Decoding the Spectrum of Anorexia Nervosa: Clinical Impact, Molecular Insights, and Therapeutic Perspectives

Anorexia nervosa (AN) is a severe psychiatric disorder with the highest mortality rate among mental illnesses, characterized by an intense fear of weight gain, persistent restriction of energy intake, and a distorted perception of body image. Despite decades of investigation, the pathogenesis of AN is only partially understood and is recognized as multifactorial, involving genetic, sociocultural, and neurobiological determinants. Beyond its core psychopathological features, AN leads to a wide spectrum of systemic complications, including cardiovascular, renal, skeletal, and endocrine dysfunctions. Increasing evidence implicates autophagy and oxidative stress as key molecular mechanisms underpinning its pathophysiology, while growing attention has been directed toward immune dysregulation and alterations in the gut-brain axis as potential mediators of disease onset and progression. Therapeutic advances, however, remain limited. Current management relies primarily on nutritional rehabilitation and psychotherapeutic interventions, while treatment outcomes are constrained by high relapse rates and the lack of pharmacological agents with proven efficacy. In this context, a more comprehensive understanding of the clinical spectrum and molecular substrates of AN is essential to improving prognosis and guiding the development of novel therapeutic strategies. This narrative review synthesizes current evidence on the non-psychopathological dimensions of AN, encompassing its clinical manifestations, systemic complications, and implicated molecular pathways. It also appraises existing treatment modalities and examines emerging interventions with translational potential. Overall, this review aims to provide clinicians and researchers with an updated and integrative overview of AN, shedding light on novel directions in ongoing research.