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-1? 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.

Public Health Relevance

The proposed study seeks to identify risk and protective profiles for the development of psychiatric and medical conditions in a high-risk sample of children. This involves a follow-up of a study of maltreated and non- maltreated preschool-age children 5 years later at age 8-10. Results of this study will provide insight into the neurobiological markers and mechanisms of illness in children at-risk for depressive and anxiety disorders and other poor health outcomes, and contribute to future treatment and prevention efforts for stress-related disorders.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Maholmes, Valerie
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Butler Hospital (Providence, RI)
United States
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Ridout, K K; Levandowski, M; Ridout, S J et al. (2018) Early life adversity and telomere length: a meta-analysis. Mol Psychiatry 23:858-871
Novick, Andrew M; Levandowski, Mateus L; Laumann, Laura E et al. (2018) The effects of early life stress on reward processing. J Psychiatr Res 101:80-103