Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder

Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors. Rece ntly, a common 44-bp deletion in the promoter region of the serotonin trans porter (5-HTTLPR) that results in reduced transcription and lower transport er protein levels was described. Toward unraveling a possible role of the 5 -HTTLPR polymorphism in childhood disruptive behaviors, we examined this ge ne in attention deficit hyperactivity disorder (ADHD), a heterogeneous chil dhood disorder in which three phenotypes are recognized by DSM IV criteria: inattentive (type I), hyperactive-impulsive (type II), and combined typo ( type III). By using the haplotype relative risk design, a group of 98 triad s (both parents and proband child) were tested for a possible association b etween 5-HTTLPR and ADHD. A significant decrease in the short/short 5-HTTLP R genotype was observed in the ADHD type III combined group (10.29% vs. 30. 88%) compared with the HRR-derived control group (likelihood ratio = 9.62, P = 0.008, n = 68 triads). Similar results were observed when allele freque ncies were compared (likelihood ratio = 3.81, P = 0.05, n = 136 alleles). T hese first findings should be interpreted cautiously until replicated in in dependently recruited clinical samples. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 105:91-95, 2001. (C) 2001 Wiley-Liss, Inc.