Orchid children: How bad-news genes came good

http://newscientist1.blogspot.com/2012/02/health-orchid-children-how-bad-news.html

Wednesday, February 1, 2012

WHY are some children better at sharing than others? One attempt to find out uses what you could call the "Bamba test". In a large, playroom-like lab, a 3-year-old spends an hour or so playing games with a friendly woman, before snack time is announced. The adult brings out two packs of Bambas - peanut-butter-flavoured corn puffs much coveted in this part of the world.
The child's pack, like every normal one, holds 24 of the treats. But when the woman opens hers, she dumps out the contents and cries: "Mine has only three!" Will the 3-year-old share without being asked?

Most do not. "Self-initiated sharing is difficult," says psychologist Arial Knafo, who runs this study at The Hebrew University of Jerusalem in Israel. "You have to detect the need, then decide to do it."

A few 3-year-olds, however, will offer up their Bambas. What's different about them? The children most likely to share carried a certain gene variant, the "7R" version of DRD4, a gene that affects levels of the important brain chemical dopamine.

What made this finding remarkable was that this gene variant has generally been tied to antisocial behaviour. A pile of previous studies found that children with the 7R variant were more likely to be naughty and hyperactive. It had been dubbed the ADHD gene, the brat gene, the drinking gene, even the slut gene. Now Knafo was effectively calling it the Bamba-sharing gene. The bad-news gene was having a good effect.

This apparently paradoxical result lies at the heart of a major revision taking place in behavioural science - a recasting of the "vulnerability gene" model of many mood and behavioural disorders. This model, tremendously influential in psychiatry and psychology, has arisen over the past couple of decades as research tied several gene variants to high risk of mood and behavioural troubles, such as depression, aggression or, in the case of DRD4, attention and conduct disorders.

Crucially, these genes only caused problems when combined with a difficult childhood. Often termed vulnerability (or risk) genes, they have been held up as a prime model of how genes interact with environment to affect mood and behaviour.



But might we have got these genes all wrong? A fresh look at the evidence is suggesting that in fact they often create greater strength and happiness in people who have fortunate childhoods. The so-called vulnerability genes, in short, make you more attuned and responsive to your environment, whether bad or good.

"These genes aren't about risk," says Jay Belsky, a psychologist at the University of California, Davis, who helped establish what is being called the plasticity gene hypothesis, among other terms. "It is responsiveness - for better or worse."

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That crucial mingling of nature and nurture seemed to be neatly elucidated a few years later by two seminal studies from epidemiologists Avshalom Caspi and Terrie Moffitt of King's College, London. They found that a short SERT raised people's risk of depression only if they suffered rough childhoods or episodes of intense stress as adults (Science, vol 301, p 386). They also showed that a variant of a gene called MAOA, which affects serotonin and several other brain chemicals, increased the chance of violent or sociopathic behaviour, but only in people who were abused as children (Science, vol 297, p 851).

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Boyce was soon joined in this line of inquiry by Bruce Ellis at the University of Arizona in Tucson. Together they speculated that this reactivity also affects mood and behaviour. Drawing on Swedish terms, they distinguished between "dandelion children", who did about the same whatever their environment, and "orchid children", who wilted under poor care but flourished if carefully tended (Development and Psychopathology, vol 17, p 271).

Then, in 1997, Belsky also raised the idea of children who were especially sensitive to their early environments. Initially unaware of Boyce and Ellis's work, he was trying to figure out why some troubled kids responded more than others to counselling or other interventions to change their behaviour.

As Belsky, Boyce and Ellis watched the vulnerability-gene studies accumulate, they realised these could be the very genes that prompted the sensitivity they had found. And when Belsky delved into the literature he found evidence showing exactly that. Many vulnerability-gene studies indeed seemed to show that the so-called bad variants of SERT, DRD4, and MAOA generated extra resilience and other assets in people with fortunate early years. Yet the literature largely ignored this upside: in paper after paper, the raw data and graphs indicated the positive effects, but the text failed to explore or even note them.

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Knafo, for instance, began exploring DRD4's effect on social behaviour, as described earlier. He has shown that as long as parenting is good, toddlers with the 7R variant are more "prosocial" than those with the more common 4R form (Development and Psychopathology, vol 23, p 53). The orchids not only shared their Bambas, but were also more likely to pick up a researcher's dropped pencil, express sympathy over a bumped knee, and help find and then comfort a lost doll.

