Citation

Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J. Biol. Psychiatry 2006; 59(8): 673-680.

Affiliation

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

Comment In:

Biol Psychiatry 2007;61(9):1112-3; author reply 1113-5

Copyright

(Copyright © 2006, Elsevier Publishing)

DOI

10.1016/j.biopsych.2005.10.026

PMID

16458264

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.

Language: en