abstract twin studies demonstrate that anorexia nervosa (an) is a highly heritable psychiatric...
TRANSCRIPT
C83%
G17%
C72%
G28%
0% 25% 50% 75% 100%
Cases
Controls
AbstractTwin studies demonstrate that Anorexia Nervosa (AN) is a highly heritable psychiatric disease. The mechanisms of genetic susceptibility to AN remain unclear. In this study we aim to determine how genotypes affect phenotypes relevant to this disease. Treatment outcome will also be investigated in relation to genotypes and phenotypes. Preliminary results concerning Dopamine Receptor D2 (DRD2) gene are presented.
DNA and phenotypic data collected from patients Candidate genes genotyped Genetic info combined with phenotypic datadiagnoses, BMItreatment course and outcomequestionnaires (novelty seeking, harm avoidance,
reward sensitivity, anxiety, obsessive-compulsive traits and others)cognitive measures (set-shifting) Statistical analysis - to see if:Distribution of genotypes / alleles is different between
patients and controlsDistribution is different between groups of AN
patients (based on phenotypic measures)
Methods and Procedure
SNP rs1800497, association with AN restrictive and purging types
Conclusions with regards to DRD2
Credo: Elucidation of genes affecting AN phenotypes will enhance cognitive and pharmacological therapies, leading to a personalization of the treatment.
Genotypes and phenotypesin Anorexia NervosaMarek Brandys1, Judith Hendriks1, Unna Danner2,3, Annemarie van Elburg2,4, Roger Adan1
The Research Training Network INTACT
ObjectivesTo determine how genes associated with AN affect its subphenotypes and treatment outcome.
Results – DRD2 genotyping
n=357
n=64
DRD2: Distribution of alleles in cases (AN) and controls
Next Steps
•DRD2 gene polymorphism is associated with AN•Allele G is more often observed in AN than in controls•It indicates the importance of dopamine signaling in the etiology of the disease•In the literature, DRD2 has been associated with Novelty Seeking, Reward Sensitivity and Impulsivity•The susceptibility to AN conferred by DRD2 polymorphism may be mediated by personality traits.
Contact Information: M.Brandys, email: [email protected] Utrecht, Universiteitsweg 1003584 CG Utrecht, The Netherlands
Odds Ratio=1.9Conf. Int.=[1.2-2.9]
p=0.004
C/C G/GC/G
How individuals with G allele are different from those without it? To check:
•Treatment Outcome•Novelty Seeking•Reward Sensitivity•Self-Reported Activity•Set-Shifting•BMI (highest ever, lowest ever)
Phenotype: e.g. reward sensitivity
G e n o t y p e s
1-Rudolf Magnus Institute of Neuroscience, Dept. of Neuroscience and Pharmacology, University Medical Center Utrecht, The Netherlands2-Rintveld Centre for Eating Disorders, Altrecht Mental Health Institute, Zeist, The Netherlands3-Dept. of Clinical & Health Psychology, Utrecht University, The Netherlands4-Rudolf Magnus Institute of Neuroscience, Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands
Interpretaion – which mechanisms may underlie it? Dopamine signaling plays role in...
•Reward processing •Hedonic eating•Homeostatic eating•Cognitive flexibility•Locomotor activity
In the future, other genes and phenotypes will be investigated in a similar fashion.
anhedonia food liking/wanting emaciation set-shifting deficit hyperactivity
Genotype: