Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene

Health Psychol. 1998 Jan;17(1):56-62. doi: 10.1037//0278-6133.17.1.56.


This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N = 231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 receptor (DRD4) gene. A significant interaction (DRD4 Genotype x Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission.

Publication types

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

MeSH terms

  • Adult
  • Depression* / genetics
  • Depression* / psychology
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Nicotine / pharmacology*
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4
  • Self Medication*
  • Smoking / epidemiology
  • Smoking / genetics*
  • Smoking / psychology
  • Smoking Cessation


  • DRD4 protein, human
  • Genetic Markers
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Nicotine