Neurobiology of Anorexia Nervosa

AN is a severe psychiatric disorder characterized by restriction of energy intake leading to a significantly low body weight, an intense fear of weight gain, and a distorted experience of one’s own body weight or shape. The course of AN can be prolonged and may lead to enduring disability, in particular for the individuals with the often called severe and enduring AN. With a 10% mortality, AN is among the most lethal of all psychiatric disorders. Unfortunately, there is still no evidence-based pharmacological treatment for AN, and the optimal treatment, psychological as well as pharmaceutical, is debated. 

One central and unexplained feature of AN is the paradoxical response to negative energy balance. While most people cannot lose a few kilos, these individuals stay in an emaciated and starved condition commonly for many years. Even after therapeutic renourishment, their bodies commonly revert to what appears to be a negative set point, i.e. the inverse of happens for obese individuals. AN genome-wide association studies have yielded significant negative single-nucleotide-based genetic correlations with BMI and other anthropometric measures, which seems to indicate a genetic predisposition for a lower body weight set point in AN. However, we do not understand the (neuro)biological underpinnings of such a set point nor the mechanisms explaining the contradictory response to underweight in AN. 

The overall goal of our group is to understand the molecular mechanisms involved in food intake in general, and in the elective starvation of AN in particular. Our main hypothesis involves dysregulated hypothalamic circuits. Upon defining the neurobiological mechanisms and molecular players involved in the paradoxical response to underweight in AN, will we be able to find new pharmacological targets, as well as vulnerability markers. Pharmacological therapy, preventing the continued starvation and the loss of weight after recovery, could be combined with the today most commonly used treatment for AN; psycho- and nutritional therapy. Finally, extending the understanding of the neurobiology of AN will reduce the stigma surrounding AN, thus promoting early treatment and reduced mortality.