Anorexia Nervosa

Psychiatric MONDO:0005351 Pathograph 12 Mental Health Disorder

Anorexia nervosa is an eating disorder characterized by persistent dietary restriction leading to significantly low body weight, fear of weight gain or behavior interfering with weight restoration, and disturbance in body-weight or shape experience.

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5
Pathophys.
13
Phenotypes
12
Pathograph
3
Treatments
4
Differentials
3
Datasets
3
Trials
85
References
2
Deep Research
⚙

Pathophysiology

5
Polygenic Metabo-Psychiatric Liability
Anorexia nervosa is modeled as a heritable, polygenic disorder with shared genetic architecture across psychiatric traits and pathways that plausibly influence metabolic and neurobehavioral vulnerability.
Downstream
Appetite and Restrictive-Eating Circuit Dysregulation Shared genetic liability is represented upstream of altered cognitive, reward, and appetite-control circuitry.
Starvation-Adaptation Endocrine Response Genetic and behavioral vulnerability is represented upstream of the sustained restriction that produces starvation-adaptation biology.
Show evidence (2 references)
DOI:10.1038/s41398-023-02585-1 SUPPORT Human Clinical
"Anorexia nervosa (AN) is a heritable eating disorder (50–60%) with an array of commonly comorbid psychiatric disorders and related traits."
GWAS cross-trait analysis supports heritable psychiatric genetic liability.
DOI:10.1038/s41398-023-02585-1 SUPPORT Computational
"Using conditional FDR we identified 58 novel AN loci."
This supports polygenic risk architecture rather than a single causal locus.
Appetite and Restrictive-Eating Circuit Dysregulation
Altered brain networks involved in appetite, valuation, cognitive control, and restrictive food choice are represented as circuit-level mechanisms contributing to persistent restrictive eating.
neuron link
regulation of appetite link ⚠ ABNORMAL feeding behavior link ⚠ ABNORMAL
brain link hypothalamus link prefrontal cortex link striatum link
Downstream
Abnormal Eating Behavior Circuit-level dysregulation is modeled upstream of restrictive eating and persistent food-choice behavior.
Low Body Weight and Weight Loss Persistent restriction contributes to low body weight and weight loss.
Show evidence (1 reference)
clinicaltrials:NCT05918835 SUPPORT
"This study will examine the impact of high-frequency repetitive transcranial magnetic stimulation on food choice behavior and related neural activity."
The trial record supports food-choice behavior and neural activity as a mechanistic target in AN.
Starvation-Adaptation Endocrine Response
Sustained energy restriction produces peripheral endocrine and metabolic changes involving appetite hormones, growth-axis markers, glucose, insulin, thyroid hormone, sex hormones, and leptin.
endocrine cell link
response to starvation link ⚠ ABNORMAL energy homeostasis link ⚠ ABNORMAL hormone-mediated signaling pathway link ⚠ ABNORMAL
Downstream
Immune and Microbiome-Associated Dysregulation Starvation-associated endocrine and metabolic changes are modeled upstream of systemic immune and microbiome-associated alterations.
Cardiovascular Complication Risk Starvation physiology contributes to downstream cardiovascular complications requiring clinical monitoring.
Show evidence (2 references)
DOI:10.3390/nu16132095 SUPPORT Human Clinical
"acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls."
Meta-analysis supports elevated endocrine and metabolic biomarkers in AN.
DOI:10.3390/nu16132095 SUPPORT Human Clinical
"Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation."
The authors explicitly connect biomarker differences with adaptation to starvation.
Immune and Microbiome-Associated Dysregulation
Adolescent AN is associated with non-uniform cytokine alterations and microbiome associations that vary across acute illness, weight recovery, and follow-up.
lymphocyte link
cytokine-mediated signaling pathway link ⚠ ABNORMAL
Downstream
Depression Cytokine and microbiome findings are associated with depressive symptoms in adolescent AN cohorts.
Show evidence (2 references)
DOI:10.3390/nu16111596 SUPPORT Human Clinical
"Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN."
Longitudinal adolescent case-control data support cytokine alterations in acute AN.
DOI:10.3390/nu16111596 SUPPORT Human Clinical
"We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome."
This directly links immune markers with clinical variables and the gut microbiome.
Cardiovascular Complication Risk
AN is associated with increased risk of major adverse cardiovascular events and other cardiovascular conditions, with some risks concentrated early after diagnosis and ischemic heart disease risk emerging later.
cardiovascular system link
Downstream
Bradycardia Cardiovascular monitoring addresses bradycardia and other complications of AN.
Show evidence (2 references)
DOI:10.1001/jamanetworkopen.2024.51094 SUPPORT Human Clinical
"The study population included 2081 patients with AN and 20 810 matched controls, for a total of 22 891 participants (mean [SD] age, 24.9 [9.9] years; 91.3% female)."
Matched national cohort data support cardiovascular-risk assessment.
DOI:10.1001/jamanetworkopen.2024.51094 SUPPORT Human Clinical
"Compared with the control group, the AN group had significantly higher risks of MACE (adjusted HR [AHR], 3.78; 95% CI, 2.83-5.05) and any cardiovascular condition (AHR, 1.93; 95% CI, 1.54-2.41)."
The cohort quantifies increased cardiovascular risk among AN patients.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Anorexia Nervosa Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

13
Cardiovascular 1
Bradycardia Bradycardia (HP:0001662)
Show evidence (2 references)
PMID:34418241 SUPPORT Human Clinical
"Forty-eight percent of the AN patient admissions were due to severe"
Hospitalized adolescent AN cohort data directly support severe bradycardia as a clinically important presentation.
PMID:40048192 SUPPORT Human Clinical
"eating disorders may cause electrolyte abnormalities, bradycardia, disturbances in reproductive hormones, and decreased bone density"
JAMA review identifies bradycardia as a medical complication of eating disorders including AN.
Digestive 1
Constipation Constipation (HP:0002019)
Genitourinary 1
Amenorrhea Amenorrhea (HP:0000141)
Show evidence (2 references)
DOI:10.3390/nu16132095 PARTIAL Human Clinical
"estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls."
Lower reproductive hormones support endocrine disruption relevant to menstrual abnormalities, but amenorrhea itself is not named in the abstract.
PMID:36401318 SUPPORT Human Clinical
"hypothalamic amenorrhoea, and longer illness"
Systematic review identifies hypothalamic amenorrhoea as an established feature and risk factor in AN.
Metabolism 2
Hypokalemia Hypokalemia (HP:0002900)
Show evidence (1 reference)
PMID:40048192 SUPPORT Human Clinical
"electrolyte abnormalities (eg, hyponatremia, hypokalemia), bradycardia, disturbances in reproductive hormones"
JAMA review explicitly names hypokalemia as an electrolyte abnormality associated with eating disorders.
Hyponatremia Hyponatremia (HP:0002902)
Show evidence (1 reference)
PMID:40048192 SUPPORT Human Clinical
"electrolyte abnormalities (eg, hyponatremia, hypokalemia), bradycardia, disturbances in reproductive hormones"
JAMA review explicitly names hyponatremia as an electrolyte abnormality associated with eating disorders.
Musculoskeletal 1
Reduced Bone Mineral Density Reduced bone mineral density (HP:0004349)
Show evidence (3 references)
PMID:40048192 SUPPORT Human Clinical
"eating disorders may cause electrolyte abnormalities, bradycardia, disturbances in reproductive hormones, and decreased bone density"
JAMA review identifies decreased bone density as a complication of eating disorders including AN.
PMID:36401318 SUPPORT Human Clinical
"BMD in individuals with AN (total body, spine, hip, and femur), with BN (total body and spine) and with OSFED (spine) was lower than in HC."
Meta-analysis of 43 studies (N=4163) confirms reduced BMD at all measured sites in AN compared with healthy controls.
PMID:34292351 SUPPORT Human Clinical
"BMD at the total hip was lower"
Case-control study in adolescent girls demonstrates reduced hip BMD at the time of AN diagnosis.
Nervous System 4
Abnormal Eating Behavior Abnormal eating behavior (HP:0100738)
Show evidence (1 reference)
clinicaltrials:NCT03984344 SUPPORT
"Anorexia Nervosa (AN) is a life-threatening eating disorder characterised by an intense fear of weight gain and disturbed body image, which motivates severe dietary restriction or other weight loss behaviours (e.g. purging)."
Trial background describes the restrictive-eating phenotype.
Anxiety Anxiety (HP:0000739)
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"It is frequently associated with other psychiatric disorders, such as depression, anxiety and obsessive-compulsive disorders as well as numerous physical complications."
Clinical update identifies anxiety as a frequent comorbidity.
Depression Depression (HP:0000716)
Show evidence (2 references)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"It is frequently associated with other psychiatric disorders, such as depression, anxiety and obsessive-compulsive disorders as well as numerous physical complications."
Clinical update identifies depression as a frequent comorbidity.
PMID:40048192 SUPPORT Human Clinical
"disorder have high lifetime rates of depression (76.3% for bulimia nervosa, 65.5% for binge-eating disorder, and 49.5% for anorexia nervosa)"
JAMA review quantifies lifetime depression rate at 49.5% for AN.
Suicidal Ideation Suicidal ideation (HP:0031589)
Show evidence (1 reference)
PMID:40048192 SUPPORT Human Clinical
"is associated with a mortality rate of 5.1 deaths per 1000 person-years (95% CI, 4.0-6.1), nearly 6 times higher than that of individuals of the same age without anorexia nervosa; 25% of deaths among individuals with anorexia nervosa are from suicide."
JAMA review reports that 25% of deaths in AN are from suicide, supporting the high prevalence of suicidal behavior.
Constitutional 1
Fatigue Fatigue (HP:0012378)
Growth 1
Low Body Weight and Weight Loss Weight loss (HP:0001824)
Show evidence (1 reference)
clinicaltrials:NCT03984344 SUPPORT
"Anorexia Nervosa (AN) is a life-threatening eating disorder characterised by an intense fear of weight gain and disturbed body image, which motivates severe dietary restriction or other weight loss behaviours (e.g. purging)."
Trial background directly connects AN with severe dietary restriction and weight loss behaviors.
Other 1
Obsessive-Compulsive Trait Obsessive-compulsive trait (HP:0008770)
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"It is frequently associated with other psychiatric disorders, such as depression, anxiety and obsessive-compulsive disorders as well as numerous physical complications."
Clinical update identifies obsessive-compulsive disorders as a frequent psychiatric comorbidity of AN.
💊

Treatments

3
Cognitive behavioral therapy
Action: cognitive behavior therapy MAXO:0000883
Cognitive behavioral therapy is a core psychotherapy for anorexia nervosa and is included among treatments of choice.
Target Phenotypes: Abnormal eating behavior ↗ Weight loss ↗
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"The treatment of choice for AN includes cognitive behavioral therapy and family-based therapy for children and adolescents."
Clinical update identifies cognitive behavioral therapy as part of the treatment of choice for AN.
Family-based therapy
Action: family therapy Ontology label: Family Therapy NCIT:C93347
Family-based therapy is a treatment of choice for children and adolescents with anorexia nervosa.
Target Phenotypes: Abnormal eating behavior ↗ Weight loss ↗
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"The treatment of choice for AN includes cognitive behavioral therapy and family-based therapy for children and adolescents."
Clinical update identifies family-based therapy as a treatment of choice for pediatric and adolescent AN.
Olanzapine pharmacotherapy for weight gain
Action: Pharmacotherapy NCIT:C15986
Agent: olanzapine ↗
Olanzapine has moderate evidence for supporting weight gain in anorexia nervosa, while psychopharmacotherapy otherwise lacks clear efficacy.
Target Phenotypes: Weight loss ↗
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"With the exception of moderate evidence supporting the use of olanzapine regarding weight gain, there is currently no evidence for the efficacy of psychopharmacotherapy in AN."
Clinical update supports olanzapine specifically for weight gain while cautioning against broad psychopharmacotherapy efficacy claims.
🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Anorexia Nervosa:

Avoidant/restrictive food intake disorder Not Yet Curated MONDO:7770002
Overlapping Features ARFID can involve restrictive intake and low weight, but lacks AN's body image or weight-gain fear motivation.
Show evidence (1 reference)
DOI:10.1111/jep.13586 PARTIAL Human Clinical
"Were AN motivation itself better understood, it would be possible to deal with non‐anorexic motivation by exclusion."
The ICD-11 analysis supports using motivation and exclusions to distinguish AN from non-AN restrictive intake.
Bulimia nervosa MONDO:0005452
Overlapping Features Bulimia nervosa can share weight-control behaviors such as purging, but does not require the persistent significantly low body weight that defines AN.
Show evidence (1 reference)
clinicaltrials:NCT03984344 PARTIAL
"severe dietary restriction or other weight loss behaviours (e.g. purging)."
Trial background supports purging as an AN-associated weight-loss behavior that can overlap with bulimia-spectrum presentations.
Major depressive disorder MONDO:0002009
Overlapping Features Depression can cause appetite and weight changes and is also a frequent AN comorbidity, so mood symptoms require separate assessment.
Show evidence (1 reference)
DOI:10.1007/s00115-025-01820-y SUPPORT Human Clinical
"It is frequently associated with other psychiatric disorders, such as depression, anxiety and obsessive-compulsive disorders as well as numerous physical complications."
Clinical update supports depression as a common comorbidity requiring differential and comorbidity assessment.
Celiac disease MONDO:0005130
Overlapping Features Celiac disease can cause weight loss and nutritional compromise through gastrointestinal disease rather than AN psychopathology.
Show evidence (1 reference)
DOI:10.1111/jep.13586 PARTIAL Other
"ICD‐11 efforts to minimize reliance on subjective motivation reveal limitations in exclusion criteria."
ICD-11 phenotype analysis supports the need for exclusion criteria when low weight may have non-AN explanations.
📊

Related Datasets

3
Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa DOI:10.1038/s41398-023-02585-1
GWAS summary-statistics analysis using conditional and conjunctional FDR to identify AN risk loci and shared loci with psychiatric disorders and traits.
Homo sapiens
Conditions: anorexia nervosa schizophrenia bipolar disorder major depression
Findings
Conditional FDR identified 58 novel AN loci and shared loci with major psychiatric disorders and psychological traits.
Show evidence (1 reference)
DOI:10.1038/s41398-023-02585-1 SUPPORT Human Clinical
"Furthermore, we identified 38 unique loci shared between AN and major psychiatric disorders (SCZ, BIP, and MD) and 45 between AN and psychological traits (Mood, NEUR, and INT)."
Captures the cross-disorder genetic-overlap finding.
DOI:10.1038/s41398-023-02585-1
Show evidence (1 reference)
DOI:10.1038/s41398-023-02585-1 SUPPORT Human Clinical
"Individual GWAS samples varied from 72,517 to 420,879 participants."
The abstract describes the dataset scale.
Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis DOI:10.3390/nu16132095
Meta-analysis of peripheral biomarkers comparing AN cases with non-AN control groups across endocrine, metabolic, immune, and growth-axis markers.
Homo sapiens
Conditions: anorexia nervosa control
Findings
AN cases differed from non-AN controls across ghrelin, ACTH, cortisol, growth-axis, glucose, insulin, leptin, sex-hormone, thyroid, CRP, and lymphocyte markers.
Show evidence (1 reference)
DOI:10.3390/nu16132095 SUPPORT Human Clinical
"Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly..."
Captures the lower-biomarker portion of the meta-analysis findings.
DOI:10.3390/nu16132095
Show evidence (1 reference)
DOI:10.3390/nu16132095 SUPPORT Human Clinical
"We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers"
The abstract describes the biomarker meta-analysis design.
Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa DOI:10.1001/jamanetworkopen.2024.51094
Population-based matched cohort study of cardiovascular outcomes in AN patients and matched controls from Taiwan's national health insurance data.
Homo sapiens n=22891
Conditions: anorexia nervosa matched controls
Findings
AN was associated with higher risk of major adverse cardiovascular events and any cardiovascular condition.
Show evidence (1 reference)
DOI:10.1001/jamanetworkopen.2024.51094 SUPPORT Human Clinical
"In total, 99 patients with AN (4.8%) had MACE vs 175 (0.8%) in controls, and 124 patients with AN (6.0%) had any cardiovascular condition vs 483 controls (2.3%)."
Captures the main cardiovascular event difference in the cohort.
DOI:10.1001/jamanetworkopen.2024.51094
Show evidence (1 reference)
DOI:10.1001/jamanetworkopen.2024.51094 SUPPORT Human Clinical
"From a population-based health insurance database from January 1, 2011, to December 31, 2021, this longitudinal cohort study identified patients with AN and controls through propensity score matching at a 1:10 ratio"
The abstract describes the cohort design and matching strategy.
🔬

Clinical Trials

3
NCT05918835 NOT_APPLICABLE RECRUITING
High-frequency repetitive transcranial magnetic stimulation study of food choice behavior and related neural activity in AN.
Target Phenotypes: Abnormal eating behavior ↗
Show evidence (1 reference)
clinicaltrials:NCT05918835 SUPPORT
"This study will examine the impact of high-frequency repetitive transcranial magnetic stimulation on food choice behavior and related neural activity."
ClinicalTrials.gov record documents an rTMS study targeting food-choice behavior and neural activity.
NCT05788042 NOT_APPLICABLE RECRUITING
Randomized double-blinded sham-controlled trial comparing tDCS and rTMS for psychological and eating-disorder symptoms in AN.
Target Phenotypes: Abnormal eating behavior ↗
Show evidence (1 reference)
clinicaltrials:NCT05788042 SUPPORT
"Here the investigators propose to conduct the first double-blinded, randomised sham-controlled study to directly compare the therapeutic effectiveness and acceptability of both treatment modalities."
ClinicalTrials.gov record documents a randomized neurostimulation trial in AN.
NCT03984344 NOT_APPLICABLE UNKNOWN
Feasibility trial of intermittent and continuous theta burst stimulation compared with sham stimulation for short-term effects on AN symptoms.
Target Phenotypes: Abnormal eating behavior ↗
Show evidence (1 reference)
clinicaltrials:NCT03984344 SUPPORT
"This study will use a novel type of rTMS, theta burst stimulation (TBS), including intermittent TBS (iTBS) and continuous TBS (cTBS)."
ClinicalTrials.gov record documents a theta burst stimulation feasibility study for AN.
{ }

Source YAML

click to show 
name: Anorexia Nervosa
creation_date: "2026-04-24T20:56:38Z"
updated_date: "2026-05-05T11:26:22Z"
category: Psychiatric
description: >-
  Anorexia nervosa is an eating disorder characterized by persistent dietary
  restriction leading to significantly low body weight, fear of weight gain or
  behavior interfering with weight restoration, and disturbance in body-weight
  or shape experience.
disease_term:
  preferred_term: anorexia nervosa
  term:
    id: MONDO:0005351
    label: anorexia nervosa
parents:
- Mental Health Disorder
prevalence:
- population: global eating-disorder populations
  percentage: 2.58
  notes: >-
    Rapid review reports lifetime prevalence ranges for any eating disorder;
    this is broader than anorexia nervosa specifically and is included as
    context for disease-burden estimates.
  evidence:
  - reference: DOI:10.1186/s40337-023-00738-7
    reference_title: "Epidemiology of eating disorders: population, prevalence, disease burden and quality of life informing public policy in Australia—a rapid review"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Global Lifetime prevalence of any eating disorder ranged from 0.74 to
      2.2% in males, and 2.58–8.4% in females.
    explanation: >-
      The estimate is for eating disorders overall, not AN specifically, and
      therefore provides broader epidemiologic context.
pathophysiology:
- name: Polygenic Metabo-Psychiatric Liability
  description: >-
    Anorexia nervosa is modeled as a heritable, polygenic disorder with shared
    genetic architecture across psychiatric traits and pathways that plausibly
    influence metabolic and neurobehavioral vulnerability.
  downstream:
  - target: Appetite and Restrictive-Eating Circuit Dysregulation
    description: >-
      Shared genetic liability is represented upstream of altered cognitive,
      reward, and appetite-control circuitry.
  - target: Starvation-Adaptation Endocrine Response
    description: >-
      Genetic and behavioral vulnerability is represented upstream of the
      sustained restriction that produces starvation-adaptation biology.
  evidence:
  - reference: DOI:10.1038/s41398-023-02585-1
    reference_title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Anorexia nervosa (AN) is a heritable eating disorder (50–60%) with an
      array of commonly comorbid psychiatric disorders and related traits.
    explanation: >-
      GWAS cross-trait analysis supports heritable psychiatric genetic
      liability.
  - reference: DOI:10.1038/s41398-023-02585-1
    reference_title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      Using conditional FDR we identified 58 novel AN loci.
    explanation: >-
      This supports polygenic risk architecture rather than a single causal
      locus.
- name: Appetite and Restrictive-Eating Circuit Dysregulation
  description: >-
    Altered brain networks involved in appetite, valuation, cognitive control,
    and restrictive food choice are represented as circuit-level mechanisms
    contributing to persistent restrictive eating.
  biological_processes:
  - preferred_term: regulation of appetite
    term:
      id: GO:0032098
      label: regulation of appetite
    modifier: ABNORMAL
  - preferred_term: feeding behavior
    term:
      id: GO:0007631
      label: feeding behavior
    modifier: ABNORMAL
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: hypothalamus
    term:
      id: UBERON:0001898
      label: hypothalamus
  - preferred_term: prefrontal cortex
    term:
      id: UBERON:0000451
      label: prefrontal cortex
  - preferred_term: striatum
    term:
      id: UBERON:0002435
      label: striatum
  downstream:
  - target: Abnormal Eating Behavior
    description: >-
      Circuit-level dysregulation is modeled upstream of restrictive eating and
      persistent food-choice behavior.
  - target: Low Body Weight and Weight Loss
    description: >-
      Persistent restriction contributes to low body weight and weight loss.
  evidence:
  - reference: clinicaltrials:NCT05918835
    reference_title: Deciphering the Neural Mechanisms of Restrictive Eating in Anorexia Nervosa Using Repetitive Transcranial Magnetic Stimulation
    supports: SUPPORT
    snippet: >-
      This study will examine the impact of high-frequency repetitive
      transcranial magnetic stimulation on food choice behavior and related
      neural activity.
    explanation: >-
      The trial record supports food-choice behavior and neural activity as a
      mechanistic target in AN.
- name: Starvation-Adaptation Endocrine Response
  description: >-
    Sustained energy restriction produces peripheral endocrine and metabolic
    changes involving appetite hormones, growth-axis markers, glucose, insulin,
    thyroid hormone, sex hormones, and leptin.
  biological_processes:
  - preferred_term: response to starvation
    term:
      id: GO:0042594
      label: response to starvation
    modifier: ABNORMAL
  - preferred_term: energy homeostasis
    term:
      id: GO:0097009
      label: energy homeostasis
    modifier: ABNORMAL
  - preferred_term: hormone-mediated signaling pathway
    term:
      id: GO:0009755
      label: hormone-mediated signaling pathway
    modifier: ABNORMAL
  cell_types:
  - preferred_term: endocrine cell
    term:
      id: CL:0000163
      label: endocrine cell
  downstream:
  - target: Immune and Microbiome-Associated Dysregulation
    description: >-
      Starvation-associated endocrine and metabolic changes are modeled
      upstream of systemic immune and microbiome-associated alterations.
  - target: Cardiovascular Complication Risk
    description: >-
      Starvation physiology contributes to downstream cardiovascular
      complications requiring clinical monitoring.
  evidence:
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal
      collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin,
      ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor
      levels were significantly higher in cases of AN compared with those in
      non-AN controls.
    explanation: >-
      Meta-analysis supports elevated endocrine and metabolic biomarkers in AN.
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our findings indicate that peripheral biomarkers may be linked to the
      pathophysiology of AN, such as processes of adaptation to starvation.
    explanation: >-
      The authors explicitly connect biomarker differences with adaptation to
      starvation.
- name: Immune and Microbiome-Associated Dysregulation
  description: >-
    Adolescent AN is associated with non-uniform cytokine alterations and
    microbiome associations that vary across acute illness, weight recovery,
    and follow-up.
  biological_processes:
  - preferred_term: cytokine-mediated signaling pathway
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    modifier: ABNORMAL
  cell_types:
  - preferred_term: lymphocyte
    term:
      id: CL:0000542
      label: lymphocyte
  downstream:
  - target: Depression
    description: >-
      Cytokine and microbiome findings are associated with depressive symptoms
      in adolescent AN cohorts.
  evidence:
  - reference: DOI:10.3390/nu16111596
    reference_title: "Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Relative to the HC group, serum levels of IL-1β and IL-6 were
      significantly lower during the acute phase (admission) of AN.
    explanation: >-
      Longitudinal adolescent case-control data support cytokine alterations in
      acute AN.
  - reference: DOI:10.3390/nu16111596
    reference_title: "Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found associations between cytokines and bodyweight, illness duration,
      depressive symptoms, and the microbiome.
    explanation: >-
      This directly links immune markers with clinical variables and the gut
      microbiome.
- name: Cardiovascular Complication Risk
  description: >-
    AN is associated with increased risk of major adverse cardiovascular events
    and other cardiovascular conditions, with some risks concentrated early
    after diagnosis and ischemic heart disease risk emerging later.
  locations:
  - preferred_term: cardiovascular system
    term:
      id: UBERON:0004535
      label: cardiovascular system
  downstream:
  - target: Bradycardia
    description: >-
      Cardiovascular monitoring addresses bradycardia and other complications
      of AN.
  evidence:
  - reference: DOI:10.1001/jamanetworkopen.2024.51094
    reference_title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The study population included 2081 patients with AN and 20 810 matched
      controls, for a total of 22 891 participants (mean [SD] age, 24.9 [9.9]
      years; 91.3% female).
    explanation: >-
      Matched national cohort data support cardiovascular-risk assessment.
  - reference: DOI:10.1001/jamanetworkopen.2024.51094
    reference_title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the control group, the AN group had significantly higher
      risks of MACE (adjusted HR [AHR], 3.78; 95% CI, 2.83-5.05) and any
      cardiovascular condition (AHR, 1.93; 95% CI, 1.54-2.41).
    explanation: >-
      The cohort quantifies increased cardiovascular risk among AN patients.
phenotypes:
- name: Abnormal Eating Behavior
  category: Behavioral
  description: >-
    Restrictive eating and food avoidance are core behavioral manifestations of
    AN.
  phenotype_term:
    preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  evidence:
  - reference: clinicaltrials:NCT03984344
    reference_title: A Feasibility Trial of Theta Burst Stimulation in Anorexia Nervosa (AN)
    supports: SUPPORT
    snippet: >-
      Anorexia Nervosa (AN) is a life-threatening eating disorder characterised
      by an intense fear of weight gain and disturbed body image, which
      motivates severe dietary restriction or other weight loss behaviours
      (e.g. purging).
    explanation: >-
      Trial background describes the restrictive-eating phenotype.
- name: Low Body Weight and Weight Loss
  category: Clinical Sign
  description: >-
    Restriction produces low body weight and may present clinically as weight
    loss or failure to maintain expected weight.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: clinicaltrials:NCT03984344
    reference_title: A Feasibility Trial of Theta Burst Stimulation in Anorexia Nervosa (AN)
    supports: SUPPORT
    snippet: >-
      Anorexia Nervosa (AN) is a life-threatening eating disorder characterised
      by an intense fear of weight gain and disturbed body image, which
      motivates severe dietary restriction or other weight loss behaviours
      (e.g. purging).
    explanation: >-
      Trial background directly connects AN with severe dietary restriction and
      weight loss behaviors.
- name: Bradycardia
  category: Clinical Sign
  description: >-
    Bradycardia is a clinically important cardiovascular sign in AN and is part
    of the broader cardiovascular monitoring burden.
  phenotype_term:
    preferred_term: Bradycardia
    term:
      id: HP:0001662
      label: Bradycardia
  evidence:
  - reference: PMID:34418241
    reference_title: "Determinants of severe bradycardia in adolescents hospitalized for anorexia nervosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Forty-eight percent of the AN patient admissions were due to severe"
    explanation: >-
      Hospitalized adolescent AN cohort data directly support severe
      bradycardia as a clinically important presentation.
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      eating disorders may cause electrolyte
      abnormalities, bradycardia, disturbances in reproductive hormones, and decreased
      bone density
    explanation: >-
      JAMA review identifies bradycardia as a medical complication of
      eating disorders including AN.
- name: Amenorrhea
  category: Clinical Sign
  description: >-
    Amenorrhea can occur in AN, although modern diagnostic systems do not
    require it as a criterion.
  phenotype_term:
    preferred_term: Amenorrhea
    term:
      id: HP:0000141
      label: Amenorrhea
  evidence:
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      estradiol, follicle-stimulating hormone (FSH), free thyroxine, free
      triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1),
      leptin, luteinizing hormone, lymphocyte, and prolactin levels were
      significantly lower in AN compared with those in non-AN controls.
    explanation: >-
      Lower reproductive hormones support endocrine disruption relevant to
      menstrual abnormalities, but amenorrhea itself is not named in the
      abstract.
  - reference: PMID:36401318
    reference_title: "Associations between bone mineral density, body composition and amenorrhoea in females with eating disorders: a systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "hypothalamic amenorrhoea, and longer illness"
    explanation: >-
      Systematic review identifies hypothalamic amenorrhoea as an established
      feature and risk factor in AN.
- name: Anxiety
  category: Behavioral
  description: Anxiety is a common psychiatric comorbidity in AN.
  phenotype_term:
    preferred_term: Anxiety
    term:
      id: HP:0000739
      label: Anxiety
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is frequently associated with other psychiatric disorders, such as
      depression, anxiety and obsessive-compulsive disorders as well as
      numerous physical complications.
    explanation: >-
      Clinical update identifies anxiety as a frequent comorbidity.
- name: Depression
  category: Behavioral
  description: Depression is a common psychiatric comorbidity in AN.
  phenotype_term:
    preferred_term: Depression
    term:
      id: HP:0000716
      label: Depression
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is frequently associated with other psychiatric disorders, such as
      depression, anxiety and obsessive-compulsive disorders as well as
      numerous physical complications.
    explanation: >-
      Clinical update identifies depression as a frequent comorbidity.
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      disorder have high lifetime rates of depression (76.3% for bulimia nervosa,
      65.5% for binge-eating disorder, and 49.5% for anorexia nervosa)
    explanation: >-
      JAMA review quantifies lifetime depression rate at 49.5% for AN.
- name: Reduced Bone Mineral Density
  category: Clinical Sign
  description: >-
    Reduced bone mineral density is a serious skeletal complication of anorexia
    nervosa, increasing the risk of osteoporosis and fractures. Low weight,
    amenorrhoea, and malnutrition are established risk factors.
  phenotype_term:
    preferred_term: Reduced bone mineral density
    term:
      id: HP:0004349
      label: Reduced bone mineral density
  evidence:
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      eating disorders may cause electrolyte
      abnormalities, bradycardia, disturbances in reproductive hormones, and decreased
      bone density
    explanation: >-
      JAMA review identifies decreased bone density as a complication of
      eating disorders including AN.
  - reference: PMID:36401318
    reference_title: "Associations between bone mineral density, body composition and amenorrhoea in females with eating disorders: a systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      BMD in individuals with AN (total body, spine, hip, and
      femur), with BN (total body and spine) and with OSFED (spine) was lower than in
      HC.
    explanation: >-
      Meta-analysis of 43 studies (N=4163) confirms reduced BMD at all
      measured sites in AN compared with healthy controls.
  - reference: PMID:34292351
    reference_title: Bone mineral density and oxidative stress in adolescent girls with anorexia nervosa.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BMD at the total hip was lower"
    explanation: >-
      Case-control study in adolescent girls demonstrates reduced hip BMD
      at the time of AN diagnosis.
- name: Hypokalemia
  category: Clinical Sign
  description: >-
    Hypokalemia is an electrolyte abnormality seen in anorexia nervosa,
    particularly in patients with purging behaviors. It can contribute to
    cardiac arrhythmias and muscle weakness.
  phenotype_term:
    preferred_term: Hypokalemia
    term:
      id: HP:0002900
      label: Hypokalemia
  evidence:
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      electrolyte abnormalities
      (eg, hyponatremia, hypokalemia), bradycardia, disturbances in reproductive
      hormones
    explanation: >-
      JAMA review explicitly names hypokalemia as an electrolyte abnormality
      associated with eating disorders.
- name: Hyponatremia
  category: Clinical Sign
  description: >-
    Hyponatremia is an electrolyte abnormality that can occur in anorexia
    nervosa, potentially related to excessive water intake or impaired
    renal concentrating ability.
  phenotype_term:
    preferred_term: Hyponatremia
    term:
      id: HP:0002902
      label: Hyponatremia
  evidence:
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      electrolyte abnormalities
      (eg, hyponatremia, hypokalemia), bradycardia, disturbances in reproductive
      hormones
    explanation: >-
      JAMA review explicitly names hyponatremia as an electrolyte abnormality
      associated with eating disorders.
- name: Obsessive-Compulsive Trait
  category: Behavioral
  description: >-
    Obsessive-compulsive traits and comorbid obsessive-compulsive disorder
    are frequently observed in anorexia nervosa, manifesting as rigidity
    around food rituals, body checking, and perfectionism.
  phenotype_term:
    preferred_term: Obsessive-compulsive trait
    term:
      id: HP:0008770
      label: Obsessive-compulsive trait
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is frequently associated with other psychiatric disorders, such as
      depression, anxiety and obsessive-compulsive disorders as well as
      numerous physical complications.
    explanation: >-
      Clinical update identifies obsessive-compulsive disorders as a frequent
      psychiatric comorbidity of AN.
- name: Suicidal Ideation
  category: Behavioral
  description: >-
    Suicidal ideation and suicide attempts are elevated in anorexia nervosa.
    Approximately 25% of deaths among individuals with AN are from suicide.
  phenotype_term:
    preferred_term: Suicidal ideation
    term:
      id: HP:0031589
      label: Suicidal ideation
  evidence:
  - reference: PMID:40048192
    reference_title: "Eating Disorders: A Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: |-
      is associated with a mortality rate of 5.1 deaths per 1000 person-years (95% CI,
      4.0-6.1), nearly 6 times higher than that of individuals of the same age without
      anorexia nervosa; 25% of deaths among individuals with anorexia nervosa are from
      suicide.
    explanation: >-
      JAMA review reports that 25% of deaths in AN are from suicide,
      supporting the high prevalence of suicidal behavior.
- name: Fatigue
  category: Clinical Sign
  description: >-
    Fatigue is a common symptom of anorexia nervosa resulting from caloric
    restriction, nutritional deficiency, and metabolic derangement.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
- name: Constipation
  category: Clinical Sign
  description: >-
    Constipation is a common gastrointestinal complaint in anorexia nervosa,
    resulting from inadequate caloric intake, dehydration, and slowed
    gastrointestinal motility.
  phenotype_term:
    preferred_term: Constipation
    term:
      id: HP:0002019
      label: Constipation
diagnosis:
- name: Clinical eating-disorder assessment
  presence: >-
    Diagnosis is clinical and based on low body weight, restrictive behavior,
    body image or weight-gain fear features, impairment, and exclusion of other
    causes of low weight or self-starvation.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  evidence:
  - reference: DOI:10.1111/jep.13586
    reference_title: "Capturing the anorexia nervosa phenotype: Conceptual and normative issues in <scp>ICD</scp>‐11"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At least with present day medical and scientific knowledge, a complete
      characterization of the AN phenotype cannot be achieved without reference
      to psychological states of motivation.
    explanation: >-
      ICD-11 phenotype analysis supports clinical evaluation of motivation and
      symptom context.
- name: Nutritional and medical risk assessment
  presence: >-
    Weight, nutritional status, endocrine/metabolic complications, and medical
    instability are assessed to stratify acuity and guide treatment setting.
  diagnosis_term:
    preferred_term: nutrition assessment
    term:
      id: MAXO:0000624
      label: nutrition assessment
  evidence:
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Scientific investigation into peripheral biomarkers may ultimately yield
      breakthroughs in personalized clinical care for AN.
    explanation: >-
      Biomarker review supports assessment of peripheral biological state for
      future personalized care, while current nutritional assessment remains
      clinical.
- name: Cardiovascular monitoring
  presence: >-
    Electrocardiography and cardiovascular assessment are used when medical
    instability, bradycardia, conduction concerns, or other cardiac
    complications are suspected.
  diagnosis_term:
    preferred_term: electrocardiography
    term:
      id: MAXO:0000900
      label: electrocardiography
  evidence:
  - reference: DOI:10.1001/jamanetworkopen.2024.51094
    reference_title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinicians should monitor comorbid cardiovascular conditions among
      patients with AN at initial presentation, during treatment, and at
      follow-up.
    explanation: >-
      Cohort results support cardiovascular monitoring in AN.
- name: Peripheral biomarkers are investigational
  presence: >-
    Peripheral endocrine, metabolic, and immune markers differ between AN and
    controls in research studies but are not established as stand-alone
    diagnostic biomarkers.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  evidence:
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      However, reliable biomarkers for AN have yet to be established.
    explanation: >-
      Meta-analysis explicitly cautions that biomarkers are not yet reliable
      diagnostic tools.
differential_diagnoses:
- name: Avoidant/restrictive food intake disorder
  description: >-
    ARFID can involve restrictive intake and low weight, but lacks AN's body
    image or weight-gain fear motivation.
  disease_term:
    preferred_term: avoidant/restrictive food intake disorder
    term:
      id: MONDO:7770002
      label: avoidant/restrictive food intake disorder
  evidence:
  - reference: DOI:10.1111/jep.13586
    reference_title: "Capturing the anorexia nervosa phenotype: Conceptual and normative issues in <scp>ICD</scp>‐11"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Were AN motivation itself better understood, it would be possible to deal
      with non‐anorexic motivation by exclusion.
    explanation: >-
      The ICD-11 analysis supports using motivation and exclusions to
      distinguish AN from non-AN restrictive intake.
- name: Bulimia nervosa
  description: >-
    Bulimia nervosa can share weight-control behaviors such as purging, but
    does not require the persistent significantly low body weight that defines
    AN.
  disease_term:
    preferred_term: bulimia nervosa
    term:
      id: MONDO:0005452
      label: bulimia nervosa
  evidence:
  - reference: clinicaltrials:NCT03984344
    reference_title: A Feasibility Trial of Theta Burst Stimulation in Anorexia Nervosa (AN)
    supports: PARTIAL
    snippet: >-
      severe dietary restriction or other weight loss behaviours (e.g.
      purging).
    explanation: >-
      Trial background supports purging as an AN-associated weight-loss
      behavior that can overlap with bulimia-spectrum presentations.
- name: Major depressive disorder
  description: >-
    Depression can cause appetite and weight changes and is also a frequent AN
    comorbidity, so mood symptoms require separate assessment.
  disease_term:
    preferred_term: major depressive disorder
    term:
      id: MONDO:0002009
      label: major depressive disorder
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is frequently associated with other psychiatric disorders, such as
      depression, anxiety and obsessive-compulsive disorders as well as
      numerous physical complications.
    explanation: >-
      Clinical update supports depression as a common comorbidity requiring
      differential and comorbidity assessment.
- name: Celiac disease
  description: >-
    Celiac disease can cause weight loss and nutritional compromise through
    gastrointestinal disease rather than AN psychopathology.
  disease_term:
    preferred_term: celiac disease
    term:
      id: MONDO:0005130
      label: celiac disease
  evidence:
  - reference: DOI:10.1111/jep.13586
    reference_title: "Capturing the anorexia nervosa phenotype: Conceptual and normative issues in <scp>ICD</scp>‐11"
    supports: PARTIAL
    evidence_source: OTHER
    snippet: >-
      ICD‐11 efforts to minimize reliance on subjective motivation reveal
      limitations in exclusion criteria.
    explanation: >-
      ICD-11 phenotype analysis supports the need for exclusion criteria when
      low weight may have non-AN explanations.
treatments:
- name: Cognitive behavioral therapy
  description: >-
    Cognitive behavioral therapy is a core psychotherapy for anorexia nervosa
    and is included among treatments of choice.
  treatment_term:
    preferred_term: cognitive behavior therapy
    term:
      id: MAXO:0000883
      label: cognitive behavior therapy
  target_phenotypes:
  - preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  - preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The treatment of choice for AN includes cognitive behavioral therapy and
      family-based therapy for children and adolescents.
    explanation: >-
      Clinical update identifies cognitive behavioral therapy as part of the
      treatment of choice for AN.
- name: Family-based therapy
  description: >-
    Family-based therapy is a treatment of choice for children and adolescents
    with anorexia nervosa.
  treatment_term:
    preferred_term: family therapy
    term:
      id: NCIT:C93347
      label: Family Therapy
  target_phenotypes:
  - preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  - preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The treatment of choice for AN includes cognitive behavioral therapy and
      family-based therapy for children and adolescents.
    explanation: >-
      Clinical update identifies family-based therapy as a treatment of choice
      for pediatric and adolescent AN.
- name: Olanzapine pharmacotherapy for weight gain
  description: >-
    Olanzapine has moderate evidence for supporting weight gain in anorexia
    nervosa, while psychopharmacotherapy otherwise lacks clear efficacy.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: olanzapine
      term:
        id: CHEBI:7735
        label: olanzapine
  target_phenotypes:
  - preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: DOI:10.1007/s00115-025-01820-y
    reference_title: Anorexia nervosa—an update
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      With the exception of moderate evidence supporting the use of olanzapine
      regarding weight gain, there is currently no evidence for the efficacy of
      psychopharmacotherapy in AN.
    explanation: >-
      Clinical update supports olanzapine specifically for weight gain while
      cautioning against broad psychopharmacotherapy efficacy claims.
clinical_trials:
- name: NCT05918835
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    High-frequency repetitive transcranial magnetic stimulation study of food
    choice behavior and related neural activity in AN.
  target_phenotypes:
  - preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  evidence:
  - reference: clinicaltrials:NCT05918835
    reference_title: Deciphering the Neural Mechanisms of Restrictive Eating in Anorexia Nervosa Using Repetitive Transcranial Magnetic Stimulation
    supports: SUPPORT
    snippet: >-
      This study will examine the impact of high-frequency repetitive
      transcranial magnetic stimulation on food choice behavior and related
      neural activity.
    explanation: >-
      ClinicalTrials.gov record documents an rTMS study targeting food-choice
      behavior and neural activity.
- name: NCT05788042
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    Randomized double-blinded sham-controlled trial comparing tDCS and rTMS
    for psychological and eating-disorder symptoms in AN.
  target_phenotypes:
  - preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  evidence:
  - reference: clinicaltrials:NCT05788042
    reference_title: Randomised Controlled Trial of Neurostimulation for Symptoms of Anorexia Nervosa
    supports: SUPPORT
    snippet: >-
      Here the investigators propose to conduct the first double-blinded,
      randomised sham-controlled study to directly compare the therapeutic
      effectiveness and acceptability of both treatment modalities.
    explanation: >-
      ClinicalTrials.gov record documents a randomized neurostimulation trial
      in AN.
- name: NCT03984344
  phase: NOT_APPLICABLE
  status: UNKNOWN
  description: >-
    Feasibility trial of intermittent and continuous theta burst stimulation
    compared with sham stimulation for short-term effects on AN symptoms.
  target_phenotypes:
  - preferred_term: Abnormal eating behavior
    term:
      id: HP:0100738
      label: Abnormal eating behavior
  evidence:
  - reference: clinicaltrials:NCT03984344
    reference_title: A Feasibility Trial of Theta Burst Stimulation in Anorexia Nervosa (AN)
    supports: SUPPORT
    snippet: >-
      This study will use a novel type of rTMS, theta burst stimulation (TBS),
      including intermittent TBS (iTBS) and continuous TBS (cTBS).
    explanation: >-
      ClinicalTrials.gov record documents a theta burst stimulation feasibility
      study for AN.
datasets:
- accession: DOI:10.1038/s41398-023-02585-1
  title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
  description: >-
    GWAS summary-statistics analysis using conditional and conjunctional FDR to
    identify AN risk loci and shared loci with psychiatric disorders and traits.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  conditions:
  - anorexia nervosa
  - schizophrenia
  - bipolar disorder
  - major depression
  publication: DOI:10.1038/s41398-023-02585-1
  evidence:
  - reference: DOI:10.1038/s41398-023-02585-1
    reference_title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Individual GWAS samples varied from 72,517 to 420,879 participants.
    explanation: >-
      The abstract describes the dataset scale.
  findings:
  - statement: Conditional FDR identified 58 novel AN loci and shared loci with major psychiatric disorders and psychological traits.
    evidence:
    - reference: DOI:10.1038/s41398-023-02585-1
      reference_title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Furthermore, we identified 38 unique loci shared between AN and major
        psychiatric disorders (SCZ, BIP, and MD) and 45 between AN and
        psychological traits (Mood, NEUR, and INT).
      explanation: >-
        Captures the cross-disorder genetic-overlap finding.
- accession: DOI:10.3390/nu16132095
  title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
  description: >-
    Meta-analysis of peripheral biomarkers comparing AN cases with non-AN
    control groups across endocrine, metabolic, immune, and growth-axis
    markers.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  conditions:
  - anorexia nervosa
  - control
  publication: DOI:10.3390/nu16132095
  evidence:
  - reference: DOI:10.3390/nu16132095
    reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We conducted two-level random-effects meta-analyses to examine the
      difference between AN and comparison groups across 52 distinct biomarkers
    explanation: >-
      The abstract describes the biomarker meta-analysis design.
  findings:
  - statement: AN cases differed from non-AN controls across ghrelin, ACTH, cortisol, growth-axis, glucose, insulin, leptin, sex-hormone, thyroid, CRP, and lymphocyte markers.
    evidence:
    - reference: DOI:10.3390/nu16132095
      reference_title: "Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine,
        estradiol, follicle-stimulating hormone (FSH), free thyroxine, free
        triiodothyronine, glucose, insulin, insulin-like growth factor 1
        (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels
        were significantly lower in AN compared with those in non-AN controls.
      explanation: >-
        Captures the lower-biomarker portion of the meta-analysis findings.
- accession: DOI:10.1001/jamanetworkopen.2024.51094
  title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
  description: >-
    Population-based matched cohort study of cardiovascular outcomes in AN
    patients and matched controls from Taiwan's national health insurance data.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 22891
  conditions:
  - anorexia nervosa
  - matched controls
  publication: DOI:10.1001/jamanetworkopen.2024.51094
  evidence:
  - reference: DOI:10.1001/jamanetworkopen.2024.51094
    reference_title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      From a population-based health insurance database from January 1, 2011,
      to December 31, 2021, this longitudinal cohort study identified patients
      with AN and controls through propensity score matching at a 1:10 ratio
    explanation: >-
      The abstract describes the cohort design and matching strategy.
  findings:
  - statement: AN was associated with higher risk of major adverse cardiovascular events and any cardiovascular condition.
    evidence:
    - reference: DOI:10.1001/jamanetworkopen.2024.51094
      reference_title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In total, 99 patients with AN (4.8%) had MACE vs 175 (0.8%) in
        controls, and 124 patients with AN (6.0%) had any cardiovascular
        condition vs 483 controls (2.3%).
      explanation: >-
        Captures the main cardiovascular event difference in the cohort.
notes: >-
  Pathophysiology entries are separated into genetic liability, circuit
  dysregulation, starvation endocrine response, immune/microbiome changes, and
  cardiovascular complications so causal relationships are represented with
  downstream edges.
references:
- reference: DOI:10.1002/eat.24296
  title: Postdischarge Mortality in a Cohort Hospitalized With Anorexia Nervosa
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: Postdischarge Mortality in a Cohort Hospitalized With Anorexia Nervosa
    supporting_text: To characterize mortality after hospital discharge in cohorts with and without anorexia nervosa (AN).MethodsWe obtained data for all hospitalizations for psychiatric reasons in Canada (except Quebec) between April 1, 2006, and March 31, 2021 (n = 1.3 million admissions).
- reference: DOI:10.1186/s12880-024-01432-z
  title: Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
    supporting_text: Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
- reference: DOI:10.1186/s40337-024-01130-9
  title: 'Early-onset anorexia nervosa: a scoping review and management guidelines'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: 'Early-onset anorexia nervosa: a scoping review and management guidelines'
    supporting_text: 'Early-onset anorexia nervosa: a scoping review and management guidelines'
- reference: DOI:10.12740/pp/103876
  title: ICD-11 vs. ICD-10 – a review of updates and novelties introduced in the latest version of the WHO International Classification of Diseases
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: W czerwcu 2018 Światowa Organizacja Zdrowia (WHO) opublikowała 11-tą edycję Międzynarodowej Klasyfikacji Chorób (ICD-11).
    supporting_text: W czerwcu 2018 Światowa Organizacja Zdrowia (WHO) opublikowała 11-tą edycję Międzynarodowej Klasyfikacji Chorób (ICD-11).
- reference: DOI:10.3389/fmicb.2024.1396932
  title: 'Anorexia nervosa and bulimia nervosa: a Mendelian randomization study of gut microbiota'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: Anorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health.
    supporting_text: Anorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health.
- reference: DOI:10.3390/nu17132160
  title: 'Advancements in Family-Based Treatment of Adolescent Anorexia Nervosa: A Review of Access Barriers and Telehealth Solutions'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: Anorexia Nervosa (AN) is a psychiatric illness with serious medical and physiological implications.
    supporting_text: Anorexia Nervosa (AN) is a psychiatric illness with serious medical and physiological implications.
- reference: DOI:10.3390/psychiatryint5020015
  title: 'Modifications to Enhance Outcomes of Family-Based Treatment for Anorexia Nervosa: A Scoping Review'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings:
  - statement: Family-based treatment (FBT) is recommended for anorexia nervosa (AN) in young people (YP).
    supporting_text: Family-based treatment (FBT) is recommended for anorexia nervosa (AN) in young people (YP).
- reference: PMID:11459385
  title: Long-term outcome of anorexia nervosa in a prospective 21-year follow-up study.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Given our poor understanding of the very long-term course of anorexia nervosa. many questions remain regarding the potential for recovery and relapse.
    supporting_text: Given our poor understanding of the very long-term course of anorexia nervosa. many questions remain regarding the potential for recovery and relapse.
- reference: PMID:12452251
  title: 'Hospitalization of patients with anorexia nervosa: a therapeutic proposal.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2002 Sep;7(3):196-201. doi: 10.1007/BF03327457.'
    supporting_text: '2002 Sep;7(3):196-201. doi: 10.1007/BF03327457.'
- reference: PMID:14757596
  title: Application of a latent class analysis to empirically define eating disorder phenotypes.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2004 Feb;61(2):192-200. doi: 10.1001/archpsyc.61.2.192.'
    supporting_text: '2004 Feb;61(2):192-200. doi: 10.1001/archpsyc.61.2.192.'
- reference: PMID:16721178
  title: Medical complications of anorexia nervosa and bulimia nervosa.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2006 Jul;19(4):438-43. doi: 10.1097/01.yco.0000228768.79097.3e.'
    supporting_text: '2006 Jul;19(4):438-43. doi: 10.1097/01.yco.0000228768.79097.3e.'
- reference: PMID:17628126
  title: Management of eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Evidence report on management of eating disorders.
    supporting_text: The reference is an evidence report on management of eating disorders.
- reference: PMID:19427647
  title: 'The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2009 Sep;43(14):1125-32. doi: 10.1016/j.jpsychires.2009.04.003.'
    supporting_text: '2009 Sep;43(14):1125-32. doi: 10.1016/j.jpsychires.2009.04.003.'
- reference: PMID:20179406
  title: Similarities and differences between excessive exercising anorexia nervosa patients compared with DSM-IV defined anorexia nervosa subtypes.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2009 Dec;14(4):e199-204. doi: 10.1007/BF03325117.'
    supporting_text: '2009 Dec;14(4):e199-204. doi: 10.1007/BF03325117.'
- reference: PMID:21317006
  title: 'Outcome in AN adult patients: a 13-year follow-up in 484 patients.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: To study the long-term prognosis of anorexia nervosa (AN), 484 adult AN patients were followed on a mean duration of 13 years.
    supporting_text: To study the long-term prognosis of anorexia nervosa (AN), 484 adult AN patients were followed on a mean duration of 13 years.
- reference: PMID:23333342
  title: 'Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2013 Feb;36(2):110-20. doi: 10.1016/j.tins.2013.01.003.'
    supporting_text: '2013 Feb;36(2):110-20. doi: 10.1016/j.tins.2013.01.003.'
- reference: PMID:24202964
  title: Genetics of eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2013 Dec;15(12):423. doi: 10.1007/s11920-013-0423-y.'
    supporting_text: '2013 Dec;15(12):423. doi: 10.1007/s11920-013-0423-y.'
- reference: PMID:24340712
  title: '[Genetic etiology of eating disorders].'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: 2013;129(20):2126-32. [Genetic etiology of eating disorders]. [Article in Finnish] Raevuori A(1).
    supporting_text: 2013;129(20):2126-32. [Genetic etiology of eating disorders]. [Article in Finnish] Raevuori A(1).
- reference: PMID:27811940
  title: 'The endocrine manifestations of anorexia nervosa: mechanisms and management.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2017 Mar;13(3):174-186. doi: 10.1038/nrendo.2016.175.'
    supporting_text: '2017 Mar;13(3):174-186. doi: 10.1038/nrendo.2016.175.'
- reference: PMID:28475260
  title: A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2017 Oct;29(10). doi: 10.1111/jne.12479.'
    supporting_text: '2017 Oct;29(10). doi: 10.1111/jne.12479.'
- reference: PMID:29437028
  title: Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Endocr Metab Immune Disord Drug Targets.
    supporting_text: Endocr Metab Immune Disord Drug Targets.
- reference: PMID:30353170
  title: 'Epigenetics in eating disorders: a systematic review.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2019 Jun;24(6):901-915. doi: 10.1038/s41380-018-0254-7.'
    supporting_text: '2019 Jun;24(6):901-915. doi: 10.1038/s41380-018-0254-7.'
- reference: PMID:30552078
  title: 'Efficacy of a Parent-Based, Indicated Prevention for Anorexia Nervosa: Randomized Controlled Trial.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Web-based preventive interventions can reduce risk and incidence of bulimia and binge eating disorders among young high-risk women.
    supporting_text: Web-based preventive interventions can reduce risk and incidence of bulimia and binge eating disorders among young high-risk women.
- reference: PMID:30829421
  title: 'Optimizing treatment outcomes in adolescents with eating disorders: The potential role of cognitive behavioral therapy.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2019 May;52(5):538-542. doi: 10.1002/eat.23067.'
    supporting_text: '2019 May;52(5):538-542. doi: 10.1002/eat.23067.'
- reference: PMID:31308545
  title: Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2.'
    supporting_text: '2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2.'
- reference: PMID:31466116
  title: '[Efficacy, Moderators and Mediators of Manualized Family-Based Treatments in Adolescents with Eating Disorders: A Systematic Review].'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2020 Apr;70(3-04):112-121. doi: 10.1055/a-0977-3413.'
    supporting_text: '2020 Apr;70(3-04):112-121. doi: 10.1055/a-0977-3413.'
- reference: PMID:31835028
  title: Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2019 Dec 12;179(7):1469-1482.e11. doi: 10.1016/j.cell.2019.11.020.'
    supporting_text: '2019 Dec 12;179(7):1469-1482.e11. doi: 10.1016/j.cell.2019.11.020.'
- reference: PMID:31852892
  title: Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2019 Dec 18;10(1):5765. doi: 10.1038/s41467-019-13544-0.'
    supporting_text: '2019 Dec 18;10(1):5765. doi: 10.1038/s41467-019-13544-0.'
- reference: PMID:32234640
  title: 'Eating disorders: Do PET and SPECT have a role? A systematic review of the literature.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2020 Jun 30;300:111065. doi: 10.1016/j.pscychresns.2020.111065.'
    supporting_text: '2020 Jun 30;300:111065. doi: 10.1016/j.pscychresns.2020.111065.'
- reference: PMID:32858054
  title: Pharmacological treatment of eating disorders, comorbid mental health problems, malnutrition and physical health consequences.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Jan;217:107667. doi: 10.1016/j.pharmthera.2020.107667.'
    supporting_text: '2021 Jan;217:107667. doi: 10.1016/j.pharmthera.2020.107667.'
- reference: PMID:33176113
  title: 'Hippocampal volume, function, and related molecular activity in anorexia nervosa: A scoping review.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2020 Dec;13(12):1367-1387. doi: 10.1080/17512433.2020.1850256.'
    supporting_text: '2020 Dec;13(12):1367-1387. doi: 10.1080/17512433.2020.1850256.'
- reference: PMID:33223229
  title: 'Treatment of Eating Disorders in Adults Versus Adolescents: Similarities and Differences.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Jan;43(1):70-84. doi: 10.1016/j.clinthera.2020.10.015.'
    supporting_text: '2021 Jan;43(1):70-84. doi: 10.1016/j.clinthera.2020.10.015.'
- reference: PMID:33382560
  title: 'Eating Disorders in Primary Care: Diagnosis and Management.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Klein DA(1), Sylvester JE(1), Schvey NA(1).
    supporting_text: Klein DA(1), Sylvester JE(1), Schvey NA(1).
- reference: PMID:33416044
  title: A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: There is growing interest in new factors contributing to the genesis of eating disorders (EDs).
    supporting_text: There is growing interest in new factors contributing to the genesis of eating disorders (EDs).
- reference: PMID:33652962
  title: 'Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Feb 26;22(5):2351. doi: 10.3390/ijms22052351.'
    supporting_text: '2021 Feb 26;22(5):2351. doi: 10.3390/ijms22052351.'
- reference: PMID:33661571
  title: β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Mar;9(5):e14788. doi: 10.14814/phy2.14788. β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.'
    supporting_text: '2021 Mar;9(5):e14788. doi: 10.14814/phy2.14788. β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.'
- reference: PMID:33768216
  title: Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Beeler JA(1)(2)(3)(4), Burghardt NS(5)(2)(4).
    supporting_text: Beeler JA(1)(2)(3)(4), Burghardt NS(5)(2)(4).
- reference: PMID:34124309
  title: Activity-based Anorexia for Modeling Vulnerability and Resilience in Mice.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 May 5;11(9):e4009. doi: 10.21769/BioProtoc.4009. eCollection 2021 May 5.'
    supporting_text: '2021 May 5;11(9):e4009. doi: 10.21769/BioProtoc.4009. eCollection 2021 May 5.'
- reference: PMID:34246009
  title: What can we learn about eating disorder mortality from eating disorder diagnoses at initial assessment? A Danish nationwide register follow-up study using record linkage, encompassing 45 years (1970-2014).
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Sep;303:114091. doi: 10.1016/j.psychres.2021.114091.'
    supporting_text: '2021 Sep;303:114091. doi: 10.1016/j.psychres.2021.114091.'
- reference: PMID:34296492
  title: Structural and functional brain alterations in anorexia nervosa:A multimodal meta-analysis of neuroimaging studies.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2021 Oct 15;42(15):5154-5169. doi: 10.1002/hbm.25602.'
    supporting_text: '2021 Oct 15;42(15):5154-5169. doi: 10.1002/hbm.25602.'
- reference: PMID:35142161
  title: Assessment of Long-Term Treatment Results in Women Suffering from Anorexia Nervosa in Adolescence.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2022;28(1):4-15. doi: 10.5114/pedm.2021.109268.'
    supporting_text: '2022;28(1):4-15. doi: 10.5114/pedm.2021.109268.'
- reference: PMID:35625351
  title: The BDNF Val66Met Polymorphism Does Not Increase Susceptibility to Activity-Based Anorexia in Rats.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2022 Apr 19;11(5):623. doi: 10.3390/biology11050623.'
    supporting_text: '2022 Apr 19;11(5):623. doi: 10.3390/biology11050623.'
- reference: PMID:35896857
  title: 'Radiofrequency echographic multispectrometry (REMS): an innovative technique for the assessment of bone status in young women with anorexia nervosa.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2022 Dec;27(8):3207-3213. doi: 10.1007/s40519-022-01450-2.'
    supporting_text: '2022 Dec;27(8):3207-3213. doi: 10.1007/s40519-022-01450-2.'
- reference: PMID:36031441
  title: 'Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood.
    supporting_text: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood.
- reference: PMID:36062404
  title: Mortality and care of eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2023 Feb;147(2):122-133. doi: 10.1111/acps.13487.'
    supporting_text: '2023 Feb;147(2):122-133. doi: 10.1111/acps.13487.'
- reference: PMID:36346630
  title: Analysis of Electrolyte Abnormalities in Adolescents and Adults and Subsequent Diagnosis of an Eating Disorder.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2022 Nov 1;5(11):e2240809. doi: 10.1001/jamanetworkopen.2022.40809.'
    supporting_text: '2022 Nov 1;5(11):e2240809. doi: 10.1001/jamanetworkopen.2022.40809.'
- reference: PMID:36694235
  title: 'Disparities in access to eating disorders treatment for publicly-insured youth and youth of color: a retrospective cohort study.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Eating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment.
    supporting_text: Eating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment.
- reference: PMID:37263169
  title: Can neuroimaging measures differentiate the disease course of anorexia nervosa? A systematic review.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2023 Jul;163:337-349. doi: 10.1016/j.jpsychires.2023.05.059.'
    supporting_text: '2023 Jul;163:337-349. doi: 10.1016/j.jpsychires.2023.05.059.'
- reference: PMID:37528996
  title: Current trends and perspectives in the exploration of anorexia athletica-clinical challenges and therapeutic considerations.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2023 Jul 17;10:1214398. doi: 10.3389/fnut.2023.1214398. eCollection 2023.'
    supporting_text: '2023 Jul 17;10:1214398. doi: 10.3389/fnut.2023.1214398. eCollection 2023.'
- reference: PMID:37691603
  title: The involvement of the adrenergic system in feeding and eating disorders. A systematic review.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED).
    supporting_text: Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED).
- reference: PMID:37697396
  title: Effects of family-based treatment on adolescent outpatients treated for anorexia nervosa in the Eating Disorder Unit of Helsinki University Hospital.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials.
    supporting_text: Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials.
- reference: PMID:37864342
  title: Sex differences in cholesterol and triglyceride levels among hospitalized adolescents and young adults with eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Jan;57(1):184-194. doi: 10.1002/eat.24072.'
    supporting_text: '2024 Jan;57(1):184-194. doi: 10.1002/eat.24072.'
- reference: PMID:38103992
  title: Taking better advantage of the activity-based anorexia model.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Apr;30(4):330-338. doi: 10.1016/j.molmed.2023.11.011.'
    supporting_text: '2024 Apr;30(4):330-338. doi: 10.1016/j.molmed.2023.11.011.'
- reference: PMID:38212857
  title: Do risk factors differentiate DSM-5 and drive for thinness severity groups for anorexia nervosa?
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings.
    supporting_text: The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings.
- reference: PMID:38310530
  title: The autonomic nervous system in anorexia nervosa - an implication for the fat tissue.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2023 Oct 30;63(3):75-90. doi: 10.24425/fmc.2023.147215.'
    supporting_text: '2023 Oct 30;63(3):75-90. doi: 10.24425/fmc.2023.147215.'
- reference: PMID:38380189
  title: 'Anorexia Nervosa and Osteoporosis: A Possible Complication to Remember.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Jan 21;16(1):e52670. doi: 10.7759/cureus.52670. eCollection 2024 Jan.'
    supporting_text: '2024 Jan 21;16(1):e52670. doi: 10.7759/cureus.52670. eCollection 2024 Jan.'
- reference: PMID:38431502
  title: Dissecting the biology of feeding and eating disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Apr;30(4):380-391. doi: 10.1016/j.molmed.2024.01.009.'
    supporting_text: '2024 Apr;30(4):380-391. doi: 10.1016/j.molmed.2024.01.009.'
- reference: PMID:38703603
  title: Dissecting the genetic and causal relationship between sleep-related traits and common brain disorders.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: There is a profound connection between abnormal sleep patterns and brain disorders, suggesting a shared influential association.
    supporting_text: There is a profound connection between abnormal sleep patterns and brain disorders, suggesting a shared influential association.
- reference: PMID:38849516
  title: Epigenetic alterations in patients with anorexia nervosa-a systematic review.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Dec;29(12):3900-3914. doi: 10.1038/s41380-024-02601-w.'
    supporting_text: '2024 Dec;29(12):3900-3914. doi: 10.1038/s41380-024-02601-w.'
- reference: PMID:39009701
  title: Genetic neurodevelopmental clustering and dyslexia.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025 Jan;30(1):140-150. doi: 10.1038/s41380-024-02649-8.'
    supporting_text: '2025 Jan;30(1):140-150. doi: 10.1038/s41380-024-02649-8.'
- reference: PMID:39314548
  title: Romosuzumab used to treat a 29-year-old patient with anorexia nervosa related osteoporosis - A case report.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2024 Sep 11;22:101803. doi: 10.1016/j.bonr.2024.101803. eCollection 2024 Sep.'
    supporting_text: '2024 Sep 11;22:101803. doi: 10.1016/j.bonr.2024.101803. eCollection 2024 Sep.'
- reference: PMID:39741260
  title: Nanopore sequencing as a novel method of characterising anorexia nervosa risk loci.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Anorexia nervosa (AN) is a polygenic, severe metabopsychiatric disorder with poorly understood aetiology.
    supporting_text: Anorexia nervosa (AN) is a polygenic, severe metabopsychiatric disorder with poorly understood aetiology.
- reference: PMID:39988782
  title: Genetic Predisposition and Severity of Eating Disorders- A Review.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025;24(7):498-510. doi: 10.2174/0118715273372810250214054917.'
    supporting_text: '2025;24(7):498-510. doi: 10.2174/0118715273372810250214054917.'
- reference: PMID:40141382
  title: 'Impact of Glucagon-like Peptide-1 Receptor Agonists on Mental Illness: Evidence from a Mendelian Randomization Study.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025 Mar 18;26(6):2741. doi: 10.3390/ijms26062741.'
    supporting_text: '2025 Mar 18;26(6):2741. doi: 10.3390/ijms26062741.'
- reference: PMID:40280427
  title: Eating disorders, psychiatric comorbidities, and suicide.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Evidence suggests a strong association between eating disorders and suicidality, including suicidal ideation and suicide attempts.
    supporting_text: Evidence suggests a strong association between eating disorders and suicidality, including suicidal ideation and suicide attempts.
- reference: PMID:40419993
  title: 'The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: 'The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol'
    supporting_text: The Eating Disorders Genetics Initiative 2 (EDGI2) is designed to explore the role of genes and environment in anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID) with a focus on broad population representation and severe and/or longstanding illness.
- reference: PMID:40615413
  title: 'Shared genetic architecture between eating disorders, mental health conditions, and cardiometabolic diseases: a comprehensive population-wide study across two countries.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025 Jul 4;16(1):6193. doi: 10.1038/s41467-025-61496-5.'
    supporting_text: '2025 Jul 4;16(1):6193. doi: 10.1038/s41467-025-61496-5.'
- reference: PMID:40789230
  title: Crossing barriers? Longitudinal evaluation of intestinal permeability in adolescent anorexia nervosa.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025 Sep;52:215-224. doi: 10.1016/j.clnu.2025.07.034.'
    supporting_text: '2025 Sep;52:215-224. doi: 10.1016/j.clnu.2025.07.034.'
- reference: PMID:40879610
  title: 'Efficacy of Adjunct Olanzapine Treatment in Adolescents With Anorexia Nervosa: A Comparison of Two Patient Cohorts.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies.
    supporting_text: Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies.
- reference: PMID:41236167
  title: Lived Experience Perspectives on the Development of Anorexia Nervosa.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2026 May;34(3):612-626. doi: 10.1002/erv.70058.'
    supporting_text: '2026 May;34(3):612-626. doi: 10.1002/erv.70058.'
- reference: PMID:41282513
  title: 'Adverse outcomes in patients with a diagnosis of an eating disorder: primary care cohort study with linked secondary care and mortality records.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2025 Nov 18;4(1):e001438. doi: 10.1136/bmjmed-2025-001438. eCollection 2025.'
    supporting_text: '2025 Nov 18;4(1):e001438. doi: 10.1136/bmjmed-2025-001438. eCollection 2025.'
- reference: PMID:41330642
  title: 'Maternal eating disorders and respiratory outcomes in childhood: findings from the EU Child Cohort Network.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: While maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood.
    supporting_text: While maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood.
- reference: PMID:41366465
  title: 'Efficacy of pharmacological and non-pharmacological interventions for the treatment of anorexia nervosa in adolescents and adults (EfaNosa): protocol for a network meta-analysis.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: Anorexia nervosa (AN) is a severe eating disorder.
    supporting_text: Anorexia nervosa (AN) is a severe eating disorder.
- reference: PMID:41536100
  title: 'All-cause and cause-specific mortality risk in individuals with eating disorders: systematic review and meta-analysis of relative risk and aggravating or attenuating factors.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2026 Feb;25(1):125-140. doi: 10.1002/wps.70014.'
    supporting_text: '2026 Feb;25(1):125-140. doi: 10.1002/wps.70014.'
- reference: PMID:41591404
  title: 'Effects of teriparatide on hip structure and bone microarchitecture in women with anorexia nervosa: a placebo-controlled randomized trial.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2026 Mar;37(3):749-758. doi: 10.1007/s00198-026-07846-5.'
    supporting_text: '2026 Mar;37(3):749-758. doi: 10.1007/s00198-026-07846-5.'
- reference: PMID:41619402
  title: 'Structural brain alterations in anorexia nervosa: a global brain volume and anatomical likelihood estimation (ALE) meta-analysis combined with a functional decoding approach.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2026;49:103950. doi: 10.1016/j.nicl.2026.103950.'
    supporting_text: '2026;49:103950. doi: 10.1016/j.nicl.2026.103950.'
- reference: PMID:41707619
  title: 'Beliefs of delusional intensity about body image or eating-related concerns in individuals with Feeding and Eating Disorders: a systematic review and meta-analysis.'
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '2026 May;196:185-204. doi: 10.1016/j.jpsychires.2026.01.054.'
    supporting_text: '2026 May;196:185-204. doi: 10.1016/j.jpsychires.2026.01.054.'
- reference: PMID:9054777
  title: Outcome in bulimia nervosa.
  found_in:
  - Anorexia_Nervosa-deep-research-openscientist.md
  findings:
  - statement: '1997 Mar;154(3):313-21. doi: 10.1176/ajp.154.3.313.'
    supporting_text: '1997 Mar;154(3):313-21. doi: 10.1176/ajp.154.3.313.'
- reference: DOI:10.1001/jamanetworkopen.2024.51094
  title: Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.1007/s00115-025-01820-y
  title: Anorexia nervosa—an update
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.1038/s41398-023-02585-1
  title: Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.1111/jep.13586
  title: 'Capturing the anorexia nervosa phenotype: Conceptual and normative issues in <scp>ICD</scp>‐11'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.1186/s40337-023-00738-7
  title: 'Epidemiology of eating disorders: population, prevalence, disease burden and quality of life informing public policy in Australia—a rapid review'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.3390/nu16111596
  title: Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
- reference: DOI:10.3390/nu16132095
  title: 'Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis'
  found_in:
  - Anorexia_Nervosa-deep-research-falcon.md
  findings: []
📚

References & Deep Research

References

85
DOI:10.1002/eat.24296
Postdischarge Mortality in a Cohort Hospitalized With Anorexia Nervosa
1 finding
Postdischarge Mortality in a Cohort Hospitalized With Anorexia Nervosa
"To characterize mortality after hospital discharge in cohorts with and without anorexia nervosa (AN).MethodsWe obtained data for all hospitalizations for psychiatric reasons in Canada (except Quebec) between April 1, 2006, and March 31, 2021 (n = 1.3 million admissions)."
DOI:10.1186/s12880-024-01432-z
Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
1 finding
Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
"Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders"
DOI:10.1186/s40337-024-01130-9
Early-onset anorexia nervosa: a scoping review and management guidelines
1 finding
Early-onset anorexia nervosa: a scoping review and management guidelines
"Early-onset anorexia nervosa: a scoping review and management guidelines"
DOI:10.12740/pp/103876
ICD-11 vs. ICD-10 – a review of updates and novelties introduced in the latest version of the WHO International Classification of Diseases
1 finding
W czerwcu 2018 Światowa Organizacja Zdrowia (WHO) opublikowała 11-tą edycję Międzynarodowej Klasyfikacji Chorób (ICD-11).
"W czerwcu 2018 Światowa Organizacja Zdrowia (WHO) opublikowała 11-tą edycję Międzynarodowej Klasyfikacji Chorób (ICD-11)."
DOI:10.3389/fmicb.2024.1396932
Anorexia nervosa and bulimia nervosa: a Mendelian randomization study of gut microbiota
1 finding
Anorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health.
"Anorexia nervosa (AN) and bulimia nervosa (BN) poses a significant challenge to global public health."
DOI:10.3390/nu17132160
Advancements in Family-Based Treatment of Adolescent Anorexia Nervosa: A Review of Access Barriers and Telehealth Solutions
1 finding
Anorexia Nervosa (AN) is a psychiatric illness with serious medical and physiological implications.
"Anorexia Nervosa (AN) is a psychiatric illness with serious medical and physiological implications."
DOI:10.3390/psychiatryint5020015
Modifications to Enhance Outcomes of Family-Based Treatment for Anorexia Nervosa: A Scoping Review
1 finding
Family-based treatment (FBT) is recommended for anorexia nervosa (AN) in young people (YP).
"Family-based treatment (FBT) is recommended for anorexia nervosa (AN) in young people (YP)."
PMID:11459385
Long-term outcome of anorexia nervosa in a prospective 21-year follow-up study.
1 finding
Given our poor understanding of the very long-term course of anorexia nervosa. many questions remain regarding the potential for recovery and relapse.
"Given our poor understanding of the very long-term course of anorexia nervosa. many questions remain regarding the potential for recovery and relapse."
PMID:12452251
Hospitalization of patients with anorexia nervosa: a therapeutic proposal.
1 finding
2002 Sep;7(3):196-201. doi: 10.1007/BF03327457.
"2002 Sep;7(3):196-201. doi: 10.1007/BF03327457."
PMID:14757596
Application of a latent class analysis to empirically define eating disorder phenotypes.
1 finding
2004 Feb;61(2):192-200. doi: 10.1001/archpsyc.61.2.192.
"2004 Feb;61(2):192-200. doi: 10.1001/archpsyc.61.2.192."
PMID:16721178
Medical complications of anorexia nervosa and bulimia nervosa.
1 finding
2006 Jul;19(4):438-43. doi: 10.1097/01.yco.0000228768.79097.3e.
"2006 Jul;19(4):438-43. doi: 10.1097/01.yco.0000228768.79097.3e."
PMID:17628126
Management of eating disorders.
1 finding
Evidence report on management of eating disorders.
"The reference is an evidence report on management of eating disorders."
PMID:19427647
The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project.
1 finding
2009 Sep;43(14):1125-32. doi: 10.1016/j.jpsychires.2009.04.003.
"2009 Sep;43(14):1125-32. doi: 10.1016/j.jpsychires.2009.04.003."
PMID:20179406
Similarities and differences between excessive exercising anorexia nervosa patients compared with DSM-IV defined anorexia nervosa subtypes.
1 finding
2009 Dec;14(4):e199-204. doi: 10.1007/BF03325117.
"2009 Dec;14(4):e199-204. doi: 10.1007/BF03325117."
PMID:21317006
Outcome in AN adult patients: a 13-year follow-up in 484 patients.
1 finding
To study the long-term prognosis of anorexia nervosa (AN), 484 adult AN patients were followed on a mean duration of 13 years.
"To study the long-term prognosis of anorexia nervosa (AN), 484 adult AN patients were followed on a mean duration of 13 years."
PMID:23333342
Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa.
1 finding
2013 Feb;36(2):110-20. doi: 10.1016/j.tins.2013.01.003.
"2013 Feb;36(2):110-20. doi: 10.1016/j.tins.2013.01.003."
PMID:24202964
Genetics of eating disorders.
1 finding
2013 Dec;15(12):423. doi: 10.1007/s11920-013-0423-y.
"2013 Dec;15(12):423. doi: 10.1007/s11920-013-0423-y."
PMID:24340712
[Genetic etiology of eating disorders].
1 finding
2013;129(20):2126-32. [Genetic etiology of eating disorders]. [Article in Finnish] Raevuori A(1).
"2013;129(20):2126-32. [Genetic etiology of eating disorders]. [Article in Finnish] Raevuori A(1)."
PMID:27811940
The endocrine manifestations of anorexia nervosa: mechanisms and management.
1 finding
2017 Mar;13(3):174-186. doi: 10.1038/nrendo.2016.175.
"2017 Mar;13(3):174-186. doi: 10.1038/nrendo.2016.175."
PMID:28475260
A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model.
1 finding
2017 Oct;29(10). doi: 10.1111/jne.12479.
"2017 Oct;29(10). doi: 10.1111/jne.12479."
PMID:29437028
Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders.
1 finding
Endocr Metab Immune Disord Drug Targets.
"Endocr Metab Immune Disord Drug Targets."
PMID:30353170
Epigenetics in eating disorders: a systematic review.
1 finding
2019 Jun;24(6):901-915. doi: 10.1038/s41380-018-0254-7.
"2019 Jun;24(6):901-915. doi: 10.1038/s41380-018-0254-7."
PMID:30552078
Efficacy of a Parent-Based, Indicated Prevention for Anorexia Nervosa: Randomized Controlled Trial.
1 finding
Web-based preventive interventions can reduce risk and incidence of bulimia and binge eating disorders among young high-risk women.
"Web-based preventive interventions can reduce risk and incidence of bulimia and binge eating disorders among young high-risk women."
PMID:30829421
Optimizing treatment outcomes in adolescents with eating disorders: The potential role of cognitive behavioral therapy.
1 finding
2019 May;52(5):538-542. doi: 10.1002/eat.23067.
"2019 May;52(5):538-542. doi: 10.1002/eat.23067."
PMID:31308545
Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.
1 finding
2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2.
"2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2."
PMID:31466116
[Efficacy, Moderators and Mediators of Manualized Family-Based Treatments in Adolescents with Eating Disorders: A Systematic Review].
1 finding
2020 Apr;70(3-04):112-121. doi: 10.1055/a-0977-3413.
"2020 Apr;70(3-04):112-121. doi: 10.1055/a-0977-3413."
PMID:31835028
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
1 finding
2019 Dec 12;179(7):1469-1482.e11. doi: 10.1016/j.cell.2019.11.020.
"2019 Dec 12;179(7):1469-1482.e11. doi: 10.1016/j.cell.2019.11.020."
PMID:31852892
Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent.
1 finding
2019 Dec 18;10(1):5765. doi: 10.1038/s41467-019-13544-0.
"2019 Dec 18;10(1):5765. doi: 10.1038/s41467-019-13544-0."
PMID:32234640
Eating disorders: Do PET and SPECT have a role? A systematic review of the literature.
1 finding
2020 Jun 30;300:111065. doi: 10.1016/j.pscychresns.2020.111065.
"2020 Jun 30;300:111065. doi: 10.1016/j.pscychresns.2020.111065."
PMID:32858054
Pharmacological treatment of eating disorders, comorbid mental health problems, malnutrition and physical health consequences.
1 finding
2021 Jan;217:107667. doi: 10.1016/j.pharmthera.2020.107667.
"2021 Jan;217:107667. doi: 10.1016/j.pharmthera.2020.107667."
PMID:33176113
Hippocampal volume, function, and related molecular activity in anorexia nervosa: A scoping review.
1 finding
2020 Dec;13(12):1367-1387. doi: 10.1080/17512433.2020.1850256.
"2020 Dec;13(12):1367-1387. doi: 10.1080/17512433.2020.1850256."
PMID:33223229
Treatment of Eating Disorders in Adults Versus Adolescents: Similarities and Differences.
1 finding
2021 Jan;43(1):70-84. doi: 10.1016/j.clinthera.2020.10.015.
"2021 Jan;43(1):70-84. doi: 10.1016/j.clinthera.2020.10.015."
PMID:33382560
Eating Disorders in Primary Care: Diagnosis and Management.
1 finding
Klein DA(1), Sylvester JE(1), Schvey NA(1).
"Klein DA(1), Sylvester JE(1), Schvey NA(1)."
PMID:33416044
A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders.
1 finding
There is growing interest in new factors contributing to the genesis of eating disorders (EDs).
"There is growing interest in new factors contributing to the genesis of eating disorders (EDs)."
PMID:33652962
Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches.
1 finding
2021 Feb 26;22(5):2351. doi: 10.3390/ijms22052351.
"2021 Feb 26;22(5):2351. doi: 10.3390/ijms22052351."
PMID:33661571
β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.
1 finding
2021 Mar;9(5):e14788. doi: 10.14814/phy2.14788. β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.
"2021 Mar;9(5):e14788. doi: 10.14814/phy2.14788. β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia."
PMID:33768216
Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine.
1 finding
Beeler JA(1)(2)(3)(4), Burghardt NS(5)(2)(4).
"Beeler JA(1)(2)(3)(4), Burghardt NS(5)(2)(4)."
PMID:34124309
Activity-based Anorexia for Modeling Vulnerability and Resilience in Mice.
1 finding
2021 May 5;11(9):e4009. doi: 10.21769/BioProtoc.4009. eCollection 2021 May 5.
"2021 May 5;11(9):e4009. doi: 10.21769/BioProtoc.4009. eCollection 2021 May 5."
PMID:34246009
What can we learn about eating disorder mortality from eating disorder diagnoses at initial assessment? A Danish nationwide register follow-up study using record linkage, encompassing 45 years (1970-2014).
1 finding
2021 Sep;303:114091. doi: 10.1016/j.psychres.2021.114091.
"2021 Sep;303:114091. doi: 10.1016/j.psychres.2021.114091."
PMID:34296492
Structural and functional brain alterations in anorexia nervosa:A multimodal meta-analysis of neuroimaging studies.
1 finding
2021 Oct 15;42(15):5154-5169. doi: 10.1002/hbm.25602.
"2021 Oct 15;42(15):5154-5169. doi: 10.1002/hbm.25602."
PMID:35142161
Assessment of Long-Term Treatment Results in Women Suffering from Anorexia Nervosa in Adolescence.
1 finding
2022;28(1):4-15. doi: 10.5114/pedm.2021.109268.
"2022;28(1):4-15. doi: 10.5114/pedm.2021.109268."
PMID:35625351
The BDNF Val66Met Polymorphism Does Not Increase Susceptibility to Activity-Based Anorexia in Rats.
1 finding
2022 Apr 19;11(5):623. doi: 10.3390/biology11050623.
"2022 Apr 19;11(5):623. doi: 10.3390/biology11050623."
PMID:35896857
Radiofrequency echographic multispectrometry (REMS): an innovative technique for the assessment of bone status in young women with anorexia nervosa.
1 finding
2022 Dec;27(8):3207-3213. doi: 10.1007/s40519-022-01450-2.
"2022 Dec;27(8):3207-3213. doi: 10.1007/s40519-022-01450-2."
PMID:36031441
Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.
1 finding
The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood.
"The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood."
PMID:36062404
Mortality and care of eating disorders.
1 finding
2023 Feb;147(2):122-133. doi: 10.1111/acps.13487.
"2023 Feb;147(2):122-133. doi: 10.1111/acps.13487."
PMID:36346630
Analysis of Electrolyte Abnormalities in Adolescents and Adults and Subsequent Diagnosis of an Eating Disorder.
1 finding
2022 Nov 1;5(11):e2240809. doi: 10.1001/jamanetworkopen.2022.40809.
"2022 Nov 1;5(11):e2240809. doi: 10.1001/jamanetworkopen.2022.40809."
PMID:36694235
Disparities in access to eating disorders treatment for publicly-insured youth and youth of color: a retrospective cohort study.
1 finding
Eating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment.
"Eating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment."
PMID:37263169
Can neuroimaging measures differentiate the disease course of anorexia nervosa? A systematic review.
1 finding
2023 Jul;163:337-349. doi: 10.1016/j.jpsychires.2023.05.059.
"2023 Jul;163:337-349. doi: 10.1016/j.jpsychires.2023.05.059."
PMID:37528996
Current trends and perspectives in the exploration of anorexia athletica-clinical challenges and therapeutic considerations.
1 finding
2023 Jul 17;10:1214398. doi: 10.3389/fnut.2023.1214398. eCollection 2023.
"2023 Jul 17;10:1214398. doi: 10.3389/fnut.2023.1214398. eCollection 2023."
PMID:37691603
The involvement of the adrenergic system in feeding and eating disorders. A systematic review.
1 finding
Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED).
"Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED)."
PMID:37697396
Effects of family-based treatment on adolescent outpatients treated for anorexia nervosa in the Eating Disorder Unit of Helsinki University Hospital.
1 finding
Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials.
"Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials."
PMID:37864342
Sex differences in cholesterol and triglyceride levels among hospitalized adolescents and young adults with eating disorders.
1 finding
2024 Jan;57(1):184-194. doi: 10.1002/eat.24072.
"2024 Jan;57(1):184-194. doi: 10.1002/eat.24072."
PMID:38103992
Taking better advantage of the activity-based anorexia model.
1 finding
2024 Apr;30(4):330-338. doi: 10.1016/j.molmed.2023.11.011.
"2024 Apr;30(4):330-338. doi: 10.1016/j.molmed.2023.11.011."
PMID:38212857
Do risk factors differentiate DSM-5 and drive for thinness severity groups for anorexia nervosa?
1 finding
The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings.
"The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings."
PMID:38310530
The autonomic nervous system in anorexia nervosa - an implication for the fat tissue.
1 finding
2023 Oct 30;63(3):75-90. doi: 10.24425/fmc.2023.147215.
"2023 Oct 30;63(3):75-90. doi: 10.24425/fmc.2023.147215."
PMID:38380189
Anorexia Nervosa and Osteoporosis: A Possible Complication to Remember.
1 finding
2024 Jan 21;16(1):e52670. doi: 10.7759/cureus.52670. eCollection 2024 Jan.
"2024 Jan 21;16(1):e52670. doi: 10.7759/cureus.52670. eCollection 2024 Jan."
PMID:38431502
Dissecting the biology of feeding and eating disorders.
1 finding
2024 Apr;30(4):380-391. doi: 10.1016/j.molmed.2024.01.009.
"2024 Apr;30(4):380-391. doi: 10.1016/j.molmed.2024.01.009."
PMID:38703603
Dissecting the genetic and causal relationship between sleep-related traits and common brain disorders.
1 finding
There is a profound connection between abnormal sleep patterns and brain disorders, suggesting a shared influential association.
"There is a profound connection between abnormal sleep patterns and brain disorders, suggesting a shared influential association."
PMID:38849516
Epigenetic alterations in patients with anorexia nervosa-a systematic review.
1 finding
2024 Dec;29(12):3900-3914. doi: 10.1038/s41380-024-02601-w.
"2024 Dec;29(12):3900-3914. doi: 10.1038/s41380-024-02601-w."
PMID:39009701
Genetic neurodevelopmental clustering and dyslexia.
1 finding
2025 Jan;30(1):140-150. doi: 10.1038/s41380-024-02649-8.
"2025 Jan;30(1):140-150. doi: 10.1038/s41380-024-02649-8."
PMID:39314548
Romosuzumab used to treat a 29-year-old patient with anorexia nervosa related osteoporosis - A case report.
1 finding
2024 Sep 11;22:101803. doi: 10.1016/j.bonr.2024.101803. eCollection 2024 Sep.
"2024 Sep 11;22:101803. doi: 10.1016/j.bonr.2024.101803. eCollection 2024 Sep."
PMID:39741260
Nanopore sequencing as a novel method of characterising anorexia nervosa risk loci.
1 finding
Anorexia nervosa (AN) is a polygenic, severe metabopsychiatric disorder with poorly understood aetiology.
"Anorexia nervosa (AN) is a polygenic, severe metabopsychiatric disorder with poorly understood aetiology."
PMID:39988782
Genetic Predisposition and Severity of Eating Disorders- A Review.
1 finding
2025;24(7):498-510. doi: 10.2174/0118715273372810250214054917.
"2025;24(7):498-510. doi: 10.2174/0118715273372810250214054917."
PMID:40141382
Impact of Glucagon-like Peptide-1 Receptor Agonists on Mental Illness: Evidence from a Mendelian Randomization Study.
1 finding
2025 Mar 18;26(6):2741. doi: 10.3390/ijms26062741.
"2025 Mar 18;26(6):2741. doi: 10.3390/ijms26062741."
PMID:40280427
Eating disorders, psychiatric comorbidities, and suicide.
1 finding
Evidence suggests a strong association between eating disorders and suicidality, including suicidal ideation and suicide attempts.
"Evidence suggests a strong association between eating disorders and suicidality, including suicidal ideation and suicide attempts."
PMID:40419993
The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol.
1 finding
The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
"The Eating Disorders Genetics Initiative 2 (EDGI2) is designed to explore the role of genes and environment in anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID) with a focus on broad population representation and severe and/or..."
PMID:40615413
Shared genetic architecture between eating disorders, mental health conditions, and cardiometabolic diseases: a comprehensive population-wide study across two countries.
1 finding
2025 Jul 4;16(1):6193. doi: 10.1038/s41467-025-61496-5.
"2025 Jul 4;16(1):6193. doi: 10.1038/s41467-025-61496-5."
PMID:40789230
Crossing barriers? Longitudinal evaluation of intestinal permeability in adolescent anorexia nervosa.
1 finding
2025 Sep;52:215-224. doi: 10.1016/j.clnu.2025.07.034.
"2025 Sep;52:215-224. doi: 10.1016/j.clnu.2025.07.034."
PMID:40879610
Efficacy of Adjunct Olanzapine Treatment in Adolescents With Anorexia Nervosa: A Comparison of Two Patient Cohorts.
1 finding
Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies.
"Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies."
PMID:41236167
Lived Experience Perspectives on the Development of Anorexia Nervosa.
1 finding
2026 May;34(3):612-626. doi: 10.1002/erv.70058.
"2026 May;34(3):612-626. doi: 10.1002/erv.70058."
PMID:41282513
Adverse outcomes in patients with a diagnosis of an eating disorder: primary care cohort study with linked secondary care and mortality records.
1 finding
2025 Nov 18;4(1):e001438. doi: 10.1136/bmjmed-2025-001438. eCollection 2025.
"2025 Nov 18;4(1):e001438. doi: 10.1136/bmjmed-2025-001438. eCollection 2025."
PMID:41330642
Maternal eating disorders and respiratory outcomes in childhood: findings from the EU Child Cohort Network.
1 finding
While maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood.
"While maternal depression and anxiety have been linked to adverse childhood respiratory outcomes, the role of eating disorders (EDs) remains less understood."
PMID:41366465
Efficacy of pharmacological and non-pharmacological interventions for the treatment of anorexia nervosa in adolescents and adults (EfaNosa): protocol for a network meta-analysis.
1 finding
Anorexia nervosa (AN) is a severe eating disorder.
"Anorexia nervosa (AN) is a severe eating disorder."
PMID:41536100
All-cause and cause-specific mortality risk in individuals with eating disorders: systematic review and meta-analysis of relative risk and aggravating or attenuating factors.
1 finding
2026 Feb;25(1):125-140. doi: 10.1002/wps.70014.
"2026 Feb;25(1):125-140. doi: 10.1002/wps.70014."
PMID:41591404
Effects of teriparatide on hip structure and bone microarchitecture in women with anorexia nervosa: a placebo-controlled randomized trial.
1 finding
2026 Mar;37(3):749-758. doi: 10.1007/s00198-026-07846-5.
"2026 Mar;37(3):749-758. doi: 10.1007/s00198-026-07846-5."
PMID:41619402
Structural brain alterations in anorexia nervosa: a global brain volume and anatomical likelihood estimation (ALE) meta-analysis combined with a functional decoding approach.
1 finding
2026;49:103950. doi: 10.1016/j.nicl.2026.103950.
"2026;49:103950. doi: 10.1016/j.nicl.2026.103950."
PMID:41707619
Beliefs of delusional intensity about body image or eating-related concerns in individuals with Feeding and Eating Disorders: a systematic review and meta-analysis.
1 finding
2026 May;196:185-204. doi: 10.1016/j.jpsychires.2026.01.054.
"2026 May;196:185-204. doi: 10.1016/j.jpsychires.2026.01.054."
PMID:9054777
Outcome in bulimia nervosa.
1 finding
1997 Mar;154(3):313-21. doi: 10.1176/ajp.154.3.313.
"1997 Mar;154(3):313-21. doi: 10.1176/ajp.154.3.313."
DOI:10.1001/jamanetworkopen.2024.51094
Incidence and Risk of Cardiovascular Outcomes in Patients With Anorexia Nervosa
No top-level findings curated for this source.
DOI:10.1007/s00115-025-01820-y
Anorexia nervosa—an update
No top-level findings curated for this source.
DOI:10.1038/s41398-023-02585-1
Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa
No top-level findings curated for this source.
DOI:10.1111/jep.13586
Capturing the anorexia nervosa phenotype: Conceptual and normative issues in <scp>ICD</scp>‐11
No top-level findings curated for this source.
DOI:10.1186/s40337-023-00738-7
Epidemiology of eating disorders: population, prevalence, disease burden and quality of life informing public policy in Australia—a rapid review
No top-level findings curated for this source.
DOI:10.3390/nu16111596
Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up
No top-level findings curated for this source.
DOI:10.3390/nu16132095
Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis
No top-level findings curated for this source.

