anorexia nervosa case presentation

BRIAN C. HARRINGTON, MD, MPH, MICHELLE JIMERSON, MD, MPH, CHRISTINA HAXTON, MA, LMFT, AND DAVID C. JIMERSON, MD

Am Fam Physician. 2015;91(1):46-52

A more recent article on eating disorders in primary care is available.

Patient information : See related handout on eating disorders , written by the authors of this article.

Eating disorders are life-threatening conditions that are challenging to address; however, the primary care setting provides an important opportunity for critical medical and psychosocial intervention. The recently published Diagnostic and Statistical Manual of Mental Disorders , 5th ed., includes updated diagnostic criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic criterion) and for bulimia nervosa (e.g., criterion for frequency of binge episodes decreased to an average of once per week). In addition to the role of environmental triggers and societal expectations of body size and shape, research has suggested that genes and discrete biochemical signals contribute to the development of eating disorders. Anorexia nervosa and bulimia nervosa occur most often in adolescent females and are often accompanied by depression and other comorbid psychiatric disorders. For low-weight patients with anorexia nervosa, virtually all physiologic systems are affected, ranging from hypotension and osteopenia to life-threatening arrhythmias, often requiring emergent assessment and hospitalization for metabolic stabilization. In patients with frequent purging or laxative abuse, the presence of electrolyte abnormalities requires prompt intervention. Family-based treatment is helpful for adolescents with anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior therapy, is effective for most patients with bulimia nervosa. The use of psychotropic medications is limited for anorexia nervosa, whereas treatment studies have shown a benefit of antidepressant medications for patients with bulimia nervosa. Treatment is most effective when it includes a multidisciplinary, team-based approach.

Eating disorders have traditionally been classified into two well-established categories. They are anorexia nervosa and bulimia nervosa. 1 Additionally, many patients have been classified as having the residual category of eating disorder not otherwise specified. 2 Revisions in the recently published Diagnostic and Statistical Manual of Mental Disorders , 5th ed., (DSM-5) may facilitate more specific eating disorder diagnoses. 3 , 4 The DSM-5 includes a diagnostic category for binge-eating disorder, which is characterized by a loss of control and the feelings of guilt, shame, and embarrassment. The disorder is not associated with self-induced vomiting or other compensatory behaviors; hence, patients are typically overweight or obese. Other feeding and eating disorders in the DSM-5 include pica, rumination disorder, and avoidant/restrictive food intake disorder. 3 This article focuses on anorexia nervosa and bulimia nervosa.

The DSM-5 diagnostic criteria for anorexia nervosa ( Table 1 3 ) are similar to the previous DSM-IV criteria with respect to behavioral and psychological characteristics involving restriction of food intake resulting in low body weight, intense fear of gaining weight or becoming fat, and disturbance of body image. 1 , 3 Notably, the DSM-5 criteria do not refer to a specific degree of weight loss required for the diagnosis, but instead provide guidelines for specifying the severity of weight loss. As in the DSM-IV, the new criteria specify two diagnostic types of anorexia nervosa (restricting type and binge eating/purging type). In a significant revision to previous criteria, diagnosis of anorexia nervosa no longer requires the presence of amenorrhea.

Bulimia nervosa involves the uncontrolled eating of an abnormally large amount of food in a short period, followed by compensatory behaviors, such as self-induced vomiting, laxative abuse, or excessive exercise. The main update in the DSM-5 criteria for bulimia nervosa ( Table 2 3 ) is a decrease in the average frequency of bingeing and purging from twice to once a week. 4

Prevalence and Etiology

Bulimia nervosa affects four to six out of 200 females in the United States. Anorexia nervosa is much less common, with a lifetime prevalence of one out of 200 females in the United States. Approximately 95% of persons with an eating disorder are 12 to 25 years of age. Although 90% of patients with an eating disorder are female, the incidence of diagnosed eating disorders in males appears to be increasing. 5

The etiology of eating disorders is unknown and probably multifactorial. Environmental influences include societal idealizations about weight and body shape. Parenting style has been discounted as a primary cause of eating disorders. However, parenting style, household stress, and parental discord may contribute to anxiety and personality traits that are risk factors for an eating disorder. An emphasis on success and external rewards may lead to overly high expectations. Children may then try to be successful with something they can control: regulating what they eat and how they look. Sexual assault or abuse has not been associated with anorexia nervosa but may be a risk factor for bulimia nervosa. 6

There is increasing evidence of biologic risk factors for eating disorders. Twin studies and other research suggest a genetic link. 7 Eating disorders have been associated with abnormal neurotransmitter systems involving serotonin and dopamine. 8 , 9 The role of hormones such as ghrelin, leptin, and oxytocin has also been investigated. 10

Clinical Presentation

Table 3 includes clinical signs of eating disorders. 11 – 13 Patients with eating disorders may often comment about being “fat” or not liking their body shape. Weight loss with anorexia nervosa may go unnoticed for some time, particularly when patients wear baggy clothes or extra layers. Patients with anorexia nervosa commonly restrict their diet to vegetables, fruit, and diet products, and often skip meals altogether. They develop mealtime rituals, such as cutting food into tiny pieces, patting liquid off with napkins, or picking food apart. Although anorexia nervosa has been associated with some cognitive deficits as demonstrated on neuropsychological tests, many patients maintain good cognitive function and verbal fluency even when malnourished. 14

Patients with eating disorders often engage in excessive physical activity despite bad weather, illness, or injury. A study found that approximately one-third of patients hospitalized for anorexia nervosa reported excessive (i.e., obligatory, obsessive, or driven) exercise during the three months before admission. 15

Patients with bulimia nervosa may arrange complex schedules to accommodate episodes of binge eating and purging, often accompanied by frequent trips to the bathroom. In addition to excessive exercise, other methods of weight control include abuse of laxatives or diuretics. Frequent self-induced vomiting can contribute to parotitis, stained teeth or enamel erosions, and hand calluses.

As cachexia progresses, patients with anorexia nervosa lose strength and endurance, move more slowly, and demonstrate decreased performance in sports. Overuse injuries and stress fractures can occur. Bradycardia, orthostatic hypotension, and palpitations may progress to potentially fatal arrhythmias. Epigastric pain and a bloating sensation are common. Laxative abuse causes hemorrhoids and rectal prolapse. Severe hypoglycemia may lead to seizures. Wounds heal poorly. Endocrine symptoms in anorexia nervosa include hypothermia (feeling cold), delayed onset of menses or secondary amenorrhea, and osteopenia progressing to osteoporosis. 11 , 12

More than one-half of patients with eating disorders meet criteria for a current or past episode of major depression. 16 Anorexia nervosa is associated with an increased risk of suicide, with the suicide standardized mortality ratio estimated to be as high as 31 in one meta-analysis. 17 Other associated psychiatric disorders include obsessive-compulsive disorder, obsessive-compulsive personality disorder, social phobia, anxiety disorders, substance use disorders, and personality disorders. Psychological symptoms include heightened emotional arousal, reduced tolerance of stress, emotional dysregulation, social withdrawal, and self-critical perfectionistic traits. 3

Screening for Eating Disorders

Annual health supervision examinations and preparticipation sports physicals are ideal screening opportunities. In addition to weight, height, and body mass index measurements, a screening tool such as the SCOFF questionnaire ( Table 4 18 ) can be used. 11 , 12 , 18 The SCOFF questionnaire has been validated only in adults but suggests an approach that can also be used with children. 12

Initial Evaluation

The first priority in the evaluation of patients with eating disorders is to identify emergency medical conditions that require hospitalization and stabilization. Before the patient is weighed, a urine sample should be obtained to assess specific gravity for hydration status, pH level, ketone level, and signs of kidney damage. Weight, height, body mass index, and body temperature should be recorded. Because patients may wear extra clothes or hide heavy items to exaggerate their weight, they should be weighed wearing only underwear and a hospital gown. An attendant or parent may have to be present while they change. Clinicians may consider having patients face away from the scale so that they do not know their weight. Blood pressure should be recorded with orthostatic vital signs.

Electrocardiography and laboratory studies such as urinalysis with specific gravity, complete blood count, complete metabolic panel, amylase and lipase measurement, phosphorous and magnesium measurement, and thyroid function tests (thyroid-stimulating hormone, thyroxine, free triiodothyronine) should be performed promptly. 11 , 12 Less urgent testing, such as bone density testing, can be deferred.

Family physicians can fill a central role in the monitoring and treatment of patients with eating disorders. A psychotherapist or psychiatrist usually is involved. Eating disorder specialists, often with backgrounds in psychiatry or adolescent medicine, are ideally involved but may not be available in some locations. A dietitian can help select nutritious and calorie-rich foods. For youth, it is critical to involve their schools. Most states require formal 504 plans that spell out special accommodations, such as snack breaks in class or allowances for missed school, to allow equal educational opportunities for students with medical disabilities.

Treatment success may be dependent on developing a therapeutic alliance with the patient, involvement of the patient's family, and close collaboration within the treatment team. Additional online resources for the treatment team, patient, and family are listed in eTable A .

Treatment should be individualized based on symptom severity, course of illness, psychiatric comorbidity, availability of psychosocial/familial support, patient motivation for undergoing treatment, regional availability of specialized treatment programs, and medical stability. Indications for hospitalization include significant electrolyte abnormalities, arrhythmias or severe bradycardia, rapid persistent weight loss in spite of outpatient therapy, and serious comorbid medical or psychiatric conditions, including suicidal ideation. 11 , 12 Table 5 includes the American Academy of Pediatrics criteria for inpatient treatment. 19 After the patient is stabilized at a local hospital, his or her condition or comorbidities may necessitate transfer to a facility specializing in eating disorder inpatient care.

