How do stressful experiences that happen in early life have such powerful direct effects on poor health decades later? When and how do these experiences become biologically embedded? To address this question, we are following a 1994-95 birth cohort of 2,232 twins (the E-Risk Study). The cohort is well- characterized, environmentally and phenotypically, with assessments at birth, 2,5,7,10,12, and 18 years, and has a dedicated biobank. Our research focuses on exposure to violence, one of the most common and severe sources of human stress. We begin by compiling cumulative dossiers of violence exposure in childhood and adolescence, including child maltreatment, sexual abuse, domestic violence, peer victimization, dating violence, and conventional crime. We then test the hypothesis that young people who are exposed to violence in childhood and adolescence will, by young adulthood, show compromised neuropsychological functioning, telomere erosion, and differential expression and epigenetic regulation of genes involved in the coordination of the stress response and the regulation of immune and inflammatory reactions. A key need in this research is for violence exposure to be disentangled from associated risk factors, including poverty, parents'mental health, and genetic liability. Analyses with the E-Risk cohort will isolat these effects of violence exposure by (a) comparing twins who are discordant for violence exposure on their psychobiological outcomes, (b) studying within-individual changes in psychobiological outcomes, using each child as his or her own control, and ultimately (c) identifying protective factors that mitigate biological embedding of exposure to violence. The E- Risk Study will be the first major developmental-longitudinal cohort study to bring together detailed assessments of multiple kinds of exposure to violence and multiple stress biomarkers, in order to characterize the mechanisms through which violence-exposed children may acquire lasting vulnerability to disease.

Public Health Relevance

The proposed research aims to uncover the genomic, biological and behavioral mechanisms that account for the enduring disease vulnerability of violence-exposed children and adolescents and to suggest effective interventions before onset of clinical disease.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-K (02))
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Maholmes, Valerie
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Duke University
Schools of Arts and Sciences
United States
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Goldman-Mellor, Sidra; Caspi, Avshalom; Arseneault, Louise et al. (2016) Committed to work but vulnerable: self-perceptions and mental health in NEET 18-year olds from a contemporary British cohort. J Child Psychol Psychiatry 57:196-203
Baldwin, Jessie R; Arseneault, Louise; Odgers, Candice et al. (2016) Childhood Bullying Victimization and Overweight in Young Adulthood: A Cohort Study. Psychosom Med 78:1094-1103
Beckley, Amber L; Caspi, Avshalom; Harrington, Honalee et al. (2016) Adult-onset offenders: Is a tailored theory warranted? J Crim Justice 46:64-81
Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise et al. (2016) The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians. Am J Psychiatry :appiajp201616030333
Matthews, Timothy; Danese, Andrea; Wertz, Jasmin et al. (2015) Social isolation and mental health at primary and secondary school entry: a longitudinal cohort study. J Am Acad Child Adolesc Psychiatry 54:225-32
Fisher, Helen L; Caspi, Avshalom; Moffitt, Terrie E et al. (2015) Measuring adolescents' exposure to victimization: The Environmental Risk (E-Risk) Longitudinal Twin Study. Dev Psychopathol 27:1399-416
Odgers, Candice L (2015) Income inequality and the developing child: Is it all relative? Am Psychol 70:722-31
Fisher, Helen L; Murphy, Therese M; Arseneault, Louise et al. (2015) Methylomic analysis of monozygotic twins discordant for childhood psychotic symptoms. Epigenetics 10:1014-23
Odgers, Candice L; Donley, Sachiko; Caspi, Avshalom et al. (2015) Living alongside more affluent neighbors predicts greater involvement in antisocial behavior among low-income boys. J Child Psychol Psychiatry 56:1055-64
Sugden, Karen; Danese, Andrea; Shalev, Idan et al. (2015) Blood Substrate Collection and Handling Procedures under Pseudo-Field Conditions: Evaluation of Suitability for Inflammatory Biomarker Measurement. Biodemography Soc Biol 61:273-84

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