Interacting effects of genetic predisposition and depression on adolescent smoking progression

Am J Psychiatry. 2004 Jul;161(7):1224-30. doi: 10.1176/appi.ajp.161.7.1224.


Objective: The goal of the present study was to identify specific genetic associations with smoking progression in adolescents and to determine whether these genetic effects on smoking practices are potentiated by depression symptoms.

Method: Effects of dopamine transporter (SLC6A3) and dopamine receptor (DRD2) genetic variants on smoking progression were evaluated in a cohort of 615 adolescents, including those who had never smoked, and in a subgroup including only adolescents who had been exposed to nicotine (i.e., smoked at least a puff of a cigarette) (N=292). These adolescents were followed from 9th to 11th grade. Depression symptoms were also assessed.

Results: In the model of adolescents with a previous smoking experience, the likelihood of progressing to a higher level of smoking by the 11th grade increased almost twofold with each additional DRD2 A1 allele. The likelihood of smoking progression with each additional A1 allele was more pronounced among adolescents with substantial depression symptoms. The model including never-smokers revealed no significant genetic effects. Neither model revealed effects of SLC6A3.

Conclusions: These results provide the first evidence, to the authors' knowledge, for an association of the DRD2 A1 allele with smoking progression among adolescents. This effect is potentiated by depression symptoms. These effects appear to be specific to adolescents who have had at least some nicotine exposure (i.e., at least a puff of a cigarette).

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adolescent Behavior / psychology*
  • Comorbidity
  • Depressive Disorder / diagnosis
  • Depressive Disorder / epidemiology*
  • Dopamine Plasma Membrane Transport Proteins
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / genetics
  • Models, Genetic
  • Nerve Tissue Proteins / genetics
  • Odds Ratio
  • Personality Inventory
  • Polymorphism, Genetic
  • Receptors, Dopamine / genetics
  • Risk-Taking
  • Smoking / epidemiology
  • Smoking / genetics*
  • Smoking / psychology
  • Surveys and Questionnaires
  • Virginia / epidemiology


  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine
  • SLC6A3 protein, human