Gene-environment interaction analysis of serotonin system markers with adolescent depression

Mol Psychiatry. 2004 Oct;9(10):908-15. doi: 10.1038/


We report analyses from a study of gene-environment interaction in adolescent depression. The sample was selected from 1990 adolescents aged 10-20 years: those with depression symptoms in the top or bottom 15% were identified and divided into high or low environmental risk groups. DNA was obtained from 377 adolescents, representing the four quadrants of high or low depression and high or low environmental risk. Markers within, or close to, each of the serotonergic genes 5HTT, HTR2A, HTR2C, MAOA (monoamine oxidase type A) and tryptophan hydroxylase (TPH) were genotyped. Environmental risk group was a nonsignificant predictor and sex was a significant predictor of the depression group. HTR2A and TPH significantly predicted the depression group, independent of the effects of sex, environmental risk group and their interaction. In addition, there was a trend for an effect of 5HTTLPR, which was significant in female subjects. Furthermore, there was a significant genotype-environmental risk interaction for 5HTTLPR in female subjects only, with the effect being in the same direction as another recent study, reaffirming that an important source of genetic heterogeneity is exposure to environmental risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Child
  • Depression / etiology*
  • Depression / genetics
  • Environment*
  • Family Health
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Life Change Events
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Transport Proteins / genetics
  • Monoamine Oxidase / genetics
  • Nerve Tissue Proteins / genetics
  • Promoter Regions, Genetic / genetics
  • Psychology, Adolescent*
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptor, Serotonin, 5-HT2C / genetics
  • Risk
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Sex Factors
  • Surveys and Questionnaires
  • Tryptophan Hydroxylase / genetics


  • Biomarkers
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Tryptophan Hydroxylase
  • Monoamine Oxidase