Etiology Of Anorexia Nervosa Research Articles

Hungry brain: about the possible contribution of neurotrophic factors to anorexia nervosa

Introduction: Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake leading to weight loss below the healthy range. It is accompanied by anxiety and distorted body perception. While the disorder often manifests during adolescence, there is a noted decrease in the average age of onset, with an increasing number of cases in childhood. Successful treatment and maintenance of healthy body weight require an understanding of the complex etiology of AN, encompassing both psychosocial and specific biological factors. Material and methods: For the review, databases PubMed, Cochrane, and Google Scholar were utilized, searching for the following keywords: anorexia nervosa, neurotrophins, neurotrophin 3, neurotrophin 4, BDNF, nerve growth factor, from the inception of the databases until September 2023. Discussion: In the biological context, neurotrophic growth factors such as neurotrophin 3 (NT-3), neurotrophin 4 (NT-4), brainderived neurotrophic factor (BDNF), and nerve growth factor (NGF) may play a significant role in the etiopathogenesis of AN. These substances are involved in processes such as neuroprotection, proliferation, maturation, and survival of neurons in both the central and peripheral nervous systems. They regulate neuronal plasticity, impact the production of neurotransmitters, and control synaptic activity. BDNF and neurotrophin 3 influence the serotoninergic and noradrenergic systems, which may be associated with neurobiological processes responsible for anxiety and mood disorders. Conclusions: Understanding the role of neurotrophins in AN has the potential to lead to more effective and personalized therapies, enabling a better comprehension of the biological mechanisms of this disorder and the development of targeted pharmacological interventions. Keywords: anorexia nervosa, bdnf, neurotrophin 3, neurotrophin 4, nerve growth factor

A new conceptual model for anorexia nervosa: A role for connective tissue?

The etiology of anorexia nervosa (AN) remains to be fully elucidated, and current theories also fail to account for the direct effect of starvation on the health of the organs and tissues, specifically the connective tissue present in most organs of the body. Individuals with hereditary disorders of connective tissue manifest with clinical symptoms that overlap with AN, as the abnormal connective tissue also contributes to many of the other extra-articular manifestations of these hereditary disorders. This article hypothesizes that a similar pathophysiology may also contribute to the clinical presentation of AN. Therefore, a better understanding is needed to elucidate: (1) the relationship between abnormal connective tissue and AN, (2) the impact of starvation toward the development of abnormal connective tissue and how this manifests clinically, (3) the etiology of autonomic nervous system changes contributing to the dysautonomia in AN, and (4) how the sensory signals sent from potentially abnormal connective tissue to the central nervous system impact interoception in AN. A conceptual model incorporating abnormal connective tissue is provided. PUBLIC SIGNIFICANCE: The etiology of AN remains poorly understood and current theories fail to account for the direct impact of starvation on the health of the organs and tissues of the body. There is significant clinical overlap between AN and hereditary connective tissue disorders. This paper attempts to provide a new conceptual model for AN in which abnormal connective tissue contributes to the underlying pathogenesis.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

Habits and Persistent Food Restriction in Patients with Anorexia Nervosa: A Scoping Review.

The aetiology of anorexia nervosa (AN) presents a puzzle for researchers. Recent research has sought to understand the behavioural and neural mechanisms of these patients' persistent choice of calorie restriction. This scoping review aims to map the literature on the contribution of habit-based learning to food restriction in AN. PRISMA-ScR guidelines were adopted. The search strategy was applied to seven databases and to grey literature. A total of 35 studies were included in this review. The results indicate that the habit-based learning model has gained substantial attention in current research, employing neuroimaging methods, scales, and behavioural techniques. Food choices were strongly associated with dorsal striatum activity, and habitual food restriction based on the self-report restriction index was associated with clinical impairment in people chronically ill with restricting AN. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and Regulating Emotions and Changing Habits (REaCH) have emerged as potential treatments. Future research should employ longitudinal studies to investigate the time required for habit-based learning and analyse how developmental status, such as adolescence, influences the role of habits in the progression and severity of diet-related illnesses. Ultimately, seeking effective strategies to modify persistent dietary restrictions controlled by habits remains essential.