Knafo found that this edge in sociability and generosity increased over the three years he followed the children. This may simply reflect the natural course of child development. Or it may reflect a positive feedback loop, as both responsive child and engaged parent react to their good chemistry. Some of the mothers probably carry the 7R variant too, since a 7R child must have at least one 7R parent. Knafo hadn't genotyped them, so he can't say.

In 2008, another team showed that DRD4's 7R variant does not just make its bearers more responsive to natural variations in their upbringing; those carrying it also respond more to experimental interventions. In a programme for mothers of difficult toddlers that trained them to be more engaged and attentive, children carrying the 7R variant benefited the most (Developmental Psychology, vol 44, p 293).

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Belsky, meanwhile, is doing bigger studies that gauge the cumulative effects of several plasticity genes. In 2010, he published an analysis drawn from a 12-year study of 1586 adolescents. He analysed five genes (SERT, MAOA, DRD4, and two other genes that regulate dopamine) and collected data on the teens' behaviour and self-control, and on the mothers' engagement in their lives.

The numbers, once crunched, showed no significant effects on girls. But the 754 boys did react differently according to their genes, showing distinct dandelion or orchid effects (Journal of Child Psychology and Psychiatry, vol 52, p 619). The boys with no or only one plasticity variant proved to be dandelions: they fared about the same regardless of how engaged their mothers were. Those with two to five plasticity variants, however, responded like orchids, and the more they had, the more sensitive they were (see diagram).

[In the print edition, there is a graph showing that the "dandelion" children actually did slightly worse with the better parents! But only slightly. Maybe if their lives are very easy, they have less empathy? The orchid children not only did dramatically better if they had more nurturing parents, but also much better than the dandelion children with nurturing parents.]

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Orchid-dandelion effects have been found in rhesus monkeys, the only primate besides humans to have the short SERT variant. Ethologist Stephen Suomi of the US National Institutes of Health in Bethesda, Maryland, has done experiments with these monkeys that cannot be done with people, such as swapping babies at birth to switch the kind of parenting they receive. Unlike dandelion monkeys, orchid monkeys tend to turn out neurotic if raised by insecure, neurotic mothers but resilient and self-assured if raised by secure, competent mothers.

The orchid hypothesis also meshes with observations of adults in psychotherapy. Since 1997, Californian psychiatrists Elaine and Arthur Aron have written about what they call "highly sensitive persons", or HSPs, who are especially responsive not just to trouble but to many of life's pleasures and subtleties. As Elaine Aron sees it, this group, comprising an estimated 15 to 20 per cent of the population, perceive life at a finer, more nuanced scale.

As the plasticity theory gained ground, the Arons and others have wondered if HSPs are essentially orchid children grown up. They argue that HSPs share with the orchid children a particularly reactive physiological and sensory response to the world.

Now the first genetic evidence is emerging to support that view. One set of preliminary results, presented at last year's annual meeting of the US Society of Biological Psychiatry in San Francisco, found that HSPs were more likely to carry the short SERT gene (see bit.ly/thFP3i). Another, also published in 2011, correlated HSP characteristics with 10 genetic variations that affect dopamine levels (PloS One, vol 6, p e21636).

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In fact, many of the orchid-theory supporters argue that even with its drawbacks, sensitivity is more often than not adaptive - and therefore selected for. This idea has gained credence by the discovery over the last decade that many of the plasticity genes have spread rapidly through humankind over the last 50,000 years.

Of the leading orchid-gene variants - the short SERT, the 7R DRD4 and the more plastic version of MAOA - none existed in humans 80,000 years ago. Since emerging, these variants have spread into 20 to 50 per cent of the population. "That's not random drift," says John Hawks, an evolutionary anthropologist at the University of Wisconsin-Madison. "They're being selected for."

Orchid genes could provide an advantage in several ways. To start with, they seem to create better mental health and greater resilience in people with secure, stimulating childhoods. The "problem" traits they can generate, such as anxiety, aggression or ADHD, could help survival in conflict-ridden or volatile environments. Plasticity genes also boost resilience at the group level by creating a mix of steady do-ers (dandelions) and individuals with greater behavioural range (orchids).
Some evolutionary anthropologists argue that these traits, particularly the restlessness and risk-taking found in many carriers of the 7R DRD4, may have helped drive human expansion. Today the 7R variant is most common in populations that migrated fastest and furthest from Africa (American Journal of Physical Anthropology, vol 145, p 382).

