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.
Bruce
Kenneth R
KR
Eating Disorders Program, Research Centre, Douglas Hospital, Department of Psychiatry, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec H4H 1R3, Canada. bruken@douglas.mcgill.ca
Steiger
Howard
H
Joober
Ridha
R
Ng Ying Kin
N M K
NM
Israel
Mimi
M
Young
Simon N
SN
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D052018:Bulimia Nervosa / Q000097:blood / Q000235:genetics / Q000523:psychology*; D005260:Female; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000097:blood / Q000235:genetics / Q000523:psychology*; D015999:Multivariate Analysis; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine