The severity of attention-deficit/hyperactivity disorder (ADHD) symptoms is a major predictor of long-term ADHD outcome. long-term ADHD outcome. reported that the strongest predictor of discrepancy between predicted achievement evaluated by measurements of intellectual function and actual academic performance is the severity of ADHD symptoms, defined as the index composed of averaged behavioral data obtained from the hyperactivity/impulsivity checklist of Retinyl glucoside manufacture DSM-IV, attention problems and hyperactivity scores from the Behavior Assessment System for Children-Parent Rating Scale, and from the total score on the Home Situations Questionnaire.4 Similar results have been reported showing that the severity of inattention and hyperactivity negatively correlates with academic performance and has deleterious effects on other aspects related to quality of life, such as risk avoidance and satisfaction. 5 Another study showed that ADHD severity was positively associated with the use of tobacco, alcohol and marijuana.6 In individuals without frank ADHD, higher levels of inattention have been found to have a adverse influence on both educational university and efficiency modification.7 Because of this evidence, utilizing a clinical approach that needs severity into account is relevant. Furthermore, the traditional approach using the diagnostic criteria for ADHD as defined in the DSM-IV Retinyl glucoside manufacture discards those individuals who, despite the severity of some of the specific symptoms, do not fit the overall numeric criteria for the diagnosis of ADHD. However, the severity of their symptoms could have a marked functional impact and these individuals may benefit from interventions.8, 9, 10 In the etiology of ADHD, genetic factors are strongly implicated.11 Recently, we identified a common variant of the gene (variant that confers susceptibility to ADHD.12 Functional studies revealed that is expressed in key brain regions Retinyl glucoside manufacture related to attention and activity, and that its variants affect metabolism in neural circuits implicated Retinyl glucoside manufacture in ADHD and are associated with response to stimulant medication. These findings were replicated in samples obtained from unrelated populations.12, 13 In addition to increasing knowledge of the genetic basis of ADHD, the discovery of the molecular substrates of ADHD opens up new avenues for the exploration of targeted therapies. In related studies, we analyzed two-locus interactions models between variants on chromosome 4q and a susceptibility haplotype on 11q encompassing the and genes. The simultaneous presence of both genetic risk variants increases the risk of ADHD by 2.5 compared with the risk when none of these variants are present.14 In addition to previous evidence linking these two regions with human behavior,15, 16, 17, 18, 19, 20 we found that this interaction also explains differences in brain metabolism as observed through proton magnetic resonance spectroscopy (1H-MRS) data and pharmacogenetic response to stimulant medication better than the presence of either variant alone. In the present study, we aimed to evaluate the hypothesis that the interaction between ADHD susceptibility factors on 4q and 11q, as well as other genomic regions, not only predicts ADHD susceptibility but the severity of the condition also, as ADHD intensity is the greatest indicator of long-term outcome. In this way, Retinyl glucoside manufacture we additionally expand upon our previous findings to place them in a context where they may have a greater impact in terms of defining interventions for affected and subsyndromal individuals. Subjects and methods Subjects We analyzed a total of 349 nuclear families consisting of a total of 1371 individuals. Participants were from a United Col4a3 States population, 4C65 years of age, ascertained from ADHD probands. Diagnosis of ADHD in children was established using the DSM-IV criteria;2 in adults, the Conners Adult ADHD Rating Scale (CAARS)21 was used. All participants were evaluated using the Vanderbilt Assessment Scale for Parents (VAS-P),22 which includes all 18 DSM-IV criteria for ADHD (questions 1C9 for inattention; questions 10C18 for hyperactivity/impulsivity), oppositional defiant disorder (ODD; questions 19C26), conduct disorder (CD; questions 27C40) and seven items from the Pediatric Behavior Scale23 screening for anxiety and depression (A/D; questions 41C47.