Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates

Abstract

In a variety of species, development of attachment to a caregiver is crucial for infant survival and partly mediated by the endogenous opioids. Functional mu-opioid receptor gene polymorphisms are present in humans (OPRM1 A118G) and rhesus macaques (OPRM1 C77G). We hypothesized that rhesus infants carrying a gain-of-function OPRM1 77G allele would experience increased reward during maternal contact and would, therefore, display increased measures of attachment. We collected behavioral data from rhesus macaques (n ‫؍‬ 97) during early infancy and at 6 months of age, across four cycles of maternal separation (4 days) and reunion (3 days). Animals were genotyped for the OPRM1 C77G polymorphism, and the effects of this allele on attachmentrelated behaviors were analyzed. Infants carrying the G allele exhibited higher levels of attachment behavior during early infancy. During prolonged periods of maternal separation, although infant macaques homozygous for the C allele exhibited decreases in their levels of distress vocalization with repeated separation, this response persisted in G allele carriers. The OPRM1 77G allele also affected social preference during reunion. C/G infants spent increasing amounts of time in social contact with their mothers as a function of repeated separation and were less likely to interact with other individuals in the social group, a pattern not observed among infants with the C/C genotype. These findings suggest a role for OPRM1 variation in the expression of attachment behavior in human subjects, especially as a function of separation from the caregiver.genetic ͉ rhesus macaque ͉ mother-infant bond ͉ C77G ͉ A118G

Convergent functional genomics of genome‐wide association data for bipolar disorder: Comprehensive identification of candidate genes, pathways and mechanisms

“…An intriguing finding is that of Oprm1 (opioid receptor mu 1) as a top candidate gene for bipolar. Oprm1 has been implicated in pain regulation [Oertel and Lotsch, 2008], substance abuse disorders [Luo et al, 2008], attachment behaviors [Barr et al, 2008], and suicide [Hishimoto et al, 2008]. Earlier work by us using animal models and a CFG approach had identified an overlap between candidate genes involved in mood regulation and pain regulation, such as Penk (preproenkephalin) [Ogden et al, 2004;Le-Niculescu et al, 2008b].…”

Psychobiological traits in the risk profile for overeating and weight gain

“…Although the exact mechanisms remain unclear, in vivo evidence supports a gain-of-function for those possessing the rarer G118 allele as seen, for instance, by increased reward from maternal attachment in rhesus macaque infants, increased stimulant effects of alcohol in humans, and a greater tendency to drug use and abuse in general. 24,25 Animal study has also shown that administration of an opioid agonist in the nucleus accumbens induces binge eating of fat, probably by increasing the hedonic properties of this food substrate. 26 In a recent studyFand, to the best of our knowledge, the only one that has examined OPRM1 genotypes in relationship to weight gainFwe found that the frequency of the G allele differed significantly between obese adults with and without binge eating disorder.…”

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

“…In the social domain, MOR selective agonists decrease separation distress vocalizations in both rats and fowl (Panksepp et al, 1980;Warnick et al, 2005). The MOR gene influences infant-mother attachment in mice and Rhesus macaques (Moles et al, 2004;Barr et al, 2008). This evidence suggests that the role of the opiate system in social reward may be mediated by MOR.…”