DOPAMINE (DA) DEFICIT THEORY is the most comprehensible biological model for attention-deficit–hyperactivity disorder (ADHD) children.1 Cytochrome 450 2D6 (CYP2D6), an enzyme that metabolizes endogenous substrates and xenobiotics, also synthesizes DA.2 Here we examined a possible role of the CYP2D6 gene in the comorbidity of oppositional defiant disorder (ODD) in ADHD. We recruited 108 non-related boys and 27 girls meeting DSM-IV criteria for ADHD, aged 6–13 years old (9.30 ± 1.59), and their psychiatric comorbid disorders were determined structurally using the Mini International Neuropsychiatric Interview for Children and Adolescents, a variant of the Mini International Neuropsychiatric Interview.3CYP2D6 gene deletion4 and Pro34Ser (rs1065852) and Ser486Thr (rs1135840)5 were examined as described.
The proportion of single deletion of CYP2D6 gene in the whole ADHD sample was 14.7%, far higher that the 3% reported in another Chinese sample.6 No homozygous deletion of the CYP2D6 gene was found in the present study. On Fisher exact test an association was seen between the single gene deletion and an increased risk of ODD in the whole sample (P = 0.043; odds ratio [OR], 3.27; 95% confidence interval [CI]: 1.11–9.60) and in boys (P = 0.042; OR, 4.27; 95%CI: 1.13–16.11). No associations were found for Pro34Ser and Ser486Thr (data not shown).
Reduced CYP2D6 activity may cause various physiological abnormalities, as seen in schizophrenia patients with neuroleptic drug-induced tardive dyskinesia.7 The present study indicates that deletion of one copy of the CYP2D6 gene, which largely reduced the activity of the enzyme, contributes at least partly to the risk of comorbid psychiatric disorders, probably ODD, in ADHD children.