It may seem odd to link such achievements to a child's willingness to share Bambas. Yet if the orchid hypothesis is right, the genes that help create some of our most grievous frailties - anxiety and aggression, melancholia and murder - may also underlie our greatest strengths, from the sharing of meals to our spread around the globe. Something to ponder next time you're offered a sweet.


http://www.theatlantic.com/magazine/archive/2009/12/the-science-of-success/7761/

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At first glance, this idea, which I’ll call the orchid hypothesis, may seem a simple amendment to the vulnerability hypothesis. It merely adds that environment and experience can steer a person up instead of down. Yet it’s actually a completely new way to think about genetics and human behavior. Risk becomes possibility; vulnerability becomes plasticity and responsiveness. It’s one of those simple ideas with big, spreading implications. Gene variants generally considered misfortunes (poor Jim, he got the “bad” gene) can instead now be understood as highly leveraged evolutionary bets, with both high risks and high potential rewards: gambles that help create a diversified-portfolio approach to survival, with selection favoring parents who happen to invest in both dandelions and orchids.

In this view, having both dandelion and orchid kids greatly raises a family’s (and a species’) chance of succeeding, over time and in any given environment. The behavioral diversity provided by these two different types of temperament also supplies precisely what a smart, strong species needs if it is to spread across and dominate a changing world. The many dandelions in a population provide an underlying stability. The less-numerous orchids, meanwhile, may falter in some environments but can excel in those that suit them. And even when they lead troubled early lives, some of the resulting heightened responses to adversity that can be problematic in everyday life—increased novelty-seeking, restlessness of attention, elevated risk-taking, or aggression—can prove advantageous in certain challenging situations: wars, tribal or modern; social strife of many kinds; and migrations to new environments. Together, the steady dandelions and the mercurial orchids offer an adaptive flexibility that neither can provide alone. Together, they open a path to otherwise unreachable individual and collective achievements.

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Most of us have genes that make us as hardy as dandelions: able to take root and survive almost anywhere. A few of us, however, are more like the orchid: fragile and fickle, but capable of blooming spectacularly if given greenhouse care. So holds a provocative new theory of genetics, which asserts that the very genes that give us the most trouble as a species, causing behaviors that are self-destructive and antisocial, also underlie humankind’s phenomenal adaptability and evolutionary success. With a bad environment and poor parenting, orchid children can end up depressed, drug-addicted, or in jail—but with the right environment and good parenting, they can grow up to be society’s most creative, successful, and happy people.
By David Dobbs
Vault49

In 2004, Marian Bakermans-Kranenburg, a professor of child and family studies at Leiden University, started carrying a video camera into homes of families whose 1-to-3-year-olds indulged heavily in the oppositional, aggressive, uncooperative, and aggravating behavior that psychologists call “externalizing”: whining, screaming, whacking, throwing tantrums and objects, and willfully refusing reasonable requests. Staple behaviors in toddlers, perhaps. But research has shown that toddlers with especially high rates of these behaviors are likely to become stressed, confused children who fail academically and socially in school, and become antisocial and unusually aggressive adults.

At the outset of their study, Bakermans-Kranenburg and her colleagues had screened 2,408 children via parental questionnaire, and they were now focusing on the 25 percent rated highest by their parents in externalizing behaviors. Lab observations had confirmed these parental ratings.

Bakermans-Kranenburg meant to change the kids’ behavior. In an intervention her lab had developed, she or another researcher visited each of 120 families six times over eight months; filmed the mother and child in everyday activities, including some requiring obedience or cooperation; and then edited the film into teachable moments to show to the mothers. A similar group of high-externalizing children received no intervention.



Video: Watch an interview with Stephen Suomi, one of the researchers featured in this story

To the researchers’ delight, the intervention worked. The moms, watching the videos, learned to spot cues they’d missed before, or to respond differently to cues they’d seen but had reacted to poorly. Quite a few mothers, for instance, had agreed only reluctantly to read picture books to their fidgety, difficult kids, saying they wouldn’t sit still for it. But according to Bakermans-Kranenburg, when these mothers viewed the playback they were “surprised to see how much pleasure it was for the child—and for them.” Most mothers began reading to their children regularly, producing what Bakermans-Kranenburg describes as “a peaceful time that they had dismissed as impossible.”

