Scientists begin to unravel the long-lasting biological effects of early life adversity, social isolation
Scientists are beginning to tease apart how stress, social isolation, and adverse early life experiences can have lifelong biological effects that lead to behavior and mental health problems, drawing on experiments on laboratory animals and studies of children raised in Romanian orphanages.
Researchers at Boston Children’s Hospital reported Thursday that mice raised in social isolation have immature versions of cells that normally help signals travel rapidly within the brain. In July, another team of researchers at the hospital found that children raised in an institutionalized setting had smaller amounts of two types of brain tissue compared with those who weren’t, but also saw hints that a degree of rescue was possible: in foster care, children’s brains seemed to be able to catch up.
For years, psychologists have known that neglect, isolation, and abuse can have lingering negative effects, including difficulties with language, attention, or social interactions. Neuroscientists have long known that there is a “critical period’’ when the brain is rapidly changing and also most vulnerable. Now, a growing cadre of scientists from a variety of disciplines are beginning to reexamine such behaviors in a search for the biological roots of lasting dysfunction. The hope is that knowledge of what happens at the cellular and genetic level might help shape future policy, behavioral interventions, or even drugs.
“We are understanding — starting to understand — the anatomical structure and molecular basis for what people have seen as the effects of experience in humans,’’ said Gabriel Corfas, a professor of neurology at Harvard Medical School and Children’s Hospital who led the mouse study. “The more we undersand the mechanism, the closer we are going to be to finding tools to either be able to do early diagnosis of problems, or finding people at risk based on genetic factors, but also to develop potential treatments.’’
The question is a complicated one to study. Experiments in animals can provide only a rudimentary insight into the complex process of human brain development. The range of experiments and brain measurements that can be made in young children are, for obvious ethical reasons, limited. But with brain imaging tools, genetics, and other experiments, scientists are beginning to unravel the biological reasons for the lasting impact of childhood experience and looking for ways to better reverse, diagnose, or identify those at greatest risk.
In a study published Thursday in the journal Science, Corfas exposed mice to social isolation or a normal or enriched environment shortly after they were weaned. Isolated mice did poorly on tests of social interaction and working memory compared with the other mice. He also found that two weeks of social isolation could permanently alter behavior and the brain structure of a key region of the brain, called the prefrontal cortex, involved in complex cognitive processes. By genetically modifying mice, he began to untangle the molecular process in the brain through which social experience has its beneficial effects. Reimmersing the mice in a stimulating or normal environment did not repair the problem.
Dr. Margaret Sheridan, an instructor at Harvard Medical School who also works at Children’s Hospital with Dr. Charles Nelson, said the results dovetail nicely with what she found through imaging studies of the brains of Romainian orphans who were randomized to receive foster care or not. Children who were never institutionalized had greater amounts of gray matter, the brain cells involved in perception, movement, speech, and thinking, and of white matter, which is involved in brain connections, compared with children who were raised in institutions.
“It’s great to see this in the mouse — you have so much control and you can find much more specifically what is going on,’’ Sheridan said. “It’s really exciting to see someone drill down and get at the mechanisms of why there might be differences in white matter after social isolation.’’
Li-Huei Tsai, the director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology said that the study also raises a slew of other questions, about what precise biological mechanism causes the brain differences to persist.
The Picower Institute held a scientific symposium this spring focused on understanding the biological effects of early life stresses, and investigators there hope to focus future research on the the mechanisms that underlie such problems more often seen as social issues, such as adverse early experiences or social isolation.
John T. Cacioppo, director of the Center for Cognitive and Social Neuroscience at the University of Chicago, has long studied the effects of social isolation and said in an e-mail that the negative effects have been shown on organisms that range from the lifespan of fruit flies to post-stroke survival in mice to human health. The body of evidence makes it clear, he said, that social behavior and processes have shaped the evolution of the brain and nervous system.
Studies have shown that even the perception of social isolation has been shown to have damaging results, he said. He pointed to one study that found participants who received feedback after filling out a personality questionnaire intended to make them envision future isolation did worse on a test of mental ability than those who received no feedback or general bad news.
“Bad news itself was not enough to cause the disruption, only bad news about social connection,’’ Cacioppo wrote.
Already, researchers are attempting to bridge the gap between animal studies and the evidence that early childhood experience can affect adults. A group of Canadian researchers have shown in animal studies that disruptions in maternal care can alter the way genes are regulated and increase animals’ vulnerability to stress. A 2009 post-mortem study of suicide victims who had experienced childhood abuse or not showed analagous genetic changes in people who experienced abuse as children.
“Data suggest these things exist, that genes do reflect stress early in life,’’ said Moshe Szyf, a professor of pharmacology at McGill University who was involved in that work. “Could we reverse them? Could we shift the critical period of isolation by treating these animals? I think there’s going to be lot happening in mental health and behavior, both using drugs and using behavioral interventions.’’
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