Performing well but not appreciating it - A trait feature of anorexia nervosa.

Despite advances in the etiology of anorexia nervosa (AN), a large subgroup of individuals does not profit optimally from treatment. Perfectionism has been found to be a risk factor predicting the onset, severity, and duration of AN episodes. To date, perfectionism has been studied predominantly by the use of self-report questionnaires, a useful approach that may, however, be impacted by demand characteristics, or other distortions of introspective or metacognitive access. Here we circumvent these problems via a behavioral paradigm in which participants perform a modified Go/NoGo task, whilst self-evaluating their performance. We compared a group of 33 adolescent females during their first episode of AN (age=16.0) with 29 female controls (age=16.2), and 23 adolescent girls recovered from AN (age=18.3) with 23 female controls (age=18.5). The controls were closely matched by intelligence quotient and age to the two clinical groups. First-episode AN and control participants performed equally well on the task (reaction time and errors of commission), whereas the recovered group displayed significantly faster reaction times but incurred the same error rate. Despite performing at least as good as and predominantly better than control groups, both clinical groups evaluated their performances more negatively than controls. We offer a novel behavioral method for measuring perfectionism independent of self-report, and we provide tentative evidence that this behavioral manifestation of perfectionism is evident during first-episode AN and persists even after recovery.

Brain-based gene expression of putative risk genes for anorexia nervosa.

The etiology of anorexia nervosa (AN) remains elusive. Recent genome-wide association studies identified the first genes liked to AN which reached genome-wide significance, although our understanding of how these genes confer risk remains preliminary. Here, we leverage the Allen Human Brain Atlas to characterize the spatially distributed gene expression patterns of genes linked to AN in the non-disordered human brain, developing whole-brain maps of AN gene expression. We found that genes associated with AN are most expressed in the brain, relative to all other body tissue types, and demonstrate gene-specific expression patterns which extend to cerebellar, temporal and basal ganglia structures in particular. fMRI meta-analyses reveal that AN gene expression maps correspond with functional brain activity involved in processing and anticipating appetitive and aversive cues. Findings offer novel insights around putative mechanisms through which genes associated with AN may confer risk.

Childhood body mass index and the subsequent risk of anorexia nervosa and bulimia nervosa among women: A large Danish population-based study.

Evidence linking childhood body mass index (BMI) with subsequent eating disorders is equivocal. Potential explanations include different study populations and size, and that anorexia nervosa (AN) and bulimia nervosa (BN) should be studied separately. We examined whether birthweight and childhood BMI were associated with subsequent risk of AN and BN in girls. We included 68,793 girls from the Copenhagen School Health Records Register born between 1960 and 1996 with information on birthweight and measured weights and heights obtained from school health examinations at ages 6-15 years. Diagnoses of AN and BN were retrieved from Danish nationwide patient registers. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 355 cases of AN (median age: 19.0) and 273 cases of BN (median age: 21.8). Higher childhood BMI was linearly associated with decreasing risk of AN and increasing risk of BN at all childhood ages. At age 6, the HR for AN was 0.85 (95% CI: 0.74-0.97) per BMI z-score and the HR for BN was 1.78 (95% CI: 1.50-2.11) per BMI z-score. Birthweight >3.75 kg was associated with increased risk of BN compared to a birthweight of 3.26-3.75 kg. Higher BMI in girls at ages 6-15 years was associated with decreasing risk of AN and increasing risk of BN. Premorbid BMI could be relevant for the etiology of AN and BN, and in identifying high risk individuals. Eating disorders are associated with elevated mortality, especially AN. Using a cohort of Copenhagen school children, we linked information on BMI at ages 6-15 years for 68,793 girls with nationwide patient registers. Low childhood BMI was associated with increased risk of AN, whereas high childhood BMI was associated with increased risk of BN. These findings may assist clinicians in identifying individuals at high-risk of these diseases.

