title: Oxytocin gene polymorphisms influence human dopaminergic function in a sex-dependent manner.
abstract: BACKGROUND
  Oxytocin, classically involved in social and reproductive activities, is increasingly recognized as an antinociceptive and anxiolytic agent, effects which may be mediated via oxytocin's interactions with the dopamine system. Thus, genetic variation within the oxytocin gene (OXT) is likely to explain variability in dopamine-related stress responses. As such, we examined how OXT variation is associated with stress-induced dopaminergic neurotransmission in a healthy human sample.
  
  
  METHODS
  Fifty-five young healthy volunteers were scanned using [¹¹C]raclopride positron emission tomography while they underwent a standardized physical and emotional stressor that consisted of moderate levels of experimental sustained deep muscle pain, and a baseline, control state. Four haplotype tagging single nucleotide polymorphisms located in regions near OXT were genotyped. Measures of pain, affect, anxiety, well-being and interpersonal attachment were also assessed.
  
  
  RESULTS
  Female rs4813625 C allele carriers demonstrated greater stress-induced dopamine release, measured as reductions in receptor availability from baseline to the pain-stress condition relative to female GG homozygotes. No significant differences were detected among males. We also observed that female rs4813625 C allele carriers exhibited higher attachment anxiety, higher trait anxiety and lower emotional well-being scores. In addition, greater stress-induced dopamine release was associated with lower emotional well-being scores in female rs4813625 C allele carriers.
  
  
  CONCLUSIONS
  Our results suggest that variability within the oxytocin gene appear to explain interindividual differences in dopaminergic responses to stress, which are shown to be associated with anxiety traits, including those linked to attachment style, as well as emotional well-being in women.
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109-0720, USA. tiflove@umich.edu
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Love
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: Marta
authors.initials: M
authors.lastname: Peciña
authors.forename: Brian
authors.initials: B
authors.lastname: Mickey
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Christian S
authors.initials: CS
authors.lastname: Stohler
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000483:Alleles; D001007:Anxiety / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D004644:Emotions / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D009769:Object Attachment; D010121:Oxytocin / Q000097:blood / Q000235:genetics*; D010146:Pain / Q000523:psychology; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000523:psychology; D009435:Synaptic Transmission
chemical_list: D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D010121:Oxytocin; D004298:Dopamine