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Biol Psychiatry. 2010 Jul 15;68(2):209-12. doi: 10.1016/j.biopsych.2010.04.006. Epub 2010 May 31.

Interaction between childhood adversity, brain-derived neurotrophic factor val/met and serotonin transporter promoter polymorphism on depression: the TRAILS study.

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Interdisciplinary Center for Psychiatric Epidemiology, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Kingdom of the Netherlands.



The three-way interaction between the functional polymorphism in the serotonin transporter gene linked promoter region, the val66met polymorphism in the brain-derived neurotrophic factor gene, and childhood adversity in the prediction of depression in children, reported by Kaufman and colleagues in 2006, has only been confirmed in adult samples. This study examines the gene-by-gene-by-environment interaction in an adolescent sample.


In a longitudinal population-based study, depression scores were assessed with the Youth Self Report at ages 11, 13.5, and 16. Pre- and perinatal adversities and childhood events were assessed in a parent interview at age 11. Long-term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected for genotyping at age 16. The study included 1096 complete data sets.


Depression score over the three measurements was not significantly predicted by any interaction between genotypes and childhood adversities.


We were unable to confirm the three-way interaction in a representative, population-based sample of adolescents. The large sample resulted in adequate power, which in combination with the reliability of our measures gives confidence in our findings.

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