And the bad behaviors dropped. A year after the intervention ended, the toddlers who’d received it had reduced their externalizing scores by more than 16 percent, while a nonintervention control group improved only about 10 percent (as expected, due to modest gains in self-control with age). And the mothers’ responses to their children became more positive and constructive.

Few programs change parent-child dynamics so successfully. But gauging the efficacy of the intervention wasn’t the Leiden team’s only goal, or even its main one. The team was also testing a radical new hypothesis about how genes shape behavior—a hypothesis that stands to revise our view of not only mental illness and behavioral dysfunction but also human evolution.

Of special interest to the team was a new interpretation of one of the most important and influential ideas in recent psychiatric and personality research: that certain variants of key behavioral genes (most of which affect either brain development or the processing of the brain’s chemical messengers) make people more vulnerable to certain mood, psychiatric, or personality disorders. Bolstered over the past 15 years by numerous studies, this hypothesis, often called the “stress diathesis” or “genetic vulnerability” model, has come to saturate psychiatry and behavioral science. During that time, researchers have identified a dozen-odd gene variants that can increase a person’s susceptibility to depression, anxiety, attention-deficit hyperactivity disorder, heightened risk-taking, and antisocial, sociopathic, or violent behaviors, and other problems—if, and only if, the person carrying the variant suffers a traumatic or stressful childhood or faces particularly trying experiences later in life.

This vulnerability hypothesis, as we can call it, has already changed our conception of many psychic and behavioral problems. It casts them as products not of nature or nurture but of complex “gene-environment interactions.” Your genes don’t doom you to these disorders. But if you have “bad” versions of certain genes and life treats you ill, you’re more prone to them.

Recently, however, an alternate hypothesis has emerged from this one and is turning it inside out. This new model suggests that it’s a mistake to understand these “risk” genes only as liabilities. Yes, this new thinking goes, these bad genes can create dysfunction in unfavorable contexts—but they can also enhance function in favorable contexts. The genetic sensitivities to negative experience that the vulnerability hypothesis has identified, it follows, are just the downside of a bigger phenomenon: a heightened genetic sensitivity to all experience.

The evidence for this view is mounting. Much of it has existed for years, in fact, but the focus on dysfunction in behavioral genetics has led most researchers to overlook it. This tunnel vision is easy to explain, according to Jay Belsky, a child-development psychologist at Birkbeck, University of London. “Most work in behavioral genetics has been done by mental-illness researchers who focus on vulnerability,” he told me recently. “They don’t see the upside, because they don’t look for it. It’s like dropping a dollar bill beneath a table. You look under the table, you see the dollar bill, and you grab it. But you completely miss the five that’s just beyond your feet.”

Though this hypothesis is new to modern biological psychiatry, it can be found in folk wisdom, as the University of Arizona developmental psychologist Bruce Ellis and the University of British Columbia developmental pediatrician W. Thomas Boyce pointed out last year in the journal Current Directions in Psychological Science. The Swedes, Ellis and Boyce noted in an essay titled “Biological Sensitivity to Context,” have long spoken of “dandelion” children. These dandelion children—equivalent to our “normal” or “healthy” children, with “resilient” genes—do pretty well almost anywhere, whether raised in the equivalent of a sidewalk crack or a well-tended garden. Ellis and Boyce offer that there are also “orchid” children, who will wilt if ignored or maltreated but bloom spectacularly with greenhouse care.

At first glance, this idea, which I’ll call the orchid hypothesis, may seem a simple amendment to the vulnerability hypothesis. It merely adds that environment and experience can steer a person up instead of down. Yet it’s actually a completely new way to think about genetics and human behavior. Risk becomes possibility; vulnerability becomes plasticity and responsiveness. It’s one of those simple ideas with big, spreading implications. Gene variants generally considered misfortunes (poor Jim, he got the “bad” gene) can instead now be understood as highly leveraged evolutionary bets, with both high risks and high potential rewards: gambles that help create a diversified-portfolio approach to survival, with selection favoring parents who happen to invest in both dandelions and orchids.

