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).
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.
Department of Psychiatry, University of Regensburg, Regensburg, Germany. monika.johann@bzk.uni-regensburg.de
Monika
M
Johann
Gabriela
G
Bobbe
Albert
A
Putzhammer
Norbert
N
Wodarz
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D000987:Antisocial Personality Disorder / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics*; D015897:Comorbidity; D017831:Diagnosis, Dual (Psychiatry) / Q000706:statistics & numerical data; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010641:Phenotype; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044405:Receptor, Serotonin, 5-HT2C; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins