Abstract

1. Genotypes and phenotypesin 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 2-Rintveld 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 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. 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) 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) Phenotype: e.g. reward sensitivity Genotype: C/C C/G G/G • 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. G e n o t y p e s • anhedonia • food liking/wanting • emaciation • set-shifting deficit • hyperactivity Results – DRD2 genotyping SNP rs1800497, association with AN restrictive and purging types Odds Ratio=1.9 Conf. Int.=[1.2-2.9] p=0.004 n=64 Credo: Elucidation of genes affecting AN phenotypes will enhance cognitive and pharmacological therapies, leading to a personalization of the treatment. n=357 DRD2: Distribution of alleles in cases (AN) and controls Contact Information: M.Brandys, email: m.brandys@umcutrecht.nl UMC Utrecht, Universiteitsweg 100 3584 CG Utrecht, The Netherlands The Research Training Network INTACT