Abstract
Background: Child abuse and genotype interact to contribute to risk for depression in children. This study examined gene-by-gene and gene-by-environment interactions. Methods: 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. Results: 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. Conclusions: 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.
Original language | English (US) |
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Pages (from-to) | 673-680 |
Number of pages | 8 |
Journal | Biological psychiatry |
Volume | 59 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2006 |
Externally published | Yes |
Keywords
- 5-HTTLPR
- BDNF
- Child abuse
- Depression
- Gene-environment interactions
- Gene-gene interactions
ASJC Scopus subject areas
- Biological Psychiatry