In perhaps the most famous study of childhood neglect, researchers have closely tracked the progress, or lack of it, in children who lived as infants in Romania's bleak orphanages and are now teenagers. A new analysis now shows that these children, who display a variety of behavioral and cognitive problems, have less white matter in their brains than do a group of comparable children in local families. The affected brain regions include nerve bundles that support attention, general cognition, and emotion processing. The work suggests that sensory deprivation early in life can have dramatic anatomical impacts on the brain and may help explain the previously documented long-term negative affects on behavior. But there's some potential good news: A small group of children who were taken out of orphanages and moved into foster homes at age 2 appeared to bounce back, at least in brain structure.

"This is an exciting and important study," says Harvard Medical School psychiatric researcher Martin Teicher, who directs the developmental biopsychiatry research program at McLean Hospital in Belmont, Massachusetts. The "crucial question" of whether children can recover from the setbacks of early adversity had not been answered before, he adds.

The work is based on MRI scans and other measures taken in Romania by researchers at the Bucharest Early Intervention Project (BEIP). The group, headed by neurologist Charles Nelson of Harvard Medical School, was spurred to action by the collapse of Romania's Nicolae Ceauceșcu regime in 1989, which had shunted tens of thousands of unwanted children into state-run orphanages. Nelson says that caretakers in the orphanages worked in factorylike shifts; children might see as many as 17 different caretakers in a week. Infants rarely enjoyed the one-on-one interactions that are considered essential to normal development.

The orphanages have sharply reduced their intake today. But more than a decade ago, when they were still in favor, BEIP's leaders saw a need for humanitarian aid; they also saw a rare opportunity to study the effects of child neglect. Drawing mainly on U.S. government research funding, BEIP offered a limited number of children a chance to move out of orphanages into foster care, providing desperately needed attention. BEIP also worked with Romanian officials to recruit orphans and other local children into clinical studies.

BEIP initially enrolled 136 children in research. Only 69 were involved in the MRI study published online today in JAMA Pediatrics. Of these, 23 were drawn from the group randomly assigned to foster care, 26 from a group assigned to remain in orphanages, and 20 from the local community, as controls. Lead author Johanna Bick, a clinical psychologist at the Boston Children's Hospital, and colleagues in the BEIP group used an MRI technique called diffusion tensor imaging to look at the microstructure of 48 white matter tracts in each child, comparing results at 2 years and 8 years of age.

The analysis found that the children who stayed in orphanages were consistently worse off - with less mature development in four key sets of white matter. The most affected tracts included nerve circuits involved in general cognitive performance, emotion, maintaining attention and executive function, and sensory processing. Another analysis suggested that the foster care group was more like the community group in brain development, but this finding appears to be less robust.

Other nonrandomized studies have reported broad cognitive deficits or reduced white matter in adults and some children who suffered neglect or maltreatment in the past. They highlighted "the same regions that we find affected by early life neglect. These results and those from BEIP converge," Bick claims.

More important, Bick says, the comparison with those children taken in by foster parents suggests that white matter losses may be reversible. What worked in Romania to improve brain development - moving children into a supportive family environment - might work elsewhere as a remedy for child neglect. "This has really important implications," she says: It suggests that the harm that takes place in a family setting may reversible, too.

In a prepared statement, psychiatric researcher Andrea Danese of King's College London praised the study but noted that more research is needed to determine how such changes in white matter are related to changes in behavior.

Bick agrees on that point. "What I'm really interested in investigating right now," she says, "is whether the improvements [seen in the foster children's white matter profiles] actually support improvements in higher order abilities," such as IQ, attention, and control of emotion. BEIP plans to collect new neurological data this year from the Romanian orphans as they turn 16.