Dopamine Transporter Gene (DAT1) Associated with Appetite Suppression to Methylphenidate in a Case–Control Study of Binge Eating Disorder
Abstract
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.
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Candidate genetic behavior investigations in BN have reported altered allelic frequencies for the DAT gene and DA receptor genes in individuals with bulimia.
“These studies compliment candidate genetic behavior investigations in BN that have reported altered allelic frequencies for the DAT gene [328] and DA receptor genes [329,330] in individuals with bulimia.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [328]
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Self-citationAlsindi, A. M., Alhamad, N. M., Alaqili, A. K., Alfaw, A. A., Alabassi, N. K., Ghazzawi, H., & Jahrami, H. (2024) · Journal of Nature and Science of Medicine · doi:10.4103/jnsm.jnsm_39_23 · Cited by 1 · see citing works
The Dopamine Transporter Gene (DAT1) in Obesity and Binge Eating Disorders
Wight, K., Reid‐Westoby, C., & Davis, C. A. (2011) · Springer eBooks · doi:10.1007/978-0-387-92271-3_168 · Cited by 1 · see citing works
Self-citationMULTILOCUS DOPAMINE GENE VARIATION, REWARD SENSITIVITY, AND ABERRANT EATING
Donofry, S. D. (2014) · D-Scholarship@Pitt (University of Pittsburgh) · Cited by 1 · see citing works
Bulik, C. M., Breithaupt, L. E., Yılmaz, Z., Gow, R. W., Trace, S. E., Kleiman, S. C., & Mazzeo, S. E. (2018) · Wiley eBooks · doi:10.1002/9781394258970.ch14 · Cited by 1 · see citing works
Pharmacogenomics of Eating Disorders
Monteleone, P., & Maj, M. (2010) · Advances in biological psychiatry · doi:10.1159/000317301
Patte, K. A. (2015) · YorkSpace (York University)
Self-citationGenetic aspects of binge eating disorder Part 2. Molecular genetics and pharmacogenetic approaches
Kibitov, A. O., & Mazo, G. E. (2016) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201611681102-108
BINGE EATING DISORDERS; UPDATED AND EMERGING APPROACHES
Teaima, M. H. M., Hamid, M. M. A., Shoman, N. A., Jasti, B., El-Nabarawi, M. A., & Yasser, M. (2021) · International Journal of Applied Pharmaceutics · doi:10.22159/ijap.2021v13i2.40214
Johnson, A. W., Klump, K. L., Culbert, K. M., Lee-Tanner, J., & Sisk, C. L. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.115216
- Authors
- Davis, C., Levitan, R. D., Kaplan, A. S., Carter, J., Reid, C., Curtis, C., Patte, K., & Kennedy, J. L.
- Affiliations
- York University (CA)
- Centre for Addiction and Mental Health (CA)
- University Health Network (CA)
- Corresponding author
- Davis, Caroline
- Venue
- Neuropsychopharmacology
- Published
- 2007-02-21
- Volume
- 32
- Issue
- 10
- Pages
- 2199-2206
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2120173014
- Cited by
- 65
- References
- 41
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 5 · 2012: 8
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- dopamine transporter gene, DAT1, binge eating disorder, methylphenidate, appetite suppression, genetic polymorphism, drug response variability, overeating, obesity treatment
- MeSH terms
- Adult, Appetite, Appetite Depressants, Brain, Double-Blind Method, Drug Resistance, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Male, Methylphenidate, Middle Aged, Case-Control Studies, Treatment Outcome, Cross-Over Studies, Dopamine Plasma Membrane Transport Proteins, Bulimia Nervosa
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