title: Imaging oxytocin × dopamine interactions: an epistasis effect of CD38 and COMT gene variants influences the impact of oxytocin on amygdala activation to social stimuli.
abstract: Although oxytocin (OT) has become a major target for the investigation of positive social processes, it can be assumed that it exerts its effects in concert with other neurotransmitters. One candidate for such an interaction is dopamine (DA). For both systems, genetic variants have been identified that influence the availability of the particular substance. A variant of the gene coding for the transmembrane protein CD38 (rs3796863), which is engaged in OT secretion, has been associated with OT plasma level. The common catechol-O-methyltransferase (COMT) val158met polymorphism is known to influence COMT activity and therefore the degradation of DA. The present study aimed to investigate OT × DA interactions in the context of an OT challenge study. Hence, we tested the influence of the above mentioned genetic variants and their interaction on the activation of different brain regions (amygdala, VTA, ventral striatum and fusiform gyrus) during the presentation of social stimuli. In a pharmacological cross-over design 55 participants were investigated under OT and placebo (PLA) by means of fMRI. Brain imaging results revealed no significant effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not find any effects apart from those already described in Sauer et al. (2012). Analyses of amygdala activation resulted in no gene main effect, no gene × substance interaction but a significant gene × gene × substance interaction. While under PLA the effect of CD38 on bilateral amygdala activation to social stimuli was modulated by the COMT genotype, no such epistasis effect was found under OT. Our results provide evidence for an OT × DA interaction during responses to social stimuli. We postulate that the effect of central OT secretion on amygdala response is modulated by the availability of DA. Therefore, for an understanding of the effect of social hormones on social behavior, interactions of OT with other transmitter systems have to be taken into account.
authors.affiliation: Department of Clinical Psychology, Central Institute of Mental Health Mannheim and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Sauer
authors.forename: Christian
authors.initials: C
authors.lastname: Montag
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
keywords: CD38; COMT; amygdala; dopamine; fMRI; oxytocin
references.citation: J Neurosci. 2008 Jun 25;28(26):6607-15
references.pmid: 18579733
references.citation: Nature. 2007 Mar 1;446(7131):41-5
references.pmid: 17287729
references.citation: Nat Neurosci. 2008 Dec;11(12):1381-2
references.pmid: 18978778
references.citation: Neuroimage. 2010 Nov 15;53(3):918-25
references.pmid: 20139013
references.citation: Eur J Neurosci. 2009 Dec 3;30(11):2151-64
references.pmid: 20128851
references.citation: Biol Psychiatry. 2008 Jan 1;63(1):3-5
references.pmid: 17888410
references.citation: Int J Neuropsychopharmacol. 2009 Apr;12(3):371-81
references.pmid: 18796186
references.citation: Biol Psychiatry. 2003 Mar 15;53(6):494-501
references.pmid: 12644354
references.citation: Neuroimage. 2012 May 1;60(4):2222-9
references.pmid: 22387174
references.citation: Eur J Neurosci. 2010 Dec;32(11):1836-42
references.pmid: 20955472
references.citation: Neuropsychopharmacology. 2005 Nov;30(11):2092-102
references.pmid: 15956988
references.citation: Eur J Neurosci. 2007 Aug;26(4):1026-35
references.pmid: 17672853
references.citation: Psychol Med. 2011 Apr;41(4):779-88
references.pmid: 20667170
