by Jo Marchant
Likewise, stress researchers have found that our bodies respond to social conflict—being criticized or rejected by others—in the same way we respond to imminent physical harm. It’s no coincidence that one of people’s most common fears is public speaking, or that one of the most effective tools psychologists have for triggering the fight-or-flight response, the Trier Social Stress Test, requires volunteers to perform in front of a panel of stone-faced judges. Carrying out similar tasks when nobody’s watching is nowhere near as stressful.
The lack of social ties, although less acute, can be just as toxic over time: even if they score low on conventional measures of stress, lonely people have high baseline levels of stress hormones and inflammation, with all of the health problems that entails.13 Social support also seems to shield us against difficult circumstances—those without it are much more susceptible to other stresses when they come.
But why do social rejection and isolation affect us so dramatically? Having no friends might not be pleasant, but it’s hardly a matter of life and death. That’s where I’m wrong, says John Cacioppo, a psychologist at the University of Chicago, Illinois, and probably the world expert on loneliness.14
He points out in his 2008 book, Loneliness, that for most of human history, becoming separated from others put us at imminent risk of starvation, predation or attack. Social isolation was indeed a death sentence, as much a threat to our survival as hunger, thirst or pain. As a result, we’ve evolved to be so desperate for human contact that if deprived of it we can even form attachments to inanimate objects, like Tom Hanks’s character in the movie Castaway, who has a meaningful relationship with a volleyball he calls Wilson.
But you don’t need to be marooned on a desert island to feel lonely. If we don’t feel cared for, we can feel lonely even when surrounded by others: at college; on a crowded bus; in a strained marriage. After all, being among a hostile tribe is just as dangerous as being alone.
The impact of loneliness, then, depends not on how many physical contacts we have but how isolated we feel. You might have only one or two close friends, but if you feel satisfied and supported there’s no need to worry about effects on your health, Cacioppo tells me. “But if you’re sitting there feeling threatened by others, feeling as if you are alone in the world, that’s probably a reason to take steps.”15
Such “loneliness in a crowd” is an increasing problem in modern society as we move around, often living far from family and friends. Studies in Western countries suggest that 20–40% of adults are lonely at any one time, with one of the loneliest populations studied being college freshmen.16 Most of us soon reach out to others or our circumstances change. But 5–7% of people report feeling intensely or persistently lonely.
One reason for their plight is that, like stress, chronic loneliness reshapes the brain, in this case making people more sensitive to social threat. Lonely people rate social interactions more negatively, are less trusting of others, and judge them more harshly. There’s an evolutionary logic to this too: in a hostile social situation it is vital to be alert to betrayal and potential harm. But it can make lonely people reluctant to reach out to others. Feeling threatened also disrupts their social skills, says Cacioppo, leaving them focused on their own needs at the expense of anyone else’s. “When you talk to a lonely person you feel like they are feasting on you,” he says. “Not in a good way.”
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IN 2007, Cacioppo published a result that opened a new window into how our physical makeup is influenced by the contents of our minds. He showed that stress—especially social stress—doesn’t just affect the brain. It filters right down to our DNA.
From a group of 230 elderly Chicagoans, Cacioppo selected eight of the loneliest, who had felt isolated for several years, and six of the most connected, who reported that they had great friends and social support. He sent samples of their blood to molecular biologist Steve Cole at the University of California, Los Angeles, who analyzed which genes were active in each group. The pattern of gene expression varies in different cell types, so Cole focused on the white blood cells of the immune system, because what these cells do—whether they cause inflammation or produce antibodies, for example—is crucial for health.
The Chicagoans’ social worldview had a dramatic effect on what was happening inside their cells.17 Of about 22,000 genes in the genome, Cole found significant differences in more than 200—which were either activated to produce more of a particular protein, or turned down to produce less. Individual genes might look different by chance; what was striking, says Cole, was the broader pattern.18
A large proportion of the lonely people’s up-regulated genes were involved in inflammation, whereas many of their down-regulated genes had roles in antiviral responses and antibody production. In sociable people, the reverse was true—biological activity in their immune cells was skewed towards fighting viruses and tumor cells and away from producing inflammation. Crucially, the difference related most strongly not to the actual size of the volunteers’ social networks but to how isolated they felt themselves to be. It was a very small study, but one of the first ever to link a state of mind with a broad, underlying change in gene expression.
The result suggests that our immune system is fine-tuned to respond to our social surroundings. It makes perfect sense that we evolved this way, says Cacioppo. In the past, people in a close-knit group would be at risk from viruses, which spread easily between individuals in close contact, or—because they would likely survive longer—from longer-term conditions such as cancer. An isolated person, by contrast, would have more to fear from physical attack, so their survival would depend on triggering branches of the immune system involved in wound healing and defense against bacterial infection. In today’s world, however, this gene expression profile is a double whammy, increasing the risk of chronic inflammation-related conditions while leaving us more susceptible to viruses and cancer.
