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Depression, Inflammation, and Clustering of Metabolic Risk Markers

Andrea Danese, MD, MSc; Terrie E. Moffitt, PhD; HonaLee Harrington, BA; Barry J. Milne, PhD; Guilherme Polanczyk, MD, PhD; Carmine M. Pariante, MD, MRCPsych, PhD; Richie Poulton, PhD; Avshalom Caspi, PhD

Arch Pediatr Adolesc Med. 2009;163(12):1135-1143.

Objective  To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems.

Design  A 32-year prospective longitudinal study of a representative birth cohort.

Setting  New Zealand.

Participants  A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study.

Main Exposures  During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation.

Main Outcome Measures  At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels.

Results  Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36-2.62), maltreatment (1.81; 1.38-2.38), or social isolation (1.87; 1.38-2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors.

Conclusions  Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The promotion of healthy psychosocial experiences for children is a necessary and potentially cost-effective target for the prevention of age-related disease.

Author Affiliations: Social, Genetic, and Developmental Psychiatry Centre (Drs Danese, Moffitt, Milne, Polanczyk, and Caspi), and Departments of Child and Adolescent Psychiatry (Dr Danese) and Psychological Medicine (Dr Pariante), Institute of Psychiatry, King's College London, London, England; Departments of Psychology and Neuroscience and Psychiatry and Behavioral Sciences, and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina (Drs Moffitt, Polanczyk, and Caspi and Ms Harrington); and Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (Dr Poulton).

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