references.citation: Nat Neurosci. 2004 Oct;7(10):1048-54
references.pmid: 15452576
references.citation: J Autism Dev Disord. 2009 Nov;39(11):1542-51
references.pmid: 19582565
references.citation: J Neurosci. 2009 Jul 15;29(28):9123-6
references.pmid: 19605649
references.citation: Diabetes. 2008 Apr;57(4):868-78
references.pmid: 18184929
references.citation: Nat Rev Genet. 2005 Jul;6(7):521-32
references.pmid: 15995696
references.citation: Autism Res. 2010 Dec;3(6):293-302
references.pmid: 21182206
references.citation: Brain Res. 1999 May 8;827(1-2):28-40
references.pmid: 10320690
references.citation: Psychoneuroendocrinology. 2012 Nov;37(11):1810-21
references.pmid: 22503421
references.citation: Trends Cogn Sci. 2009 Jan;13(1):27-35
references.pmid: 19084465
references.citation: Biol Psychiatry. 2007 Nov 15;62(10):1187-90
references.pmid: 17617382
references.citation: J Neurosci. 2005 Jan 26;25(4):836-42
references.pmid: 15673663
references.citation: Neuroimage. 2010 Oct 1;52(4):1712-9
references.pmid: 20510373
references.citation: J Neurosci. 2005 Dec 7;25(49):11489-93
references.pmid: 16339042
references.citation: Mol Psychiatry. 2013 Aug;18(8):849-50
references.pmid: 22824810
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5981-5
references.pmid: 1321430
references.citation: Neuropharmacology. 2010 Jan;58(1):50-5
references.pmid: 19540855
references.citation: Eur J Neurosci. 2009 Oct;30(7):1349-57
references.pmid: 19769589
references.citation: Mol Psychiatry. 2007 Mar;12(3):307-17
references.pmid: 17211439
references.citation: Mol Psychiatry. 2010 Sep;15(9):918-27
references.pmid: 19417742
references.citation: Neuron. 2008 May 22;58(4):639-50
references.pmid: 18498743
references.citation: Stress. 2012 Jan;15(1):1-10
references.pmid: 21682649
references.citation: Neuroscience. 2003;121(3):537-44
references.pmid: 14568015
references.citation: Psychiatry Res. 2009 Oct 30;169(3):249-52
references.pmid: 19732960
references.citation: Neuroscience. 2003;116(1):127-37
references.pmid: 12535946
references.citation: Am J Hum Genet. 2004 Nov;75(5):807-21
references.pmid: 15457404
references.citation: Psychoneuroendocrinology. 2013 May;38(5):694-701
references.pmid: 22999263
references.citation: Nat Neurosci. 2002 Jun;5(6):514-6
references.pmid: 11992114
references.citation: Biol Psychol. 2011 Apr;87(1):106-12
references.pmid: 21356267
references.citation: Arch Gen Psychiatry. 2006 Dec;63(12):1396-406
references.pmid: 17146014
references.citation: Neuroimage. 2002 Sep;17(1):317-23
references.pmid: 12482086
references.citation: Prog Brain Res. 2008;170:277-90
references.pmid: 18655889
references.citation: Biol Psychiatry. 2012 Aug 1;72(3):198-206
references.pmid: 22418012
references.citation: Neuropsychopharmacology. 2002 Dec;27(6):1036-40
references.pmid: 12464460
references.citation: Biol Psychiatry. 2012 Aug 1;72(3):175-81
references.pmid: 22336563
references.citation: Science. 2003 Feb 21;299(5610):1240-3
references.pmid: 12595695
references.citation: Neurosci Res. 2010 Jun;67(2):181-91
references.pmid: 20435366
references.citation: Horm Behav. 2012 Mar;61(3):400-9
references.pmid: 22326707
references.citation: Neuropsychopharmacology. 2012 May;37(6):1474-82
references.pmid: 22278094
references.citation: J Neurosci. 2012 Oct 10;32(41):14109-17
references.pmid: 23055480
references.citation: Psychiatry Res. 2008 May 30;163(1):13-20
references.pmid: 18440204
references.citation: Arch Gen Psychiatry. 1996 Feb;53(2):137-43
references.pmid: 8629889
references.citation: Nat Rev Neurosci. 2011 Aug 19;12(9):524-38
references.pmid: 21852800
references.citation: J Neurosci. 2002 Oct 15;22(20):9099-103
references.pmid: 12388617