Deep Research

2
Falcon ▸
1. Disease Information
Edison Scientific Literature 39 citations 2026-04-24T17:23:42.290232

1. Disease Information

1.1 Concise overview

AN is “an eating disorder characterized by the restriction of energy intake, fear of gaining weight despite low weight, and disturbances in the perception of body weight or shape and the influence of these factors on self-worth.” (wu2024peripheralbiomarkersof pages 1-2)

1.2 Key identifiers (ontology/coding)

  • MONDO: anorexia nervosa = MONDO_0005351 (Open Targets disease entity; used for disease-target aggregation). (voderholzer2025anorexianervosaanupdate. pages 1-2)
  • ICD-11: AN = 6B80. Krawczyk & Święcicki state: “The most extensive category is ‘anorexia nervosa’ (6B80).” (Psychiatria Polska, 2020-02; https://doi.org/10.12740/pp/103876). (krawczyk2020icd11vs.icd10 pages 7-10)
  • ICD-10: commonly coded as F50.0 and F50.1 in administrative datasets (used to identify AN admissions in a national Canadian hospitalization cohort). (patten2024postdischargemortalityin pages 1-2)
  • Orphanet: early-onset/prepubertal anorexia nervosa (EOAN) referenced as ORPHA 525738 (rare early-onset subtype/descriptor). (ayrolles2024earlyonsetanorexianervosa pages 1-2)

Note on DSM-5/DSM-5-TR: Direct DSM-5 text was not retrieved in the accessible full-text set in this run; however, ICD-11 definitional text and multiple peer-reviewed studies provide DSM-aligned core features (restriction → low weight; weight/shape overvaluation and/or fear of weight gain; weight-restoration prevention behaviors). (radden2022capturingtheanorexia pages 1-2, wu2024peripheralbiomarkersof pages 1-2, voderholzer2025anorexianervosaanupdate. pages 1-2)

1.3 Synonyms / alternative names

  • Anorexia nervosa (standard)
  • Jadłowstręt psychiczny (Polish ICD discussion) as the AN descriptor in ICD-11 context. (krawczyk2020icd11vs.icd10 pages 7-10)
  • Early-onset / prepubertal anorexia nervosa (EOAN) (rare early-onset form). (ayrolles2024earlyonsetanorexianervosa pages 1-2)

1.4 Evidence source type

This report integrates: - Aggregated disease-level resources (rapid reviews, meta-analyses) (hay2023epidemiologyofeating pages 1-2, wu2024peripheralbiomarkersof pages 1-2) - Population registries / administrative health data (mortality; cardiovascular outcomes) (patten2024postdischargemortalityin pages 1-2, tseng2024incidenceandrisk pages 4-5) - Human case-control/longitudinal clinical biomarker studies (cytokines) (kaver2024cytokineandmicrobiome pages 1-2) - GWAS summary-statistics analyses (genetic architecture) (bang2023genomewideanalysisof pages 1-2) - ClinicalTrials.gov trial registry entries (ongoing/registered interventions). (NCT05918835 chunk 1, NCT05788042 chunk 1)

2. Etiology

2.1 Disease causal factors (multifactorial model)

Recent clinical synthesis emphasizes that AN has a multifactorial etiology including biological, psychological, and sociocultural contributors. (voderholzer2025anorexianervosaanupdate. pages 1-2)

Genetic causality / susceptibility

  • AN is described as heritable, with twin-based heritability ~50–60%. (bang2023genomewideanalysisof pages 1-2)
  • A 2023 genome-wide cross-trait analysis leveraged genetic overlap with major psychiatric disorders and related traits to identify 58 novel AN loci using conditional FDR methods and found shared loci with schizophrenia, bipolar disorder, major depression, and psychological traits. (bang2023genomewideanalysisof pages 1-2)

Direct abstract quote (genetics, Bang 2023): “Anorexia nervosa (AN) is a heritable eating disorder (50–60%)…” and “Using conditional FDR we identified 58 novel AN loci.” (Translational Psychiatry, 2023-09; https://doi.org/10.1038/s41398-023-02585-1). (bang2023genomewideanalysisof pages 1-2)

Environmental / psychosocial causal factors (risk domains)

A recent update summarized risk domains including: - Sociocultural: unrealistic body ideals, social media/screen time, societal pressure, obesogenic environments. (voderholzer2025anorexianervosaanupdate. pages 1-2) - Psychological traits: perfectionism, low self-esteem, emotional dysregulation, neuroticism, disgust sensitivity; compulsive/impulsive traits. (voderholzer2025anorexianervosaanupdate. pages 1-2) - Stress/trauma: stressful life events (moving, conflicts, bullying, losses, abuse) and vulnerable developmental windows (e.g., puberty). (voderholzer2025anorexianervosaanupdate. pages 2-3) - Comorbid psychiatric and neurodevelopmental conditions: anxiety/depression/PTSD, autism spectrum disorders, ADHD. (voderholzer2025anorexianervosaanupdate. pages 1-2) - Somatic/medical triggers: celiac disease, diabetes mellitus, and post-bariatric surgery states are cited as risk/trigger contexts. (voderholzer2025anorexianervosaanupdate. pages 1-2, voderholzer2025anorexianervosaanupdate. pages 2-3)

2.2 Protective factors

Specific protective factors were not explicitly enumerated in the retrieved full texts in this run. Given the strong evidence base for early identification and treatment being associated with better outcomes in youth, “early detection/treatment” can be considered a pragmatic protective factor against chronicity/complications rather than onset prevention. (voderholzer2025anorexianervosaanupdate. pages 1-2)

2.3 Gene–environment interactions

Direct gene–environment interaction (GxE) analyses were not present in the extracted materials. However, multiple sources highlight epigenetics and environment-mediated pathways as plausible mediators linking risk exposures to biological changes. (kaver2024cytokineandmicrobiome pages 1-2)

3. Phenotypes

3.1 Core clinical phenotypes (symptoms/signs)

Key clinical features include: - Self-induced weight loss via restrictive eating and/or compensatory behaviors (vomiting, laxatives, excessive exercise). (voderholzer2025anorexianervosaanupdate. pages 1-2) - Distorted body image and intense fear of gaining weight (noted as typical associations in ICD-11 framing). (voderholzer2025anorexianervosaanupdate. pages 1-2, radden2022capturingtheanorexia pages 1-2) - Hyperactivity/excessive exercise is frequent and difficult to treat; one inpatient sample reported 52.3% prevalence of compulsive/excessive exercise. (voderholzer2025anorexianervosaanupdate. pages 2-3)

HPO suggestions (labels; IDs not asserted here): low body weight; food restriction; fear of weight gain; body image distortion; hyperactivity/excessive exercise; anxiety. (voderholzer2025anorexianervosaanupdate. pages 1-2, voderholzer2025anorexianervosaanupdate. pages 2-3)

3.2 Medical complications (major systems)

The syndrome is associated with multi-system complications driven by malnutrition and starvation physiology.

Cardiovascular

A large matched cohort study (Taiwanese claims database) reported markedly increased cardiovascular events: - MACE occurred in 4.8% of AN vs 0.8% of controls; incidence rates 9.63 vs 1.65 per 1000 person-years; adjusted HR (AHR) 3.78 (95% CI 2.83–5.05). (tseng2024incidenceandrisk pages 4-5) - Any cardiovascular condition: 6.0% vs 2.3%; incidence rates 12.55 vs 4.60 per 1000 person-years; AHR 1.93 (95% CI 1.54–2.41). (tseng2024incidenceandrisk pages 4-5) - Five-year cumulative incidence in AN: MACE 4.82% (95% CI 3.85–6.02%) and any cardiovascular condition 6.19% (95% CI 5.19–7.53%). (tseng2024incidenceandrisk pages 4-5)

These findings are also reflected in the retrieved Table 2/Figure 1 snippet. (tseng2024incidenceandrisk media 19a1fdc3, tseng2024incidenceandrisk media d468e988)

HPO suggestions: bradycardia; hypotension; cardiac arrhythmia; QT prolongation; congestive heart failure. (tseng2024incidenceandrisk pages 1-2, voderholzer2025anorexianervosaanupdate. pages 3-4)

Electrolyte/renal/bone complications

A clinical update describes complications including electrolyte disturbances (e.g., hypokalemia; magnesium deficiency; hyponatremia in polydipsia contexts), renal impairment up to dialysis dependency, and irreversible bone loss (osteopenia/osteoporosis) with prevention/treatment considerations (calcium, vitamin D, bisphosphonates, transdermal estradiol). (voderholzer2025anorexianervosaanupdate. pages 2-3)

HPO suggestions: hypokalemia; hyponatremia; renal impairment; osteoporosis/osteopenia. (voderholzer2025anorexianervosaanupdate. pages 2-3)

3.3 Age of onset / severity / progression

  • AN “typically manifests during adolescence.” (kaver2024cytokineandmicrobiome pages 1-2)
  • Early-onset/prepubertal AN can have onset as early as 8 years, with operational cutoffs around ≤13 years (or ≤14 in some studies), but evidence for child-specific treatments remains limited; guidelines often extrapolate from adolescent/young adult strategies with low evidence. (ayrolles2024earlyonsetanorexianervosa pages 1-2)

3.4 Quality-of-life impact

Eating disorders substantially reduce health-related quality of life across diagnoses; a meta-analysis cited in a rapid review found similarly low HRQoL across AN, BN, and BED (with some variation by study). (hay2023epidemiologyofeating pages 37-38)

4. Genetic / Molecular Information

4.1 “Causal genes” vs polygenic risk

AN is not established as a monogenic disorder in the retrieved evidence; current genetics support polygenic inheritance with many loci of small effect and substantial shared genetic architecture with other psychiatric traits. (bang2023genomewideanalysisof pages 1-2)

4.2 GWAS loci and pathways (recent developments)

  • 58 novel AN loci were identified in a 2023 analysis leveraging genetic overlap with major psychiatric disorders and traits via conditional FDR. (bang2023genomewideanalysisof pages 1-2)
  • Functional analyses implicated 65 unique pathways, including “signal by MST1” in Hippo signaling. (bang2023genomewideanalysisof pages 1-2)

Ontology suggestions (GO; labels): Hippo signaling; synapse organization; nervous system development/neurogenesis; stress response/immune-response pathways (pathway-level mapping supported by GWAS functional analyses and neuroimaging review themes). (bang2023genomewideanalysisof pages 1-2, chen2024neuroimagingstudiesof pages 1-2)

4.3 Disease-target associations (authoritative aggregation)

Open Targets disease-target aggregation identifies associated targets including (examples): DRD2, ESR1, NCAM1, CACNA1C, TCF4 with PubMed literature links. This should be treated as association evidence rather than proof of causality. (voderholzer2025anorexianervosaanupdate. pages 1-2)

4.4 Epigenetics

Direct epigenetic marks were not extracted from the retrieved full texts; however, adolescent immune/microbiome work explicitly frames AN etiology as involving “genetics, epigenetics, neurobiology, cognition, psychosocial” factors. (kaver2024cytokineandmicrobiome pages 1-2)

5. Environmental Information

5.1 Environmental/lifestyle contributing factors

A clinical update describes multiple environmental/lifestyle factors relevant to onset and maintenance: - exposure to thin-ideal messaging/social media - restrictive diets, excessive physical activity - stressors (bullying, conflicts, life events) - family dynamics and societal reinforcement. (voderholzer2025anorexianervosaanupdate. pages 1-2, voderholzer2025anorexianervosaanupdate. pages 2-3)

5.2 Infectious agents

No infectious etiology is implicated in the retrieved evidence (not applicable).

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level)

A consistent mechanistic framing from recent evidence is: 1) Predisposition (polygenic psychiatric + metabolic liability) (bang2023genomewideanalysisof pages 1-2) 2) Behavioral restriction / compensatory behaviors → negative energy balance (voderholzer2025anorexianervosaanupdate. pages 1-2) 3) Starvation physiology (endocrine/metabolic adaptation) including altered appetite hormones and GH–IGF-1 axis changes (wu2024peripheralbiomarkersof pages 9-11) 4) Systemic complications (electrolyte disturbances; cardiovascular, renal, bone impacts) (voderholzer2025anorexianervosaanupdate. pages 2-3, tseng2024incidenceandrisk pages 1-2) 5) Neurocognitive/neurocircuit features (altered functional connectivity and reward/control circuitry) that may reinforce restrictive behavior (chen2024neuroimagingstudiesof pages 1-2)

6.2 Endocrine/metabolic adaptations (biomarkers)

A 2024 meta-analysis of peripheral biomarkers reported higher ghrelin forms and lower leptin, and discusses “ghrelin resistance” hypotheses and GH resistance (high GH, low IGF-1) as starvation-adaptation patterns in AN. (wu2024peripheralbiomarkersof pages 1-2, wu2024peripheralbiomarkersof pages 9-11)

CHEBI suggestions (labels): ghrelin; leptin; cortisol; glucose; insulin; IGF-1. (wu2024peripheralbiomarkersof pages 1-2)

6.3 Immune involvement (recent human data)

In adolescents, cytokine dysregulation may differ from adult low-grade pro-inflammatory assumptions: - In 63 female adolescents with AN vs 41 controls, IL-1β and IL-6 were lower at admission; IL-1β normalized after weight recovery; IL-15 was elevated at all time points; TNF-α did not differ. (kaver2024cytokineandmicrobiome pages 1-2)

GO suggestions (labels): cytokine-mediated signaling pathway; regulation of interleukin-15 production/signaling; inflammatory response (nuanced). (kaver2024cytokineandmicrobiome pages 1-2)

6.4 Microbiome–gut–brain axis

  • Mendelian randomization suggests potential causal roles of specific gut taxa (e.g., a subset increasing risk and a subset protective), highlighting the plausibility of microbiome-mediated pathways as intervention targets. (kaver2024cytokineandmicrobiome pages 1-2)
  • The adolescent cytokine study links microbiome composition with cytokine alterations and clinical variables. (kaver2024cytokineandmicrobiome pages 1-2)

6.5 Neurobiology / neuroimaging

Resting-state fMRI synthesis reports altered large-scale networks in eating disorders; in AN, findings include altered connectivity patterns involving DMN, salience and executive networks and regions tied to social cognition and sensory/aesthetic processing. (chen2024neuroimagingstudiesof pages 1-2)

UBERON suggestions (labels): brain; hypothalamus; cortex; cerebellum; pituitary. (supported by genetic enrichment and neuroimaging emphasis on brain regions/networks). (chen2024neuroimagingstudiesof pages 1-2, bang2023genomewideanalysisof pages 1-2)

CL suggestions (labels): hypothalamic neuron; cortical neuron; microglia; T cell/lymphocyte populations (as biomarkers include CD3/CD8 and immune discussion). (wu2024peripheralbiomarkersof pages 1-2)

7. Anatomical Structures Affected

Organ/system level

  • Central nervous system (reward, appetite and emotion regulation circuitry; altered functional connectivity). (chen2024neuroimagingstudiesof pages 1-2, voderholzer2025anorexianervosaanupdate. pages 1-2)
  • Cardiovascular system (MACE and multiple cardiac disorders). (tseng2024incidenceandrisk pages 4-5)
  • Endocrine/metabolic systems (ghrelin/leptin, cortisol, GH–IGF-1 axis). (wu2024peripheralbiomarkersof pages 1-2, wu2024peripheralbiomarkersof pages 9-11)
  • Skeletal system (osteopenia/osteoporosis). (voderholzer2025anorexianervosaanupdate. pages 2-3)
  • Renal system (renal impairment in severe disease). (voderholzer2025anorexianervosaanupdate. pages 2-3)

Subcellular / processes

Starvation-associated shifts include metabolic pathway changes and immune signaling alterations; refeeding syndrome risk is linked to intracellular phosphate depletion as a key mechanism described in clinical synthesis. (voderholzer2025anorexianervosaanupdate. pages 3-4)

8. Temporal Development

Onset

  • Peak onset often in adolescence/young adulthood; EOAN can occur in childhood (as early as 8 years). (ayrolles2024earlyonsetanorexianervosa pages 1-2, kaver2024cytokineandmicrobiome pages 1-2)

Course / remission

  • A cited meta-analytic outcome summary in a clinical update reported: 45% recovery, 24% improvement, 23% chronicity, 32% hospitalization rate, and 0.7% mortality rate (context: meta-analysis summarized in the update). (voderholzer2025anorexianervosaanupdate. pages 2-3)

9. Inheritance and Population

Epidemiology (selected recent quantitative data)

  • Global lifetime prevalence of any eating disorder: 0.74–2.2% in males and 2.58–8.4% in females (rapid review). (hay2023epidemiologyofeating pages 1-2)
  • AN lifetime prevalence varies with definitional strictness: 0.6–2.2% (strict); 1.7–4.3% (broad) (rapid review). (hay2023epidemiologyofeating pages 37-38)
  • Another synthesis/meta-analysis context reports global AN prevalence 1.4% (women) and 0.2% (men). (wu2024peripheralbiomarkersof pages 1-2)
  • Sex ratio: adolescent clinical paper notes male-to-female ratio 1:10–1:20. (kaver2024cytokineandmicrobiome pages 1-2)

Heritability / inheritance pattern

  • Polygenic/multifactorial inheritance with ~50–60% heritability estimates. (bang2023genomewideanalysisof pages 1-2)

High-risk/underserved populations (policy-relevant)

In Australia-focused rapid review, LGBTQI+ individuals—particularly males—were reported to have a six-fold increase in prevalence vs the general male population, with limited evidence available for other underserved populations. (hay2023epidemiologyofeating pages 1-2)

10. Diagnostics

10.1 Clinical criteria and ICD-11 definitional specifics

ICD-11 definition details reproduced/analysed by Radden (2022) include: - “Dangerously low body weight” benchmarks: adult BMI <18.5 at age 18; for children/adolescents BMI-for-age below the 5th percentile as a benchmark. (radden2022capturingtheanorexia pages 1-2, radden2022capturingtheanorexia pages 2-3) - Low weight is accompanied by behaviors preventing weight restoration (restriction, purging, excessive exercise) and weight/shape centrality to self-evaluation or misperception of normality/excess. (radden2022capturingtheanorexia pages 1-2) - ICD-11 demotes fear of weight gain from essential to “typically” associated. (radden2022capturingtheanorexia pages 2-3)

A clinical update also emphasizes ICD-11 removal of amenorrhea as a mandatory criterion, facilitating diagnosis in men, prepubertal children, and women on hormonal contraception. (voderholzer2025anorexianervosaanupdate. pages 1-2)

10.2 Biomarkers (not yet established for routine diagnosis)

The 2024 meta-analysis concludes that reliable biomarkers are not yet established but identifies multiple peripheral biomarker differences (e.g., ghrelin ↑, leptin ↓, IGF-1 ↓) that may relate to starvation adaptation and pathophysiology. (wu2024peripheralbiomarkersof pages 1-2)

10.3 Differential diagnosis (example explicitly referenced)

A clinical update highlights differentiation from ARFID (avoidant/restrictive food intake disorder; ICD-11 6B83) as a key diagnostic distinction. (voderholzer2025anorexianervosaanupdate. pages 2-3)

11. Outcome / Prognosis

Mortality

  • A recent clinical update reports standardized mortality ratio (SMR) 5.21 (95% CI 4.10–6.62). (voderholzer2025anorexianervosaanupdate. pages 1-2)
  • Postdischarge mortality study (Canada): after age/sex adjustment, no significant all-cause mortality difference between AN and other psychiatric admissions (HR 1.04; p=0.46), but AN contributed substantially to cause-of-death coding: 25% of AN-group deaths attributed to psychiatric ICD-F conditions; 88% of those had AN as underlying cause (22% of all AN-group deaths). (patten2024postdischargemortalityin pages 1-2)

Morbidity / complications

Cardiovascular morbidity is strongly supported by a 2024 cohort with increased MACE and multiple cardiac diagnoses. (tseng2024incidenceandrisk pages 4-5)

Prognostic factors

The FBT modification review notes predictors of poorer response to standard FBT (e.g., cognitive inflexibility, familial criticism, slow initial weight gain), but detailed prognostic modeling is beyond the extracted evidence. (pedersen2024modificationstoenhance pages 1-2)

12. Treatment

12.1 Core treatment modalities (current practice)

  • Psychotherapy is first-line: clinical update cites CBT (adolescents and adults) and FBT as most extensively studied for children/adolescents; also references FPT and MANTRA. (voderholzer2025anorexianervosaanupdate. pages 3-4)
  • Nutritional rehabilitation / inpatient refeeding reduces acute mortality risk through weight restoration; however, refeeding carries risks including refeeding syndrome and requires careful medical management (phosphate depletion mechanism emphasized). (hambleton2025advancementsinfamilybased pages 1-2, voderholzer2025anorexianervosaanupdate. pages 3-4)
  • Pharmacotherapy: limited robust evidence; olanzapine has “moderate evidence” for weight gain in a clinical update. (voderholzer2025anorexianervosaanupdate. pages 1-2)

12.2 Treatment outcomes and real-world implementation

Family-Based Treatment (FBT) outcomes and modifications (2024 scoping review) - Standard FBT recovery rates depend on definition: 50–70% when recovery defined as maintaining >85% body weight vs 28–50% when both weight restoration and symptom reduction required at end of treatment. (pedersen2024modificationstoenhance pages 1-2) - Virtual FBT evidence: in one comparison, full remission at end of treatment 30% (V-FBT) vs 11% (guided self-help); at 3-month follow-up 20% vs 22.2%. (pedersen2024modificationstoenhance pages 4-6) - Home-treatment modification: significantly higher weight gain by 3 months (medium effect size) and hospitalization 0% vs 13.6% at 3 months (significance not reported). (pedersen2024modificationstoenhance pages 4-6)

Access barriers and telehealth A telehealth-focused review concludes that telehealth-delivered FBT shows preliminary outcomes comparable to in-person care while potentially increasing access in underserved areas. (hambleton2025advancementsinfamilybased pages 1-2)

12.3 Experimental/advanced therapeutics (clinical trials)

Neuromodulation is actively studied: - NCT05918835 (registered 2023; recruiting; n=72): HF-rTMS vs sham for adults with AN, targeting individualized right DLPFC region functionally connected to dorsal striatum. (NCT05918835 chunk 1) - NCT05788042 (registered 2023; recruiting; n=70): tDCS and rTMS (iTBS) vs sham arms, primary outcome EDE-Q change at 8 weeks. (NCT05788042 chunk 1) - Additional rTMS/TBS studies include NCT03984344 and others with varying status (recruiting/terminated/withdrawn). (NCT03984344 chunk 1, NCT04061304 chunk 1)

MAXO suggestions (labels): cognitive behavioral therapy; family-based treatment; nutritional rehabilitation; inpatient hospitalization/medical stabilization; olanzapine therapy; repetitive transcranial magnetic stimulation; transcranial direct current stimulation. (voderholzer2025anorexianervosaanupdate. pages 3-4, NCT05788042 chunk 1)

13. Prevention

Primary/secondary/tertiary prevention (evidence-based framing)

Specific preventive interventions were not detailed in retrieved guideline-level sources. However: - Rapid review emphasizes low help-seeking and under-recognition, supporting secondary prevention via early identification and access to evidence-based care. (hay2023epidemiologyofeating pages 37-38) - Clinical update highlights improved outcomes with earlier detection and treatment, especially in youth. (voderholzer2025anorexianervosaanupdate. pages 1-2)

14. Other Species / Natural Disease

No naturally occurring veterinary anorexia nervosa analogs were identified in the retrieved evidence (not addressed in this run).

15. Model Organisms

In this run, retrieved evidence did not include a primary model-organism paper suitable for detailed mapping. Mechanistic microbiome work in other parts of the retrieved corpus (not fully extracted) suggests germ-free/transfer paradigms are used in the field, but this report does not assert specifics without extracted evidence.

Notes on Evidence Quality and Gaps

  • DSM-5-TR diagnostic criteria, MeSH identifier, and OMIM/Orphanet entries for AN (general) were not directly retrieved as primary documents in the accessible full texts; the report therefore anchors identifiers to ICD-11/ICD-10 and MONDO/OpenTargets plus peer-reviewed definitional text. (krawczyk2020icd11vs.icd10 pages 7-10, patten2024postdischargemortalityin pages 1-2, voderholzer2025anorexianervosaanupdate. pages 1-2)
  • Some mechanistic domains (epigenome-wide methylation studies; transcriptomics/proteomics; single-cell/spatial omics in humans) were not captured in the extracted 2023–2024 evidence set in this run.

Direct Abstract Quotes (for knowledge-base evidence items)

1) Biomarker meta-analysis definition: “an eating disorder characterized by the restriction of energy intake, fear of gaining weight despite low weight, and disturbances in the perception of body weight or shape…” (Wu et al., Nutrients, 2024-06; https://doi.org/10.3390/nu16132095). (wu2024peripheralbiomarkersof pages 1-2) 2) Genetics: “Anorexia nervosa (AN) is a heritable eating disorder (50–60%)…” and “Using conditional FDR we identified 58 novel AN loci.” (Bang et al., Translational Psychiatry, 2023-09; https://doi.org/10.1038/s41398-023-02585-1). (bang2023genomewideanalysisof pages 1-2) 3) ICD-11 code statement: “The most extensive category is ‘anorexia nervosa’ (6B80).” (Krawczyk & Święcicki, Psychiatria Polska, 2020-02; https://doi.org/10.12740/pp/103876). (krawczyk2020icd11vs.icd10 pages 7-10)

Key Figure/Table Evidence (visual)

Tseng et al. (JAMA Network Open, 2024-12-19) Figure 1 and Table 2 (cumulative incidence and adjusted hazard ratios for cardiovascular outcomes in AN vs controls) were retrieved as cropped evidence images. (tseng2024incidenceandrisk media 19a1fdc3, tseng2024incidenceandrisk media d468e988)

References

  1. (wu2024peripheralbiomarkersof pages 1-2): Ya-Ke Wu, Hunna J. Watson, Aaron C. Del Re, Jody E. Finch, Sabrina L. Hardin, Alexis S. Dumain, Kimberly A. Brownley, and Jessica H. Baker. Peripheral biomarkers of anorexia nervosa: a meta-analysis. Nutrients, 16:2095, Jun 2024. URL: https://doi.org/10.3390/nu16132095, doi:10.3390/nu16132095. This article has 22 citations.

  2. (bang2023genomewideanalysisof pages 1-2): Lasse Bang, Shahram Bahrami, Guy Hindley, Olav B. Smeland, Linn Rødevand, Piotr P. Jaholkowski, Alexey Shadrin, Kevin S. O’ Connell, Oleksandr Frei, Aihua Lin, Zillur Rahman, Weiqiu Cheng, Nadine Parker, Chun C. Fan, Anders M. Dale, Srdjan Djurovic, Cynthia M. Bulik, and Ole A. Andreassen. Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa. Translational Psychiatry, Sep 2023. URL: https://doi.org/10.1038/s41398-023-02585-1, doi:10.1038/s41398-023-02585-1. This article has 36 citations and is from a peer-reviewed journal.

  3. (tseng2024incidenceandrisk pages 1-2): Mei-Chih Meg Tseng, Kuan-Rau Chiou, Joni Yu-Hsuan Shao, and Hung-Yi Liu. Incidence and risk of cardiovascular outcomes in patients with anorexia nervosa. JAMA Network Open, 7:e2451094, Dec 2024. URL: https://doi.org/10.1001/jamanetworkopen.2024.51094, doi:10.1001/jamanetworkopen.2024.51094. This article has 13 citations and is from a peer-reviewed journal.

  4. (chen2024neuroimagingstudiesof pages 1-2): Xiong Chen, Chunqi Ai, Zhongchun Liu, and Gang Wang. Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders. BMC Medical Imaging, Oct 2024. URL: https://doi.org/10.1186/s12880-024-01432-z, doi:10.1186/s12880-024-01432-z. This article has 29 citations and is from a peer-reviewed journal.

  5. (voderholzer2025anorexianervosaanupdate. pages 1-2): Ulrich Voderholzer, Silke Naab, Ulrich Cuntz, and Sandra Schlegl. Anorexia nervosa-an update. Der Nervenarzt, May 2025. URL: https://doi.org/10.1007/s00115-025-01820-y, doi:10.1007/s00115-025-01820-y. This article has 5 citations.

  6. (patten2024postdischargemortalityin pages 1-2): Scott B. Patten, Gina Dimitropoulos, Julia Hews‐Girard, Amelia Austin, Vandad Sharifi, Jeanne Williams, Anees Bahji, and Andrew Bulloch. Postdischarge mortality in a cohort hospitalized with anorexia nervosa. The International Journal of Eating Disorders, 57:2482-2486, Sep 2024. URL: https://doi.org/10.1002/eat.24296, doi:10.1002/eat.24296. This article has 3 citations.

  7. (wu2024peripheralbiomarkersof pages 9-11): Ya-Ke Wu, Hunna J. Watson, Aaron C. Del Re, Jody E. Finch, Sabrina L. Hardin, Alexis S. Dumain, Kimberly A. Brownley, and Jessica H. Baker. Peripheral biomarkers of anorexia nervosa: a meta-analysis. Nutrients, 16:2095, Jun 2024. URL: https://doi.org/10.3390/nu16132095, doi:10.3390/nu16132095. This article has 22 citations.

  8. (kaver2024cytokineandmicrobiome pages 1-2): Larissa Käver, Clara Voelz, Hannah E Specht, Anna C Thelen, Lara Keller, Brigitte Dahmen, Nadia Andrea Andreani, Klaus Tenbrock, Ronald Biemann, Katrin Borucki, Astrid Dempfle, John F Baines, Cordian Beyer, Beate Herpertz-Dahlmann, Stefanie Trinh, and Jochen Seitz. Cytokine and microbiome changes in adolescents with anorexia nervosa at admission, discharge, and one-year follow-up. Nutrients, May 2024. URL: https://doi.org/10.3390/nu16111596, doi:10.3390/nu16111596. This article has 12 citations.

  9. (tseng2024incidenceandrisk pages 4-5): Mei-Chih Meg Tseng, Kuan-Rau Chiou, Joni Yu-Hsuan Shao, and Hung-Yi Liu. Incidence and risk of cardiovascular outcomes in patients with anorexia nervosa. JAMA Network Open, 7:e2451094, Dec 2024. URL: https://doi.org/10.1001/jamanetworkopen.2024.51094, doi:10.1001/jamanetworkopen.2024.51094. This article has 13 citations and is from a peer-reviewed journal.

  10. (pedersen2024modificationstoenhance pages 1-2): Signe Holm Pedersen, Lasse Carlsson, and Mette Bentz. Modifications to enhance outcomes of family-based treatment for anorexia nervosa: a scoping review. Psychiatry International, 5:217-230, May 2024. URL: https://doi.org/10.3390/psychiatryint5020015, doi:10.3390/psychiatryint5020015. This article has 5 citations.

  11. (pedersen2024modificationstoenhance pages 4-6): Signe Holm Pedersen, Lasse Carlsson, and Mette Bentz. Modifications to enhance outcomes of family-based treatment for anorexia nervosa: a scoping review. Psychiatry International, 5:217-230, May 2024. URL: https://doi.org/10.3390/psychiatryint5020015, doi:10.3390/psychiatryint5020015. This article has 5 citations.

  12. (hambleton2025advancementsinfamilybased pages 1-2): Ashlea Hambleton, Daniel Le Grange, Stephen Touyz, and Sarah Maguire. Advancements in family-based treatment of adolescent anorexia nervosa: a review of access barriers and telehealth solutions. Nutrients, 17:2160, Jun 2025. URL: https://doi.org/10.3390/nu17132160, doi:10.3390/nu17132160. This article has 4 citations.

  13. (krawczyk2020icd11vs.icd10 pages 7-10): Piotr Krawczyk and Łukasz Święcicki. Icd-11 vs. icd-10 – a review of updates and novelties introduced in the latest version of the who international classification of diseases. Psychiatria Polska, 54:7-20, Feb 2020. URL: https://doi.org/10.12740/pp/103876, doi:10.12740/pp/103876. This article has 93 citations.

  14. (ayrolles2024earlyonsetanorexianervosa pages 1-2): Anaël Ayrolles, Julia Clarke, Nathalie Godart, Céline André-Carletti, Clémentine Barbe, Anne Bargiacchi, Corinne Blanchet, Florence Bergametti, Valérie Bertrand, Emmanuelle Caldagues, Marylene Caquard, Danielle Castellotti, Richard Delorme, Laurence Dreno, Dominique Feneon Landou, Priscille Gerardin, Selim Guessoum, Ludovic Gicquel, Juliane Léger, Stéphanie Legras, Lucile Noel, Anne Fjellestad-Paulsen, Hélène Poncet-Kalifa, Flora Bat-Pitault, and Coline Stordeur. Early-onset anorexia nervosa: a scoping review and management guidelines. Journal of Eating Disorders, Nov 2024. URL: https://doi.org/10.1186/s40337-024-01130-9, doi:10.1186/s40337-024-01130-9. This article has 12 citations and is from a peer-reviewed journal.

  15. (radden2022capturingtheanorexia pages 1-2): Jennifer Radden. Capturing the anorexia nervosa phenotype: conceptual and normative issues in icd-11. Journal of evaluation in clinical practice, 28:807-813, Jun 2022. URL: https://doi.org/10.1111/jep.13586, doi:10.1111/jep.13586. This article has 8 citations and is from a peer-reviewed journal.

  16. (hay2023epidemiologyofeating pages 1-2): Phillipa Hay, Phillip Aouad, Anvi Le, Peta Marks, Danielle Maloney, Sarah Barakat, Robert Boakes, Leah Brennan, Emma Bryant, Susan Byrne, Belinda Caldwell, Shannon Calvert, Bronny Carroll, David Castle, Ian Caterson, Belinda Chelius, Lyn Chiem, Simon Clarke, Janet Conti, Lexi Crouch, Genevieve Dammery, Natasha Dzajkovski, Jasmine Fardouly, John Feneley, Nasim Foroughi, Mathew Fuller-Tyszkiewicz, Anthea Fursland, Veronica Gonzalez-Arce, Bethanie Gouldthorp, Kelly Griffin, Scott Griffiths, Ashlea Hambleton, Amy Hannigan, Mel Hart, Susan Hart, Ian Hickie, Francis Kay-Lambkin, Ross King, Michael Kohn, Eyza Koreshe, Isabel Krug, Jake Linardon, Randall Long, Amanda Long, Sloane Madden, Siân McLean, Thy Meddick, Jane Miskovic-Wheatley, Deborah Mitchison, Richard O’Kearney, Roger Paterson, Susan Paxton, Melissa Pehlivan, Genevieve Pepin, Andrea Phillipou, Judith Piccone, Rebecca Pinkus, Bronwyn Raykos, Paul Rhodes, Elizabeth Rieger, Karen Rockett, Sarah Rodan, Janice Russell, Haley Russell, Fiona Salter, Susan Sawyer, Beth Shelton, Urvashnee Singh, Sophie Smith, Evelyn Smith, Karen Spielman, Sarah Squire, Juliette Thomson, Marika Tiggemann, Ranjani Utpala, Lenny Vartanian, Andrew Wallis, Warren Ward, Sarah Wells, Eleanor Wertheim, Simon Wilksch, Michelle Williams, Stephen Touyz, and Sarah Maguire. Epidemiology of eating disorders: population, prevalence, disease burden and quality of life informing public policy in australia—a rapid review. Journal of Eating Disorders, Feb 2023. URL: https://doi.org/10.1186/s40337-023-00738-7, doi:10.1186/s40337-023-00738-7. This article has 189 citations and is from a peer-reviewed journal.

  17. (NCT05918835 chunk 1): Alexandra F Muratore, PhD. Effects of rTMS on Food Choice in Anorexia Nervosa. New York State Psychiatric Institute. 2023. ClinicalTrials.gov Identifier: NCT05918835

  18. (NCT05788042 chunk 1): Trial of Enhanced Neurostimulation for Anorexia. The George Institute. 2023. ClinicalTrials.gov Identifier: NCT05788042

  19. (voderholzer2025anorexianervosaanupdate. pages 2-3): Ulrich Voderholzer, Silke Naab, Ulrich Cuntz, and Sandra Schlegl. Anorexia nervosa-an update. Der Nervenarzt, May 2025. URL: https://doi.org/10.1007/s00115-025-01820-y, doi:10.1007/s00115-025-01820-y. This article has 5 citations.

  20. (tseng2024incidenceandrisk media 19a1fdc3): Mei-Chih Meg Tseng, Kuan-Rau Chiou, Joni Yu-Hsuan Shao, and Hung-Yi Liu. Incidence and risk of cardiovascular outcomes in patients with anorexia nervosa. JAMA Network Open, 7:e2451094, Dec 2024. URL: https://doi.org/10.1001/jamanetworkopen.2024.51094, doi:10.1001/jamanetworkopen.2024.51094. This article has 13 citations and is from a peer-reviewed journal.

  21. (tseng2024incidenceandrisk media d468e988): Mei-Chih Meg Tseng, Kuan-Rau Chiou, Joni Yu-Hsuan Shao, and Hung-Yi Liu. Incidence and risk of cardiovascular outcomes in patients with anorexia nervosa. JAMA Network Open, 7:e2451094, Dec 2024. URL: https://doi.org/10.1001/jamanetworkopen.2024.51094, doi:10.1001/jamanetworkopen.2024.51094. This article has 13 citations and is from a peer-reviewed journal.

  22. (voderholzer2025anorexianervosaanupdate. pages 3-4): Ulrich Voderholzer, Silke Naab, Ulrich Cuntz, and Sandra Schlegl. Anorexia nervosa-an update. Der Nervenarzt, May 2025. URL: https://doi.org/10.1007/s00115-025-01820-y, doi:10.1007/s00115-025-01820-y. This article has 5 citations.

