Aim: To examine the relationship between a childhood diagnosis of ADHD with or without ODD/CD and the development of later alcohol/drug use disorder (psychoactive substance use disorder(PSUD)) and nicotine dependence in a large European sample of ADHD probands, their siblings and healthy control subjects. Participants, Design,

Setting: Subjects (n=1017) were part of the Belgian, Dutch and German part of the International Multicenter ADHD Genetics (IMAGE) study. IMAGE families were identified through ADHD probands aged 5-15 years attending outpatient clinics, and control subjects from the same geographic areas. After a follow-up period (m: 4.4 years) this subsample was reassessed at a mean age of 16.4 years.

Measurements: PSUD and nicotine dependence were assessed using the Diagnostic Interview Schedule for Children, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test, and Fagerström test for Nicotine Dependence.

Findings: The ADHD sample was at higher risk of developing (Hazard Ratio (HR) = 1.77, 95%CI= 1.05-3.00) and nicotine dependence (HR = 8.61, 95% CI = 2.44-30.34) than healthy controls. The rates of these disorders were highest for ADHD youth who also had conduct disorder, but could not be accounted for by this comorbidity. We did not find an increased risk of developing PSUD (HR = 1.18, 95% CI = .62-2.27) or nicotine dependence (HR = 1.89, 95% CI = .46-7.77) among unaffected siblings of ADHD youth.

Conclusions: A childhood diagnosis of attention deficit hyperactivity disorder is a risk factor for psychoactive substance use disorder and nicotine dependence in adolescence and comorbid conduct disorder, but not oppositional defiant disorder, further increases the risk of developing psychoactive substance use disorder and nicotine dependence.