Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)

Abstract

Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands ( 2 = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission ( 2 = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P Ͻ 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson 2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype 2 = 21.28; P = 0.0032, 3 df and allele 2 = 30.88, P = 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.

MAOA, maltreatment, and gene–environment interaction predicting children's mental health: new evidence and a meta-analysis

“…This finding is not inconsistent with previously published results of a significant main effect of the high-activity MAOA genotype on increasing risk for antisocial behavior and ADHD. [59][60][61] Moreover, closer inspection of other G Â E studies involving the MAOA polymorphism reveals similar findings, albeit at marginally significant levels. 3,6,7 For instance, Foley et al 6 found a nonsignificant trend (P < 0.14) for the high-activity MAOA allele increasing risk for conduct disorder; after adjusting for the interaction between the MAOA polymorphism and maltreatment, the main effect became significant (P = 0.04).…”

ADHD risk alleles associated with opiate addiction: study of addicted parents and their children

“…A high rate of similarity between the carrier state of the parents and their children was also observed by others, (28) but inheritance of risk alleles for ADHD is a complex process as there seems to be a preferential transmission of paternal over maternal alleles (28,29).…”

A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population

“…30 Dysregulation of monoamine pathways has long been implicated as one of the mechanisms involved in the etiology of ADHD. Several groups [31][32][33][34][35][36] have set out to test whether MAOA confers risk for ADHD, however, definite conclusion has not yet been received. Our data may serve as a support for previous positive reports of linkage/association for MAOA, especially in Chinese Han population.…”