Gene Variant May Help Children Cope with 'Problem Parents'


by Jim Schnabel

April 11, 2011

How do some children manage to cope so well despite having “toxic parents?” They may have a gene variant that sensitizes the reward and motivation circuits in their brains. According to a new study, a group of children carrying the gene variant were significantly more likely to have better relationships with problem parents than were their siblings who lacked the variant.

“The literature on social resilience has tended to focus on how aspects of the child's environment affect and support the child; but this finding [highlights] a way in which some children may influence their own environment to better support their needs,” says William Copeland, a clinical psychologist and epidemiologist at Duke University, and lead author of the study, which appeared online in the journal Neuropsychopharmacology on Feb. 16.

Copeland and his colleagues enrolled 226 Caucasian children from a rural, impoverished part of North Carolina; determined how close each child was to his or her parent(s); and performed DNA analyses to find out whether each child carried a certain variant of the gene for the mu-opioid brain cell receptor.

Named for the addictive, plant-derived opiate drugs that stimulate them powerfully, opioid receptors are normally activated in a more moderate way by the brain’s own opiate-like neurotransmitters, including endorphins. The mu-opioid receptors are the principal opioid receptors involved in generating a sense of euphoria and pain relief from pleasant experiences or morphine-like drugs. As such, one of their key functions is to help determine the sensitivity of reward and motivation networks in the brain.

For an infant or small child, few things are as rewarding as a parent’s presence. In animal studies, the use of drugs that block the mu-opioid receptors in an infant’s brain typically makes the infant more anxious and clingy. “It’s like opiate withdrawal,” says James Curley, a researcher at Columbia University who has done experiments with monkeys in this field. By contrast, hitting mu-opioid receptors with morphine seems to produce a sense of satiety that weakens the desire for social attachment.

The pleasure-sensitive allele

Copeland and his colleagues focused their analysis on a common variant of the mu-opioid gene known as A118G, or the “G allele.” The variant appears to make the mu-opioid receptor more sensitive, with the result that reward circuits hit higher highs for a given stimulus, and lower lows when it is withdrawn. A similar gene variant is linked to stronger attachment behaviors in infant monkeys, and the researchers wondered if the G allele would be associated with stronger attachment behaviors in human children too.

The children and their parents are enrolled in a larger, ongoing mental health research project, in which they were interviewed using standard psychiatric questionnaires about many aspects of their lives. From this data, Copeland and his colleagues quantified for each child/parent relationship the enjoyment of parent-child activities, frequency of arguments, and separation anxiety symptoms.

The researchers divided the children into two groups, those with parents whose availability was likely to be normal, and those with “problem parents” whose availability was probably below normal. About 60 percent of the parents were judged to be in the latter category because they reported having had at least one criminal conviction or a significant mental health problem, including substance abuse.

Copeland and his colleagues found that among the children of “non-problem” parents, those with the A118G variant did not show significantly stronger attachment to their parents than did non-A118G children. But in households with problem parents, whose availability was presumed to be lower, children without the A118G variant appeared to have much worse relations with their parents, while children with the A118G variant had correspondingly better relations—as if the situation allowed them to grab an unusually large share of a resource that would normally have been rationed more equitably. 

Social attachment as a basic pleasure

The study carries many caveats, including the fact that it didn’t measure attachment behavior directly, as is possible in animal studies; didn’t separate out child and parent contributions to each relationship; and didn’t sample parental DNA. Curley notes that the G allele in parents might also have been influencing the quality of the child-parent relationship.

In a study now in press at Behavioral Neuroscience, for which Curley has written a commentary, a group led by University of Chicago researchers have found that an A118G-like allele is associated with more attachment-oriented behavior in mothers – among rhesus macaque monkeys in the wild. “Females that had the G allele showed more frequent protective restraining of their infants; in other words they more often prevented them from leaving, by pulling their tails or their legs when the infants tried to get away,” says senior author Dario Maestripieri.

The researchers also found that the mothers with the G allele had higher levels of oxytocin in their spinal fluid. “So the physiological mechanism responsible for this attachment behavior might involve oxytocin, because oxytocin has been implicated in mother-infant attachment, in both animal and human studies,” says Maestripieri. “There also are studies that suggest an interaction between the opioid and oxytocin systems.”

Two other recent studies in humans indicate that A118G can affect adult social relationships, by increasing the pleasure experienced from those relationships and also by increasing the pain of social rejection. “So if you put this into a broad evolutionary framework,” says Curley, “it seems that mu-opioid receptors are modulating behavior in terms of unique attachments to individuals. And it may be doing that across the lifespan both in mother-child attachments and in adult attachments.”

Some researchers have even speculated that A118G, which occurs more frequently in Asian populations than in Caucasian populations, and hardly at all in African populations, helps account for different degrees of social cohesion in these ethnic groups – differences that have been assumed to be cultural.

Separately, A118G is also suspected of enhancing the pleasure from drugs that hit the brain’s reward circuits, as well as pain and craving when such drugs are withdrawn – and although studies so far have been inconclusive, there are suggestions that it can make people more susceptible to addiction. To the extent that addiction impairs survival or fertility, A118G should have been selected against by evolution – pushing it out of the gene pool. But its effects in boosting relationships might have made up for its addiction-related drawbacks. “A study published in 2009 showed that this G allele has undergone positive selection not long ago,” says Curley, “so maybe it was promoting attachment behaviors that were important for survival in our recent evolutionary past.”