Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use

J Abnorm Psychol. 2016 May;125(4):565-75. doi: 10.1037/abn0000143. Epub 2016 Feb 4.


Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent nonspecific neurobiological underpinnings for an externalizing pathway to addiction. (PsycINFO Database Record

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aggression
  • Alcohol Drinking / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Juvenile Delinquency
  • Longitudinal Studies
  • Male
  • Marijuana Smoking / genetics
  • Models, Psychological
  • Norepinephrine Plasma Membrane Transport Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Dopamine D4 / genetics
  • Receptors, GABA-A / genetics
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Social Behavior Disorders / genetics*
  • Substance-Related Disorders / genetics*
  • Temperament*


  • DRD4 protein, human
  • GABRA2 protein, human
  • GABRA6 protein, human
  • Norepinephrine Plasma Membrane Transport Proteins
  • Receptors, GABA-A
  • SLC6A2 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Dopamine D4