Publication

Identifying genetic predictors of depression risk: 5-HTTLPR and BDNF Val66Met polymorphisms are associated with rumination and co-rumination in adolescents

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Last modified
  • 05/21/2025
Type of Material
Authors
    Lindsey B. Stone, Brown UniversityJohn E. McGeary, Brown UniversityRohan Palmer, Emory UniversityBrandon E. Gibb, Binghamton University State University of New York
Language
  • English
Date
  • 2013-12-18
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2013 Stone, McGeary, Palmer and Gibb.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-8021
Volume
  • 4
Issue
  • NOV
Start Page
  • 246
Grant/Funding Information
  • Support for this research was provided in part by the National Institute of Child Health and Human Development grants HD048664 and HD057066 awarded to Dr. Gibb, the Medical Research Service of the Department of Veteran Affairs Shared equipment grants (ShEEP) and a shared equipment grant (S10RR023457) from the National Center for Research Resources (NCRR) awarded to Dr. McGeary, and AA021113 from the National Institute on Alcohol Abuse and Alcoholism awarded to Dr. Palmer.
Abstract
  • Background: Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associations to cognitive and interpersonal endophenotypes of depression (rumination and co-rumination), and further exploring developmental and sex moderation. Method: In Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during the child's lifetime were recruited from the community. Replication tests were carried out in Study II, a sample of 87 youth with similar recruitment. Results: In Study I, the Val66Met single-nucleotide polymorphism (SNP) was associated with rumination in adolescents, but not children, such that adolescents homozygous for the Val allele reported higher rumination levels. Further, a cumulative genetic score (CGS) (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination, specifically among adolescent girls. Both genetic associations maintained significance after covarying for current depressive symptomology, and the other endophenotype. Finally, both genetic associations exhibited similar effect sizes in Study II, although results did not reach statistical significance. Conclusions: Results replicate a previously reported association between the brain derived neurotrophic factor (BDNF) Val allele and rumination in adolescents, and provide preliminary support for a CGS predictive of co-rumination in adolescent girls. The current study indicates that candidate genes may demonstrate utility as consistent genetic markers of depression risk when focused on specific phenotypes, and supports the need to explore potential differential effects of developmental stage and sex. However, given the small sample sizes and possibility of chance findings, these results should be interpreted with caution pending replication.
Author Notes
  • Correspondence: John E. McGeary, Providence VA Medical Center, Research Service, Bldg 35, 803 Chalkstone Ave., Providence, RI 02908-4799, USA e-mail: john_mcgeary@brown.edu
Keywords
Research Categories
  • Biology, Genetics
  • Psychology, Developmental

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