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.
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: Laura P Chen; M Hassan Murad; Molly L Paras; Kristina M Colbenson; Amelia L Sattler; Erin N Goranson; Mohamed B Elamin; Richard J Seime; Gen Shinozaki; Larry J Prokop; Ali Zirakzadeh Journal: Mayo Clin Proc Date: 2010-05-10 Impact factor: 7.616
Authors: Elizabeth P Hayden; Daniel N Klein; Lea R Dougherty; Thomas M Olino; Margaret W Dyson; C Emily Durbin; Haroon I Sheikh; Shiva M Singh Journal: Psychol Sci Date: 2010-10-04
Authors: Francesca Cirulli; Andreas Reif; Sabine Herterich; K Peter Lesch; Alessandra Berry; Nadia Francia; Luigi Aloe; Christina S Barr; Stephen J Suomi; Enrico Alleva Journal: Psychoneuroendocrinology Date: 2010-12-09 Impact factor: 4.905
Authors: Nicholas F Wymbs; Catherine Orr; Matthew D Albaugh; Robert R Althoff; Kerry O'Loughlin; Hannah Holbrook; Hugh Garavan; Janitza L Montalvo-Ortiz; Stewart Mostofsky; James Hudziak; Joan Kaufman Journal: Child Abuse Negl Date: 2020-02-14