Archive for the ‘OPRM1’ Category

John Keats, by William Hilton (died 1839). See...
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If you slam your hand in the car door and experience physical pain, medical science can offer you a “pain killer!“.  Certainly morphine (via its activation of the mu opioid receptor (OPRM1)) will make you feel a whole lot better.  However, if your boyfriend or girlfriend breaks up with you and you experience emotional pain, its not so clear whether medical science has, or should offer, such a treatment.  Most parents and doctors would not offer a pain killer.  Rather, it’s off to sulk in private, perhaps finding relief in the writings of countless poets who’ve attested to the acute pain that ensues when emotional bonds are broken.

Love hurts! But why should this be? Why does the loss of love hurt so much?

From a purely biological point of view, it seems obvious that during certain periods of life – childhood for instance – social bonds are important for survival.  Perhaps anything that helped make the breaking of such bonds feel bad, might be selected for?  Its a very complex evolutionary genetic problem to be sure.  One way to begin to solve this question might be to study genes like OPRM1 and ask how and why they might be important for survival.

Such is the case for Christina Barr and colleagues, who, in their paper, “Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates” [doi:10.1073/pnas.0710225105] examine relationships between emotional bonds and genetics in rhesus macaques.  The team examines an amino acid substitution polymorphism in the N-terminus of the OPRM1 protein (C77G which leads to an Arginine to Proline change at position 26).  This polymorphism is similar to the human polymorphism (covered here) A118G (which leads to an Asparagine to Aspartate change at position 40).  Binding studies showed that both the 77G and 118G alleles have a higher affinity for beta-endorphin peptides.

Interestingly, Barr and colleagues find that the classical “pain gene” OPRM1 G-allele carrier macaques display higher levels of attachment to their mothers during a critical developmental phase (18-24 months of age).  These G-allele carriers were also more prone to distress vocalizations when temporarily separated from their mothers and they also spent more time (than did CC controls) with their mothers when reunited.  Hence, there ?may be? some preliminary credence to the notion that a gene involved in feeling pleasant/unpleasant might have been used during evolution to reinforce social interactions between mother and child.  The authors place their results into a larger context of the work of John Bowlby who is known for developing a theory of attachment and the consequences of attachment style on later phases of emotional life.

Click here for a previous interview with Dr. Barr and a post on another related project of hers.

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William Faulkner
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What hurts more – a broken toe or a broken heart?  Ask a parent and their forlorn 15 year-old who was not invited to the party that everyone is going to, and you might get different answers.  In some cases, the internal anguish of social exclusion or estrangement, may even – paradoxically – be relieved by self-infliction of physical pain, which is construed by some neuro-psychiatrists as a coping mechanism, wherein endogenous opioids are released by the physical injury (cutting, for instance) and may then soothe the internal feeling of anguish.

While there are many social, and psychological factors pertaining to the way in which people cope with internal and external pain, a recent research article from Dr. Naomi Eisenberger’s lab sheds light on a very basic aspect of this complex process – that is – the similarities and differences of neural mechanisms underlying social and physical pain.  In their recent paper, “Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection” [doi:10.1073/pnas.0812612106] the authors asked healthy participants to lay in an MRI scanner and play a video game of catch / toss the ball with other “real people” by way of a computer interface.  During the game, the participant was rudely socially excluded by the other two players in order to induce the feelings of social rejection.  Participants also completed an instrument known as the “Mehrabian Sensitivity to Rejection Scale” and were genotyped for an A-to-G SNP (rs1799971) located in the opioid receptor (OPRM1) gene.  Previous research as found that the G-allele of OPRM1 is less expressed and that individuals who carry the GG form tend to need higher doses of opioids to feel relief from physical pain, and GG rhesus monkeys (interestingly, we share the same ancient A-to-G polymorphism with our primate ancestors) demonstrate more distress when separated from their mothers.

The results of the study show that the participants who carry the AA genotype are somewhat less sensitive to social rejection and also show less brain activity in the anterior cingulate cortex (an area whose activity has long been associated with responses to physical pain) as well as the anterior insula (an area often times associated with unpleasant gut feelings) when excluded during the ball-toss game.  Further statistical analyses showed that the activity in the cingulate cortex was a mediator of the genetic association with rejection sensitivity – suggesting that the genetic difference exerts its effect by way of its role in the anterior cingulate cortex.   Hence, they have localized where in the brain, this particular genetic variant exerts its effect.  Very cool indeed!!

Stepping back, I can’t help but think of the difficulties people have in coping with internal anguish, which – if not understood by their peers – can, mercilessly, lead to further exclusion, estrangement and stigmatization.  Studies like this one reveal – from behavior, to brain, to genome – the basic biology of this important aspect of our social lives, and can help to reverse the marginalization of people coping with internal anguish.


The picture is of William Faulkner who is quoted, “Given the choice between the experience of pain and nothing, I would choose pain.”  I wonder if he was an AA or a G-carrier?  I feel rather lucky to find that my 23andMe profile shows an AA at this site.

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