Abstract
Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date.
Highlights
Today, the neuropeptides OXT and AVP are, perhaps, the most interesting molecules for social neuroscience (Insel, 2010; Meyer-Lindenberg et al, 2011; Zink and Meyer-Lindenberg, 2012)
This review summarizes findings on the impact of different OXT and AVP receptor polymorphism on social cognition and behaviors, and on some of the most common mental disorders associated with deficits in social function
Notwithstanding the fact that results from rodents are not easy to extrapolate to primates (for instance, Fink et al (2006) found that polymorphisms upstream of AVPR1a, which have been associated with differences in social bonding, are evolutionarily distinct between primates and rodents), a substantial body of evidence obtained through linkage and association studies suggests that OXTR and AVPR polymorphisms could be part of the genetic sources of the heterogeneity observed in social traits and psychiatric disorders (Meyer-Lindenberg et al, 2011)
Summary
The neuropeptides OXT and AVP are, perhaps, the most interesting molecules for social neuroscience (Insel, 2010; Meyer-Lindenberg et al, 2011; Zink and Meyer-Lindenberg, 2012). There exist genotype-environment interactions, where the effect of environment on some traits depends on the genotype and, the effect of a given genotype depends on FIGURE 2 | OXTR and AVPR are G-protein coupled receptor expressed in key structures of the brain Their genes present characteristic polymorphisms associated with differences in human social (and pathological) behaviors. Notwithstanding the fact that results from rodents are not easy to extrapolate to primates (for instance, Fink et al (2006) found that polymorphisms upstream of AVPR1a, which have been associated with differences in social bonding, are evolutionarily distinct between primates and rodents), a substantial body of evidence obtained (initially) through linkage and association studies suggests that OXTR and AVPR polymorphisms could be part of the genetic sources of the heterogeneity observed in social traits and psychiatric disorders (Meyer-Lindenberg et al, 2011). Rs237893, rs237894, the patients sample (122 Swedish sample; G Overrepresented in controls; rs237911, rs237901, females); Swedish and allele for s5 in the Overrepresented in controls rs810568, rs2228486 Belgiansin the control Belgian sample; sample (117 females)
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