In this study, we demonstrated in Romanian children an association between shorter relative telomere length in middle childhood and increased exposure to early institutional care. These results offer further support for the hypothesis that alterations in cellular aging may be one pathway by which early adversity impacts health outcomes.17,20,22
These findings complement recent data that early childhood experiences, including abuse, childhood adversity and childhood serious illness, are associated with shorter relative telomere length in adults. This study extends these findings to include adversity as a result of exposure to the deprivation associated with early institutional rearing and is the first study to demonstrate that the association between adversity and telomere length is detectable during childhood.19,44
Our findings are also consistent with studies that demonstrate that epigenetic alterations, such as methylation, are associated with other forms of early adversity including child abuse and prenatal maternal depression.45-50
Interestingly, in longitudinal studies examining methylation, early childhood appears to be a time period of more extensive epigenetic remodeling.42,51,52
Because epigenetic regulation of telomere length also is established in early childhood, these findings raise an intriguing and testable hypothesis. That is, early adversity results in widespread changes in methylation 53
that affect both gene specific regulation and telomere length regulation, thereby resulting in an increased risk due to not only altered gene regulation, but also decreased telomere length. Although later environmental changes, such as placement in an enriched environment, can occur, these may or may not alter established epigenetic patterns. Reduced telomere length, and perhaps a greater rate of telomere length decline over time due to epigenetically established regulation of telomere length attrition, may persist even after the adverse environment is ameliorated. 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 crtical telomere length difference may not be observable until later in life.8
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.
The second important contribution of this study is the identification of gender differences in the interaction between telomere length and institutional exposure at different time points. This finding adds to the other gender difference detected in the Bucharest Early Intervention Project study, where foster care was more effective in reducing psychiatric symptomatology and disorders in females than in males at 54 months of age.38
One hypothesis to explain these findings is the existence of a gender-specific sensitive period to early adversity. Alternatively, gender differences in stress responsiveness, and thus the impact of adversity at the cellular level, may exist. Although these gender findings clearly need to be replicated, support for gender differences in stress responsiveness have been demonstrated.54,55
Several limitations to this study exist. First, DNA was collected over a 3-year age range. Although all analyses controlled for the age at which telomere DNA was collected, future studies in children should examine telomere length within a reduced age range, though limited differences in telomere length during later childhood and adolescence has been demonstrated. Second, we had a limited ability to assess for prenatal exposures, which might be differentially associated with placement in the institution, as well as independently contribute to the differences in telomere length. To address this potential confounder, we controlled for birth weight as a proxy for prenatal health. Third, although we postulate that telomere length is related to the overall adversity associated with institutional care, we cannot exclude the possibility that the causative exposure was a particular aspect of their care that is highly correlated with percent time, such as nutritional status. Malnutrition has been associated with institutional care and postulated to be associated with the known deficits in physical growth demonstrated in institutionalized children.56
Thus, telomere shortening may not be due to, per se, the total cumulative exposure to severe psychosocial deprivation, but rather, exposure to a particular aspect of this type of experience. Future studies examining the association of telomere length in children with well-defined measurements of community, household and individual level exposures including nutrition, toxins and adverse life events may refine this relation. Still, our findings are in agreement with previous studies demonstrating associations between telomere length and childhood adversity providing support for our main hypothesis that the cumulative exposure of institutionalization is driving this association. Fourth, this is the first study to examine the association between early adversity and telomere length, using buccal swab DNA and not DNA extracted from peripheral blood. Although differences in telomere length between cell types (that is, between lymphocytes and epithelial cells) exist, there is also evidence to support that correlation exists between telomere length in different cell types, and a previous study has demonstrated that telomere length from buccal cell DNA is associated with increased risk of Alzheimer’s disease.57
The establishment of telomere length extracted from DNA samples obtained non-invasively as a valid biomarker of early experience, and a predictor of negative health outcomes, would represent a significant advancement for the field; thus, it is important to note that our findings are consistent with previous studies of the impact of early childhood events on telomere length in DNA from lymphocytes or peripheral blood mono-nuclear cell.
The biological significance of shorter telomere length in children is unknown. Although in adults, shortened telomere length is associated with increased rates of cardiovascular disease, elevated rates of cancer and cognitive decline, these associations have not been demonstrated in children. Few longitudinal studies of telomere length have been done and little is known about the ‘typical’ rate of telomere change for children, though studies have demonstrated a rapid decline in telomere length in early childhood.41,42
Future longitudinal studies of telomere length in children exposed to a range of adversities would be highly relevant.
Although evidence of the negative health impact of early and chronic toxic stress continues to accumulate, the biological mechanism by which psychological stress is translated into negative health outcomes is not yet well defined. Future studies are needed to examine the association between telomere length, institutional care and other outcomes including cognitive, psychological and neurobiological measures. It will be interesting to examine the rate of telomere length attrition longitudinally and determine whether early adverse experiences lead to a persistent accelerated rate of telomere decline or instead result in an initial ‘scar’ on telomere length without impacting the rate of telomere attrition over the life course. Clear evidence that early adversity has lasting negative health consequences exists; however, objective quantification of cumulative adversity exposure has been challenging. Telomere length may represent an objective epigenetic biomarker of early adversity and putatively one mechanism by which early adversity gets ‘under the skin’ and into our biology.