Anorexia and bulimia in late antiquity and early Byzantine period in the eastern Mediterranean region

The purpose of this study is to identify clinical manifestations of eating disorders in the Eastern Mediterranean region from the first century AD until the seventh century AD and evaluate relevant awareness among the physicians of the era. The authors searched original medical texts written in Greek by physicians practicing in the Eastern Mediterranean region from the first century AD to the seventh century AD. The search focused on passages that include possible references to clinical entities analogous to anorexia nervosa (AN) and bulimia nervosa (BN) as described in the DSM-5 and the contemporary literature. Descriptions of conditions that resemble AN or BN can be found in the work of Galen, Oribasius, Aetius of Amida, Leon Philoumenos, Alexander Trallian, and Paul of Egina. Successive physicians confirmed the observations of their predecessors and add to the description of the clinical presentations and their etiology. This research provides evidence of awareness of presentations resembling currently defined eating disorders in the Eastern Mediterranean region during a period with different norms and values. Observations from the period can serve as a point for reflection about the characteristics and etiology of AN and BN in the 21st century.

Intestinal barrier integrity in anorexia nervosa (a pilot study)

ObjectiveThere is no conclusive evidence for involvement of intestinal barrier alteration in the etiology of anorexia nervosa (AN). The aims of this pilot study were to identify serum markers of intestinal barrier integrity in patients with AN and to determine the relationships between those markers and body mass index (BMI), eating disorder symptoms, gastrointestinal complaints, and liver synthesis function (international normalized ratio [INR]).MethodTwenty‐five outpatients with AN prior to starting treatment and 28 healthy controls (HC) were assessed. BMI and serum markers of intestinal barrier integrity were measured, including zonulin family peptides (ZFP), lipopolysaccharide‐binding protein (LBP), and intestinal fatty‐acid‐binding protein (i‐FABP). Eating disorder symptoms and gastrointestinal complaints were evaluated via questionnaires.ResultsThe serum ZFP concentration was significantly lower in patients with AN than in HC (44.2 [7.4] vs. 49.2 [5.6] ng/ml, mean [standard deviation], p = .008). LBP and i‐FABP did not differ between the two groups. In patients with AN, serum ZFP was significantly predicted by BMI (β = 0.479, p = .009), age (β = 0.411, p = .020), and INR (β = −0.388, p = .028). No such associations were found for either gastrointestinal complaints or eating disorder symptoms.DiscussionAbnormal levels of serum ZFP were observed in patients with AN. Further studies with other assessment methods are warranted to examine intestinal barrier function in AN.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02745067.

Genome-wide DNA methylation profiling in anorexia nervosa discordant identical twins

Up until now, no study has looked specifically at epigenomic landscapes throughout twin samples, discordant for Anorexia nervosa (AN). Our goal was to find evidence to confirm the hypothesis that epigenetic variations play a key role in the aetiology of AN. In this study, we quantified genome-wide patterns of DNA methylation using the Infinium Human DNA Methylation EPIC BeadChip array (“850 K”) in DNA samples isolated from whole blood collected from a group of 7 monozygotic twin pairs discordant for AN. Results were then validated performing a genome-wide DNA methylation profiling using DNA extracted from whole blood of a group of non-family-related AN patients and a group of healthy controls. Our first analysis using the twin sample revealed 9 CpGs associated to a gene. The validation analysis showed two statistically significant CpGs with the rank regression method related to two genes associated to metabolic traits, PPP2R2C and CHST1. When doing beta regression, 6 of them showed statistically significant differences, including 3 CpGs associated to genes JAM3, UBAP2L and SYNJ2. Finally, the overall pattern of results shows genetic links to phenotypes which the literature has constantly related to AN, including metabolic and psychological traits. The genes PPP2R2C and CHST1 have both been linked to the metabolic traits type 2 diabetes through GWAS studies. The genes UBAP2L and SYNJ2 have been related to other psychiatric comorbidity.

Unveiling Metabolic Phenotype Alterations in Anorexia Nervosa through Metabolomics

Anorexia nervosa (AN) is a mental disorder characterized by an intense fear of weight gain that affects mainly young women. It courses with a negative body image leading to altered eating behaviors that have devastating physical, metabolic, and psychological consequences for the patients. Although its origin is postulated to be multifactorial, the etiology of AN remains unknown, and this increases the likelihood of chronification and relapsing. Thus, expanding the available knowledge on the pathophysiology of AN is of enormous interest. Metabolomics is proposed as a powerful tool for the elucidation of disease mechanisms and to provide new insights into the diagnosis, treatment, and prognosis of AN. A review of the literature related to studies of AN patients by employing metabolomic strategies to characterize the main alterations associated with the metabolic phenotype of AN during the last 10 years is described. The most common metabolic alterations are derived from chronic starvation, including amino acid, lipid, and carbohydrate disturbances. Nonetheless, recent findings have shifted the attention to gut-microbiota metabolites as possible factors contributing to AN development, progression, and maintenance. We have identified the areas of ongoing research in AN and propose further perspectives to improve our knowledge and understanding of this disease.

