocin on physiologic responding during personal combat imagery in Vietnam veterans with posttraumatic stress disorder. Psychiatry Res, 48:107-117
66. Preti A, Melis M, Siddi S, Vellante M, Doneddu G, Fadda R (2014) Oxytocin and autism: a systematic review of randomized controlled trials. J Child Adolesc Psychopharmacol, 24:54-68.
67. Resendez SL, Aragona BJ (2013) Aversive motivation and the maintenance of monogamous pair bonding. Rev Neurosci, 24:51-60.
68. Rubin LH, Carter CS, Drogos L, Pournajafi-Nazarloo H, Sweeney JA, Maki PM (2010) Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophr Res,124:13–21.
69. Rubin LH, Carter CS, Drogos L, Jamadar R, Pournajafi-Nazarloo H, Sweeney JA et al. (2011) Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia. Schizophr Res, 130:266-270.
70. Sarnyai Z, Kovács GL (2014) Oxytocin in learning and addiction: From early discoveries to the present. Pharmacol Biochem Behav, 119:3-9.
71. Sasaki T, Hashimoto K, Oda Y, Ishima T, Kurata T, Takahashi J et al. (2015) Decreased levels of serum oxytocin in pediatric patients with attention deficit/hyperactivity disorder. Psychiatry Res, 228:746-751.
72. Savaskan E, Ehrhardt R, Schulz A, Walter M, Schachinger H (2008) Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology, 33:368-374.
73. Strathearn L, Fonagy P, Amico J, Montague PR (2009) Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacology, 34:2655-2666.
74. Souza RP, de Luca V, Meltzer HY, Lieberman JA, Kennedy JL (2010a) Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes. Int J Neuropsychopharmacol,13:793-798.
75. Souza RP, Ismail P, Meltzer HY, Kennedy JL (2010b) Variants in the oxytocin gene and risk for schizophrenia. Schizophr Res, 121:279-80.
76. Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T et al. (2005) Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA, 102:16096-16101.
77. Turan T, Uysal C, Asdemir A, Kılıç E (2013) May oxytocin be a trait marker for bipolar disorder? Psychoneuroendocrinology, 38:2890-2896.
78. Uvnäs-Moberg K (1998) Antistress pattern induced by oxytocin. News Physiol Sci, 13:22-26.
79. Uvnäs-Moberg K, Alster P, Svensson TH (1992) Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats. Psychopharmacol,109:473-476.
80. Uvnäs-Moberg K, Petersson M (2005) Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Z Psychosom Med Psychother, 51:57-80.
81. Uvnäs-Moberg K, Widström AM, Nissen E, Björvell H (1990) Personality traits inwomen 4 days postpartumand their correlationwith plasma levels of oxytocin and prolactin. J Psychosom Obstet Gynecol, 11:261-273.
82. Viviani D, Stoop R (2008) Opposite effects of oxytocin and vasopressin on the emotional expression of the fear response. Prog Brain Res, 170:207-218.
83. 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. Psychoneuroendocrinol, 38:694-701.
84. Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T et al. (2009) Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci, 29:2259-2271.
85. Young KA, Gobrogge KL, Liu Y, Wang Z (2011) The neurobiology of pair bonding: insights from a socially monogamous rodent. Front Neuroendocrinol, 32:53-69.
86. Zik JB, Roberts DL (2015) The many faces of oxytocin: implications for psychiatry. Psychiatry Res, 226:31-37. Gökçe Nur Say, Yrd.Doç.Dr., Ondokuz Mayıs Üniversitesi, Samsun; Mahmut Müjdeci, Arş.Gör., Ondokuz Mayıs Üniversitesi, Samsun.