Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children.
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.
Kaufman
Joan
J
Child and Adolescent Research and Education Program, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA. joan.kaufman@yale.edu
Yang
Bao-Zhu
BZ
Douglas-Palumberi
Heather
H
Grasso
Damion
D
Lipschitz
Deborah
D
Houshyar
Shadi
S
Krystal
John H
JH
Gelernter
Joel
J
D000293:Adolescent; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D003863:Depression / Q000235:genetics* / Q000523:psychology*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D012944:Social Support; D011795:Surveys and Questionnaires; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008715:Methionine; D014633:Valine