The role of the HTR1D gene in anorexia nervosa

Abstract

Anorexia nervosa is an uncommon but very severe disease that leads to serious malnutrition sometimes resulting in death. Genetic research has found associations between SNPs in the HTR1D gene and anorexia nervosa. In the current paper, we investigate this relationship using a bottom-up approach. The HTR1D gene codes for the serotonin 1D (5-HT1D receptor) which has been found to be present in low abundance throughout the brain and can act as an auto- and heteroreceptor. Although many studies have shown that the hyperactivity of the serotonin system is involved in eating behaviour and anorexia nervosa, no direct evidence exists that supports the involvement of the 5-HT1D receptor. Nonetheless, ligands binding to the 5-HT1B and 5-HT1D receptor have shown to influence eating behaviour. We propose a model which states that abnormal expression of the 5-HT1D receptor in the raphe nuclei, hypothalamus and parabrachial nucleus leads to a preference of lower food intake. Eating more leads to anxiety and distress. Children with SNPs in the HTR1D gene may experience these symptoms without knowing how to deal with them. Once they have their first dieting experience their symptoms reduce due to decreased tryptophan (the precursor of serotonin) intake which leads to lower serotonin activity. Patients with anorexia nervosa may associate the reduction in symptoms with decreased food intake and therefore become reluctant to eat. At the moment, little direct evidence supporting our model exists. Therefore, further research is required and suggestions are given.