BIOLOGICAL CHILD AND ADOLESCENT PSYCHIATRY - SHORT COMMUNICATION Cathechol-O-methyltransferase Val 158 Met polymorphism is associated with disruptive behavior disorders among children and adolescents with ADHD Ange ´lica Salatino-Oliveira • Julia P. Genro • Ana P. Guimara ˜es • Rodrigo Chazan • Cristian Zeni • Marcelo Schmitz • Guilherme Polanczyk • Tatiana Roman • Luis A. Rohde • Mara H. Hutz Received: 30 June 2011 / Accepted: 10 January 2012 Ó Springer-Verlag 2012 Abstract COMT Val 158 Met polymorphism has been associated with both symptoms of attention-deficit/hyper- activity disorder (ADHD) and disruptive behavior disor- ders (DBD): that is, oppositional defiant disorder (ODD) and conduct disorder (CD) often comorbid with ADHD. The aim of this study was to test the association between COMT Val 158 Met polymorphism and the presence of DBD in children with ADHD (n = 516). Homozygous Val/Val children showed a higher prevalence of ADHD comorbid with DBD (v 2 = 5.762; p = 0.016; OR = 1.58; CI 95% = 1.07–2.35). Our findings replicate previous results and suggest a role for COMT in the etiology of DBD in children and adolescents with ADHD. Keywords ADHD Á DBD Á ODD Á CD Á Val 158 Met Introduction Attention-deficit/hyperactivity disorder (ADHD) is a very heterogeneous disorder characterized by symptoms of inattention, impulsivity and hyperactivity. This neurode- velopmental disorder is one of the most prevalent mental health disorders in childhood and adolescence, affecting 5.3% of children worldwide (Polanczyk et al. 2007). Based on the high prevalence of comorbidity between opposi- tional defiant disorder (ODD) and/or conduct disorder (CD) with ADHD (up to 60% in some clinical samples), several investigators based on family and twin studies have sug- gested that ADHD and ODD or CD share a common genetic component and the comorbid group might repre- sent a more severe subtype of ADHD (Connor et al. 2010; Hamilton and Armando 2008; Stergiakouli and Thapar 2010). The presence of comorbid ODD or CD symptoms in patients with ADHD can negatively affect the course and prognosis of ADHD itself, as well as subsequent behaviors and psychiatric diagnoses, family dynamics and educa- tional outcomes (Connor et al. 2010; Thapar et al. 2006). The human catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11, encodes an enzyme that catalyzes one of the main degradation pathways of cate- cholamine neurotransmitters—dopamine (DA) and norepi- nephrine (NE) (Tenhunen et al. 1993; Tenhunen et al. 1994). About 60% of the degradation of DA in the pre- frontal cortex (PFC) is performed by this enzyme (Diaz- Asper et al. 2006). The Val 158 Met (rs4680) polymorphism is a functional genetic variant, which consists of a guanine to adenine mutation, resulting in a valine (Val) to methionine (Met) substitution. The Met amino acid results in a protein with a fourfold reduction in enzymatic activity. Therefore, Met carriers show higher brain levels of DA, especially in the PFC (Chen et al. 2004; Lotta et al. 1995). This func- tional polymorphism has been associated with several characteristics related to antisocial behavior comorbid with ADHD. Previous findings suggest that homozygous Val/Val children with ADHD present more CD symptoms and A. Salatino-Oliveira Á J. P. Genro Á A. P. Guimara ˜es Á T. Roman Á M. H. Hutz (&) Departamento de Gene ´tica, Instituto de Biocie ˆncias, UFRGS, Caixa Postal 15053, Porto Alegre, RS 91501-970, Brazil e-mail: mara.hutz@ufrgs.br R. Chazan Á C. Zeni Á M. Schmitz Á G. Polanczyk Á L. A. Rohde Division of Child and Adolescent Psychiatry, Hospital de Clı ´nicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil G. Polanczyk Á L. A. Rohde Instituto de Psiquiatria do Desenvolvimento para a Infa ˆncia e Adolesce ˆncia, Sao Paulo, Brazil 123 J Neural Transm DOI 10.1007/s00702-012-0766-2