  23. (hay2023epidemiologyofeating pages 37-38): Phillipa Hay, Phillip Aouad, Anvi Le, Peta Marks, Danielle Maloney, Sarah Barakat, Robert Boakes, Leah Brennan, Emma Bryant, Susan Byrne, Belinda Caldwell, Shannon Calvert, Bronny Carroll, David Castle, Ian Caterson, Belinda Chelius, Lyn Chiem, Simon Clarke, Janet Conti, Lexi Crouch, Genevieve Dammery, Natasha Dzajkovski, Jasmine Fardouly, John Feneley, Nasim Foroughi, Mathew Fuller-Tyszkiewicz, Anthea Fursland, Veronica Gonzalez-Arce, Bethanie Gouldthorp, Kelly Griffin, Scott Griffiths, Ashlea Hambleton, Amy Hannigan, Mel Hart, Susan Hart, Ian Hickie, Francis Kay-Lambkin, Ross King, Michael Kohn, Eyza Koreshe, Isabel Krug, Jake Linardon, Randall Long, Amanda Long, Sloane Madden, Siân McLean, Thy Meddick, Jane Miskovic-Wheatley, Deborah Mitchison, Richard O’Kearney, Roger Paterson, Susan Paxton, Melissa Pehlivan, Genevieve Pepin, Andrea Phillipou, Judith Piccone, Rebecca Pinkus, Bronwyn Raykos, Paul Rhodes, Elizabeth Rieger, Karen Rockett, Sarah Rodan, Janice Russell, Haley Russell, Fiona Salter, Susan Sawyer, Beth Shelton, Urvashnee Singh, Sophie Smith, Evelyn Smith, Karen Spielman, Sarah Squire, Juliette Thomson, Marika Tiggemann, Ranjani Utpala, Lenny Vartanian, Andrew Wallis, Warren Ward, Sarah Wells, Eleanor Wertheim, Simon Wilksch, Michelle Williams, Stephen Touyz, and Sarah Maguire. Epidemiology of eating disorders: population, prevalence, disease burden and quality of life informing public policy in australia—a rapid review. Journal of Eating Disorders, Feb 2023. URL: https://doi.org/10.1186/s40337-023-00738-7, doi:10.1186/s40337-023-00738-7. This article has 189 citations and is from a peer-reviewed journal.

  24. (radden2022capturingtheanorexia pages 2-3): Jennifer Radden. Capturing the anorexia nervosa phenotype: conceptual and normative issues in icd-11. Journal of evaluation in clinical practice, 28:807-813, Jun 2022. URL: https://doi.org/10.1111/jep.13586, doi:10.1111/jep.13586. This article has 8 citations and is from a peer-reviewed journal.

  25. (NCT03984344 chunk 1): Theta Burst Stimulation in Anorexia Nervosa. King's College London. 2020. ClinicalTrials.gov Identifier: NCT03984344

  26. (NCT04061304 chunk 1): A Clinical Trial Into the Efficacy of rTMS Treatment for Treating Anorexia Nervosa and Bulimia Nervosa. University of Manitoba. 2020. ClinicalTrials.gov Identifier: NCT04061304

OpenScientist ▸
1. Disease Information
openscientist-autonomous 71 citations 2026-05-05T04:23:40.601442

1. Disease Information

Overview

Anorexia nervosa is a complex eating disorder primarily characterized by a low body-mass index resulting from persistent restriction of energy intake relative to requirements, an intense fear of gaining weight or becoming fat, and a disturbance in the way one's body weight or shape is experienced. The disorder was first described in medical literature in the 19th century and remains one of the most lethal psychiatric conditions. As stated in the landmark GWAS publication: "Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness" (PMID: 31308545).

Key Identifiers

Database Identifier
MONDO MONDO:0005351
OMIM 606788
Orphanet ORPHA:36297
ICD-10 F50.0 (Anorexia nervosa), F50.1 (Atypical anorexia nervosa)
ICD-11 6B80
MeSH D000856
DSM-5 307.1

Synonyms and Alternative Names

  • AN
  • Anorexia nervosa, restricting type (AN-R)
  • Anorexia nervosa, binge-eating/purging type (AN-BP)
  • Anorexia athletica (subtype in athletes)
  • Mental anorexia

Information Sources

This report integrates data from aggregated disease-level resources (GWAS meta-analyses, systematic reviews, population registries) and individual patient-level cohort studies. Key data sources include the Psychiatric Genomics Consortium (PGC), ENIGMA Eating Disorders Working Group, Danish Psychiatric Central Research Register, and multiple multinational clinical cohort studies.

2. Etiology

Disease Causal Factors

AN is a multifactorial disorder arising from the interaction of genetic, neurobiological, psychological, and environmental factors. It is now recognized as a metabo-psychiatric disorder, reflecting the discovery that genetic risk factors span both psychiatric liability and metabolic/anthropometric traits (PMID: 31308545; PMID: 38431502).

Genetic Risk Factors

Heritability and GWAS findings: Twin studies consistently estimate AN heritability at 48–74%, while SNP-based heritability is approximately 11–17%. As reported: "Genetic studies, particularly genome-wide association studies (GWAS), have identified key loci associated with ED susceptibility, with heritability estimates for these disorders ranging between 48% and 74%" (PMID: 39988782).

The 2019 PGC-ED GWAS meta-analysis of approximately 17,000 AN cases and 55,000 controls identified eight genome-wide significant loci, implicating genes involved in both psychiatric and metabolic pathways (PMID: 31308545).

Key susceptibility loci and candidate genes:

Gene/Locus Chromosome Function Evidence
FOXP1 3p13 Transcription factor; neurodevelopment GWAS locus; poly-T STR in 3'UTR identified
CADM1 11q23.3 Cell adhesion; synapse formation GWAS significant
IP6K2/PRKAR2A 3p21.31 Kinase signaling GWAS locus; polymorphic SVA-D element
NCKIPSD 3p21.31 Cytoskeleton regulation GWAS significant
PTBP2 1p21.3 RNA processing; neuronal GWAS significant
BDNF 11p14.1 Neurotrophin; feeding regulation Candidate gene; Val66Met polymorphism
HTR2A (5-HT2A) 13q14.2 Serotonin receptor Candidate gene meta-analyses

Targeted nanopore sequencing has identified additional poorly characterized variants in GWAS regions, including a polymorphic SINE-VNTR-Alu element (SVA-D) near IP6K2/PRKAR2A and a poly-T short tandem repeat in the 3'UTR of FOXP1, which may affect post-transcriptional processing (PMID: 39741260).

Cross-disorder genetic architecture: AN shares genetic correlations with multiple psychiatric disorders. Genomic structural equation modeling places AN within a "compulsive disorders" factor alongside OCD and Tourette syndrome (PMID: 39009701). Cross-disorder meta-analysis has identified 109 loci associated with at least two psychiatric disorders, with pleiotropic loci showing heightened brain expression beginning prenatally (PMID: 31835028).

AN is negatively genetically correlated with body fat percentage and fat-free mass, and Mendelian randomization identifies AN as potentially causal for decreased fat mass (PMID: 31852892).

Environmental Risk Factors

  • Age and sex: Peak onset during adolescence (10–20 years); female:male ratio approximately 8–10:1
  • Family history: First-degree relatives have 7–12× increased risk
  • Childhood perfectionism and obsessive traits: Significantly associated with AN development; 40.4% of restrictive eaters display obsessive traits (PMID: 20179406)
  • Weight/shape teasing: Established risk factor across severity levels (PMID: 38212857)
  • Childhood obesity: History of overweight predisposes to eating disorder development
  • Relational factors: Unmet emotional needs, feelings of non-belonging, exposure to conditional worth messaging about body/eating (PMID: 41236167)
  • Athletic participation: Athletes in aesthetic sports have significantly higher prevalence (PMID: 37528996)
  • Cultural factors: Western cultural idealization of thinness plays a salient role in rising incidence

Protective Factors

  • Positive family emotional environment and secure attachment
  • Healthy body image promotion (non-weight-focused)
  • Early intervention for emotional distress
  • Genetic protective variants: not well characterized, but some population-specific alleles may confer resilience

Gene-Environment Interactions

Epigenetic mechanisms are increasingly recognized as mediating gene-environment interactions in AN. Exposure to environmental stressors—particularly malnutrition itself—induces changes in DNA methylation, potentially contributing to disease chronification. Epigenome-wide association studies suggest potential reversibility of malnutrition-induced epigenetic changes upon recovery (PMID: 38849516; PMID: 30353170).

3. Phenotypes

Core Behavioral and Psychological Phenotypes

Phenotype HPO Term Frequency Onset Severity
Restrictive eating / food refusal HP:0011968 (Feeding difficulties) ~100% Adolescence Variable to severe
Intense fear of weight gain HP:0000831 ~100% Adolescence Moderate to severe
Body image distortion — ~100%; delusional intensity in 23.6% Adolescence Variable
Excessive exercise HP:0000752 (Hyperactivity) 31–80% Adolescence Variable
Amenorrhea HP:0000141 ~70–90% in females After weight loss Reversible with weight restoration
Depressed mood HP:0000716 ~45% comorbid depression/dysthymia Variable Variable
Obsessive-compulsive features HP:0000722 (OCD) 40.4% (restrictive subtype) Premorbid or concurrent Variable
Anhedonia HP:0000746 Common During illness Moderate to severe

Regarding body image beliefs, a meta-analysis found overvalued ideas in 32.5% and delusional-like beliefs in 23.6% of AN patients, with greater belief rigidity correlating with poorer insight (PMID: 41707619).

Physical Manifestations and Clinical Signs

Phenotype HPO Term Frequency Clinical Significance
Low BMI / Emaciation HP:0004325 (Decreased body weight) ~100% Defining feature
Hypothermia HP:0002045 Common Adaptive to starvation
Bradycardia HP:0001662 Common Cardiovascular complication
Lanugo hair HP:0002232 ~30% Physical sign
Acrocyanosis HP:0001063 (Acrocyanosis) Common Peripheral vascular
Osteopenia/Osteoporosis HP:0000939 / HP:0000938 Up to 50% Potentially irreversible
Purpura — Occasional Bleeding diathesis

Laboratory Abnormalities

Finding HPO/LOINC Frequency Notes
Hypokalemia HP:0002900 Common (purging subtype) aOR 1.98 for ED diagnosis
Hyponatremia HP:0002902 Less common aOR 5.26 for ED diagnosis
Hypophosphatemia HP:0002148 Common, especially refeeding aOR 2.83 for ED diagnosis
Hypomagnesemia HP:0002917 Common Monitor during refeeding
Metabolic alkalosis — Common (purging) aOR 2.60 for ED diagnosis
Hypercholesterolemia HP:0003124 13–18% Paradoxical; associated with lower BMI
Elevated cortisol HP:0003118 Common Adaptive hypercortisolaemia
Low leptin — Common Suppressed adipokine
Elevated ghrelin — Common Orexigenic compensation
Elevated peptide YY — Common Paradoxically elevated
Low estradiol HP:0008214 Common Hypogonadotropic hypogonadism
Low IGF-1 — Common Growth hormone resistance

Electrolyte abnormalities may precede formal ED diagnosis by a median of 386 days, with 18.4% of individuals later diagnosed with an ED having preceding electrolyte abnormalities versus 7.5% of controls (aOR 2.12, 95% CI: 1.86–2.41) (PMID: 36346630).

Quality of Life Impact

AN produces severe impairment across all domains of daily functioning. Role impairment and comorbidity with other mental disorders are highly common (PMID: 19427647). Within the first year of diagnosis, patients are approximately 7× more likely to develop coded depression (HR 7.3, 95% CI: 6.6–8.1) and 9× more likely to engage in self-harm (HR 9.4, 95% CI: 8.2–10.7) compared to matched controls (PMID: 41282513).

4. Genetic/Molecular Information

Causal Genes and Pathogenic Variants

AN is a polygenic disorder without single causal gene mutations. The eight GWAS-significant loci implicate genes involved in neurodevelopment, synaptic function, and metabolic regulation. An estimated ~11,500 genetic variants are thought to contribute to the full heritability landscape (PMID: 31308545).

Candidate genes with robust evidence:

  • BDNF (Brain-Derived Neurotrophic Factor): Reduced circulating levels in AN patients; Val66Met polymorphism associated with worse outcomes in humans, though not confirmed in rat ABA models (PMID: 35625351)
  • HTR2A (Serotonin 2A Receptor): Meta-analytic support as a susceptibility gene for both AN and bulimia nervosa (PMID: 24202964)
  • FOXP1: Transcription factor involved in neurodevelopment; poly-T STR in 3'UTR may affect post-transcriptional processing (PMID: 39741260)

Genetic Correlations with Other Traits

AN shows a unique pattern of genetic correlations that distinguish it from other psychiatric disorders:

Trait Genetic Correlation Direction Significance
OCD Positive Compulsive disorders cluster
Schizophrenia Positive (moderate) Shared psychiatric liability
Major depression Positive Shared internalizing factor
BMI / Body fat % Negative Metabo-psychiatric origins
Type 2 diabetes Negative Metabolic component
HDL cholesterol Positive Metabolic component
Physical activity Positive Metabolic component
Education years Positive Cognitive component

Epigenetic Information

Five epigenome-wide association studies (EWASs) have been published on AN, suggesting potential reversibility of malnutrition-induced epigenetic changes upon recovery. Differential DNA methylation may serve as a biomarker for disease status or early diagnosis and may be involved in disease chronification (PMID: 38849516). The field remains nascent, with most studies limited by small sample sizes and candidate gene approaches (PMID: 30353170).

Chromosomal Abnormalities

No specific chromosomal abnormalities are causally linked to AN. Linkage studies have suggested susceptibility loci on chromosomes 1 and 10 for eating disorders broadly (PMID: 24340712).

5. Environmental Information

Environmental Factors

  • Sociocultural environment: Western cultural idealization of thinness is consistently implicated in rising incidence. The disorder is more prevalent in higher socio-demographic index countries.
  • Prenatal/perinatal factors: Maternal eating disorders are associated with higher risk of wheezing and asthma in offspring (OR: 1.25, 95% CI: 1.06–1.47), suggesting intergenerational effects (PMID: 41330642).

Lifestyle Factors

  • Dieting behavior: Dietary restriction is the most proximal behavioral risk factor
  • Excessive exercise: Both a symptom and perpetuating factor; athletes in aesthetic sports are at markedly elevated risk (PMID: 37528996)
  • Sleep disruption: Bidirectional causal relationships between insomnia/sleep traits and AN identified via Mendelian randomization (PMID: 38703603)

Infectious Agents

AN is not caused by infectious agents. However, gut microbiome dysbiosis is increasingly recognized as a contributing factor in pathophysiology (see Section 6).

6. Mechanism / Pathophysiology

Molecular Pathways

Serotonergic system (GO:0007210 — serotonin receptor signaling pathway): Dysregulated serotonin neurotransmission is central to AN neurobiology. The 5-HT system mediates both aversive/inhibitory signaling and appetite regulation. As described: "Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems" (PMID: 23333342).

Dopaminergic reward system (GO:0007212 — dopamine receptor signaling pathway): Altered reward circuitry is implicated in AN pathogenesis. Hyperdopaminergic mice show augmented vulnerability to activity-based anorexia (ABA), and reward deficits may underlie the paradoxical food avoidance seen in AN (PMID: 33768216; PMID: 28475260).

Opioid system: β-endorphin (a POMC gene product) is elevated in female mice undergoing ABA, and mu opioid receptor activation promotes food anticipatory activity, a key ABA feature (PMID: 33661571).

Adrenergic system: Catecholamine dysregulation is involved in AN pathophysiology; catecholamine levels may be higher in AN patients than in healthy controls, with higher norepinephrine concentrations in adipose tissue suggesting local sympathetic nervous system dominance (PMID: 37691603; PMID: 38310530).

Endocannabinoid system: Peripheral cannabinoid signaling is disrupted in AN, affecting both central appetite regulation and peripheral metabolic processes in adipose tissue, liver, pancreas, and skeletal muscle (PMID: 29437028).

Endocrine Dysregulation

The endocrine manifestations of AN are pervasive and represent one of the most clinically significant aspects of the disease. As comprehensively reviewed: "Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated" (PMID: 27811940).

Causal chain:

Chronic energy restriction
    → Reduced adipose tissue → Suppressed leptin (CHEBI:81571)
    → Hypothalamic dysfunction
→ Decreased GnRH → Hypogonadotropic hypogonadism → Amenorrhea + Bone loss
→ Increased CRH → Hypercortisolaemia → Bone loss + Immune suppression
→ GH resistance → Low IGF-1 → Growth impairment
→ Decreased T3 → Non-thyroidal illness → Reduced metabolic rate
    → Gut peptide dysregulation → Elevated ghrelin + Paradoxical elevated PYY
    → Autonomic dysfunction → Sympathetic dysregulation in adipose tissue

Gut Microbiome

AN patients show reduced alpha diversity and lower short-chain fatty acid (SCFA) levels. Dysbiosis affects immune system responses, intestinal permeability, and neurotransmitter production via the gut-brain axis (PMID: 33416044; PMID: 33652962). Interestingly, recent evidence challenges the "leaky gut" concept in adolescent AN: zonulin and lipopolysaccharide-binding protein (LBP) levels are decreased rather than increased, suggesting reduced rather than increased paracellular intestinal permeability, and these alterations persist despite weight recovery (PMID: 40789230).

Microbiota-derived proteins may stimulate the autoimmune system, altering neuroendocrine control of mood and satiety. Microbial richness increases upon weight regain or fecal microbiota transplantation (PMID: 33416044).

Metabolic Changes

  • Energy metabolism: Resting energy expenditure is very low in underweight patients but increases dramatically early in refeeding (PMID: 16721178)
  • Lipid metabolism: Paradoxical hypercholesterolemia in acute illness; cholesterol levels are higher in females than males and correlate with severity of malnutrition (PMID: 37864342)
  • Bone metabolism: Decreased bone formation, increased bone resorption; osteoporosis affects up to 50% of patients and may be irreversible (PMID: 38380189)

Brain Structure and Function

AN is associated with the largest brain structural deficits of any psychiatric disorder investigated by the ENIGMA consortium. A coordinated analysis of 685 AN patients and 963 controls revealed: "In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions" (PMID: 36031441).

A comprehensive meta-analysis confirmed: "Results showed significant global brain volume reductions in gray matter (GM), white matter (WM), and increases in cerebrospinal fluid (CSF) in acute AN (N = 1130 patients; N = 40 papers), gradually improving upon weight rehabilitation. However, even after 1.5 years of recovery, significantly lower global GM volume compared to healthy controls was found" (PMID: 41619402).

Key affected brain regions include the bilateral anterior and median cingulate cortex, with decreased both gray matter volume and resting-state functional activity (PMID: 34296492). The hippocampus shows volumetric and functional impairments contributing to memory and learning deficits (PMID: 33176113).

GO terms: GO:0007268 (chemical synaptic transmission), GO:0048167 (regulation of synaptic plasticity), GO:0007610 (behavior)

Cell types involved: CL:0000540 (neuron), CL:0000127 (astrocyte), CL:0000128 (oligodendrocyte), CL:0000129 (microglial cell)

7. Anatomical Structures Affected

Organ Level

Primary organs: - Brain (UBERON:0000955): Gray matter volume reduction, cortical thinning, white matter changes - Bone (UBERON:0001474): Osteopenia/osteoporosis; up to 50% of patients affected - Heart (UBERON:0000948): Bradycardia, arrhythmias, QTc prolongation - Endocrine glands (hypothalamus, pituitary, thyroid, adrenal, gonads): Global endocrine dysregulation

Secondary organs (complications): - Kidney (UBERON:0002113): Renal failure risk 6× higher in first year (HR 6.0, 95% CI: 4.2–8.5) (PMID: 41282513) - Liver (UBERON:0002107): Liver disease risk 6.7× higher in first year (HR 6.7, 95% CI: 3.8–11.7) - Gastrointestinal tract (UBERON:0005409): Gastric dilatation, delayed gastric emptying, constipation - Skin (UBERON:0002097): Lanugo, xerosis, acrocyanosis, purpura

Body systems involved: Cardiovascular, nervous, digestive, endocrine, musculoskeletal, integumentary, reproductive, renal, hematologic

Tissue and Cell Level

  • Nervous tissue: Neurons (CL:0000540), glial cells in cortical and subcortical regions
  • Bone tissue: Osteoblasts (CL:0000062), osteoclasts (CL:0000092) — imbalanced remodeling
  • Adipose tissue: Adipocytes (CL:0000136) — severe depletion
  • Cardiac muscle: Cardiomyocytes (CL:0000746) — atrophy
  • Intestinal epithelium: Enterocytes (CL:0000584) — altered permeability

Brain Localization (UBERON terms)

  • Cingulate cortex (UBERON:0003027): Both structural and functional deficits
  • Hippocampus (UBERON:0002421): Volumetric and memory impairments
  • Hypothalamus (UBERON:0001898): Endocrine dysregulation center
  • Prefrontal cortex (UBERON:0000451): Enhanced executive inhibition of reward drives
  • Precuneus (UBERON:0035150): Cortical thinning

8. Temporal Development

Onset

  • Typical age of onset: Adolescence (10–20 years); cumulative lifetime prevalence analysis shows the majority of eating disorders have initial onset in this window (PMID: 19427647)
  • Onset pattern: Usually insidious, beginning with dietary restriction that progressively intensifies
  • Prolonged emotional distress typically precedes symptom onset, with opportunities for early prevention/intervention often missed (PMID: 41236167)

Progression

  • Disease course pattern: Variable — episodic/relapsing-remitting in many; chronic-progressive in 10–20%
  • Disease stages:
  • Early: Restrictive eating, initial weight loss, psychological symptoms
  • Intermediate: Medical complications emerge (amenorrhea, bradycardia, electrolyte disturbances)
  • Advanced: Severe malnutrition, multi-organ involvement, psychiatric comorbidity
  • End-stage: Organ failure, refractory to treatment, high mortality risk

Long-term Outcomes

In a landmark 21-year follow-up study: "Fifty-one per cent of the patients were found to be fully recovered at follow-up, 21% were partially recovered and 10% still met full diagnostic criteria for anorexia nervosa. Sixteen per cent were deceased, due to causes related to anorexia nervosa. The standardized mortality rate was 9.8" (PMID: 11459385).

A 13-year follow-up of 484 patients found 60.3% recovered, 25.8% relatively good outcome, and 6.4% each with bad and severe outcomes. Recovery rate increased with elapsing relapse-free time (p=0.02) (PMID: 21317006).

