![]() ![]() Values retrieved from 8.Įarlier results hinted at a significant negative genetic correlation between AN and body mass index (BMI) 9, 17. The error bar represents the 95% confidence interval. Genetic correlations between anorexia nervosa and selected top traits. 11 further identified that AN-associated genes were enriched in the prefrontal cortex. ![]() ![]() Analysis of tissue enrichment for AN-associated genes revealed a significant association with the central nervous system, and comparison to single-cell gene expression datasets from mice revealed significant associations with hippocampal pyramidal neurons and striatal medium spiny neurons. Combining existing samples 9 with the Anorexia Nervosa Genetics Initiative (ANGI) 10 yielded a European ancestry dataset including 16,992 AN cases and 55,525 controls, from 17 countries, and identified 8 genome-wide significant loci, including 4 single-gene loci: CADM1, MGMT, FOXP1 and PTBP2 8. We take as a starting point the most recent genome-wide association study (GWAS) of AN performed by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) 8. In this review, we describe the state of the science across biological levels and approaches and conclude by discussing progress towards this more integrated understanding.Ĭandidate gene and linkage literature in eating disorders was rife with unreplicated small-sample studies and was minimally informative beyond signaling the likely complexity of their genetics 6. A hierarchically connected research approach, reflecting the biological interconnectivity, will provide a more complete understanding of the biology of eating disorders, providing the foundations for developing much-needed novel treatments. Integrating results from different approaches is vital. These levels of biology are interconnected, but are investigated using different scientific approaches, with limited crosstalk to date. Preclinical, clinical, genetic studies (of binge eating), and neuroimaging data converged on dysfunction in systems regulating eating behavior and reward (i.e., dopaminergic and noradrenergic), and support the repositioning of lisdexamfetamine in BED 138.īiological effects within eating disorders range from the subcellular (genetic variants and their effects on gene expression and structure), through the cellular (signaling) and intercellular (neurons and neuronal circuits), to organismal effects (eating disorders and disorder-related behaviors) 5. Evidence-based treatments for BED include CBT, second-generation antidepressants, and since 2015, lisdexamfetamine an FDA approved stimulant originally prescribed for the treatment of attention deficit hyperactivity disorder 137. ![]() Onset is typically early adulthood but can be at any time and in individuals spanning the normal to obese weight ranges 1. We highlight ongoing and future work designed to identify implicated biological pathways that will inform staging models based on biology as well as targeted prevention and tailored intervention and galvanize interest in developing pharmacologic agents that target the core biology of the illnesses for which we currently have few effective pharmacotherapeutics.īED is marked by recurrent binge eating that causes distress, the absence of regular compensatory behaviors, and behavioral and emotional features such as eating rapidly or when not hungry, and feeling embarrassed or disgusted by one’s behavior 1. This review covers overlapping advances in these key domains and encourages greater integration of hypotheses and findings to create a more unified science of eating disorders. Until now, however, these approaches have advanced the field in parallel, with inadequate crosstalk. Our understanding of their genetics and neurobiology is evolving thanks to global cooperation on genome-wide association studies (GWAS), neuroimaging, and animal models. Eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder) are a heterogeneous class of complex illnesses marked by weight and appetite dysregulation coupled with distinctive behavioral and psychological features. ![]()
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