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Scientists begin to unravel long-term effects of early adversity

Scientists have begun to tease apart how stress, social isolation, and deprivation early in life can harm children’s brains and lead to behavior and mental health problems later in life.

Researchers at Boston Children’s Hospital reported last week that mice raised in isolation not only behave differently, they have thinner insulation around brain cells in a key region of the brain. These changes cause signals to travel more sluggishly through the brain and appear to be irreversible.

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In July, another team at the hospital found that children raised in Romanian orphanages had smaller amounts of two types of brain tissue than those who weren’t, but the researchers also saw hints that a degree of rescue was possible: In foster care, one type of tissue involved in brain connectivity 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 found that there is a formative “critical period” early in life when the brain — including the infrastructure for language and vision — is being molded by experience, or by deprivation.

Now, a growing cadre of scientists from a variety of disciplines is trying to understand the connections among early social experience, biology, and developmental problems that lead to long-lasting dysfunction. The hope is that knowledge of what happens at the cellular and genetic level might help shape government child protection policies and social programs and point to behavioral interventions or even drugs that could reverse the damage.

“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 neurology professor at Harvard Medical School and Children’s Hospital who led the mouse study. “The more we understand 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 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 ethical reasons, limited. But brain imaging tools and genetic tools are enabling scientists to explore the issue.

In the study published this month in the journal Science, Corfas exposed mice shortly after they were weaned to one of three environments: social isolation, normal, or enriched. Isolated mice spent significantly less time showing interest in another mouse and did poorly on a memory task, which forced them to learn and remember how to navigate a maze. After two weeks of social isolation, cells that generate an insulating layer were immature in a key region of the brain, called the prefrontal cortex, which is involved in complex cognitive processes. Reimmersing the mice in a socially stimulating environment did not reverse the effects of isolation on their brains or behavior.

Margaret Sheridan, a psychologist at Children’s Hospital, said the results dovetail with what she and colleagues reported this summer in the Proceedings of the National Academy of Sciences in which they used imaging techniques to study the brains of Romanian children.

Some of the children were raised by parents, others raised in institutions, and a third group was raised in orphanages and later put in foster care. Those who had never been institutionalized had greater amounts of gray matter — the brain tissue 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.

But unlike what Corfas found in mice, children who were moved to foster care had greater amounts of white matter, compared with those who remained in orphanages, suggesting their brains could rebound.

The difference illuminates the limitations and the possibilities of animal experiments. Human brain development is a longer and more complex process than in a rodent, but Corfas was also able to unravel much more precisely what is happening, at the level of cells and proteins.

Li-Huei Tsai, director of the Picower Institute for Learning and Memory at Massachusetts Institute of Technology, said the study raises important questions about the precise genetic mechanism that triggers the striking brain changes.

The Picower Institute held a scientific symposium this spring focused on the biological effects of early life stresses, and investigators there hope to focus future research on unraveling the biological repercussions of environmental experiences, ranging from poverty to stress.

John T. Cacioppo, director of the Center for Cognitive and Social Neuroscience at the University of Chicago, said in an e-mail that negative effects of social isolation have been shown in a broad range of organisms. Isolation, he said, shortens the lives of fruit flies, makes mice less likely to recover from a stroke, and in people is associated with negative effects on everything from IQ to blood pressure. The body of evidence makes it clear, he said, that social behavior and processes have shaped the evolution of the brain and nervous system.

“Greater integration of animal and human research should facilitate the translation of basic research efforts to clinically relevant treatments and outcomes,” Cacioppo wrote.

Already, researchers are attempting to bridge that gap. A group of Canadian researchers, in a post-mortem analysis of brains of suicide victims, found in 2009 a particular difference in how a gene involved in stress responses was regulated in those who experienced childhood abuse. Similar changes had been found in rat brains.

“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? . . . I think there’s going to be lot happening in mental health and behavior, both using drugs and using behavioral interventions.”

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.
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