The focus of initial treatment for patients who have anorexia nervosa with cachexia is restoring nutritional health, with weight gain as a surrogate marker. Feeding tubes may be needed in severe cases when the patient has a high resistance to eating. Refeeding syndrome can occur in a malnourished individual when a rapid increase in food intake results in dramatic fluid and electrolyte shifts, and is potentially fatal. Thus, hospitalization should be considered for initial treatment of any seriously malnourished patient to allow for daily monitoring of key markers such as weight, heart rate, temperature, hydration, and serum phosphorus level. 20

Nutritional Intervention and Weight Restoration . Patients with anorexia may eat only 500 kcal a day, whereas the average daily caloric requirement for a sedentary adolescent is 1,800 kcal for females and 2,200 kcal for males. 21 A reasonable initial target for weight restoration is 90% of the average weight expected for the patient's age, height, and sex. 12 , 22 Growth charts are available from the Centers for Disease Control and Prevention at http://www.cdc.gov/growthcharts/charts.htm . Initiation or resumption of menses is an important marker of biologic health in females. In one report, 86% of females with anorexia nervosa who achieved the 90% body mass index goal resumed menses within six months. 22 The patient's pre–eating disorder weight history may help in determining a target body mass index. For growing adolescents, the goal weight may need to be adjusted every three to six months. Weight gain may not begin until caloric intake significantly exceeds sedentary requirements. Strenuous physical activity and sports should be restricted.

Nutritional guidance focuses on healthy food intake and regaining the energy needed to resume activities. Although calorie counting is important, it generally should not be discussed with the patient. Daily menus should include three full meals and a structured snack schedule that is monitored by parents or the school nurse. A multivitamin plus vitamin D and calcium supplements are recommended.

Psychotherapy . Psychotherapy is the foundation for successful treatment of an eating disorder. Family-based treatment (the Maudsley method) is one of the more promising approaches for adolescents with anorexia nervosa. 23 – 25 Goals of psychotherapy include reduction of distorted body image and dysfunctional eating habits, return to social engagement, and resumption of full physical activities. 26 Family members need support and help learning how to care for the patient. Clinical trials have shown significant improvement in bulimia nervosa with cognitive behavior therapy and interpersonal psychotherapy. 27 Group therapy is used in many eating disorder treatment programs. Alternate adjunctive therapies such as equine therapy (based on the idea that caring for horses through grooming and other interactions is healing) may hold promise, although they are not evidence-based therapies. 28 Mindfulness practices such as meditation and yoga benefit patients with anxiety and may provide low-energy physical activity. 29

Medications . Studies have shown only limited benefit of medications in the treatment of anorexia nervosa. Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), may help mitigate symptoms of depression and suicidal ideation in patients with anorexia nervosa. However, they have not proved beneficial in facilitating weight restoration or preventing relapse. 30 , 31 Although case reports and recent preliminary studies have suggested a role for atypical antipsychotics such as olanzapine (Zyprexa), controlled studies have not demonstrated significant benefit in patients with anorexia nervosa. 11 , 32 – 35 Larger placebo-controlled studies will be needed to evaluate this approach. If psychotropic medications are attempted, the patient should be closely monitored, possibly in an inpatient or residential setting, and supervised by a psychiatrist or eating disorder specialist.

In patients with bulimia nervosa, studies have suggested SSRIs may be beneficial in decreasing the frequency of binge eating and purging. 35 – 37 Thus, the addition of an SSRI might be considered for patients who are not responding to an initial trial of psychotherapy and for patients with major depression or another comorbid disorder responsive to antidepressant medications.

Although approximately one-half of patients with anorexia nervosa fully recover, about 30% achieve only partial recovery, and 20% remain chronically ill. 38 Anorexia nervosa has the highest mortality rate of any mental health disorder, with an estimated all-cause standardized mortality ratio of 1.7 to 5.9. 39 , 40 The prognosis for bulimia nervosa is more favorable, with up to 80% of patients achieving remission with treatment. However, the 20% relapse rate represents a significant clinical challenge, and the disorder is associated with an elevated all-cause standardized mortality ratio of 1.6 to 1.9. 39 , 40

Data Sources : Literature searches on Ovid Medline were performed. Key terms were anorexia nervosa, bulimia nervosa, eating disorder, etiology, diagnosis, signs and symptoms, and treatment. The search included meta-analyses, randomized controlled trials, clinical trials, and review articles. The search was limited to human, English, and full text. Subsequent Ovid Medline searches were conducted looking for specific topics such as zinc and eating disorders. Additional searches included the archives for the journals Pediatrics and American Family Physician , Agency for Healthcare Research and Quality evidence reports, the Cochrane database, the National Guideline Clearinghouse database, the U.S. Preventive Services Task Force, the American Academy of Pediatrics, the American Psychiatric Association, and the Society for Adolescent Health and Medicine. Search dates: November 18, 2013; December 1, 2013; July 14, 2014; and October 22, 2014.

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Monteleone P, Maj M. Dysfunctions of leptin, ghrelin, BDNF and endocannabinoids in eating disorders: beyond the homeostatic control of food intake. Psychoneuroendocrinology. 2013;38(3):312-330.

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Stedal K, Rose M, Frampton I, Landrø NI, Lask B. The neuropsychological profile of children, adolescents, and young adults with anorexia nervosa. Arch Clin Neuropsychol. 2012;27(3):329-337.

Bewell-Weiss CV, Carter JC. Predictors of excessive exercise in anorexia nervosa. Compr Psychiatry. 2010;51(6):566-571.

Yager J, Andersen AE. Clinical practice. Anorexia nervosa. N Engl J Med. 2005;353(14):1481-1488.

Preti A, Rocchi MB, Sisti D, Camboni MV, Miotto P. A comprehensive meta-analysis of the risk of suicide in eating disorders. Acta Psychiatr Scand. 2011;124(1):6-17.

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Campbell K, Peebles R. Eating disorders in children and adolescents: state of the art review. Pediatrics. 2014;134(3):582-592.

Golden NH, Keane-Miller C, Sainani KL, Kapphahn CJ. Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome [published correction appears in J Adolesc Health . 2014;54(1):116]. J Adolesc Health. 2013;53(5):573-578.

Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids . Washington, DC: The National Academies Press; 2005.

Golden NH, Jacobson MS, Sterling WM, Hertz S. Treatment goal weight in adolescents with anorexia nervosa: use of BMI percentiles. Int J Eat Disord. 2008;41(4):301-306.

Couturier J, Kimber M, Szatmari P. Efficacy of family-based treatment for adolescents with eating disorders: a systematic review and meta-analysis. Int J Eat Disord. 2013;46(1):3-11.

Lock J, Le Grange D, Agras WS, Moye A, Bryson SW, Jo B. Randomized clinical trial comparing family-based treatment with adolescent-focused individual therapy for adolescents with anorexia nervosa. Arch Gen Psychiatry. 2010;67(10):1025-1032.

Stiles-Shields C, Hoste RR, Doyle PM, Le Grange D. A review of family-based treatment for adolescents with eating disorders. Rev Recent Clin Trials. 2012;7(2):133-140.

Carter FA, Jordan J, McIntosh VV, et al. The long-term efficacy of three psychotherapies for anorexia nervosa: a randomized, controlled trial. Int J Eat Disord. 2011;44(7):647-654.

Murphy R, Straebler S, Cooper Z, Fairburn CG. Cognitive behavioral therapy for eating disorders. Psychiatr Clin North Am. 2010;33(3):611-627.

Selby A, Smith-Osborne A. A systematic review of effectiveness of complementary and adjunct therapies and interventions involving equines. Health Psychol. 2013;32(4):418-432.

Klein J, Cook-Cottone C. The effects of yoga on eating disorder symptoms and correlates: a review. Int J Yoga Therap. 2013;23:41-50.

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Walsh BT, Kaplan AS, Attia E, et al. Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial [published corrections appear in JAMA . 2006;296(8):934, and JAMA . 2007;298(17):2008]. JAMA. 2006;295(22):2605-2612.

McKnight RF, Park RJ. Atypical antipsychotics and anorexia nervosa: a review. Eur Eat Disord Rev. 2010;18(1):10-21.

Bissada H, Tasca GA, Barber AM, Bradwejn J. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008;165(10):1281-1288.

Kafantaris V, Leigh E, Hertz S, et al. A placebo-controlled pilot study of adjunctive olanzapine for adolescents with anorexia nervosa. J Child Adolesc Psychopharmacol. 2011;21(3):207-212.

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Anorexia nervosa case presentation.

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C?MO CITAR (Vancouver)

• Patient Care & Health Information
• Diseases & Conditions
• Anorexia nervosa

Anorexia (an-o-REK-see-uh) nervosa — often simply called anorexia — is an eating disorder characterized by an abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight. People with anorexia place a high value on controlling their weight and shape, using extreme efforts that tend to significantly interfere with their lives.

To prevent weight gain or to continue losing weight, people with anorexia usually severely restrict the amount of food they eat. They may control calorie intake by vomiting after eating or by misusing laxatives, diet aids, diuretics or enemas. They may also try to lose weight by exercising excessively. No matter how much weight is lost, the person continues to fear weight gain.

Anorexia isn't really about food. It's an extremely unhealthy and sometimes life-threatening way to try to cope with emotional problems. When you have anorexia, you often equate thinness with self-worth.

Anorexia, like other eating disorders, can take over your life and can be very difficult to overcome. But with treatment, you can gain a better sense of who you are, return to healthier eating habits and reverse some of anorexia's serious complications.

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The physical signs and symptoms of anorexia nervosa are related to starvation. Anorexia also includes emotional and behavioral issues involving an unrealistic perception of body weight and an extremely strong fear of gaining weight or becoming fat.

It may be difficult to notice signs and symptoms because what is considered a low body weight is different for each person, and some individuals may not appear extremely thin. Also, people with anorexia often disguise their thinness, eating habits or physical problems.

Physical symptoms

Physical signs and symptoms of anorexia may include:

• Extreme weight loss or not making expected developmental weight gains
• Thin appearance
• Abnormal blood counts
• Dizziness or fainting
• Bluish discoloration of the fingers
• Hair that thins, breaks or falls out
• Soft, downy hair covering the body
• Absence of menstruation
• Constipation and abdominal pain
• Dry or yellowish skin
• Intolerance of cold
• Irregular heart rhythms
• Low blood pressure
• Dehydration
• Swelling of arms or legs
• Eroded teeth and calluses on the knuckles from induced vomiting

Some people who have anorexia binge and purge, similar to individuals who have bulimia. But people with anorexia generally struggle with an abnormally low body weight, while individuals with bulimia typically are normal to above normal weight.

Emotional and behavioral symptoms

Behavioral symptoms of anorexia may include attempts to lose weight by:

• Severely restricting food intake through dieting or fasting
• Exercising excessively
• Bingeing and self-induced vomiting to get rid of food, which may include the use of laxatives, enemas, diet aids or herbal products

Emotional and behavioral signs and symptoms may include:

• Preoccupation with food, which sometimes includes cooking elaborate meals for others but not eating them
• Frequently skipping meals or refusing to eat
• Denial of hunger or making excuses for not eating
• Eating only a few certain "safe" foods, usually those low in fat and calories
• Adopting rigid meal or eating rituals, such as spitting food out after chewing
• Not wanting to eat in public
• Lying about how much food has been eaten
• Fear of gaining weight that may include repeated weighing or measuring the body
• Frequent checking in the mirror for perceived flaws
• Complaining about being fat or having parts of the body that are fat
• Covering up in layers of clothing
• Flat mood (lack of emotion)
• Social withdrawal
• Irritability
• Reduced interest in sex

When to see a doctor

Unfortunately, many people with anorexia don't want treatment, at least initially. Their desire to remain thin overrides concerns about their health. If you have a loved one you're worried about, urge her or him to talk to a doctor.

If you're experiencing any of the problems listed above, or if you think you may have an eating disorder, get help. If you're hiding your anorexia from loved ones, try to find a person you trust to talk to about what's going on.

The exact cause of anorexia is unknown. As with many diseases, it's probably a combination of biological, psychological and environmental factors.

• Biological. Although it's not yet clear which genes are involved, there may be genetic changes that make some people at higher risk of developing anorexia. Some people may have a genetic tendency toward perfectionism, sensitivity and perseverance — all traits associated with anorexia.
• Psychological. Some people with anorexia may have obsessive-compulsive personality traits that make it easier to stick to strict diets and forgo food despite being hungry. They may have an extreme drive for perfectionism, which causes them to think they're never thin enough. And they may have high levels of anxiety and engage in restrictive eating to reduce it.
• Environmental. Modern Western culture emphasizes thinness. Success and worth are often equated with being thin. Peer pressure may help fuel the desire to be thin, particularly among young girls.

Risk factors

Anorexia is more common in girls and women. However, boys and men have increasingly developed eating disorders, possibly related to growing social pressures.

Anorexia is also more common among teenagers. Still, people of any age can develop this eating disorder, though it's rare in those over 40. Teens may be more at risk because of all the changes their bodies go through during puberty. They may also face increased peer pressure and be more sensitive to criticism or even casual comments about weight or body shape.

Certain factors increase the risk of anorexia, including:

• Genetics. Changes in specific genes may put certain people at higher risk of anorexia. Those with a first-degree relative — a parent, sibling or child — who had the disorder have a much higher risk of anorexia.
• Dieting and starvation. Dieting is a risk factor for developing an eating disorder. There is strong evidence that many of the symptoms of anorexia are actually symptoms of starvation. Starvation affects the brain and influences mood changes, rigidity in thinking, anxiety and reduction in appetite. Starvation and weight loss may change the way the brain works in vulnerable individuals, which may perpetuate restrictive eating behaviors and make it difficult to return to normal eating habits.
• Transitions. Whether it's a new school, home or job; a relationship breakup; or the death or illness of a loved one, change can bring emotional stress and increase the risk of anorexia.

Complications

Anorexia can have numerous complications. At its most severe, it can be fatal. Death may occur suddenly — even when someone is not severely underweight. This may result from abnormal heart rhythms (arrhythmias) or an imbalance of electrolytes — minerals such as sodium, potassium and calcium that maintain the balance of fluids in your body.

Other complications of anorexia include:

• Heart problems, such as mitral valve prolapse, abnormal heart rhythms or heart failure
• Bone loss (osteoporosis), increasing the risk of fractures
• Loss of muscle
• In females, absence of a period
• In males, decreased testosterone
• Gastrointestinal problems, such as constipation, bloating or nausea
• Electrolyte abnormalities, such as low blood potassium, sodium and chloride
• Kidney problems

If a person with anorexia becomes severely malnourished, every organ in the body can be damaged, including the brain, heart and kidneys. This damage may not be fully reversible, even when the anorexia is under control.

In addition to the host of physical complications, people with anorexia also commonly have other mental health disorders as well. They may include:

• Depression, anxiety and other mood disorders
• Personality disorders
• Obsessive-compulsive disorders
• Alcohol and substance misuse
• Self-injury, suicidal thoughts or suicide attempts

There's no guaranteed way to prevent anorexia nervosa. Primary care physicians (pediatricians, family physicians and internists) may be in a good position to identify early indicators of anorexia and prevent the development of full-blown illness. For instance, they can ask questions about eating habits and satisfaction with appearance during routine medical appointments.

If you notice that a family member or friend has low self-esteem, severe dieting habits and dissatisfaction with appearance, consider talking to him or her about these issues. Although you may not be able to prevent an eating disorder from developing, you can talk about healthier behavior or treatment options.

• Sim LA (expert opinion). Mayo Clinic, Rochester, Minn. Jan. 31, 2018.
• Anorexia nervosa. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. Arlington, Va.: American Psychiatric Association; 2013. http://dsm.psychiatryonline.org. Accessed Nov. 13, 2017.
• Hales RE, et al. Anorexia nervosa. In: The American Psychiatric Publishing Textbook of Psychiatry. 6th ed. Washington, D.C.: American Psychiatric Publishing; 2014. http://psychiatryonline.org. Accessed Nov. 13, 2017.
• Klein D, et al. Anorexia nervosa in adults: Clinical features, course of illness, assessment, and diagnosis. https://www.uptodate.com/contents/search. Accessed Nov. 13, 2017.
• Mehler P. Anorexia nervosa in adults and adolescents: Medical complications and their management. https://www.uptodate.com/contents/search. Accessed Nov. 13, 2017.
• Mehler P. Anorexia nervosa in adults: Evaluation for medical complications and criteria for hospitalization to manage these complications. https://www.uptodate.com/contents/search. Accessed Nov. 13, 2017.
• Pike K. Anorexia nervosa in adults: Cognitive behavioral therapy (CBT). https://www.uptodate.com/contents/search. Accessed Nov. 13, 2017.
• Walsh BT. Anorexia nervosa in adults: Pharmacotherapy. https://www.uptodate.com/contents/search. Accessed Nov. 13, 2017.
• Anorexia nervosa. Merck Manual Professional Version. http://www.merckmanuals.com/professional/psychiatric-disorders/eating-disorders/anorexia-nervosa. Accessed Nov. 13, 2017.
• Harrington BC, et al. Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia nervosa. American Family Physician. 2015;91:46.
• Brockmeyer T, et al. Advances in the treatment of anorexia nervosa: A review of established and emerging interventions. Psychological Medicine. In press. Accessed Nov. 13, 2017.
• Davis H, et al. Pharmacotherapy of eating disorders. Current Opinion in Psychiatry. 2017;30:452.
• Herpertz-Dahlmann B. Treatment of eating disorders in child and adolescent psychiatry. Current Opinion in Psychiatry. 2017;30:438.
• Fogarty S, et al. The role of complementary and alternative medicine in the treatment of eating disorders: A systematic review. Eating Behaviors. 2016;21:179.
• Eating disorders. National Alliance on Mental Illness. https://www.nami.org/Learn-More/Mental-Health-Conditions/Eating-Disorders/Overview. Accessed Nov. 13, 2017.
• Lebow J, et al. Is there clinical consensus in defining weight restoration for adolescents with anorexia nervosa? Eating Disorders. In press. Accessed Dec. 4, 2017.
• Lebow J, et al. The effect of atypical antipsychotic medications in individuals with anorexia nervosa: A systematic review and meta-analysis. International Journal of Eating Disorders. 2013;46:332.
• Five things to know about safety of dietary supplements for children and teens. National Center for Complementary and Integrative Health. https://nccih.nih.gov/health/tips/child-supplements. Accessed Feb. 9, 2018.

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Anorexia Nervosa: A Case Study

Oct 04, 2014

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Anorexia Nervosa: A Case Study. By: Colleen Shank Sodexo Dietetic Intern April 30, 2014. Presentation of Anorexia Nervosa.

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• body weight
• weight loss
• weight loss started
• significantly low body weight

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Anorexia Nervosa: A Case Study By: Colleen Shank Sodexo Dietetic Intern April 30, 2014

Presentation of Anorexia Nervosa • “Up to 24 million people of all ages and genders suffer from an eating disorder (anorexia, bulimia and binge eating disorder) in the U.S (The Renfrew Center Foundation for Eating Disorders)” • “Only 35% of people that receive treatment for eating disorders get treatment at a specialized facility for eating disorders” (Noordenbox, 2002)

Presentation of Anorexia Nervosa • “A review of nearly fifty years of research confirms that anorexia nervosa has the highest mortality rate of any psychiatric disorder” (Arcelus, Mitchell, Wales, & Nielsen, 2011) • “20% of people suffering from anorexia will prematurely die from complications related to their eating disorder, including suicide and heart problems” (The Renfrew Center Foundation for Eating Disorders)

Presentation of Anorexia Nervosa Overview of how one may suffer from AN: Body image distortion Restrictive intake and or binging/purging Excessive exercise Severe weight loss Fear of becoming fat Physiological changes Psychological changes

Presentation of Anorexia Nervosa Two types: • Restricting type • Energy intake is restricted • Binge-eating/purge type • Vomiting • Excessive exercising • Both types suffer from fear of gaining weight

Presentation of Anorexia Nervosa Diagnosis criteria: DSM-5 • Restriction of energy intake relative to requirements leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. • Intense fear of gaining weight or becoming fat, even though underweight. • Disturbance in the way in which one's body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or denial of the seriousness of the current low body weight The Alliance for Eating Disorders

Presentation of Anorexia Nervosa Types of Questions: • Gender, height, weight • How often one feels, experiences, likes, or avoids certain things • Avoiding foods when hungry, feeling guilty after eating, eat diet foods, etc. • How often one partakes in certain behaviors • Vomiting, binging, and exercising Screening Tools: EDI-3 Eat-26 • Can be given by health Care professionals • Can be accessed online • Can help assess risk • Do not diagnose eating disorders

Presentation of Anorexia Nervosa Physical Signs & Symptoms: • Weight loss • Tiredness • Thinning hair • Hair loss • Dry skin • Swelling of arms/legs • Lanugo • Intolerance to cold

Presentation of Anorexia Nervosa Internal Changes: • Body systems are affected • Examples: cardiovascular, neuroendocrine, renal, and gastrointestinal systems • Slow heart rate • Anemia • Stomach gets smaller • Constipation • Dehydration • Amenorrhea • Osteoporosis • Hypothermia • Hypotension

Presentation of Anorexia Nervosa Psychological Signs & Symptoms: • Not wanting to eat • Fear of weight gain • Extreme exercise • Depression • Preoccupation with food • Lying • Lack of social interaction

Presentation of Anorexia Nervosa Tests/Labs: • CBC • Electrolytes • Total protein • Minerals • H/H • Glucose • B12 • Etc. Tests/Labs: • Height, weight, BMI • Look at • Heart • Liver • Kidneys • Bones • Thyroid • Etc.

