Download cognitive measures (set-shifting)

Genotypes and phenotypes
in Anorexia Nervosa
Marek Brandys1, Judith Hendriks1, Unna Danner2,3, Annemarie van Elburg2,4,
Roger Adan1
1-Rudolf
Magnus Institute of Neuroscience, Dept. of Neuroscience and Pharmacology, University Medical Center Utrecht, The Netherlands
Centre for Eating Disorders, Altrecht Mental Health Institute, Zeist, The Netherlands
3-Dept. of Clinical & Health Psychology, Utrecht University, The Netherlands
4-Rudolf Magnus Institute of Neuroscience, Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The
Netherlands
2-Rintveld
Abstract
Conclusions with regards to DRD2
Twin 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.
•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.
Objectives
To determine how genes associated with AN
affect its subphenotypes and treatment
outcome.
Methods and Procedure
 DNA and phenotypic data collected from
patients
 Candidate genes genotyped
 Genetic info combined with phenotypic data
 diagnoses, BMI
 treatment course and outcome
 questionnaires (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 controls
 Distribution is different between groups of AN patients
(based on phenotypic measures)
Results – DRD2 genotyping
SNP rs1800497, association with AN restrictive and purging types
C
72%
Cases
n=64
C
83%
Controls
n=357
0%
G
28%
25%
50%
G
17%
75%
Odds Ratio=1.9
Conf. Int.=[1.2-2.9]
p=0.004
Next Steps
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
Genotype: C/C
C/G
G/G
Interpretaion – which
G e nmechanisms
o t y p e s may
underlie it? Dopamine signaling plays role in...
•Reward processing

anhedonia
•Hedonic eating

food liking/wanting
•Homeostatic eating

emaciation
•Cognitive flexibility

set-shifting deficit

hyperactivity
•Locomotor activity
In the future, other genes and phenotypes will
be investigated in a similar fashion.
Credo: Elucidation of genes affecting AN phenotypes
will enhance cognitive and pharmacological therapies,
leading to a personalization of the treatment.
100%
DRD2: Distribution of alleles in cases (AN) and controls
Contact Information:
M.Brandys, email: [email protected]
UMC Utrecht, Universiteitsweg 100
3584 CG Utrecht, The Netherlands
The Research Training Network
INTACT