Serotonin-System Polymorphisms (5-HTTLPR and -1438G/A) and Responses of Patients With Bulimic Syndromes to Multimodal Treatments

Background: We tested the hypothesis that individuals carrying low-function alleles of the serotonin transporter (5-HTTLPR) and 5-HT2A receptor gene (-1438G/A) promoter polymorphisms would show relatively poor treatment responses on indices of bulimic and concurrent symptoms.

Method: Participants included 111 women with bulimia-spectrum eating disorders (DSM-IV-TR criteria), 98 of whom were followed through 4- to 8-month spans of specialized multimodal treatment to enable examination of relationships between genotypes and prospective changes in eating and general psychiatric symptoms. Given a hierarchically structured dataset and a desire to control for effects of variations in adjunctive pharmacotherapy, individual therapy, group therapy, or day treatment, we used multilevel modeling techniques. The study was conducted between October 2001 and May 2007.

Results: After effects of treatments were removed, 5-HTTLPR low-function allele carriers showed smaller treatment reductions in binge eating (p < .01) and in anxiety and depression (p < .05), whereas low-function -1438G/A G carriers showed smaller reductions in binge eating (p < .01) and impulsivity (p < .05).

Conclusions: This study documents an expected association between poorer bulimia-treatment response and low-function alleles of 5-HTTLPR and -1438G/A--and suggests that such effects cannot be attributed to mediating influences of medication or psychotherapy responsiveness alone. A better understanding of hereditary, serotonin-mediated factors affecting bulimic individuals' progress during therapy may facilitate the development of more effective treatments.

J Clin Psychiatry 2008;69(10):1565-1571