Presentation of Anorexia Nervosa Examples of Abnormalities: • Abnormal lipoprotein profile • Low zinc • Low vitamin B-12 • Alkalosis • Low chloride and potassium • Elevated bicarbonate • Hypomagnesmia • Hypophosphatemia • Lymphocytosis • Low resting metabolic rate • Mitral valve prolapse

Presentation of Anorexia Nervosa Treatment: • Requires a team • Physician, Psychologist/Psychiatrist, RD • Not all treatment plans are the same • Everyone needs a treatment plan specific to them • Inpatient, outpatient, both

Presentation of Anorexia Nervosa Treatment: Psychological • Different types of therapy • CBT • IPT • SSCM • Research? Treatment: Psychological • One-on-one • Group • Family • Discover underlying issues

Presentation of Anorexia Nervosa Treatment: Pharmacotherapy • Not to treat AN specifically • Used to treat underlying issues • Antidepressants, antipsychotics • Olanzapine, Fluoxetine, Prozac, Risperidone • Research? • Can drugs help improve weight gain?

Presentation of Anorexia Nervosa MNT: AND Position Paper • “Nutrition intervention, includingnutrition counseling by a registered dietitian, is an essential component of the team treatment of patients with anorexia nervosa, bulimia nervosa, and other eating disorders during assessment and treatment across the continuum of care”

Presentation of Anorexia Nervosa MNT: RDs Role • Assess the patient • Determine nutrition risks • Define nutrition diagnosis • Identify nutrition intervention • Write nutrition prescription • Define nutritional goals

Presentation of Anorexia Nervosa MNT: RD Assessment • What is important to assess? • Of course the RD will assess physical signs and symptoms but there are other things that should be included in their assessment of the patient • Current dietary intake • Present eating patterns • History related to foods • Nutrient deficiencies • Supplement use • Risk of refeeding syndrome

Presentation of Anorexia Nervosa Treatment: Current Guidelines • Intake recommendations • Calculating needs • Kcal • Starting point • Increase by 100-200kcals • Macronutrients • CHO: 50-55% • PRO: 15-20% • Fat: 25-30% • Micronutrients? • Weight gain • Differences between in and out patient settings • Increase in kcal needs

Presentation of Anorexia Nervosa Treatment: Refeeding Syndrome • Refeeding a starved patient • Clinical implications • Low Mg, K, P • Thiamine deficiency • Must be aware of the affects • Must follow protocol to help prevent refeeding • Monitor electrolytes and fluids

Presentation of Anorexia Nervosa Treatment: Nutrition Support • Need for nutrition support depends on needs of the patient • PN should only be used when medically necessary

Presentation of C.H. Basics: • Age: 56 • Sex: Female • Lives at home with her mother and sister • Dates of hospital stay: January 15, 2014-February 14, 2014 • Date transferred to Manor Care: February 14, 2014

Presentation of C.H. Hospital Stay: • Dx: FTT secondary to malnutrition, Pancytopenia, Hypothermia related to malnutrition, Bradycardia related to hypothermia, and Hypotension related to dehydration • PMH: Anorexia, Anemia

Presentation of C.H. Hospital Stay: • Reason for going to ER: inability to ambulate and weakness • Vital 1.5 • 3 day calorie count • Labs: Labs: BG 49, HGB 3.7, Creatinine 0.67, BUN 60 • Per patient: • Reported that weight loss started several months ago • No menstruation anymore • No diarrhea, blood in the stool • Was on iron pill but stopped taking due to negative side effects • Has struggled with weight since age 11

Presentation of C.H. Manor Care: • Admit dx: FTT, (GERD), Refeeding Syndrome, Pancytopenia, and History of intussusception • Her admission note states she was "in an anorexic and malnourished state" • Admit weight 76.6#, Height 62.0”, BMI 14.0 • Stage 3 gluteal wound • Left hip wound

Presentation of C.H. Manor Care: • No smoking, drinking, drug use history • February 18, 2014 • AOA involved • Mother and sister were not allowed to bring in food to patient

Presentation of C.H. Manor Care: Plan • Physical and occupational therapy • Continue current diet, supplements, folic acid, MVI, zinc, labs as scheduled • Follow up with GI at the hospital as scheduled • Wound: local care with santyl, daily dressing change/pressure relief, nutritional support

Presentation of C.H. • Ca: 8.9 • Alb: 3.6 • Total pro: 6.3 • GFR: >60 • WBC: 6.6 • RBC: 3.96 L • HGB: 9.3 L • HCT: 31.3 L • MCV: 79.1 L • MCH: 23.4 L Manor Care: • Labs from February 21, 2014 • Random glucose: 78 • BUN: 12 • Creat: 0.40 • K: 4.2 • NA: 136 • AST: 21 • ALT: 30 • Alkphos: 66 • Total bilirubin: 0.3

Presentation of C.H. Manor Care: Medications • Cholecalciferol 2000 unit po daily • Heparin 5000 units SQ • Folic acid 1mg po daily • MVI po daily • Protonix 40mg po daily • Zinc sulfate 220mg po daily • As needed: Miralax, Colace, Tylenol, MOM, Dulcolax, • Ferrous liquid 220g po daily (added at a later date 3x/week)

Presentation of C.H. Manor Care: • On admission was placed on gluten intolerance diet and enhanced food • Prior to RD assessment • Was later changed to a regular diet • No history of Celiac Disease

Presentation of C.H. Manor Care: RD Assessment • February 19, 2014 • Current weight 77.2#, BMI 14.1 • Interview • Pt prefers “plain foods” • Pt reports allergy to guar gum • Consumption of meals 75-100% • Eats meals slowly (1-1.5hours) • No diarrhea, constipation, steatorrhea, communication, dental/oral, or functional problems noted

Presentation of C.H. Manor Care: RD Assessment • Calculated needs (with IBW 110#: • 35kcal/kg = 1750kcal/day • 1.5g/kg pro= 75g/day • 30mL/kg fluid= 1500mL/day • Diet order: Regular diet, Supplement TID • No longer giving enhanced foods due to pt liking plain foods • Recommendations: weekly CMP, CBC, P, Mg, LFTs, iron supplement

Presentation of C.H. Manor Care: • Weekly weights • 2/14/14 76.6# • 2/18/14 77.2 # • 2/24/14 77.6# • 3/4/14 82 #

Presentation of C.H. Manor Care: Med Options Assessment • Mental health evaluation (2 visits) • Main issue: AN • Patient has difficulty with mood functioning, behavioral functioning, and lack of insight • "I am not an anorexic" • "I do eat- I like food but I have a difficult time keeping the weight on"

Presentation of C.H. Manor Care: My interaction with C.H • Usual intake • 3 meals per day (breakfast, lunch, and dinner) as well as snacks in between meals • UBW: 110-115# • Since she has been sick she reports her weight has been 85-90# • States she does not usually keep track of weight • Reports she could feel she was losing weight when she started getting sick • Reports when she was taking her iron pill that would help her gain weight

Update on C.H. • Was d/c on March 4, 2014 • D/c to home with mother and sister • No further info on AOA • Weight at d/c 82#

Sources • Eating Disorder Statistics. ANAD. http://www.anad.org. Accessed April 20, 2014. • Get the Facts on Eating Disorders. NEDA. https://www.nationaleatingdisorders.org. Accessed March 13, 2014. • Anorexia Nervosa. National Association of Anorexia Nervosa and Associated Disorders. http://www.anad.org/. Accessed March 13, 2014. • Feeding and Eating Disorders. APAhttp://www.dsm5.org. Accessed March 13, 2014 • DSM-5 Diagnostic Criteria. The Alliance for Eating Disorders. http://www.allianceforeatingdisorders.com. Accessed March 19, 2014. • The Eating Attitudes Test (EAT-26). Eat-26. http://www.eat-26.com/. Accessed April 3, 2014. • Mayo Clinic Staff. Anorexia Nervosa. Mayo Clinic. http://www.mayoclinic.org. Updated January 5, 2012. Accessed March 19, 2014. • Anorexia Nervosa. The New York Times. http://www.nytimes.com. Reviewed March 18, 2013. Accessed April 3, 2014. • Anorexia Nervosa Biochemical and Nutrient Issues. Academy of Nutrition and Dietetics Nutrition Care Manual. http://www.nutritioncaremanual.org. Accessed April 3, 2014. 

Treatment Basics. NEDA. https://www.nationaleatingdisorders.org. Accessed April 4, 2014. • Eating Disorders. How can a psychologist help someone recover? APA. https://www.apa.org/. Revised October 2011. Accessed April 10, 2014. • Le Grange, D., Lock, J. Family-based Treatment of Adolescent Anorexia Nervosa: The Maudsley Approach. Maudsley Parents. http://www.maudsleyparents.org/whatismaudsley.html. Accessed April 10, 2014. • DeAngelis, T. Promising Treatments for anorexia and bulimia. Monitor on Psychology. March 2002; 33 (3): 38. http://www.library.illinois.edu/learn/research/citation/ama.html. Accessed April 10, 2014. • Schmidt U, Oldershaw A, Jichi F, et al. Out-patient psychological therapies for adults with anorexia nervosa: randomised controlled trial. The British Journal of Psychology. 2012, (201):392-399. DOI: 10.1192/bjp.bp.112.112078. Accessed April 10, 2014. • Carter, F, Jordan, J, McIntosh, V. V.W, et al. The long-term efficacy of three psychotherapies for anorexia nervosa: A randomized, controlled trial. Int. J. Eat. Disord. 2011; (44): 647–654. DOI: 10.1002/eat.20879. Accessed April 10, 2014.

YagerJ, Devlin M, Halmi K, et al. Guideline Watch: Practice Guideline for the Treatment of Patients with Eating Disorders. 3rd ed. APA. 2012. http://psychiatryonline.org/pdfaccess. Accessed April 10, 2014. • Mickley D. Medication for Anorexia Nervosa and Bulimia Nervosa. Eating Disorders Recovery Today. 2004; 2(4). http://www.eatingdisordersrecoverytoday.com. Accessed April 11, 2014. • Attia E, Kaplan A, Walsh B, et al. Olanzapine versus placebo for out-patients with anorexia nervosa [Abstract]. Psychological Medicine. 2011; 41(10): 2177-2182. DOI: http://dx.doi.org/10.1017/S0033291711000390 Accessed April 11, 2014. • Hagman J, Gralla J, Sigel E, et al. A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study. JAACAP. 2011; 50(9): 915-924. DOI:10.1016/j.jaac.2011.06.009. • Walsh T, Kaplan A, Attia E, et al. Fluoxetine After Weight Restoration in Anorexia NervosaA Randomized Controlled Trial. JAMA. 2006;295(22):2605-2612. DOI:10.1001/jama.295.22.2605. • Ozier A, Henry B. Position of the American Dietetic Association: Nutrition Intervention in the Treatment of Eating Disorders. JADA. 2011;111:1236-1241. http://www.eatright.org/ Accessed April 11, 2014.

Waterhous T, Jacob M. Practice Paper of the American Dietetic Association: Nutrition Intervention in the Treatment of Eating Disorder. ADA. 2011; 11(8): 1261. http://www.eatright.org/ Accessed April 10, 2014. • Parent Toolkit. NEDA. 47. http://www.nationaleatingdisorders.org/sites/default/files/Toolkits/parenttoolkit/. Accessed April 11, 2014. • Anorexia Nervosa Nutrition Prescription. Academy of Nutrition and Dietetics Nutrition Care Manual. http://www.nutritioncaremanual.org. Accessed April 10, 2014. • Schebendach J. Nutrition in Eating Disorders. In: Mahan LK, Escott-Stump S. Krause’s Food & Nutrition Therapy. St. Louis, MO; Saunders Elsevier; 2008: 563-586.  • Anorexia Nervosa Nutrition Support. Academy of Nutrition and Dietetics Nutrition Care Manual. http://www.nutritioncaremanual.org. Accessed April 11, 2014. • Robb A, Silber T, Orrell- Valente J, Valadez-Meltzer A, et al. Supplemental Nocturnal Nasogastric Refeeding for Better Short-Term Outcome in Hospitalized Adolescent Girls With Anorexia Nervosa. Am J Psychiatry. 2002;159:1347-1353. DOI:10.1176/appi.ajp.159.8.1347. Accessed April 11, 2014.

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Affiliation.

• 1 University of Edinburgh, Department of Psychiatry, Royal Edinburgh Hospital, Morningside Park.
• PMID: 8173558
• DOI: 10.1002/1098-108x(199403)15:2<125::aid-eat2260150204>3.0.co;2-o

As part of a larger prognostic study of anorexia nervosa, clinical features at presentation of 24 males with anorexia are described, and compared with a female group matched for date of admission. Data were extracted from the original case records and follow-up interview. The study confirms the view that males display the classical syndrome of anorexia nervosa, but differs from previous studies in several respects. Age at onset (mean 18.6 years) and at presentation (mean 20.2 years) is later, with a mean duration of illness at presentation of only 1.6 years. A premorbid tendency to obesity is confirmed; maximum weight loss during the illness amounted to 42% matched population mean weight (MPMW), and weight at presentation was 78.5% MPMW, somewhat higher than the female group. In keeping with earlier studies, binging and vomiting were noted commonly, in around half of sufferers, but laxative abuse was less frequent and excessive exercising more frequent in males. Depressive and obsessional symptoms are common in both groups, and a strong family history of affective disorders and alcohol abuse was noted in over one third.

Publication types

• Comparative Study
• Anorexia Nervosa / diagnosis
• Anorexia Nervosa / psychology*
• Anorexia Nervosa / therapy
• Body Weight
• Family / psychology
• Follow-Up Studies
• Gender Identity*
• Hospitalization
• Personality Development
• Sex Factors
• Social Environment

• Open access
• Published: 29 April 2024

Inclusion of the severe and enduring anorexia nervosa phenotype in genetics research: a scoping review

• Sarah Ramsay 1 ,
• Kendra Allison 2 ,
• Heide S. Temples 2 ,
• Luigi Boccuto 1 &
• Sara M. Sarasua 1  

Journal of Eating Disorders volume  12 , Article number:  53 ( 2024 ) Cite this article

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Anorexia nervosa has one of the highest mortality rates of all mental illnesses. For those who survive, less than 70% fully recover, with many going on to develop a more severe and enduring phenotype. Research now suggests that genetics plays a role in the development and persistence of anorexia nervosa. Inclusion of participants with more severe and enduring illness in genetics studies of anorexia nervosa is critical.

The primary goal of this review was to assess the inclusion of participants meeting the criteria for the severe enduring anorexia nervosa phenotype in genetics research by (1) identifying the most widely used defining criteria for severe enduring anorexia nervosa and (2) performing a review of the genetics literature to assess the inclusion of participants meeting the identified criteria.

Searches of the genetics literature from 2012 to 2023 were performed in the PubMed, PsycINFO, and Web of Science databases. Publications were selected per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The criteria used to define the severe and enduring anorexia nervosa phenotype were derived by how often they were used in the literature since 2017. The publications identified through the literature search were then assessed for inclusion of participants meeting these criteria.

most prevalent criteria used to define severe enduring anorexia nervosa in the literature were an illness duration of ≥ 7 years, lack of positive response to at least two previous evidence-based treatments, a body mass index meeting the Diagnostic and Statistical Manual of Mental Disorders-5 for extreme anorexia nervosa, and an assessment of psychological and/or behavioral severity indicating a significant impact on quality of life. There was a lack of consistent identification and inclusion of those meeting the criteria for severe enduring anorexia nervosa in the genetics literature.

This lack of consistent identification and inclusion of patients with severe enduring anorexia nervosa in genetics research has the potential to hamper the isolation of risk loci and the development of new, more effective treatment options for patients with anorexia nervosa.

Plain English Summary

Anorexia nervosa (AN) is a serious illness with a high death rate. Many of those with AN do not recover and have continuing severe psychological and physical symptoms that greatly impact their quality of life. Research has shown that genetics plays an important role, along with environment, in the development and persistence of AN. This review highlights the continued lack of consensus on defining criteria for severe and enduring AN in the literature and the continued focus on younger females with shorter illness durations in AN genetics research. Greater efforts are needed to include older participants with severe AN of longer duration in genetics research in hopes of developing more effective treatments for this underrepresented group.

Anorexia nervosa (AN) is a devastating illness with a high mortality rate. The standardized mortality ratio (SMR) calculates whether those in a given study population are equally, more or less likely to die compared to a reference population [ 1 ]. With an estimated SMR between 5.9 and 15.9 (i.e., 6–16 times excess mortality), AN is considered one of the deadliest mental disorders [ 2 , 3 ].

Studies indicate that the overall incidence rate for AN has remained relatively stable (4% female lifetime-0.3% male lifetime) since the 1970s [ 2 , 4 ]. The symptomology and presentation of AN have evolved along cultural lines; however, it is not simply a manifestation of modern cultural and social pressures. Accounts of deliberate self-starvation date back to the beginning of written history [ 5 ].

Although the exact etiology of AN is still unclear, a substantial body of evidence indicates that genetics plays a considerable role [ 6 , 7 ]. Genetic studies dating from the late 20th century have shown that AN is highly familial. The lifetime risk of developing AN for female relatives of individuals with AN is 11 times greater than that for female relatives of individuals without AN [ 8 ]. Heritability (h 2 twin ) estimates from twin studies range from ∼ 48–74% [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The large range in estimates may be due to the use of broader participant inclusion criteria in AN studies to increase study group size. Broadening the inclusion criteria results in a more heterogeneous sample and decreased heritability estimates, while narrowing the definition of AN yields higher and more consistent estimates [ 17 ].

Although recovery from AN is possible, for approximately 20% of affected individuals the condition takes on a more intractable phenotype [ 18 , 19 ]. While AN symptoms vary from person to person, it has been suggested that a unique severe and enduring anorexia nervosa (SE-AN) subtype exists; however, aligning on clear defining criteria has proved challenging [ 20 ].

Since the 1980s, a small number of literature reviews of varying breadth and depth have been conducted in attempts to better define SE-AN. The most comprehensive to date, a 2017 review by Broomfield and colleagues identified illness duration and previous unsuccessful treatment as the criteria most often used in the literature to define AN severity [ 21 ]. A 2018 editorial by Hay and Touz, which referenced the Broomfield review, expanded the suggested criterion to include significantly diminished quality of life and narrowed the duration criterion to a minimum of three years and the therapeutic intervention exposure criterion to at least two previous evidence-based treatments [ 22 ]. In a 2021 follow-up review, with the aim of defining a neuropsychological profile for SE-AN, Bloomfield et al. identified intelligence, set-shifting and decision-making as features warranting further attention and noted that additional data are needed to align on defining severity criteria [ 23 ]. In short, there continues to be a lack of consensus on how to best define SE-AN.

Psychiatric illness is often diagnosed in a binary manner; an individual is assessed as either having the illness or not. In reality, due to their complex nature, psychiatric illnesses are better defined on a continuum [ 24 , 25 ]. Genome-wide association studies (GWAS) often use a binary case-control design. However, as Yang et al. [ 26 ] noted, with an equal population sample size, a quantitative trait (for example, symptom severity) association study will have greater power than a case-control association study. The difference is because in a case-control study, an individual with mild symptoms is not differentiated from one with severe symptoms. Relating this to AN, there would be no differentiation between an individual who met the DSM-5 criteria for mild illness, of short duration and who was responsive to first-line treatment, and an individual who met the extreme illness criteria, with a duration of over a decade and lack of positive response to multiple treatment modalities. Delineating participants based on illness severity when performing genetic data analysis of those with AN may improve the chances of identifying significant variants.

The potential value of defining more phenotypically similar groups based on quantitative phenotypes and comorbidities in genetic studies of psychiatric illness has been demonstrated in major depressive disorder (MDD), schizophrenia, autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) [ 27 , 28 , 29 , 30 ]. Individuals with more severe MDD symptoms have been found to have increased genetic risk for other psychiatric disorders [ 29 ], and polygenic risk scores (PRS) for schizophrenia correlate with symptom severity [ 28 ]. Genetic risk score (GRS), PRS and polygenic score (PGS) are the terms most often used in the literature when referring to values estimating an individual’s lifetime risk of developing a phenotype (disorder) based only on their genetics [ 31 ]. The scores are generated by combining the number of risk alleles at all the risk variants in an individual’s genome. Disease-associated risk variants are based on the latest and most comprehensive GWAS for the disorder at the time of the analysis.

Studies delineating and comparing subgroups of individuals with AN based on defined quantitative criteria may result in the discovery of rare variants associated with symptom severity, and individuals manifesting a more severe phenotype may be more likely to show higher heritability estimates and thus represent a subgroup of patients for which genetics findings may be beneficial. However, this hypothesis cannot be adequately tested to the rigorous standards required without a more precise definition of what constitutes a severe and enduring phenotype, and greater attention given to specifically identifying and including this group in genetic studies [ 32 ].

The aim of this review is to first, as an extension of the Broomfield et al. review [ 21 ], identify the criteria most widely used to describe the phenotypic severity of AN by including articles published since 2017 and, second, evaluate the genetics literature for inclusion of individuals meeting these criteria.

Delineating criteria for the severe and enduring anorexia nervosa phenotype

To better identify and delineate research participants manifesting a severe and enduring phenotype in the genetics literature, it was necessary to discern the most often used defining criteria for this subgroup of AN. The terms Anorexia Nervosa AND severe AND (Enduring OR Chronic) were used, with no year limit, to search titles and abstracts in PubMed, PsycINFO, and Web of Science. Articles were also limited to human subjects.

One of the articles identified was an extensive review by Broomfield et al. of how the literature labeled and defined AN severity up to 2017 [ 21 ]. The current search was limited to articles published after the Broomfield 2017 review to focus on the most recent literature. The references were not required to be attempting to empirically define a severe or enduring anorexia nervosa phenotype. The goal was to determine how those with a longer lasting and more severe clinical presentation are currently referred to in the literature. After removing commentaries on other references, clarifications, and updates from previous studies with the same authors and criteria, redundant references, and those not referring to a severe or enduring anorexia nervosa phenotype, 37 publications remained. Of these 37 publications, there were 22 research papers (6 clinical trials, 16 studies), 4 case reports, 6 expert panel/position papers/or opinion/editorial papers, 2 literature reviews and 3 general reviews. These references are listed in Table  1 , along with a book chapter [ 33 ] identified through reviewing the references of the selected papers, that was not included in the Broomfield 2017 review, bringing the total publications included to 38. The mean age, mean BMI, duration of illness in years, and history of previous treatment, as well as any other measures of illness severity, were extracted from the articles and are shown in Table  1 . A second reviewer, using the RANBETWEEN function in Microsoft Excel, selected 10% of the articles at random from Table  1 . to review for meeting inclusion criteria and accuracy of the data extracted.

Articles were reviewed to determine which criteria are used most often in the literature in regard to the severe enduring phenotype. Specifically, articles with a central purpose of better defining a severe and or enduring/chronic AN phenotype or the need for better treatment options (for example [ 34 , 35 ]), and articles including case studies or participants in one or more study groups defined as having a severe and or enduring/chronic AN phenotype (for example [ 36 , 37 ]) were included. The tabulation from the Broomfield review was combined with the current total. Given that the four Dalton articles referenced the same data, they were counted as only one reference. The results are outlined in Fig.  1 .

Number of references from Table  1 representing the specific duration of illness, number of previous unsuccessful treatments and body mass index (BMI) subgroups indicated either in defining severe and enduring anorexia nervosa or as inclusion criteria for participants. The totals indicated include both the references from the 2017 Broomfield review [ 21 ] and the current work

Literature review: inclusion of participants meeting the severe and enduring AN phenotype in genetics research

The search outlined in this section followed the process depicted in the PRISMA flow diagram [ 38 ] in Fig.  2 , which captures the literature selection flow. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist was utilized [ 39 ]. The goal was to assess whether participants meeting the criteria identified as the most widely used to define a severe and enduring phenotype are being included in genetics research, and, if included, whether these participants were assessed as an independent group.

PRISMA flow diagram for the literature search

The terms Anorexia Nervosa AND (genetic OR gene OR hereditary) in titles and abstracts were used for the following searches. Articles were limited to human subjects, and review articles were excluded. The goal was to be as inclusive as possible in the initial searches of each database. The search was limited to the last decade of published literature to assess current practices in genetics research. This span of time encompasses the five years leading up to and following the identification of the first genome wide significant locus for AN [ 40 ] and the publication of Broomfield et al., both of which were published in 2017. The inclusion dates were as follows: PubMed, 1-Jan-2012 to 6-Oct-2023 (date of search); PsycINFO, 1-Jan-2012 to 10-Oct-2023 (date of search); and Web of Science, 1-Jan-2012 to 12-Oct-2023 (date of search).

Searches of PubMed, PsycINFO and Web of Science conducted with the search criteria resulted in 240, 206 and 235 hits, respectively. Titles and keywords were reviewed, and 277 articles were eliminated for redundancy (see “identification” in Fig.  2 ). During the first screening, the abstracts for the remaining 404 were reviewed, and 211 were eliminated for the reasons depicted in the PRISMA diagram (“Records selected for Review 1”). The remaining 193 publications progressed to the second screening.

In the second screening, noted as “Records selected for Review 2” in the PRISMA diagram, the methods sections of the remaining 193 articles were reviewed for details on age, psychological assessments, anorexia subtype, duration of illness, prior treatment history, and other indications of disease severity. Studies did not need to specifically call out a subgroup of participants as being severe and or enduring; however, those not including participant data for at least three of the following four criteria were eliminated because they did not provide adequate information for the assessment of participant phenotype severity and intractability: (1) duration of illness; (2) body mass index (BMI); (3) prior treatment history; and (4) severity as measured by one or more clinical, social, or psychological scales. This resulted in the elimination of an additional 115 articles. A total of 78 articles were ultimately included in the information extraction process; the results are presented in Table  2 .

The data were extracted by reviewing both the methods and results sections of each paper for the following participant data: (1) mean duration of illness in years; (2) mean BMI in kg/m 2 ; (3) prior treatment history; (4) and severity as measured by one or more clinical, social, or psychological scales. Participant gender, mean age, and groups of eating disorders included in the studies (i.e., AN-restricting, AN-binge purge, bulimia, binge eating) were also extracted. A second reviewer, using the RANBETWEEN function in Microsoft Excel, selected 10% of the articles at random from Table  2 to review for meeting inclusion criteria and accuracy of the data extracted.

Defining severe enduring anorexia nervosa in the research literature

A review of the literature revealed that the terms severe, chronic, and enduring identified by Broomfield et al., in 2017 [ 21 ] continue to be widely used to label the more intractable AN phenotype. How these labels are defined in the literature, when they are defined, continues to vary greatly. The age of study participants, BMI, duration of illness, and previous treatment history were extracted from each reference and are recorded in Table  1 .

The primary inclusion criteria presented in the articles reviewed were as follows:

The Broomfield review [ 21 ] identified duration as the primary criterion used to define the severe and enduring AN phenotype, and this continues to be true. Several articles reviewed included duration of illness as a criterion for inclusion in their study or clearly delineated a subgroup using duration as one criterion. The stringency of how duration was measured varied.

In their audit of care received by patients with “early stage” versus “severe and enduring” AN, Ambwani et al. [ 36 ] defined a duration of < 3 years for early stage and ≥7 years for severe and enduring AN, as recommended by Robinson et al. and Touyz et al. [ 41 , 42 ]. This was also the case for Calugi et al. [ 43 ], who used ≥7 years in their study of cognitive behavioral therapy effectiveness. The patient described in the case study by Voderholzer et al. [ 44 ] had AN for seven years. In the four papers by Dalton et al. studying the impact of transcranial magnetic stimulation on severe and enduring AN, the duration inclusion criterion for study participation was ≥3 years of AN symptoms [ 45 , 46 , 47 , 48 ]. Whereas Knyahnytska et al. [ 49 ] included a duration of > 5 years as a criterion for treatment resistance in their insula H-coil transcranial stimulation therapy study. In the selection of a subset of participants from the Anorexia Nervosa Genetics Initiative (ANGI) to include in their assessment of the polygenic association of severity and long-term outcome in AN, Johansson et al. [ 50 ] included in their criteria for the severe enduring subtype a ≥ 5 year follow-up time, defined by the authors as years between initial registration and ANGI recruitment. Finally, in two of the three studies evaluating the effectiveness of deep brain stimulation, an illness duration of ≥ 10 years was required for participant inclusion [ 51 , 52 ], with the third requiring > 7 years [ 53 ]. Case study, clinical trial and study participants included in groups indicated as manifesting a severe and enduring phenotype tended to have illness of longer duration. For example, participants in the Calugi et al. [ 43 ] study had a mean duration of 12.3(4.7 SD) years, and the three case study subjects had illness durations of 7 [ 44 ], 11 [ 54 ], 25 [ 55 ], and 26 [ 37 ] years.

Position papers, commentaries, and reviews also varied greatly in defining duration requirements. For example, in their German language case study on palliative care for severe AN, Westermair et al. [ 56 ] proposed a long duration of illness, e.g., 10 years, as a criterion, whereas Hay and Touyz [ 22 ] and Herpetz-Dahlmann [ 57 ] used a duration of > 3 years. Other authors fell between the two extremes; Bianchi et al. [ 58 ] defined severe and enduring AN participants as those who had the disorder for six years or more, and Marzola et al. [ 59 ] used a seven-year demarcation. However, these two papers also proposed that duration should not be used alone when defining AN severity. The usefulness of duration as a criterion was also questioned by Wildes et al. [ 60 ]. In an attempt to define the severe and enduring phenotype empirically, Wildes found no evidence for a chronic subgroup of AN, instead proposing that this group may be better classified on the basis of impact on quality of life and severity of injurious behaviors. As indicated in Fig.  1 , a duration of 7 or more years was used most frequently, followed by 10 years.

Body mass index (BMI):

The DSM-5 defines four levels of AN severity: mild, BMI greater than 17 kg/m 2 ; moderate, BMI of 16–16.99 kg/m 2 ; severe, BMI of 15–15.99 kg/m 2 ; and extreme, BMI of less than 15 kg/m 2 [ 61 ]. Once again, the literature indicates a wide range of BMIs in articles attempting to define severe and enduring AN and/or for participation in studies targeting this group of individuals. The two studies of deep brain stimulation with duration criteria of ≥ 10 years for participation also had BMI requirements falling into the DSM extreme category [ 51 , 52 ]. Deep brain stimulation involves a high degree of risk, and the authors delineated that only individuals with the most severe cases should be included. Similar to duration of illness, participants included in groups indicated as manifesting a severe and enduring phenotype in case studies, clinical trials and studies, tended to have substantially lower BMIs than required per the inclusion criteria. For example, participants in the Bemer et al. bone mineral density (BMD) study had a mean BMI of 12.60 ± 1.60 kg/m 2 , which was well below the < 16 kg/m 2 criteria [ 62 ].

Notably, several studies included a low weight cutoff for participation. For example, in their transcranial magnetic stimulation studies, Dalton et al. [ 45 , 46 , 47 , 48 ] required a BMI > 14 kg/m 2 for participation. The reason provided in the study protocol for the low weight cutoff was “safety precaution” [ 63 ]. The deep brain stimulation studies conducted by Park et al. [ 64 ] required that participants be severely underweight but with a low-weight BMI criterion of > 13 kg/m 2 . Although reasons were not given for the low weight cutoff, they stated that participants needed to have a BMI > 13 kg/m 2 for surgery, which is understandable given its invasive nature.

Again, as with duration of illness, the literature suggests that BMI should not be used as the sole determinant of severity in AN. In their editorial on the challenges of defining severe and enduring AN, Hay and Touyz [ 22 ] recognized the utility of the DSM-5 BMI severity categories but also noted that for those with unremitting AN for a decade or more, having a BMI above the DSM severe range is still associated with marked morbidity.

Psychological assessment:

All the studies reviewed included an assessment of symptoms such as psychological stress, disordered eating, depression, anxiety, obsessiveness, and quality of life. For example, Wildes et al. [ 60 ], used the Research and Development Corporation (RAND) 36-Item Health Survey 1.0 (SF-36) to measure health-related quality of life, and found that these scores better classified AN subgroups than BMI and duration of illness. A score of ≤45 on the Global Assessment of Functioning (GAF) found in the DSM-4, which assesses the severity of mental illness [ 65 ], was used by Oudijn et al. [ 51 ] for inclusion in their deep brain stimulation studies. A plethora of tools was used in assessing eating disorder pathology, with the Eating Disorder Examination Questionnaire (EDE-Q) [ 66 ] and/or various iterations of the EDE-Q being the most prevalent.

Treatment response:

Lack of positive response to prior treatment, variously described as treatment resistance, treatment refractoriness, and failure to respond, was also included in assessing AN severity in several of the articles. The number and type of previous treatments required for inclusion in studies varied. For inclusion in deep brain stimulation studies, Park et al. [ 67 ] required a lack of positive response to ≥2 “typical modes” of treatment, as did Oudijn et al. [ 51 ]. The participant inclusion criteria used by Dalton et al. [ 48 ] for transcranial stimulation studies included the need to have completed at least one “previous course of National Institute for Health and Care Excellence” recommended “specialist psychotherapy or specialist day-patient or inpatient treatment”. The clearest classification criterion for treatment resistance was proposed by Hay and Touyz et al. [ 68 ]: “exposure to at least two evidence-based treatments delivered by an appropriate clinician or treatment facility together with a diagnostic assessment and formulation that incorporates an assessment of the person’s eating disorder health literacy with an assessment of the person’s stage of change”, which was referenced in the reviews of treatment options for those with severe enduring AN by Zhu et al. and Wonderlich et al. [ 20 , 69 ]. In contrast, Smith and Woodside [ 70 ] defined treatment resistance as “patients with two or more incomplete inpatient admissions and no complete admissions”. Emphasis was placed on patients failing to complete treatment rather than the treatment failing to help patients, although the authors did note that approximately 10% of patients treated at their inpatient facility were “unable to benefit”. As indicated in Fig.  1 , the criterion of two or more treatment attempts was most frequently used.

In summary, the literature indicates that a combination of assessments and criteria, including an illness duration of ≥ 7 years, lack of positive response to at least two previous evidence-based treatments, a BMI meeting the DSM-5 for extreme AN, and an assessment of psychological and/or behavioral severity indicating a significant impact on quality of life, were the most prevalent means of defining the severe and enduring AN phenotype. As the DSM-5 includes clear definitions of severe and extreme BMI (15–15.99 kg/m 2 and < 15 kg/m 2 , respectively), the criteria for severe BMI were also used in assessing the genetics literature in the following section.

Inclusion of participants meeting severe enduring anorexia nervosa-defining criteria in studies of anorexia nervosa genetics

The 78 articles identified as meeting the search criteria defined in the methods section were assessed for whether the following inclusion criteria were used and how they were defined:

Duration of illness,

Prior treatment history,

Severity as measured by one or more clinical, social, or psychological scales.

As mentioned previously, neither the statistical strength of the studies nor the study outcomes were assessed, as the purpose was to determine whether genetic studies included those meeting the severe and enduring phenotype criteria defined in the first aim through assessing prevalence of use in the literature. The studies consisted of Genome-Wide Association Studies (GWAS) as well as analyses of polymorphisms, expression, and gene methylation, including but not limited to the leptin ( LEP ) and the leptin receptor ( LEPR ) genes, the fat mass and obesity-associated gene ( FTO ), and the oxytocin receptor ( OXTR ) gene [ 16 , 71 , 72 , 73 ]. The gender of the study participants was also recorded where reported (Table  2 ).

Most of the 78 articles, including those specifically stating that the study was of severe AN, did not include criteria defined in the first aim. Most notably, only one article specifically stated that participants included had at least one prior treatment attempt [ 50 ].

Of the 71 studies reporting mean BMI, the mean BMI for all groups was 15.73 kg/m 2 (SD 1.48). For 15 studies (21%), the mean BMI was > 17 kg/m 2 (mild DSM-5). Sixteen studies (22%) had a mean BMI of 16–16.99 kg/m 2 (moderate DSM-5). Twenty-three studies (32%) had a mean BMI of ≤15.99 kg/m 2 (severe DSM-5), and 17 studies (21.8%) included at least one group with a mean BMI of ≤15 kg/m 2 , required to meet the DSM-5 definition of extreme AN. Only one study included a lifetime minimum BMI of ≤15 kg/m 2 as an inclusion criterion [ 74 ].

The duration of illness and or minimum duration required for inclusion in studies were reported for 23 (29%) of the 78 articles. Of those 23 studies, 3 (13%) had participants with a mean duration of illness ≤ 3 years, 12 (52%) had a mean of 3.1–6.99 years, and 6 (26%) had a mean of ≥ 7 years. Five of the 23 studies required a duration of illness ≥3 years as a participant inclusion criterion. None of the articles identified required duration of illness ≥7 years as an inclusion criterion.

Assessment of psychological stress, disordered eating, depression, anxiety, obsessiveness, and quality of life was another facet of defining the severity of AN in the studies evaluated. Across the 54 studies identifying defined assessment modalities, 38 different tools, checklists and guidelines were used in various combinations, including the following: Hamilton Anxiety Rating Scale (HARS), Clinical Global Impression anxiety scale (CGI), State-Trait Anxiety Inventory form (STAI); depression: Beck Depression Inventory (BDI), Children’s Depression Inventory (CDI), Montgomery-Asberg Depression Rating Scale (MADRS); alexithymia: Toronto Alexithymia Score (TAS); obsessive-compulsive and impulsive symptoms: Young-Brown Obsessive-Compulsive Symptoms (YBC-EDS), Leyton Obsessional Inventory-Child Version (LOI-CV); Barratt Impulsiveness Scale (BIS); and perfectionism: Child and Adolescent Perfectionism Scale (CAPS). Numerous eating disorder assessment tools, including the Eating Disorders Inventory (EDI), Eating Disorder Examination Questionnaire (EDE-Q), Eating Attitudes Test (EAT), and the Structured Interview for Anorexia and Bulimia Nervosa (SIAB) were also used. Table  3 shows a list of tools and how often they were used.

Historically, the focus of AN research has been on teens and young adults. The current assessment found that, of the 71 studies in which the mean age was reported or could be calculated, the mean of the mean ages reported for study participants was 20.9 (4.26 SD) years. Furthermore, the reported mean age of study participants in 36 (51%) of the 71 studies was ≤19.9 years, 21 (30%) had a mean age of 20-24.9 years, 14 (20%) had a mean age of 25-29.9 years, and only one study had an overall group mean age of ≥ 30 years, although eight studies included individual groups with means ≥ 30 years. Figure  3 provides a summary of the BMI, age and duration findings discussed above.

Number of articles in Table  1 representing the body mass index (BMI), age and duration subgroups indicated. NR = Not reported. A. BMI: 71 of the 78 articles reported BMI (kg/m 2 ), 17 of those 71 had participant mean BMI ≤ 15; Age: 72 of the 78 articles reported age, of those 72, one had a mean participant age over 30 years; Duration: 23 of the 78 articles included duration, of those 23, 6 had participant mean illness duration of ≥ 7 years

Incidence rates for AN are reported to be ten times lower in males, although this is considered an underestimation due to underreporting and underdetection [ 2 ]. Only 16 (20%) of the 78 studies included male participants.

Based on the min/max and standard deviations of the mean provided for duration of illness and BMI, it was clear that many of the articles included subsets of individuals meeting the criteria noted herein for severe and enduring AN. However, as data for those specific individuals were often not delineated, it was not possible to determine how the study conclusions may have differed for said subgroups. For example, the mean duration of illness reported by Hernández et al. [ 75 ] for the AN restricting type (AN-R) subgroup was 4.03 (4.44 SD) years, indicating that at least some of the participants met the duration criteria.

Nevertheless, there were examples of results being assessed against some measures of severity, including duration. The Booij et al. study [ 76 ] AN-R group participant duration of illness was 54.9 (30 SD) months; range: 12–84. They specifically assessed methylation against the cumulative duration of illness and observed associations between duration and methylation levels at 142 probes. The mean duration of illness in the AN-R group in the Steiger et al. study [ 77 ] was 96.00 ± 98.91 (12–456) months. They also assessed duration and found an association between chronicity of illness and methylation status at 64 probes mapping to 55 genes.

Other authors evaluated genetic correlation with the severity of various psychological assessments including quality of life, depression, food behaviors, anxiety, and obsessiveness [ 75 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. For example, Acevedo and colleagues found a correlation between specific single nucleotide polymorphisms (SNPs) of the oxytocin receptor gene ( OXTR ), and increased severity of eating disorder symptoms in those with AN [ 78 ]. A polymorphism in the promotor region of the serotonin transporter gene ( 5-HTTLPR ), previously associated with stress and depression [ 91 ], may impact depression and long-term outcomes in those with AN [ 79 ]. Research also suggests a possible correlation between specific haplotypes of the DHEA-producing enzyme cytochrome P450 CYP17A [ 81 ] and the C861 allele of the serotonin receptor 1Dβ gene ( HTR1B ) and severity of anxiety in those with AN.

An example of potential utility in assessing the severe and enduring AN phenotype and the need for larger studies and more funding is the 2022 study by Johansson et al. [ 50 ] evaluating polygenic association with AN severity and long-term outcomes. Here, the authors delineated severe and enduring AN criteria, including duration of illness, clinical impairment, BMI, and having undergone at least one previous treatment attempt. They also specified requirements for the AN subtype, thereby narrowing the population. The study, which included 2843 participants followed for up to 16 years (mean: 5.3 years), provided evidence supporting the possible clinical utility of PGSs for assessing eating disorder risk but also noted the need for larger studies and sample sizes to increase statistical power.

In summary, based on the literature reviewed, genetic studies of AN continue to focus largely, but not exclusively, on younger female participants with shorter durations of illness. These findings are not surprising given that the majority of those diagnosed with AN are female, the lack of clearly defined criteria for severe and enduring AN and the need for large numbers of participants to assess significance in genetics research.

Attempts to provide criteria for labeling those with severe mental illness as chronic or treatment-resistant need to be executed with care, as has been critically reviewed for illnesses such as schizophrenia and depression [ 92 , 93 ]. Care should also be taken when defining criteria for severity of AN, which has a higher mortality rate than depression or schizophrenia [ 94 ]. However, not defining AN severity more clearly and not focusing on a more severe and enduring phenotype in research may decrease the likelihood of identifying the possible underlying biological etiology of AN. As noted by Wonderlich et al. [ 20 ] and responding commentaries by Dalle Grave [ 95 ], Wildes [ 96 ], and McIntosh [ 97 ], a lack of consensus and studies specifically targeting those with severe and enduring AN has resulted in patients being subjected to repetitive employment of largely ineffective treatment strategies resulting in a sense of hopelessness and shame and increasing the risk of suicide [ 98 ]. This review of the literature found that a duration of illness ≥7 years and an unsuccessful response to previous evidence-based treatment were the most common inclusion criteria employed, as were various measures of psychological and physical severity.

AN was once thought to be primarily caused by dysfunctional family dynamics and social and cultural pressures [ 99 ]. We now have evidence that genetics plays a significant role in its etiology. In recent years, there has been an evidence-based push to reconceptualize AN as a metabopsychiatric disorder [ 7 ]. Functional magnetic resonance imaging (fMRI) continues to provide data on the functioning of the brains of those with AN [ 100 ]. The use of large-scale GWAS and genome-wide methylation studies has been gradually revealing the interplay between genetics and environment in AN etiology and persistence, and genetic correlations with other psychiatric disorders [ 16 , 101 , 102 ]. These are all positive advances; however, as evidenced by the individuals included in these studies, female teens and young adults with shorter durations of illness appear to be the primary participants.

Historically, males have been underrepresented in AN research [ 103 ]. Until 2013, the DSM listed amenorrhea as a criterion for AN, thereby reinforcing the notion that AN affects only females [ 61 ]. According to the literature reviewed, males continue to be underrepresented in AN research.

The challenge of recruiting participants for inclusion in large-scale genetic studies of AN is significant. Of the indicated criteria, the most challenging for researchers to assess is the lack of response to prior evidence-based treatment. Most of the treatments described as evidence-based are not administered according to a defined protocol, making retrospective assessment nearly impossible. Furthermore, those with more severe symptoms of longer duration are often treated in a plethora of settings over many years.

For many of the publications, the data indicate that there were participants meeting the criteria defined in the first aim. However, as these individuals were not assessed as a group, it was not possible to determine whether outcomes for this subset may have differed from those with a less severe presentation. The purpose of the publications that either did not perform these assessments or did not report them in their studies was not to delineate this level of detail, so their absence is understandable. One of the reasons for this may be the small number of individuals meeting the criteria for severe and enduring AN, coupled with the need for a large enough “n” to provide any meaningful statistical assessment, which in turn points back to the need for larger studies and additional funding.

Nevertheless, several studies made concerted efforts to focus on a defined severe and enduring phenotype. For example, Kushima et al. [ 74 ] limited their study cohort to those reporting a lifetime lowest BMI < 15 kg/m 2 , with the median for included participants reported as 11.3 kg/m 2 , and a mean age of 37.9 years. The authors specifically stated that they focused on the “severe subgroup of patients because patients with severe symptoms or treatment-resistance are more likely to carry rare deleterious variants of large effect”, citing a schizophrenia study [ 104 ] as support.

The ultimate goal of AN research is to identify contributing factors to the manifestation and intractability of the disease and, in turn, develop superior evidence-based treatments tailored to the patient. Will next generation sequencing gene panels help in the diagnosis of AN [ 105 ]? Kushima et al. [ 74 ] suggested that rare copy number variants associated with neurodevelopmental disorders may correlate with more severe eating disorder subtypes. Is it possible to identify those at higher risk of developing severe and enduring illness earlier and in turn treat those patients based on their specific genetic and environmental circumstances instead of employing generic therapy that may work for most patients with eating disorders but is less effective for those in this cohort? Can artificial intelligence be employed to better identify risk in individuals with AN [ 106 ]? Will we one day regularly employ genetic testing and pharmacogenetics in treating mental illness, including AN [ 107 , 108 ]? Several international projects, including ANGI and the Comprehensive Risk Evaluation for Anorexia Nervosa in Twins (CREAT) are attempting to answer these questions and many more [ 109 , 110 ]. Although these projects do not focus specifically on the severe and enduring phenotype, the availability of in-depth participant health and demographic information paired with genetic analysis should allow for studies of these subsets.

The criteria for evaluating the severity and intractability of AN are evolving, as is the understanding of the disorder. The purpose of a scoping review is to map the literature on an evolving topic and to identify gaps. As such, unlike a systematic review, this review does not attempt to assess the quality of the research conducted, but rather the inclusiveness of study participants. The authors do not attempt to define the severe and enduring phenotype or suggest how the research community should create consensus on the definition. However, by assessing the current literature, we highlight the gaps between the intent to focus on those with severe and enduring AN and the inclusion of this group in published research.

Conclusion and future directions

In conclusion, this review provides an overview of the currently used criteria employed by the research community to define the severity of AN and assesses the last decade of genetics research for the inclusion of study participants meeting these criteria. We found that the following combination of assessments and criteria was used most often in the literature to define AN severity and intractability:

Illness duration of ≥ 7 years.

lack of positive response to at least two previous evidence-based treatments.

A BMI meeting the DSM-5 criteria for extreme AN.

An assessment of psychological and/or behavioral severity indicating a significant impact on quality of life.

We also found, especially in recent years, that there has been an attempt to better define severe and enduring AN in hopes of identifying patients, tailoring treatment, and improving outcomes. However, although a small subset of genetic studies reviewed specifically attempted to focus on a severe and enduring phenotype, there was a lack of aligned defining criteria. Furthermore, there is a continued focus on younger females with shorter disease durations.

Those with AN are often stigmatized, and their shame is amplified by the perception that AN is voluntary or even a lifestyle choice [ 111 , 112 , 113 ]. Those with severe and long-lasting illness are less likely to respond to currently available treatment modalities and have higher levels of mortality [ 20 ]. However, they also represent a subgroup of individuals for which genetic findings may be especially helpful [ 74 ]. Therefore, it is suggested that future genetics studies make a concerted effort to include older participants, those with longer illness durations, and those whose quality of life is most significantly impacted. It is also critically important that more objective, empirically based techniques, such as biomarker and brain structure and function analysis, be developed to more definitively classify the severe and enduring phenotype, which to this point has primarily been categorized through subjective means [ 32 , 60 , 96 , 114 ]. There has been considerable effort in recent years to expand the definition of AN in hopes of being more inclusive and identifying those who may benefit from treatment. However, although expansion has increased the sample size for genetic studies, it could be that focusing on those with longer-lasting and more severe symptomology, even though this is a much smaller group of those with AN, would provide a better chance of identifying the genetic etiology of the disorder. Recent advances have left us far better equipped to make significant progress in developing evidence-based treatments for those with severe and enduring AN. However, these advances require the inclusion of this subgroup in both research and practice.

Limitations

One limitation of the current review is that due to the wide range of similar terminology used to refer to a severe and enduring AN phenotype in the published literature, the searches performed may have left out pertinent articles and viewpoints. Furthermore, although comprehensive for the three electronic databases, the literature search did not include gray literature; thus, information from sources such as dissertations may have been missed.

Data availability

No datasets were generated or analysed during the current study.

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The authors would like to thank Dr. Michael Lutter for his valuable insight and review of the paper.

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Ramsay, S., Allison, K., Temples, H.S. et al. Inclusion of the severe and enduring anorexia nervosa phenotype in genetics research: a scoping review. J Eat Disord 12 , 53 (2024). https://doi.org/10.1186/s40337-024-01009-9

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DOI : https://doi.org/10.1186/s40337-024-01009-9

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