Association of the promoter polymorphism -1438G/A of the 5-HT2A receptor gene with behavioral impulsiveness and serotonin function in women with bulimia nervosa.

Separate lines of research suggest that the functional alterations in the serotonin (5-HT) 2A receptor are associated with 5-HT tone, behavioral impulsiveness, and bulimia nervosa (BN). We explored the effect of allelic variations within the 5-HT2A receptor gene promoter polymorphism -1438G/A on trait impulsiveness and serotonin function in women with BN. Participants included women with BN having the A allele (i.e., AA homozygotes and AG heterozygotes, BNA+, N = 21); women with BN but without the A allele (i.e., GG homozygotes, BNGG, N = 12), and normal eater control women having the A allele (NEA+, N = 19) or without the A allele (NEGG; N = 9). The women were assessed for psychopathological tendencies and eating disorder symptoms, and provided blood samples for measurement of serial prolactin responses following oral administration of the post-synaptic partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). The BNGG group had higher scores than the other groups on self-report measures of non-planning and overall impulsiveness and had blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other Axis I mental disorders. Findings indicate that women with BN who are GG homozygotes on the -1438G/A promoter polymorphism are characterized by increased impulsiveness and lower sensitivity to post-synaptic serotonin activation. These findings implicate the GG genotype in the co-aggregation of impulsive behaviors and alterations of post-synaptic 5-HT functioning in women with BN.