A next generation sequencing gene panel for use in the diagnosis of anorexia nervosa.

The aim of this study was to increase knowledge of genes associated with anorexia nervosa (AN) and their diagnostic offer, using a next generation sequencing (NGS) panel for the identification of genetic variants. The rationale underlying this test is that we first analyze the genes associated with syndromic forms of AN, then genes that were found to carry rare variants in AN patients who had undergone segregation analysis, and finally candidate genes intervening in the same molecular pathways or identified by GWAS or in mouse models. We developed an NGS gene panel and used it to screen 68 Italian AN patients (63 females, 5 males). The panel included 162 genes. Family segregation study was conducted on available relatives of probands who reported significant genetic variants. In our analysis, we found potentially deleterious variants in 2 genes (PDE11A and SLC25A13) associated with syndromic forms of anorexia and predicted deleterious variants in the following 12 genes: CD36, CACNA1C, DRD4, EPHX2, ESR1, GRIN2A, GRIN3B, LRP2, NPY4R, PTGS2, PTPN22 and SGPP2. Furthermore, by Sanger sequencing of the promoter region of NNAT, we confirmed the involvement of this gene in the pathogenesis of AN. Family segregation studies further strengthened the possible causative role of CACNA1C, DRD4, GRIN2A, PTGS2, SGPP2, SLC25A13 and NNAT genes in AN etiology. The major finding of our study is the confirmation of the involvement of the NNAT gene in the pathogenesis of AN; furthermore, this study suggests that NGS-based testing can play an important role in the diagnostic evaluation of AN, excluding syndromic forms and increasing knowledge of the genetic etiology of AN. Level I, experimental study.

De novo deleterious variants that may alter the dopaminergic reward pathway are associated with anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. Up to now, four genome-wide association studies of AN have been conducted to date and identified only few significant loci. However, both previous studies focused on common variation and on rare exonic variants. Currently, de novo variants are one of the most significant risk factors for neurodevelopmental disorders and psychiatric disorders. We analyzed by whole exome sequencing a cohort of nine female AN individuals and their parents (mother and father), and focused our analysis on de novo variants. Here, we found seven de novo missense variants in potential genes in nine studied AN patients. Four of these genes (CSMD1, CREB3, PTPRD and GAB1) belong to a same signaling pathway involving neuron differentiation and dopamine pathway. This study provides a list of interesting genes such as CSDM1 and CREB3 that are candidates to be involved in the etiology of anorexia nervosa. basic research.

Histone deacetylase 4 (HDAC4): a new player in anorexia nervosa?

Anorexia nervosa (AN) and other eating disorders continue to constitute significant challenges for individual and public health. AN is thought to develop as a result of complex interactions between environmental triggers, psychological risk factors, sociocultural influences, and genetic vulnerability. Recent research developments have highlighted a novel potentially relevant component in the AN etiology-activity of the histone deacetylase 4 (HDAC4) gene that has emerged in several recent studies related to AN. HDAC4 is a member of the ubiquitously important family of epigenetic modifier enzymes called histone deacetylases and has beenimplicated in processes related to the formation and function of the central nervous system (CNS), bone, muscle, and metabolism. In a family affected by eating disorders, a missense mutation in HDAC4 (A786T) was found to segregate with the illness. The relevance of this mutation in eating-related behaviors was further confirmed with mouse models. Despite the fact thatHDAC4 has not been identified as a significant signal in genome-wide association studies in AN, several studies have found significant or near-significant methylation differences in HDAC4 locus in peripheral tissues of actively ill AN patients in comparison with different control groups. Limitations of these studies include a lack of understanding ofto what extent the changes in methylation are predictive of AN as such changes might also occur as a consequence of the disease. It remains to be determined how methylation in peripheral tissues correlates with that in the CNS and how different methylation patterns affect HDAC4 expression. The present review discusses the findings and potential roles of HDAC4 in AN. Its emerging roles in learning and neuroplasticity may be specific and relevant for the etiology of AN and potentially lead to novel therapeutic approaches.