The researchers have since replicated that preliminary result in a larger sample,19 and Cole has seen the same effect in other types of social adversity in humans and other primates, from macaques placed in unstable social groups, to people caring for dying spouses.20
Cole is now starting to test whether it’s possible to reverse this adverse genetic profile. For example, a 2012 trial of 79 women recently diagnosed with breast cancer found that group stress-management therapy reduced expression of inflammation-related genes and pushed women back towards an anti-viral profile.21 “Our conclusion was that mood matters,” says Michael Antoni, of the University of Miami, Florida, who led the study.22
Not everyone agrees, in particular James Coyne, a health psychologist and emeritus professor at the University of Pennsylvania in Philadelphia and prominent skeptic of positive psychology. Particularly when it comes to cancer, researchers who claim that psychological factors can influence disease progression put pressure on patients, he argues, and risk blaming those who don’t recover for not thinking in the right way or attending the right classes. “They claim that if you make the right choices, you’ll be healthy. And if you don’t, you’ll die.”23
Whether social support helps cancer patients to live longer has been controversial ever since Stanford psychologist David Spiegel found that group therapy doubled survival time in a 1989 trial of 86 women with metastatic breast cancer.24 There have been plenty of attempts since to replicate that result, of which eight concluded that therapy does improve survival and seven have found no difference.25 Results from epidemiological studies are mixed too, but in 2013, Harvard researchers who followed 734,000 patients found that for all the cancer types they looked at, people who were married were 20% less likely to die from their cancer, even after controlling for practical advantages such as help getting to appointments and taking medication on time.26
Overall, Spiegel claims the balance of evidence is in favor of there being a significant effect on survival,27 whereas Coyne concludes that “the whole idea that psychological factors can affect the lives of
cancer patients is rubbish.” He describes Antoni’s trials as too small to show anything useful and like researching the money you get from the tooth fairy: investigating a mechanism when it hasn’t been established that there’s an effect to be explained.28
“Everything we’re doing is preliminary,” responds Antoni. “We do need to be cautious. But each year, studies are showing results in a similar direction. They are showing that if we change the psychology, physiological changes do parallel that.” Antoni is now following 200 women for up to 15 years after receiving therapy, to see if this has any effect on cancer recurrence or survival time.
In general, the idea that social relationships influence gene expression in a way that’s relevant for health is supported by insights from an emerging field called behavioral epigenetics. Epigenetics refers to a process in which DNA in a cell becomes physically modified, or tagged, in a way that controls long-term how genes in that cell are activated. This is what allows cells in our bodies to develop into different tissues—skin, nerves, white blood cells—even though they all contain the same DNA. Scientists used to think that once epigenetic tags were set in the embryo, they were fixed for life. But research now suggests that some of them at least can be altered later—and by social cues.
Some of the crucial experiments involve rats. When mothers nurture their young by licking and grooming them, the female pups grow up to be doting mothers themselves, with a healthy physiological response to stress. Meanwhile neglected pups grow up sexually promiscuous and hypersensitive to stress, and they ignore their own offspring. Researchers recently discovered why: when the pups are licked and groomed, it affects the epigenetic tagging of genes that encode receptors for the sex hormone estrogen, and for the rat equivalent of cortisol.29
The same difference in the cortisol receptor gene shows up in human suicide victims who were abused during childhood30—a hint that similar processes may occur in humans too. Other studies show that patterns of epigenetic modification differ depending on socioeconomic circumstances, between institutionalized children and those raised by their biological parents, and even sometimes between identical twins.31
We’ve already heard how when children are exposed to adversity, their maturing brains become sensitized to stress. Epigenetics provides a second way in which early trauma—in particular a harsh social environment—can become programmed into our physiology, helping to explain why people brought up in tough environments later suffer from so much chronic disease. The research so far is preliminary—people are not the same as rats. But it’s possible that adversity we experience in infancy (or in the womb) tags our genes in a way that subsequently raises inflammation levels and makes our immune system hypersensitive to threat.
New-age and holistic healers have seized on the concept of epigenetics as proof of what they claimed all along—that we can control our DNA and therefore heal ourselves using our minds.32 Such claims are vastly exaggerated and misleading—researchers are only just starting to work out the balance between epigenetic changes fixed in childhood and those that remain fluid later in life. They’re also not sure how early these changes occur (although extrapolating from animal studies suggests that we may be most susceptible before about age two). Pinning down the precise nature, mechanisms and timing of these changes—let alone their implications for health—is going to be a mind-boggling task.
But already it seems clear that we don’t inherit from our parents a single “biological self.”33 Instead our genomes encode a wide variety of potential selves, and our social environment—including our perception of that environment—helps to determine which of those selves we become.
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IN HER brick bungalow in Milledgeville, Georgia, 69-year-old Susan reaches for the bookshelf and takes down a large, glass jar filled with colored cards. She picks some out to show me: they’re a mix of simple chores and rewards, from “wipe off kitchen cupboard doors” and “dust furniture in one room” to “go out for dinner” and “extra TV time.” The jar is a memento of a pioneering trial she took part in, more than a decade ago.
