Pilot Study Revealed Association of DRD4 Promoter Variants with ADHD Associated Functional Deficit in Indian Probands

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is often associated with cognitive deficit. Since brain regions regulating cognition has higher expression of Dopamine receptor 4 (DRD4), we explored association between functional DRD4 promoter variants and cognition of ADHD probands. Methods: Subjects recruited following DSM-IV-TR were assessed for Short Attention Span (SAS) and Erratic Organization Capability (EOC), based on scores obtained through Conner#x2019;s Parent Rating Scale and DSM-IV-TR as well as computerized games. Functional variants were analyzed in ADHD probands, their parents and age-matched controls. Results: Probands exhibited significant impairment in SAS and EOC. rs10902180, rs747303, rs936462, showed association with cognitive deficit. Probands with co-morbid learning disability showed higher cognitive impairment. Significant interactive effects were evident between the markers. Conclusion: Impaired in information processing and scholastic performance, strong genotype-phenotype correlations more robust in ADHD cases with learning difficulty, suggest significant contribution of DRD4 in ADHD etiology, possibly due to attenuated receptor functioning.