Child's Telomeres May Tell of Early-Life Adversity

Shortening of telomeres, specialized nucleoprotein complexes located at the end of chromosomes that act as buffers and promote chromosomal stability, may be a cellular-level biomarker of early-life adversity, according to a report in the May 10 Molecular Psychiatry.

This new finding emerges from the ongoing study of a remarkable group of children who have participated in Romania's first foster-care program.

Their group history began in 2000, the year Nathan Fox, Ph.D., a professor of human development at the University of Maryland, and colleagues from Harvard and Tulane universities, created the Bucharest Early Intervention Project (BEIP) with a MacArthur Foundation Grant. The project initially aimed to address the needs of the large number of children living in maternity hospitals and orphanages in post-Communist Romania, where there was no foster-care system.

Fox and his colleagues identified a group of 136 children aged 6 months to 30 months living in six Romanian orphanages. In a randomized clinical trial, half of the children were moved into newly created supervised foster-care homes, while the rest remained in orphanages. Positive results were so quick and so dramatic that Romania soon set up its own foster-care network to get children out of institutions. At age 8, only 14 of the children studied remained in orphanages.

Credit: Paula Burch-Celentano, Tulane University

Studies of the BEIP children have led to multiple publications addressing the brain and behavioral development of institutionalized children. In this latest contribution, Stacy Drury, M.D., Ph.D., an assistant professor of psychiatry and neurology and an assistant professor of pediatrics at Tulane University School of Medicine, and her colleagues hypothesized that the cumulative amount of time a child spent in institutional care in early life would be inversely related to telomere length in middle childhood and that children who had spent a greater percentage of their early life in institutional care would have significantly shorter telomere length than children who had less exposure to institutional care.

"Shortened telomeres confer a host of negative health outcomes, including cardiovascular disease, diabetes, and cognitive decline," Drury told Psychiatric News. Acceleration of the cellular aging process occurs with psychological distress, and telomere shortening may represent one mechanism by which early adversity is translated into increased morbidity and mortality across health indices, Drury and colleagues explained in their report.

DNA samples were collected from the children from ages 6 to 10. The researchers then quantified the institutional exposure of each child at baseline and at 54 months of age. "We have incredibly detailed records for each child," said Drury. "It's a testament to the initial study design that we can count the number of days of institutional care for each child."

They found that children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified the effect: The total percentage of time in institutional care at baseline significantly predicted telomere length in girls, whereas for boys, the total amount of institutionalization at 54 months was most predictive of telomere length in middle childhood.

"This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children," said the researchers.

Drury said she hopes to learn more about the long-term changes in these children. "We have just received funding to do a longitudinal study of these same children at age 12," she noted. "We know these kids took an ‘early hit’ to their telomeres, so now we're asking if those telomeres will be shorter forever. Is there a wide open window, where we can make changes in the caregiving relationship and slow or reverse the changes? Or is there a critical window, after which repair can't occur?"

Drury and her colleagues discussed the implications of permanent damage to the telomeres of their study subjects: "If longitudinal studies of telomere length in children exposed to early adversity reveal that children exhibit more rapid reductions in telomere length, despite environmental enhancement, this may provide greater understanding for not only the lasting negative impact of early adversity across the lifespan, but also the delayed onset of some of the negative health consequences, as a critical telomere-length difference may not be observable until later in life," they said. "Approaches to increase the plasticity of epigenetic regulation, as well as intensive focus on early interventions and exposure to enhanced early environments, would then become even more critical areas of research."

"I feel really lucky to be working with this project," said Drury. "It's an amazing study database. Seeing at the level of DNA just how these adversities can impact children shows us how much we really need to focus on and protect the caregiving relationships in every child's life."

The research was supported by the Harvard Center for the Developing Child, the John D. and Catherine T. MacArthur Foundation Research Network on "Early Experience and Brain Development," the Binder Family Foundation, and the Center for Training Research and Education at Tulane University School of Medicine.

"Telomere Length and Early Severe Social Deprivation: Linking Early Adversity and Cellular Aging" is posted at <www.nature.com/mp/journal/vaop/ncurrent/abs/mp201153a.html>.