Abstract
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.
Highlights
This is supported by genetic studies linking SNPs and haplotypes of oxytocin receptor gene (OXTR) to individual differences in social behavior
The discovery that neuropeptides can be non-invasively delivered to the brain in humans has raised considerable interest in the therapeutic potential of oxytocin for the treatment of disorders characterized by social functioning deficits
We investigated whether sensitivity to oxytocin administration is influenced by genetic variation of OXTR
Summary
The neuropeptide oxytocin has a key role in the regulation of complex social cognition and behaviors, including mammalian pair bonding, maternal behavior, recognition of conspecifics and responses to social stress. Human studies have documented a number of effects of intranasally administered oxytocin on social behavior and social cognition. For instance, a single dose of intranasal oxytocin increases trusting behavior, attention to the eye region of faces and the accuracy with which individuals interpret emotional information from eyes. Oxytocin reduces subjective and physiological responses to social stress and enhances the stress-buffering effect of social support. Neuroimaging studies have shown that one of the mechanisms through which oxytocin influences social cognition is by attenuating amygdala responses to social stimuli such as emotional faces.11–14There has been considerable interest in the therapeutic potential of oxytocin for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. Whereas the results of virtually all of these studies suggest that oxytocin has the potential to improve social cognition and social behavior in healthy individuals and patient populations, there is considerable variability in individual responsiveness to oxytocin administration, with some individuals showing strong behavioral effects in response to intranasal oxytocin and others seeming to show minimal or no effects. These findings suggest that oxytocin administration may interact with pre-existing interindividual variation that influences the efficacy of oxytocin signaling in the central nervous system. Whereas the results of virtually all of these studies suggest that oxytocin has the potential to improve social cognition and social behavior in healthy individuals and patient populations, there is considerable variability in individual responsiveness to oxytocin administration, with some individuals showing strong behavioral effects in response to intranasal oxytocin and others seeming to show minimal or no effects.. Whereas the results of virtually all of these studies suggest that oxytocin has the potential to improve social cognition and social behavior in healthy individuals and patient populations, there is considerable variability in individual responsiveness to oxytocin administration, with some individuals showing strong behavioral effects in response to intranasal oxytocin and others seeming to show minimal or no effects.3 These findings suggest that oxytocin administration may interact with pre-existing interindividual variation that influences the efficacy of oxytocin signaling in the central nervous system. Research investigating the genetic modulation of sensitivity to oxytocin administration has implications for basic research and implications for clinicians who would like to predict which patients may or may not benefit from oxytocin administration, and in general may help to refine personalized oxytocin-based therapies for mental disorders
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