In this view, having both dandelion and orchid kids greatly raises a family’s (and a species’) chance of succeeding, over time and in any given environment. The behavioral diversity provided by these two different types of temperament also supplies precisely what a smart, strong species needs if it is to spread across and dominate a changing world. The many dandelions in a population provide an underlying stability. The less-numerous orchids, meanwhile, may falter in some environments but can excel in those that suit them. And even when they lead troubled early lives, some of the resulting heightened responses to adversity that can be problematic in everyday life—increased novelty-seeking, restlessness of attention, elevated risk-taking, or aggression—can prove advantageous in certain challenging situations: wars, tribal or modern; social strife of many kinds; and migrations to new environments. Together, the steady dandelions and the mercurial orchids offer an adaptive flexibility that neither can provide alone. Together, they open a path to otherwise unreachable individual and collective achievements.

This orchid hypothesis also answers a fundamental evolutionary question that the vulnerability hypothesis cannot. If variants of certain genes create mainly dysfunction and trouble, how have they survived natural selection? Genes so maladaptive should have been selected out. Yet about a quarter of all human beings carry the best-documented gene variant for depression, while more than a fifth carry the variant that Bakermans-Kranenburg studied, which is associated with externalizing, antisocial, and violent behaviors, as well as ADHD, anxiety, and depression. The vulnerability hypothesis can’t account for this. The orchid hypothesis can.

Can liability really be so easily turned to gain? The pediatrician W. Thomas Boyce, who has worked with many a troubled child in more than three decades of child-development research, says the orchid hypothesis “profoundly recasts the way we think about human frailty.” He adds, “We see that when kids with this kind of vulnerability are put in the right setting, they don’t merely do better than before, they do the best—even better, that is, than their protective-allele peers. “Are there any enduring human frailties that don’t have this other, redemptive side to them?”

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Suomi made another remarkable discovery. He and others assayed the serotonin-transporter genes of seven of the 22 species of macaque, the primate genus to which the rhesus monkey belongs. None of these species had the serotonin-transporter polymorphism that Suomi was beginning to see as a key to rhesus monkeys’ flexibility. Studies of other key behavioral genes in primates produced similar results; according to Suomi, assays of the SERT gene in other primates studied to date, including chimps, baboons, and gorillas, turned up “nothing, nothing, nothing.” The science is young, and not all the data is in. But so far, among all primates, only rhesus monkeys and human beings seem to have multiple polymorphisms in genes heavily associated with behavior. “It’s just us and the rhesus,” Suomi says.

This discovery got Suomi thinking about another distinction we share with rhesus monkeys. Most primates can thrive only in their specific environments. Move them and they perish. But two kinds, often called “weed” species, are able to live almost anywhere and to readily adapt to new, changing, or disturbed environments: human beings and rhesus monkeys. The key to our success may be our weediness. And the key to our weediness may be the many ways in which our behavioral genes can vary.

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The coup also showed something more straightforward: that a genetic trait tremendously maladaptive in one situation can prove highly adaptive in another. We needn’t look far to see this in human behavior. To survive and evolve, every society needs some individuals who are more aggressive, restless, stubborn, submissive, social, hyperactive, flexible, solitary, anxious, introspective, vigilant—and even more morose, irritable, or outright violent—than the norm.

All of this helps answer that fundamental evolutionary question about how risk alleles have endured. We have survived not despite these alleles but becauseof them. And those alleles haven’t merely managed to slip through the selection process; they have been actively selected for. Recent analyses, in fact, suggest that many orchid-gene alleles, including those mentioned in this story, have emerged in humans only during the past 50,000 or so years. Each of these alleles, it seems, arose via chance mutation in one person or a few people, and began rapidly proliferating. Rhesus monkeys and human beings split from their common lineage about 25 million to 30 million years ago, so these polymorphisms must have mutated and spread on separate tracks in the two species. Yet in both species, these new alleles proved so valuable that they spread far and wide.

As the evolutionary anthropologists Gregory Cochran and Henry Harpending have pointed out, in The 10,000 Year Explosion (2009), the past 50,000 years—the period in which orchid genes seem to have emerged and expanded—is also the period during which Homo sapiens started to get seriously human, and during which sparse populations in Africa expanded to cover the globe in great numbers.

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