Dopamine transporter gene (DAT1) associated with appetite suppression to methylphenidate in a case-control study of binge eating disorder.
Response to psychomotor stimulants is highly variable across individuals. Such inconsistencies are influenced by many factors including drug dose and polymorphic differences in genes that encode proteins, such as the dopamine transporter (DAT1), which are relevant to the site of action of these substances. The current study used a double blind, crossover (methylphenidate vs placebo) design to assess DAT1 genotype differences on appetite ratings to a snack-food cue in subjects with binge eating disorder (BED) (n=32) and healthy age-matched controls (n=46). ANOVA results indicated a significant genotype x diagnostic group interaction whereby BED subjects with at least one copy of the 9-repeat allele showed a significant suppression of appetite in response to methylphenidate compared with controls with this allele, or to subjects with the 10/10 genotype (irrespective of diagnosis) whose drug response was indistinguishable from placebo. The most probable explanation for these findings is that some, currently unknown, genetic variant, which is overrepresented in those with BED, interacts with DAT1 to suppress appetite in response to stimulant administration. The current findings have implications for treatment response to drugs currently in use (or being developed) for the treatment of overeating and overweight.
Davis
Caroline
C
Department of Kinesiology and Health Sciences, York University, Toronto, ON, Canada. cdavis@yorku.ca
Levitan
Robert D
RD
Kaplan
Allan S
AS
Carter
Jacqueline
J
Reid
Caroline
C
Curtis
Claire
C
Patte
Karen
K
Kennedy
James L
JL
D000328:Adult; D001066:Appetite / Q000187:drug effects* / Q000235:genetics; D001067:Appetite Depressants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D052018:Bulimia Nervosa / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D018592:Cross-Over Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008875:Middle Aged; D016896:Treatment Outcome
D001067:Appetite Depressants; D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate