The Biology of Anorexia Nervosa: A New Narrative Overview

Abstract

Anorexia nervosa, one of the most deadly mental disorders, is a pathophysiologically complex mosaic of numerous extensively investigated pathways, and the current state of knowledge cannot provide us with one definite answer regarding its etiopathogenesis. Although classified as a psychiatric disorder, traditionally viewed as a consequence of the psychological features, the model explaining the onset and development of anorexia is multifactorial with growing interest in its metabolic origin. The clinical presentation varies in severity, but ultimately every organ in the diseased body is affected. There are many biological alterations that simply act in accordance with severe malnutrition and weight loss; nevertheless, there is an evident dysfunction in the course of adaptive pathways that induce or at least potentiate those changes. Based on human and animal studies, the most relevant streams in AN pathophysiology seem to point toward a relatively adequate peripheral response that fails to properly stimulate feeding-related neurohormonal brain circuits. This metabolic origin of AN is supported by molecular identifications of specific genetic polymorphisms. Endocrine adaptations involve among others hyperghrelinemia, hypoleptinemia, hypogonadotropic hypogonadism, and CRH hypersecretion. Those hormonal shifts interact not only with appetite-regulating brain regions but also affect energy expenditure, physical activity, behavior, cognition, as well as rewarding/motivational drive. This narrative review aims to present emerging biological concepts underlying anorexia nervosa.