Journal of Abnormal Child Psychology

, Volume 41, Issue 2, pp 281–294 | Cite as

5-HTTLPR X Stress in Adolescent Depression: Moderation by MAOA and Gender

  • Heather A. Priess-Groben
  • Janet Shibley HydeEmail author


Depression surges in adolescence, especially among girls. Most evidence indicates that the short allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) interacts with stress to influence the onset of depression. This effect appears to be less robust in adolescents, particularly among boys, and may be moderated by other genetic polymorphisms. Seeking to explain the adolescent gender difference in depression, this study examined the effects of 5-HTTLPR (rs25531), the monoamine oxidase A-upstream variable number tandem repeat (MAOA-uVNTR), and negative life events (NLE). A community-based longitudinal sample of 309 adolescents reported depressive symptoms and NLE at ages 11, 13, and 15. 5-HTTLPR and MAOA-uVNTR genotypes were ascertained via buccal swabs. A significant four-way interaction of 5-HTTLPR, MAOA-uVNTR, NLE at age 13, and gender predicted depressive symptoms at age 15. Girls were most likely to exhibit elevated depressive symptoms when experiencing NLE if they possessed low-expression MAOA-uVNTR alleles and short 5-HTTLPR alleles, whereas low-expression MAOA-uVNTR alleles but long 5-HTTLPR alleles were implicated in boys. The results indicate that the commonly reported 5-HTTLPR by stress interaction for depression may be limited to individuals with low-expression MAOA-uVNTR alleles. These data also provide new evidence that the short allele of 5-HTTLPR confers susceptibility to stress differently for females compared with males.


Depression Adolescent development Gender differences Behavioral genetics 



This research was supported, in part, by Award Number F31MH084476 from the National Institute of Mental Health to Heather A. Priess-Groben. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. This research was also supported by a University of Wisconsin Graduate School grant to Janet Shibley Hyde.

We thank Lyn Abramson and Luke Hyde for their comments on an earlier draft.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Heather A. Priess-Groben
    • 1
    • 2
  • Janet Shibley Hyde
    • 1
    Email author
  1. 1.Department of PsychologyUniversity of Wisconsin—MadisonMadisonUSA
  2. 2.University of MichiganAnn ArborUSA

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