[Serotonin 2A receptor gene polymorphism and clinical efficacy of fluvoxamine in children with autistic disorder]

Abstract

Fluvoxamine, a selective serotonin reuptake inhibitor which modulates serotoninergic activities, is a useful drug for patients with an autistic disorder. Genetic variation of the serotonin receptor may influence the efficacy of fluvoxamine treatment. We studied the correlation between clinical responses to fluvoxamine and serotonin receptor gene polymorphism (5-HT2AR) in children with an autistic disorder. Eighteen patients completed a 12-week double-blind, placebo-controlled, randomized crossover study. Clinical global impression (CGI) by child neurologists and interviews for parents were assessed after 12 weeks of fluvoxamine treatment. Behavioral assessments consisting of 20 items by newly created Behavioral Assessment Scale (BAS) were obtained before as well as 6 and 12 weeks after treatment. For genotyping of 5-HT2AR, 102 T/C polymorphism was analyzed by the PCR method. Seven cases of T/T, 6 of T/C and 5 of C/C were identified. The patients with the genotype T/C responded more favorably when estimated by CGI and parents' report at 12 weeks of treatment. Although not significant statistically (p = 0.0578), the number of improved BAS items in these patients were larger after fluvoxamine than placebo treatment. On analyses of individual BAS items, the patients with the genotype C/C showed improvement of unnatural facial expression, which was significant at 6 weeks, but not at 12 weeks, of fluvoxamine treatment. In the patients with the genotype T/C, eye movements and emotional changes were significantly improved at 12 weeks of treatment. Our results suggested that genetic polymorphism of 102 T/C in the 5-HT2AR gene may have influence on the response to fluvoxamine treatment for patients with an autistic disorder. Because of the small numbers of subject studied here, further studies are needed. The methods of fluvoxamine treatment, such as appropriate dosage and treatment duration, should also be clarified.