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Biol Psychiatry. 2006 Apr 15;59(8):673-80. Epub 2006 Feb 3.

Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children.

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  • 1Child and Adolescent Research and Education Program, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA. joan.kaufman@yale.edu



Child abuse and genotype interact to contribute to risk for depression in children. This study examined gene-by-gene and gene-by-environment interactions.


The study included 196 children: 109 maltreated and 87 nonmaltreated comparison subjects. Measures of psychiatric symptomatology and social supports were obtained using standard research instruments, and serotonin transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor (BDNF) (variant val66met) genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled by means of ancestral proportion scores computed based on genotypes of ancestry informative markers in the entire sample.


There was a significant three-way interaction between BDNF genotype, 5-HTTLPR, and maltreatment history in predicting depression. Children with the met allele of the BDNF gene and two short alleles of 5-HTTLPR had the highest depression scores, but the vulnerability associated with these two genotypes was only evident in the maltreated children. A significant four-way interaction also emerged, with social supports found to further moderate risk for depression.


To the best of our knowledge, this is the first investigation to demonstrate a gene-by-gene interaction conveying vulnerability to depression. The current data also show a protective effect of social supports in ameliorating genetic and environmental risk for psychopathology.

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