title: Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children.
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.
authors.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
authors.forename: Joan
authors.initials: J
authors.lastname: Kaufman
authors.forename: Bao-Zhu
authors.initials: BZ
authors.lastname: Yang
authors.forename: Heather
authors.initials: H
authors.lastname: Douglas-Palumberi
authors.forename: Damion
authors.initials: D
authors.lastname: Grasso
authors.forename: Deborah
authors.initials: D
authors.lastname: Lipschitz
authors.forename: Shadi
authors.initials: S
authors.lastname: Houshyar
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: 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
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008715:Methionine; D014633:Valine