Childhood maltreatment is a major public health problem that is linked to high rates of mood and anxiety
disorders, and a growing literature documents risk for conditions such as obesity, cardiovascular disease,
asthma, and diabetes. These conditions are often chronic and severe, and they exact tremendous costs in
terms of suffering, disability, treatment, and loss of productivity. Existing social services programs for
maltreated children suffer from a lack of available data regarding which children are at risk for which psychiatric
outcomes and from a lack of focus on risk for other adverse health conditions. In order to develop more
targeted and specific interventions and treatments, we need to better understand the trajectory and
mechanisms of risk and protective factors. There is evidence that the pathophysiological effects of adversity
begin early in life, and that clinical or sub-clinical effects of major adversity can be seen in childhood.
Maltreated children, particularly those living in poverty, are at especially high risk for early-onset disorders, but
childhood maltreatment is usually clandestine and therefore very difficult to study. This study involves a 5-year
follow up assessment of a sample of impoverished maltreated preschool-aged children and demographically
matched non-maltreated children. Existing data include details of maltreatment experiences, socioeconomic
factors and neighborhood characteristics, and additional adversities such as parental loss, homelessness, and
traumas. Data on protective factors include home and neighborhood resources, parenting, and social services.
In our initial work, adverse experiences were linked to depressive symptoms and blunted cortisol levels, and
epigenetic changes to glucocorticoid signaling genes were significant mediators of these relationships. We also
found that levels of salivary inflammatory cytokine IL-1β increased as a function of stress exposure. In our
work with healthy un-medicated adults, we have shown that attenuated plasma cortisol concentrations are
linked to several indices of the metabolic syndrome, and that childhood stress and psychiatric conditions are
associated with telomere shortening and a measure of mitochondrial DNA proliferation, indicators of cellular
stress and aging. In the proposed 5-year follow-up, we will test a model of risk and resilience for medical and
psychiatric outcomes obtained from medical records, from interviews and questionnaires completed by children
and caregivers, and tests of cognitive/affective, metabolic, endovascular, and pulmonary function. Behavioral,
social, and biological mechanisms of risk and resilience will be examined. Statistical models will be aimed at
identifying profiles of risk and protective factors and biological mechanisms that are most likely to be useful
targets for intervention.