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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.

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  • Authors

    Love TM, Enoch MA, Hodgkinson CA, Peciña M, Mickey B, Koeppe RA, Stohler CS, Goldman D, Zubieta JK

    Source

    Biological psychiatry 72:3 2012 Aug 1 pg 198-206

    MeSH

    Adult
    Alleles
    Anxiety
    Dopamine
    Emotions
    Female
    Genotype
    Humans
    Image Processing, Computer-Assisted
    Linkage Disequilibrium
    Magnetic Resonance Imaging
    Male
    Object Attachment
    Oxytocin
    Pain
    Polymorphism, Genetic
    Polymorphism, Single Nucleotide
    Positron-Emission Tomography
    Receptors, Dopamine D2
    Receptors, Dopamine D3
    Sex Characteristics
    Stress, Psychological
    Synaptic Transmission

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22418012