The trial was run by the University of Georgia’s Gene Brody. When he began studying impoverished families in rural black belt communities, he knew that their kids were at risk for behavioral problems such as alcohol abuse. But not all of them succumbed. So his first question was, why not?
He spent ten years studying thousands of families in places like Milledgeville, comparing kids who go off the rails with those who seem resilient to the stress of their surroundings. What allows some individuals to stay psychologically strong in such a tough environment? The one thing that protected the kids better than anything else, it turned out, was a particular style of parenting. Just like in the rats, the right care from a parent at this crucial stage in development protected them later in life.34
The most resilient kids were brought up by firm, vigilant parents—perhaps more strict than you’d find in populations living in less threatening environments. But crucially, these parents were also affectionate, communicative and highly engaged in their children’s lives. Brody called it “nurturant-involved” parenting. These kids knew where the boundaries were, and that there would be sanctions for bad behavior. But they also knew this was because their parents loved and cared about them.
Brody designed a seven-week course to teach these principles to parents (and grandparents) attending with their 11-year-old sons and daughters. The course emphasized discipline as well as communication skills, with sessions on topics like “supporting our youth” and “making and enforcing rules.” He called it the Strong African American Families (SAAF) project. Then he ran a randomized controlled trial with nearly 700 families, to see what difference the course would make.35
Susan and her granddaughter Jessica were part of that original study. Susan says she already raised her kids and grandkids in a strict, loving way, but that she learned some useful tricks on Brody’s course, like the reward jar. Whereas Jessica’s older brother Kevin is in and out of jail, Jessica, now 24, did well in school and is at art college in Atlanta studying design and marketing. Susan proudly shows me one of Jessica’s paintings on the wall—it’s beautiful, showing two tall African women and a child, silhouetted against red earth, black hills and a yellow sky.
When he looked across all 700 families, Brody found that whereas parent-child relationships in the control group declined in the months following the course, in SAAF families, these relationships got stronger. This in turn improved behavior: after five years, the SAAF kids were drinking only half as much as the controls.
But was there any lasting effect on physiology? To answer that question, Brody recently collaborated with Northwestern University’s Greg Miller. The pair collected blood samples from nearly 300 of the families after eight years, when the kids were 19, and measured six different inflammation markers. Those in the SAAF group had significantly lower levels of every single one.36 The effect was strongest for the most disadvantaged families, and it was mediated by changes in parenting: the more parents had shifted towards the nurturant-involved style, the lower their kids’ inflammation.
It was a stunning result. Years later, long after these children had left home, this short intervention at age 11 was still dramatically affecting their biology. Miller and Brody are continuing to follow the trial participants, to see whether these differences in inflammation levels do indeed translate into health benefits as they age.
Across town from Susan’s house, Monica and her teenage daughter Takisha have just finished the SAAF course when I visit. Monica says the classes have helped her to think about how to communicate with her daughter more positively, such as when Takisha said she wanted to be a singer. “She really don’t have a voice for singing,” says Monica. “But I didn’t realize I was tearing her down by saying that. This gave me another way to talk to her about the singing and not make her feel bad, to help her see that she has other options.”
Nurturant parenting might have reduced inflammat
ion levels in the SAAF study by influencing health behaviors; that’s something Miller wants to look at more. But the young people in the two groups didn’t differ in body weight or rates of smoking. Instead, he thinks the communication skills training highlighted by Monica is at least part of the explanation. “I suspect that it helped forge relationships and communication strategies between parents and their children that still are to this day a source of support for the kids.”37
Monica feels that it’s too late to change her own situation, but hopes she can support Takisha to live a full life. “I want her to have opportunities, to go see the world. I don’t think that’s too much to ask.”
The primary aim of the SAAF course is to help make that happen—showing children like Takisha how to build a strong self-image and resist peer pressure, and helping parents like Monica to support their kids through tough circumstances. If Takisha can stay out of trouble and do well in school now, she has a better chance of one day going to college and building a future career. But the results of Brody and Miller’s trial suggest that strengthening Monica and Takisha’s bond might do much more than that. By making Takisha more resilient to the biological effects of adversity, it might protect her against chronic disease for the rest of her life.
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BRODY’S WORK shows that intervention in childhood might be able to halt the trajectory of stress sensitivity before it leads to chronic disease. But what if we miss that window? Seven hundred miles north of Milledgeville, researchers are working to strengthen social connections at the opposite end of life, among elderly residents of inner-city Baltimore.
We’ve already heard how as we get older, the brain’s prefrontal cortex, crucial for self-regulation, rational thinking and social relationships, starts to decline more rapidly than other parts of the brain—a process that is accelerated in people who are lonely or chronically stressed and that ultimately leads to dementia.38 Michelle Carlson, a neuroscientist at Johns Hopkins Bloomberg School of Public Health, Maryland, was looking for ways to slow that decline. Old people tend to be isolated and sidelined, becoming less and less engaged in the community as they age. Carlson wondered what would happen if they were immersed instead in a rich social environment.