63 - TRANSCRIPTOMIC IMPUTATION ANALYSIS IN ANOREXIA NERVOSA IDENTIFIES BOTH METABOLIC AND PSYCHIATRIC AETIOLOGIES

Background Anorexia Nervosa (AN) is a complex and serious eating disorder, occurring in ~1% of individuals. Despite having the highest mortality rate of any psychiatric disorder, little is known about the aetiology of the AN, and few effective treatments exist. Global efforts to collect large samples from individuals with AN have been highly successful, and a recent study consequently identified the first genome-wide significant locus involved in AN, with significant genetic correlations with multiple metabolic indices. This result, coupled with other recent studies and epidemiological evidence, implies that previous characterizations of AN as a purely psychiatric disorder should be revisited. Rather, it seems that both psychiatric and metabolic systems may be involved. Methods In order to elucidate more of the system-specific aetiology of AN, we applied transcriptomic imputation methods to 3,495 cases and 10,982 controls, collected by the PGC-ED working group. Transcriptomic Imputation (TI) methods approaches use machine-learning methods to impute tissue-specific gene expression from large genotype data using curated eQTL reference panels. These offer an exciting opportunity to compare gene associations across neurological and metabolic tissues. Here, we applied CommonMind Consortium (CMC) and GTEx-derived gene expression prediction models for 12 brain tissues and 12 tissues with potential metabolic involvement (Adipose, Adrenal Gland, 2 Colon, 3 Esophagus, Liver, Pancreas, Small Intestine, Spleen, Stomach). In total, these analyses include 234,968 gene-tissue association tests. Results We identified 35 significant gene-tissue associations within the large chromosome 12 region described in the recent PGC-ED GWAS. We applied a forward-stepwise conditional analysis analogous to GCTA-CoJo in order to identify independent associations within this region and across tissues, and identified two independently associated genes, both in metabolic tissues; RPS26, in the Spleen (p=2.59e-08), and C12orf49, in the Thyroid (p=4.01e-06). We also identified two further regions with genome-wide significant gene-tissue associations, both in brain tissues; REEP5, in the DLPFC (p=8.52e-07), and CUL3, in the Caudate Basal Ganglia (p=1.8e-06). Discussion Our results support a model of AN risk influenced by both metabolic and psychiatric factors. We plan to follow these analyses with investigations of the overlap between AN and other psychiatric and metabolic phenotypes, as well as analysis of potentially implicated molecular pathways.

M43 - A CROSS-DISORDER GENOME-WIDE ASSOCIATION STUDY OF ANOREXIA NERVOSA AND OBSESSIVE-COMPULSIVE DISORDER

Background This work is presented on behalf of the Eating Disorders and Tourette's/Obsessive-Compulsive Disorder Working Groups of the Psychiatric Genomics Consortium. Anorexia Nervosa (AN) is a serious psychiatric disorder with high mortality and morbidity, and Obsessive-Compulsive Disorder (OCD) is an idiopathic psychiatric condition that often follows a chronic course. Overlap of hallmark symptoms (e.g., compulsivity, cognitive rigidity), notable comorbidity, shared family history, and a high genetic correlation provide converging lines of evidence for shared etiology of AN and OCD, but the biological mechanisms behind this shared risk have yet to be uncovered. The aim of the present study was to examine the shared genetic risk factors for AN and OCD. Methods Under the umbrella of the Psychiatric Genomics Consortium, we conducted a meta-analysis of the most recent and largest AN and OCD Genome-Wide Association Studies (GWASes) to investigate risk variants common to both disorders. A total of 6,183 cases (3,495 AN and 2,688 OCD) and 18,013 controls were included in the meta-analysis of 8,062,640 variants conducted using METAL through the Ricopili pipeline. Results Although no variant reached genome-wide significance, the closest nearby genes for the variants with p Discussion In this first cross-disorder GWAS for AN and OCD, our preliminary results provide encouraging evidence for the shared genetic architecture of these two psychiatric disorders. Additional approaches such as gene- and gene-set based analyses, partitioned heritability analyses, and those making use of gene-expression data are underway and will supplement current results.

