Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.
Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration.
Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany.|Department of Psychology, University of British Columbia, Vancouver, BC, Canada.
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Chen
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
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Kumsta
Graduate School of Decision Sciences, University of Konstanz, Konstanz, Germany.|Department of Economics, Chair of Applied Research in Economics, University of Konstanz, Konstanz, Germany.
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Dvorak
Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany.|Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany.
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Domes
Department of Psychology, National University of Singapore, Singapore, Singapore.
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Yim
Department of Psychology, National University of Singapore, Singapore, Singapore.
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Ebstein
Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany.|Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany.
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Heinrichs
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000235:genetics / Q000494:pharmacology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics; D021641:Recognition, Psychology; D012919:Social Behavior; D013647:Task Performance and Analysis; D055815:Young Adult
D018045:Receptors, Oxytocin; D010121:Oxytocin