Anorexia Nervosa: finding the genetic background of rigid behavior an endophenotype of Anorexia Nervosa

Abstract

Anorexia Nervosa is from all the psychiatric diseases the disease with the highest mortality rate. Anorexia Nervosa is currently under intense investigation, however the underlining cause of Anorexia Nervosa is still not known primarily because its complexity. AN consist of several distinct behavioral component that contribute to the disease in distinct manners. Human genetic studies have tried to find the genes responsible for AN, however because of heterogeneity due to a lack of statistical power only several studies developed significant results. Several studies that did develop significant result pointed towards DRD4, DRD2, 5-HT2A, BDNF, HRTD1 and ORPD1 as susceptible genes that contribute to the disease. The technique to perform Genome Wide Association studies might help to solve this problem. Additionally the use of endophenotyping will help to solve heterogeneity in the patient groups by focusing on behavioral domains such as activity, rigidity or anxiety. Besides the human genetic studies mice studies have contributed to our knowledge of AN. Distinct mice models and KO mice have resulted in the association of multiple genes to AN such as leptin, POMC, NPY, AGrP, dopamine, M3, CRCH2 and the anx gene. Mice models combined with endophenotyping might result in the discovery of the genetic background of specific behaviors. The specific behaviors that contribute to AN consist of anxiety, rigidity, depression, perfectionism and activity. Therefore I proposed a set shifting test in mice to discover the genes responsible for rigid behavior. Rigid behavior was selected because it is an endophenotype that makes the disease more sever and the duration of the disease longer. Rigid behavior is tested with a set shifting task in mice in which BL6 is compared to AJ. Further QTL analysis with CSS (Chromosomal Substitution Strains) should result in susceptible regions on the chromosomes of the mice. First Data of the comparison between the BL6 and AJ for the set shifting task already shown