Genetic variation in the vasopressin receptor 1a gene ( AVPR1A ) associates with pair-bonding behavior in humans

Abstract

Pair-bonding has been suggested to be a critical factor in the evolutionary development of the social brain. The brain neuropeptide arginine vasopressin (AVP) exerts an important influence on pair-bonding behavior in voles. There is a strong association between a polymorphic repeat sequence in the 5 flanking region of the gene (avpr1a) encoding one of the AVP receptor subtypes (V1aR), and proneness for monogamous behavior in males of this species. It is not yet known whether similar mechanisms are important also for human pair-bonding. Here, we report an association between one of the human AVPR1A repeat polymorphisms (RS3) and traits reflecting pair-bonding behavior in men, including partner bonding, perceived marital problems, and marital status, and show that the RS3 genotype of the males also affects marital quality as perceived by their spouses. These results suggest an association between a single gene and pair-bonding behavior in humans, and indicate that the well characterized influence of AVP on pair-bonding in voles may be of relevance also for humans.monogamy ͉ neuropeptide ͉ polymorphism ͉ social behavior P rimate social organization is often characterized by bonded relationships, and recent analyses suggest that it may have been the particular demands for pair-bonding behavior that triggered the evolutionary development of the primate social brain (1). The brain neuropeptide arginine vasopressin (AVP), acting through the receptor subtype V1aR, plays a key role in the regulation of pairbonding behavior in male rodents, as revealed by a series of elegant studies on closely related vole species, i.e., montane voles (Microtus montanus), meadow voles (Microtus pennsylvanicus), and prairie voles (Microtus ochrogaster) (2). In prairie voles, which in contrast to montane and meadow voles are socially monogamous and highly social, pair-bond formation and related behaviors are facilitated by AVP and prevented by a V1aR antagonist (3). Supporting the theory that the striking difference in pair-bonding between monogamous and nonmonogamous voles is related to the influence of AVP on this behavior, the neuroanatomical distribution of V1aR differs considerably between these vole species (4) and is associated with sexual and social fidelity among prairie voles (5). Moreover, partner preference is enhanced in the nonmonogamous meadow vole when the V1aR density is increased in relevant brain areas by using viral vector gene transfer (6). Although there are no major differences in the coding sequence of the gene encoding V1aR (avpr1a) between prairie, montane or meadow voles, the former species displays a 428-base pair sequence in the 5Ј flanking region that is not found in the latter two species. When the avpr1a of the prairie vole, including the sequence in the 5Ј region, is transgenically inserted into the nonmonogamous species mouse (7), more pronounced social behavior, similar to that displayed by prairie voles, is generated. Furthermore, variation in the 5Ј flanking region of prairie vole avpr1a affects brain ex...

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