title: Research review: gene-environment interaction research in youth depression - a systematic review with recommendations for future research.
abstract: BACKGROUND
  Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions (GxE). However, there has been no systematic review of GxE in youth depression to date.
  
  
  METHODS
  The goal of this article was to systematically review evidence on the contribution of GxE to the risk of child and adolescent depression. Through a search of PubMed and PsycINFO databases to 1 April 2010, we identified 20 candidate gene-environment interaction studies focused on depression in youth (up to age 26) and compared each study in terms of the following characteristics: research design and sample studied; measure of depression and environment used; genes explored; and GxE findings in relation to these factors.
  
  
  RESULTS
  In total, 80% of studies (n = 16) found at least one significant GxE association. However, there was wide variation in methods and analyses adopted across studies, especially with respect to environmental measures used and tests conducted to estimate GxE. This heterogeneity made it difficult to compare findings and evaluate the strength of the evidence for GxE.
  
  
  CONCLUSIONS
  The existing body of GxE research on depression in youth contains studies that are conceptually and methodologically quite different, which contributes to mixed findings and makes it difficult to assess the current state of the evidence. To decrease this heterogeneity, we offer 20 recommendations that are focused on: (a) reporting GxE research; (b) testing and reporting GxE effects; (c) conceptualizing, measuring and analyzing depression; (d) conceptualizing, measuring and analyzing environment; (e) increasing power to test for GxE; and (f) improving the quality of genetic data used. Although targeted to GxE research on depression, these recommendations can be adopted by GxE researchers focusing on other mental health outcomes.
authors.affiliation: Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA. erindunn@hsph.harvard.edu
authors.forename: Erin C
authors.initials: EC
authors.lastname: Dunn
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.forename: S V
authors.initials: SV
authors.lastname: Subramanian
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Sandro
authors.initials: S
authors.lastname: Galea
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
mesh_terms: D000293:Adolescent; D000375:Aging; D002648:Child; D003863:Depression / Q000235:genetics* / Q000523:psychology*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D012107:Research Design / Q000639:trends*