Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system

The neuropeptide oxytocin has had key roles throughout mammalian evolution in the regulation of complex social cognition and behaviors, such as attachment, parental care, pair-bonding, as well as social exploration and recognition. Recently, studies have begun to provide evidence that the function of this neuropeptide is impaired in mental disorders associated with social deficits. In this review, we focus on the genetic mechanisms of inter-individual variation in the social neuropeptide signaling. We discuss molecular genetic studies which identified variations in specific genes contributing to individual differences in social behavior and cognition, with a focus on the gene coding for the oxytocin receptor (OXTR) emerging as a particularly promising candidate. We conclude that molecular studies are warranted to elucidate functional consequences of variants that have shown stable associations with sociobehavioral phenotypes. With regard to the variability in individual responses to oxytocin administration, we advocate the need for pharmacogenetic approaches in order to test how the efficacy of oxytocin administration is modulated by genetic variation of OXTR or other genes involved in oxytocin signaling.

► The neuropeptide oxytocin is important for the regulation of complex social cognition and behavior. ► Common variants of the oxytocin receptor gene (OXTR) have been associated with social behavioral phenotypes. ► Imaging studies show that these variants affect brain regions important for social behavior. ► Functional consequences of variants associated with sociobehavioral phenotypes should be investigated. ► Pharmacogenetic studies can test whether efficacy of oxytocin administration is influenced by OXTR variation.