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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Childhood maltreatment predicts adult inflammation in a life-course study

Andrea Danese^*, Carmine M. Pariante, Avshalom Caspi^*,,, Alan Taylor^*, and Richie Poulton^¶

*Medical Research Council Social, Genetic, and Developmental Psychiatry Centre and Department of Psychological Medicine, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Departments of Psychology and Neuroscience, Psychiatry, and Behavioral Science, and Institute of Genome Sciences and Policy, Duke University, Durham, NC 27708-0086; and ^¶Dunedin School of Medicine, University of Otago, Dunedin 9015, New Zealand

Communicated by Burton H. Singer, Princeton University, Princeton, NJ, November 30, 2006 (received for review September 20, 2006)

Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between childhood maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR) = 1.80, 95% confidence interval (CI) = 1.26–2.58]. The effect of childhood maltreatment on adult inflammation was independent of the influence of co-occurring early life risks (RR = 1.58, 95% CI = 1.08–2.31), stress in adulthood (RR = 1.64, 95% CI = 1.12–2.39), and adult health and health behavior (RR = 1.76, 95% CI = 1.23–2.51). More than 10% of cases of low-grade inflammation in the population, as indexed by high C-reactive protein, may be attributable to childhood maltreatment. The association between maltreatment and adult inflammation also generalizes to fibrinogen and white blood cell count. Childhood maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.

C-reactive protein | development | epidemiology | risk factor | stress

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0610362104/DC1.

To whom correspondence should be addressed. E-mail: a.caspi{at}iop.kcl.ac.uk

© 2007 by The National Academy of Sciences of the USA

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