Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor)

Alcohol Clin Exp Res. 2003 Oct;27(10):1527-34. doi: 10.1097/01.ALC.0000090143.00703.07.


Background: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities.

Methods: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent.

Results: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively.

Conclusions: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alcoholism / epidemiology
  • Alcoholism / genetics*
  • Alcoholism / psychology
  • Antisocial Personality Disorder / epidemiology
  • Antisocial Personality Disorder / genetics
  • Antisocial Personality Disorder / psychology
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Carrier Proteins / genetics*
  • Comorbidity
  • Diagnosis, Dual (Psychiatry) / statistics & numerical data
  • Female
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Phenotype*
  • Receptor, Serotonin, 5-HT2C / genetics*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2C
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins