TY - JOUR PY - 2006// TI - Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children JO - Biological psychiatry A1 - Kaufman, Joan A1 - Yang, Bao-Zhu A1 - Douglas-Palumberi, Heather A1 - Grasso, Damion A1 - Lipschitz, Deborah A1 - Houshyar, Shadi A1 - Krystal, J. H. A1 - Gelernter, Joel SP - 673 EP - 680 VL - 59 IS - 8 N2 - 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.

Language: en

LA - en SN - 0006-3223 UR - http://dx.doi.org/10.1016/j.biopsych.2005.10.026 ID - ref1 ER -