Critical Periods

  • Adolescence (10–19 years): Primary window of vulnerability and optimal intervention
  • Transition from adolescent to adult services: Risk of discontinuity in care (PMID: 33223229)
  • First 2 years of illness: Key predictors of long-term outcome established; early response to treatment predicts better outcomes

9. Inheritance and Population

Epidemiology

Measure Value Source
Lifetime prevalence (women) 0.48–1.4% PMID: 19427647; PMID: 41366465
Lifetime prevalence (men) ~0.2% PMID: 41366465
Incidence Increasing globally Multiple sources
Sex ratio (F:M) ~8–10:1 Population registries

Inheritance Pattern

AN follows a multifactorial/polygenic inheritance pattern. Key genetic architecture features:

  • Heritability: 48–74% (twin studies); moderate heritability confirmed in population-level register data from Denmark and Sweden covering >67,000 individuals with eating disorders (PMID: 40615413)
  • Penetrance: Incomplete and age-dependent
  • Expressivity: Highly variable — spectrum from subclinical features to life-threatening illness
  • Polygenicity: Estimated ~11,500 variants explain 90% of genetic heritability

Population Demographics

  • Sex distribution: Predominantly female; however, male cases are likely underdiagnosed and males with EDs have unmet needs (PMID: 34246009)
  • Ethnic/racial disparities: Latinx and Asian patients are half as likely as White patients to receive recommended treatment (aOR 0.49 and 0.55, respectively) (PMID: 36694235)
  • Geographic distribution: Higher prevalence in Western/high-income countries, but increasingly recognized globally
  • Insurance disparities: Publicly insured patients are one-third as likely to receive recommended treatment (PMID: 36694235)

10. Diagnostics

Clinical Criteria

DSM-5 Diagnostic Criteria (307.1): 1. Restriction of energy intake relative to requirements, leading to significantly low body weight 2. Intense fear of gaining weight or persistent behavior interfering with weight gain 3. Disturbance in the way body weight or shape is experienced

Subtypes: - Restricting type (AN-R) - Binge-eating/purging type (AN-BP)

Severity based on BMI: - Mild: BMI ≥ 17 kg/m² - Moderate: BMI 16–16.99 kg/m² - Severe: BMI 15–15.99 kg/m² - Extreme: BMI < 15 kg/m²

Latent class analysis has empirically identified four phenotypic classes, with obsessive-compulsive features differentiating among restricting AN subgroups (PMID: 14757596).

Laboratory Tests

Test Purpose Key Findings
Complete metabolic panel Electrolyte screening Hypokalemia, hyponatremia, hypophosphatemia
Magnesium, phosphate Refeeding syndrome risk Often depleted
CBC Hematologic status Anemia, leukopenia, thrombocytopenia
Thyroid function Endocrine assessment Low T3 (non-thyroidal illness)
Gonadotropins, estradiol Reproductive function Low (hypogonadotropic hypogonadism)
Cortisol HPA axis assessment Elevated
IGF-1 Growth/nutritional status Low (GH resistance)
ECG Cardiac monitoring Bradycardia, QTc prolongation
DXA / REMS Bone density Osteopenia/osteoporosis

REMS (Radiofrequency echographic multispectrometry) shows good agreement with DXA for BMD assessment in AN and may be particularly useful during fertile age and pregnancy (PMID: 35896857).

Imaging Studies

  • Brain MRI: May reveal gray matter volume reductions and cortical thinning; lower brain volumes of the cerebellum and subcortical gray matter at admission predict worse outcomes (PMID: 37263169)
  • PET/SPECT: Research tools for serotonergic and dopaminergic receptor density mapping; clinical utility not established (PMID: 32234640)

Screening Tools

  • SCOFF questionnaire: Brief 5-question screening tool
  • EAT-26 (Eating Attitudes Test): 26-item self-report measure
  • EDI-2 (Eating Disorder Inventory): Comprehensive psychometric assessment
  • Electrolyte monitoring: Otherwise unexplained electrolyte abnormalities may identify individuals who benefit from ED screening (PMID: 36346630)

Genetic Testing

Genetic testing is not currently part of standard clinical practice for AN. However, the Eating Disorders Genetics Initiative 2 (EDGI2) is advancing polygenic risk scoring that may eventually enable risk stratification (PMID: 40419993).

Differential Diagnosis

  • Bulimia nervosa (binge-purge without low weight)
  • Avoidant/restrictive food intake disorder (ARFID) (no body image distortion)
  • Binge eating disorder
  • Major depressive disorder with appetite loss
  • Medical conditions causing weight loss (malignancy, Crohn's disease, hyperthyroidism, Addison's disease)
  • Body dysmorphic disorder (significantly higher delusionality than AN) (PMID: 41707619)

11. Outcome/Prognosis

Mortality

AN has the highest mortality rate of all mental disorders:

Measure Value Source
All-cause mortality RR vs. general population 5.52 (95% CI: 4.47–6.82) PMID: 41536100
Suicide-related mortality RR 9.86 (95% CI: 5.63–17.27) PMID: 41536100
Mortality at 21-year follow-up 16% PMID: 11459385
All-cause mortality HR (first year) 4.6 (95% CI: 3.1–7.0) PMID: 41282513
Suicide HR (first year) 13.7 (95% CI: 4.8–38.8) PMID: 41282513

Eating disorders are independent risk factors for suicide, with bulimia nervosa (HR 2.59) and other eating disorders (HR 2.31) maintaining significance even after adjusting for psychiatric comorbidities. For AN specifically, the association became non-significant after adjustment for comorbid psychiatric conditions (PMID: 40280427).

Mortality rates may be influenced by treatment quality: one Italian center with an integrated multidisciplinary treatment network found SMR of 1.19 (95% CI: 0.79–1.81), not significantly different from the general population (PMID: 36062404).

Recovery and Long-term Outcomes

Timeframe Full Recovery Partial Recovery Active AN Deceased
13-year follow-up (N=484) 60.3% 25.8% 6.4% (bad) + 6.4% (severe) 1.2%
21-year follow-up 51% 21% 10% 16%

Prognostic Factors

Poor prognostic factors: - Low BMI at discharge - Low energy and fat intake - High drive for excessive exercise - High perfectionism and interpersonal distrust - High anxiety - Psychiatric comorbidity - Binge/purge subtype transition - Higher levels of depression and compulsivity (PMID: 17628126) - Lower brain volumes at admission (PMID: 37263169) - Older age at onset

Favorable prognostic factors: - Adolescent age at treatment - Early symptom improvement - Maintaining contact with mother - Shorter duration of illness before treatment - Higher pre-treatment BMI (PMID: 37697396)

Complications

Within 10 years of diagnosis, patients experience excess adverse outcomes (PMID: 41282513): - 110 excess renal failure events per 10,000 individuals - 26 excess liver disease events per 10,000 individuals - 95 excess all-cause deaths per 10,000 individuals - 341 excess unnatural deaths per 100,000 individuals

12. Treatment

Psychotherapy (First-line)

Family-Based Treatment (FBT) — MAXO:0000950 (counseling): The leading evidence-based treatment for adolescent AN. "In 5 randomized controlled trials (RCTs) in anorexia nervosa (N=560) remission rates were between 21.2-42% at end of treatment, between 21.8-40% at 6-month follow-up, and between 29-49% at 12-month follow-up" (PMID: 31466116).

In a naturalistic Finnish study, 61.5% of adolescents achieved full weight restoration (EBW ≥95%) with FBT, and 42.3% required no further treatment (PMID: 37697396).

Cognitive Behavioral Therapy-Enhanced (CBT-E) — MAXO:0000376 (cognitive behavioral therapy): Recommended as a second-line approach for adolescents when FBT is not effective or applicable, and as a primary approach for adults. CBT-E shows moderate to large effect sizes regardless of previous FBT failure (PMID: 30829421; PMID: 33223229).

Pharmacotherapy

No medications are currently FDA-approved specifically for AN. Key pharmacological considerations:

Medication Evidence Notes
Olanzapine Weekly weight gain 0.898 vs. 0.677 kg (p=0.004) Promising adjunctive treatment; "The OLZ group achieved greater weekly weight gain (0.898 vs. 0.677 kg, p = 0.004)" (PMID: 40879610)
Fluoxetine Limited evidence for relapse prevention Not effective for acute weight restoration
Dronabinol Promising preliminary results Cannabinoid receptor agonist
SSRIs For comorbid depression Not for core AN symptoms
Teriparatide Trends in improved bone structure (IT cortical thickness +13%) For AN-related osteoporosis (PMID: 41591404)
Romosuzumab Significant BMD increase in case report Novel anti-sclerostin antibody for AN osteoporosis (PMID: 39314548)

Nutritional Rehabilitation (MAXO:0001298 — dietary modification)

Weight gain of 2.2–4.4 lb per week stabilizes cardiovascular health (PMID: 33382560). Refeeding syndrome risk requires careful monitoring of phosphate, magnesium, and potassium levels.

Hospitalization (MAXO:0010363 — inpatient care)

Hospitalization effectively overcomes the acute phase and promotes lasting changes. A multidisciplinary approach comprising clinical/nutritional, psychotherapeutic, family, occupational, and body therapy components is recommended (PMID: 12452251).

Treatment Strategy and Future Directions

  • Integrated multidisciplinary networks may significantly reduce mortality (PMID: 36062404)
  • GLP-1 receptor agonists are being investigated via Mendelian randomization for potential effects on AN (PMID: 40141382)
  • Psychedelic-assisted therapy, novel monoaminergic drugs, and hormone analogues are emerging areas of investigation (PMID: 32858054)
  • Probiotics and microbiome-targeted therapies show early promise for restoring gut-brain axis function (PMID: 33652962)

13. Prevention

Primary Prevention

  • Media literacy programs to counter thin-ideal internalization
  • Body image education emphasizing positive body focus rather than weight/dieting (PMID: 33382560)
  • Family support programs for building healthy emotion regulation skills
  • Athlete screening: Targeted prevention in aesthetic sports populations (PMID: 37528996)

Secondary Prevention (Early Detection)

  • Electrolyte screening: Unexplained electrolyte abnormalities in adolescents should prompt ED assessment (PMID: 36346630)
  • BMI trend monitoring: Subtle weight changes should be investigated in primary care (PMID: 33382560)
  • Web-based parent interventions: The E@T program showed significant increase in expected body weight at 12-month follow-up (Cohen d=0.42), though parent adherence was low (PMID: 30552078)

Tertiary Prevention

  • Long-term psychiatric monitoring, as 6% of treated patients attempt suicide even years after initial treatment (PMID: 35142161)
  • Ongoing bone density monitoring and treatment
  • Relapse prevention through continued therapeutic support; relapse risk declines after 4 years symptom-free (PMID: 9054777)

Genetic Counseling

While genetic testing is not standard, families with affected members should be informed of the elevated familial risk (7–12× for first-degree relatives). The EDGI2 initiative may eventually enable polygenic risk-based screening (PMID: 40419993).

14. Other Species / Natural Disease

Animal Models of Relevance

While AN does not occur naturally in animals in the same form as in humans, self-starvation behaviors have been documented in various species:

  • Activity-based anorexia (ABA) in rodents: The most widely used animal model, in which rats or mice with unlimited running wheel access and restricted food availability develop paradoxical hypophagia, hyperactivity, and life-threatening weight loss, recapitulating key features of human AN including hypothermia and anhedonia (PMID: 28475260; PMID: 38103992)

Comparative Biology

The POMC/opioid system and dopaminergic reward circuitry involved in AN are evolutionarily conserved across mammals, supporting the translational relevance of rodent models. However, the cognitive and psychological components of AN (body image distortion, fear of weight gain) cannot be modeled in animals, representing a fundamental limitation.

15. Model Organisms

Activity-Based Anorexia (ABA) Model

Species: Primarily Mus musculus (NCBI Taxon: 10090) and Rattus norvegicus (NCBI Taxon: 10116)

Protocol: Combining limited food access with unlimited running wheel access produces paradoxical decrease in food intake, hyperactivity, and life-threatening weight loss (PMID: 34124309).

Phenotype recapitulation: - Severely restricted food intake - Excessive exercise/hyperactivity - Dramatic weight loss - Loss of reproductive cycles - Hypothermia - Anhedonia - Elevated POMC mRNA and beta-endorphin - Body image distortion — NOT modeled - Fear of weight gain (cognitive component) — NOT modeled - Voluntary nature of food restriction — NOT modeled

Genetic Models

Model Key Finding Reference
Hyperdopaminergic mice Increased dopamine augments ABA vulnerability PMID: 33768216
MOR knockout mice Blunted food anticipatory activity in both sexes PMID: 33661571
BDNF Val68Met rats No effect on ABA susceptibility or feeding behavior PMID: 35625351
C57BL/6 vulnerability/resilience Resilient mice show adaptive food intake increase and weight stabilization PMID: 34124309

Research applications: The ABA model enables investigation of neurobiological mechanisms, pharmacological interventions, genetic susceptibility factors, and the distinction between vulnerable and resilient phenotypes (PMID: 38103992).

Key Findings — Detailed Evidence

Finding 1: AN is a Complex Metabo-Psychiatric Disorder with the Highest Psychiatric Mortality

The reconceptualization of AN as a metabo-psychiatric disorder represents a paradigm shift in understanding this illness. The 2019 PGC-ED GWAS meta-analysis demonstrated that genetic risk factors for AN span both psychiatric liability (correlations with OCD, schizophrenia, depression) and metabolic traits (negative correlations with BMI, body fat, type 2 diabetes; positive correlations with HDL cholesterol and physical activity). This dual nature means that AN cannot be adequately understood through either a purely psychiatric or purely metabolic lens. The mortality data are stark: the most current meta-analysis confirms AN has the highest all-cause mortality ratio (RR=5.52) and suicide-related mortality (RR=9.86) of all eating disorders and indeed all mental illnesses.

Finding 2: Global Endocrine Dysregulation

The pervasive endocrine dysfunction in AN extends across virtually every hormonal axis and represents both an adaptive response to chronic starvation and a self-perpetuating pathological mechanism. The paradoxical elevation of peptide YY (an anorexigenic hormone) in the context of severe underweight may contribute to the maintenance of food restriction. The endocrine changes have direct consequences for bone health (osteoporosis via estrogen deficiency and hypercortisolism), cardiovascular health, and reproductive function. Critically, most endocrine disturbances are reversible with sustained weight restoration, providing both therapeutic targets and indicators of recovery.

Finding 3: Brain Structural Deficits

The ENIGMA consortium's finding that AN produces the largest cortical thickness deficits of any psychiatric disorder (Cohen's d up to 0.95) has profound implications for understanding cognitive function, treatment response, and long-term outcomes in AN. The deficits are widespread, colocalize with cortical hub regions, and are directly associated with BMI. While partially reversible with weight restoration, global gray matter volume remains significantly lower even after 1.5 years of recovery, suggesting some degree of lasting neural impact. Lower brain volumes at admission predict worse clinical outcomes, supporting neuroimaging as a potential prognostic tool.

Finding 4: Family-Based Treatment Efficacy and Treatment Landscape

FBT remains the treatment with the strongest evidence base for adolescent AN, though remission rates of 29–49% at 12-month follow-up highlight the substantial proportion of patients who do not respond. The absence of any FDA-approved pharmacological treatment for AN is a critical gap. Olanzapine shows the most promising data as an adjunctive agent (significantly greater weekly weight gain at approximately 9 mg/day), while novel bone-targeted therapies (teriparatide, romosuzumab) address the skeletal complications. The finding that long-term outcomes may be improved by integrated multidisciplinary treatment networks — potentially normalizing mortality rates — underscores the importance of care delivery models.

Mechanistic Model

GENETIC VULNERABILITY (48-74% heritability, 8+ GWAS loci)
    |
    Polygenic risk across psychiatric + metabolic pathways
    (Serotonin, dopamine, BDNF, FOXP1, CADM1)
    |
ENVIRONMENTAL TRIGGERS
    |-- Sociocultural pressure (thin ideal)
    |-- Psychological traits (perfectionism, anxiety, OCD)
    |-- Relational factors (unmet needs, conditional worth)
    +-- Dieting / caloric restriction
 |
DISEASE INITIATION
    |-- Reward circuit dysregulation (decreased dopamine signaling)
    |-- Enhanced executive inhibition of feeding drives
    +-- Serotonin-mediated anxiety reduction through restriction
 |
SELF-PERPETUATING MECHANISMS
    |-- Starvation --> Endocrine dysregulation
    |     |-- Decreased Leptin --> Hypothalamic dysfunction
    |     |-- Increased Cortisol --> Bone loss + immune suppression
    |     |-- Decreased GnRH --> Hypogonadism --> Amenorrhea
    |     +-- Paradoxical increased PYY --> Maintained anorexia
    |-- Starvation --> Brain volume loss (d=0.95)
    |     +-- Cognitive rigidity --> Impaired treatment response
    |-- Starvation --> Gut dysbiosis
    |     +-- Altered gut-brain signaling
    |-- Starvation --> Epigenetic changes
    |     +-- Possible disease chronification
    +-- Beta-endorphin elevation --> Exercise reward
 +-- Hyperactivity reinforcement
      |
CLINICAL MANIFESTATIONS
    |-- Psychiatric: Depression, anxiety, OCD, suicidality
    |-- Skeletal: Osteoporosis (50%), fractures
    |-- Cardiac: Bradycardia, arrhythmias
    |-- Metabolic: Electrolyte disturbances, hypercholesterolemia
    |-- Renal/Hepatic: Organ damage (HR 6.0-6.7)
    +-- Neurological: Persistent GM volume reduction
 |
OUTCOMES (without adequate treatment)
    |-- Recovery: ~50-60%
    |-- Chronic illness: ~10-20%
    +-- Death: SMR 5.52 (highest of all psychiatric disorders)

Evidence Base

Landmark Studies

Study PMID Contribution
PGC-ED GWAS (Watson et al., 2019) 31308545 Identified 8 risk loci; established metabo-psychiatric paradigm
ENIGMA-ED Brain Structure (2022) 36031441 Largest cortical thickness deficits of any psychiatric disorder
Mortality Meta-Analysis (2025) 41536100 Definitive mortality data: SMR 5.52, suicide RR 9.86
Endocrine Review (Misra and Klibanski, 2014) 27811940 Comprehensive endocrine characterization
FBT Systematic Review (2019) 31466116 Treatment efficacy data: remission 29-49% at 12 months
21-Year Follow-up (Zipfel et al., 2000) 11459385 Long-term outcomes: 51% recovery, 16% mortality
Brain Volume Meta-Analysis (2025) 41619402 Persistent GM volume reduction after 1.5 years recovery
Adverse Outcomes Cohort (2025) 41282513 Multi-organ adverse outcome quantification
Cross-Disorder Genetics (2019) 31835028 109 shared loci across 8 psychiatric disorders
Genetic Correlations with Body Composition (2019) 31852892 AN causal for decreased fat mass via MR

Limitations and Knowledge Gaps

  1. Genetic architecture: Only 8 GWAS-significant loci identified to date; the EDGI2 initiative aims to dramatically expand sample sizes across diverse ancestral backgrounds, which is essential given that most genetic studies have been conducted in European-ancestry populations.

  2. Pharmacological treatment gap: No approved medications for core AN symptoms; olanzapine and other agents show promise but large-scale RCTs are lacking. The network meta-analysis protocol (EfaNosa, PMID: 41366465) will provide the first systematic comparison of all available treatments.

  3. Male AN is understudied: Males represent 10–13% of clinical samples but are likely underdiagnosed. Mortality and morbidity data for males are limited due to small sample sizes (PMID: 34246009).

  4. Epigenetic studies remain in infancy: Sample sizes are small, methods are heterogeneous, and longitudinal data are limited. Whether epigenetic changes are causes, consequences, or biomarkers of illness remains unclear (PMID: 38849516).

  5. Brain recovery trajectory: While acute brain volume deficits are well-documented, the timeline and completeness of neurological recovery remain uncertain, with evidence suggesting persistent deficits beyond 1.5 years of recovery.

  6. Treatment matching: No validated predictors exist for matching individual patients to optimal treatment modality (FBT vs. CBT-E vs. other approaches).

  7. Microbiome causality: While gut dysbiosis is documented in AN, whether it is cause, consequence, or both remains unclear. The unexpected finding of reduced rather than increased intestinal permeability challenges prevailing hypotheses.

  8. Racial/ethnic and socioeconomic disparities: Significant disparities in treatment access exist; culturally adapted interventions are lacking.

Proposed Follow-up Experiments/Actions

  1. Expand GWAS in diverse populations: Support EDGI2 recruitment across non-European ancestries to identify population-specific and shared risk loci, potentially doubling the number of significant loci.

  2. Longitudinal epigenome-wide association studies: Design EWAS with >500 participants at multiple time points (acute, weight-restored, 2+ years recovered) to distinguish state vs. trait epigenetic markers and identify biomarkers for relapse risk.

  3. RCT comparing FBT vs. CBT-E in adolescents: Directly compare the two leading psychotherapies with standardized outcome measures and treatment matching analysis to identify which patients benefit from each approach.

  4. Placebo-controlled multi-site olanzapine trial: Conduct definitive phase III trial with sufficient power to establish olanzapine as adjunctive therapy for AN, including both weight and psychological outcomes.

  5. Neuroimaging prognostic biomarker validation: Prospective multi-site study using standardized MRI protocols to validate brain structural measures as prognostic tools for treatment response and long-term outcome.

  6. Microbiome intervention trials: Randomized trials of fecal microbiota transplantation or targeted probiotic supplementation in AN patients during refeeding to assess impact on gut-brain axis function, mood, and treatment response.

  7. Polygenic risk score clinical utility: Test whether polygenic risk scores can identify high-risk individuals for targeted prevention, particularly in families with affected members and in athletic populations.

  8. GLP-1 receptor agonist safety monitoring: Given the widespread use of GLP-1 receptor agonists for obesity, establish systematic monitoring for emergence or exacerbation of eating disorder symptoms in treated populations.

  9. Bone therapy optimization: Conduct larger RCTs of romosuzumab and teriparatide in AN-related osteoporosis to establish evidence-based treatment protocols for this common and potentially irreversible complication.

  10. Culturally adapted interventions: Develop and test ED treatment programs specifically designed for underserved populations (Latinx, Asian, publicly insured youth) to address documented disparities in treatment access and outcomes.

Report generated from systematic analysis of 89 publications spanning genetics, neurobiology, clinical outcomes, and therapeutics of anorexia nervosa. All citations verified against PubMed abstracts.