Summary Eating disorders such as anorexia nervosa, bulimia nervosa and binge-eating disorder, have a deep social impact, concluding with death in cases of severe disease. Eating disorders affect up to 5% of the population in the industrialized countries, but probably the phenomenon is under-detection and under-diagnosis. Eating disorders are multifactorial disorders, resulting from the interaction between environmental triggers, psychological factors, but there is also a strong genetic component. In fact, genetic factors predispose for approximately 33-84% to anorexia nervosa, 28-83% to bulimia nervosa, and 41-57% to binge eating disorder. Twins and family studies have provided an unassailable proof on the heritability of these disorders. Other types of genetic studies, including genome-wide association studies, whole genome sequencing and linkage analysis, allowed to identify the genes and their variants associated with eating disorders and moreover global collaborative efforts have led to delineate the etiology of these disorders. Next Generation Sequencing technologies can be considered as an ideal diagnostic approach to identify not only the common variants, such as single nucleotide polymorphism, but also rare variants. Here we summarize the present knowledge on the molecular etiology and genetic determinants of eating disorders including serotonergic genes, dopaminergic genes, opioid genes, appetite regulation genes, endocannabinoid genes and vitamin D3.

<h4>Objective</h4>Anorexia nervosa (AN) is a disorder with a significantly high prevalence. Affective disorders, including depressive disorder (DD), often coexist with this eating disorder (ED). In this review we will focus on its prevalence, associated vulnerability factors, clinical manifestations, possible etiological factors and its prognosis.<h4>Methods</h4>A bibliographic search was carried out in the PubMed database selecting those articles that approached the subject of comorbidity between AN and DD. The search was limited to articles published from January 1990 to December 2021.<h4>Results</h4>Of the 1891 abstracts reviewed, 33 studies met inclusion criteria. The prevalence of this comorbidity was extremely variable between studies, which exposed their heterogeneity. As to symptomatology this comorbidity presents itself with more severity, greater expression of psychological traits and greater cognitive impairment. Certain personality traits are postulated as vulnerability factors. Genetic factors such as neurochemicals seem to be involved in its pathogenesis.<h4>Conclusion</h4>The comorbidity between DD and ED have important influence in its symptomatic expression, severity and prognosis. Some of the analyzed studies provide consistent data, but there are others that are contradictory. It would be necessary to increase the number of studies and use a unified methodology.

Background and aims Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN. Methods A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines. Results The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT , DRD2 , DRD3 , and DAT1 , regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR , TFAP2B , and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN. Conclusion There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder. Systematic review registration : [ https://clinicaltrials.gov/ ], identifier [CRD42023452548].

To grade the evidence about risk factors for eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) with an umbrella review approach. This was a systematic review of observational studies on risk factors for eating disorders published in PubMed/PsycInfo/Embase until December 11th, 2019. We recalculated random-effect meta-analyses, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals, grading significant evidence (p < 0.05) from convincing to weak according to established criteria. Quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. Of 2,197 meta-analyses, nine were included, providing evidence on 50 risk factors, 29,272 subjects with eating disorders, and 1,679,385 controls. Although no association was supported by convincing evidence, highly suggestive evidence supported the association between childhood sexual abuse and bulimia nervosa (k = 29, 1,103 cases with eating disorders, 8,496 controls, OR, 2.73, 95%CI 1.96-3.79, p = 2.1 x 10-9, AMSTAR-2 moderate quality) and between appearance-related teasing victimization and any eating disorder (k = 10, 1,341 cases with eating disorders, 3,295 controls, OR 2.91, 95%CI 2.05-4.12, p = 1.8x10-9, AMSTAR-2 moderate quality). Suggestive, weak, or no evidence supported 11, 29, and 8 associations, respectively. The most credible evidence indicates that early traumatic and stressful events are risk factors for eating disorders. Larger collaborative prospective cohort studies are needed to identify risk factors for eating disorders, particularly anorexia nervosa.