Associations between dimensions of anorexia nervosa and obsessive–compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. In path analyses (N=732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

How the Incorrect Belief That Eating Disorders Are Predominantly Genetic Is Maintained

The incorrect belief that anorexia nervosa is predominantly genetic is maintained in the psychiatric literature by a series of misquotations and misrepresentations of research data. An example of this type of scholarship is as an editorial in The American Journal of Psychiatry. Data from family and twin studies referenced in the editorial provide compelling evidence that the genetic contribution to the etiology of anorexia nervosa is small. The incorrect belief that anorexia nervosa is predominantly genetic is maintained, in addition, by statistical procedures such as heritability estimates. The incorrect belief that anorexia nervosa is predominantly genetic should not be endorsed by the American Psychiatric Association, in either its journals, in its published books, or in DSM–V.

Association between maternal body mass index in early pregnancy and anorexia nervosa in daughters.

The etiology of anorexia nervosa is poorly understood. Although genetic factors play a major role, maternal factors, and obstetric complications are possible environmental causes. We investigated the association between maternal overweight and obesity in early pregnancy and risk of anorexia nervosa in daughters. A retrospective cohort study including all live singleton females born in Sweden from 1992 through 2002. Anorexia nervosa diagnosis was identified by using the nation-wide Swedish Patient and Cause of Death Registers. Multivariable Cox hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% CIs, adjusting for confounders. Stratified Cox regressions were applied to data on siblings to adjust for unmeasured familial confounding. Among 486,688 live singleton females, 2,414 (0.50%) were diagnosed with anorexia nervosa through 2012. The aHR of anorexia nervosa decreased linearly by maternal BMI (p-value for trend < .001). When compared with daughters of normal weight mothers (body mass index [BMI] 18.5-24.9), aHRs (95%CI) of anorexia nervosa were 0.74 (0.65-0.84) in daughters of overweight mothers (BMI 25-29.9) and 0.61 (0.47-0.78) in daughters of mothers with obesity Grade I (BMI 30-34.9). In sibling control analysis, no associations were observed between maternal BMI and aHRs of anorexia nervosa in offspring. The rate of anorexia nervosa decreased with maternal overweight and obesity in a dose-response manner. However, the sibling control analysis suggests that these findings are not consistent with causals effects of maternal BMI on anorexia nervosa in offspring.

Anorexia: Highlights in Traditional Persian medicine and conventional medicine.

Anorexia and impaired appetite (Dysorexia) are common symptoms with varying causes, and often need no serious medical intervention. Anorexia nervosa (AN) is a chronic psychiatric disease with a high mortality rate. In Traditional Persian Medicine (TPM), anorexia is a condition in which anorexic patients lose appetite due to dystemperament. This review aims to discuss the common points of traditional and conventional approaches rather than introducing Persian medical recommendations suitable for nowadays use. For this purpose, Avicenna's Canon of Medicine, main TPM resources and important databases were reviewed using the related keywords. Despite complex hormonal explanation, etiology of AN in conventional approach is not completely understood. In TPM approach, the etiology and recommended interventions are thoroughly defined based on humoral pathophysiology. In TPM approach, disease states are regarded as the result of imbalances in organs' temperament and humors. In anorexia with simple dystemperament, the physician should attempt to balance the temperament using foods and medicaments which have opposite quality of temperament. Lifestyle, spiritual diseases (neuro - psychological) and gastrointestinal worms are the other causes for reducing appetite. Also, medicines and foods with warm temperaments (such as Pea soup and Mustard) are useful for these patients (cold temperament). Although the pathophysiology of AN in TPM is different in comparison with conventional views, TPM criteria for treatment this disorder is similar to those of current medicine. Recommending to have spiritual support and a healthy lifestyle are common in both views. Simple safe interventions recommended by TPM may be considered as alternative medical modalities after being confirmed by well-designed clinical trials.