DEFINITION
The term etymology is Greek: an- (lack, absence) and orexis (appetite), thus meaning a lack of desire to eat. The sole word anorexia indicate a symptom, whereas the term nervous anorexia (NA in the following text) is the name of the disease mainly characterized by this symptom.
NA, in fact, has been defined by the American Psychiatric Association as an eating disorder that is characterized by the lack or loss of appetite, known as anorexia. Other features include excess fear of becoming overweight; body image disturbance; significant weight loss; refusal to maintain minimal normal weight; and amenorrhea. (APA, Thesaurus of Psychological Index Terms, 1994).
Actually, people with NA continue to feel hunger, but deny themselves all but very small quantities of food. The average caloric intake of a person with NA is 600-800 kcal per day, but there are
extreme cases of complete self-starvation.
MeSH Anorexia Nervosa
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Autism
EPIDEMIOLOGY
Prevalence of NA in estimated to be between 0,3% and 2%, varying with the study, and incidence is 8 new cases every 100.000 people per year. The disease begin mostly between 12 and 25 years,
with a peak in the teenage and less frequent manifestations in younger or older individuals. The incidence in female is about ninefold the male one, but, actually, the real proportion is unknown,
considering the lack of attention that male nervous anorexia had until few years ago. Geographical variations are consistent: being NA a disease strongly linked with wellness, it is diffused in richer countries while pretty unknown in poorest. In particular, Norway and Japan seems to be the countries with the worse morbidity, having respective prevalence of 5,7% and 4,8%.
CLASSIFICATION
NA is classified as an Axis I disorder in the Diagnostic and Statistical Manual of Mental Health Disorders (DSM-IV). The diagnostic criteria for NA includes intense fear of gaining weight, a refusal to maintain body weight above 85% of the expected weight for a given age and height, and three consecutive missed periods and either refusal to admit the seriousness of the weight loss, or undue influence of shape or weight on one’s self image, or a disturbed experience in one’s shape or weight.
There are two types: the binge-eating/purging type is characterized by overeating or purging, and the restricting type is not. There is also a third type called “ Meyer’s cronical anorexia”. It differs from the others two types because it starts in child and lead to a growth retard.
SYMPTOMS
A person with NA may exhibit a number of signs and symptoms. The main signs are related to body’s changes and patients perception of these, such as:
- rapid, dramatic weight loss;
- obsession with calories and fat content, fear of gaining weight or becoming overweight and preoccupation with food, recipes, or cooking (may cook elaborate dinners for others but not eat themselves);
- purging: uses laxatives, diet pills or may engage in self-induced vomiting, eventually running to the bathroom after eating in order to vomit and quickly get rid of the calories;
- may engage in frequent, strenuous exercise;
- perceives self to be overweight despite being told by others they are too thin;
- solitude: may avoid friends and family; becomes withdrawn and secretive;
- clothing: some may wear baggy, loose-fitting clothes to cover weight loss if they have been confronted about their health and wish to hide it, while others will wear baggy clothing to hide what they see as an unattractive and overweight body.
DIAGNOSIS
Questionaries (EAT-26, EDS3, EDSIS ) and medical test are used to make the diagnosis.
There have been criticisms over various aspects of the diagnostic criteria utilized for NA in the DSM-IV. Including the requirement of maintaining a body weight below 85% of the expected weight and
the requirement of amenorrhea for diagnosis; some women have all the symptoms of NA and continue to menstruate. Those who do not meet these criteria are usually classified as eating disorder not otherwise specified.
According to the WHO International Classification of Disease, 10th version (ICD-10), the criteria are similar, but in addition, it is specifically mentioned:
- the ways that individuals might induce weight-loss or maintain low body weight (avoiding fattening foods, self-induced vomiting, self-induced purging, excessive exercise, excessive use of appetite suppressants or diuretics);
- if onset is before puberty, that development is delayed or arrested;
- certain physiological features, including “endocrine disorder involving hypothalamic-pituitary-gonadal axis is manifest in women as amenorrhoea and in men as loss of sexual interest and potency. There may also be elevated levels of growth hormons, raised cortisol levels, changes in the peripheral metabolism of thyroid hormone and abnormalities of insulin secretion”.
Medical test used are:
- Complete Blood Count (CBC): used to assess the presence of various disorders such as leukopenia, thrombocytosis and anemia which may result from malnutrition;
- Chem-20: a group of twenty separate chemical tests performed on blood serum. Tests include cholesterol, protein and electrolytes such as potassium, chlorine and sodium and tests specific to liver and kidney function;
- glucose tolerance test;
- LH response to GnRH: tests the pituitary gland’s response to GnRh a hormone produced in the hypothalumus. Central hypogonadism is often seen in NA cases;
- blood urea nitrogen (BUN) test: urea nitrogenum to test kidney function. A low BUN level may indicate the effects of malnutrition;
- thyroid screen;
- parathyroid hormone (PTH) test: to diagnose hypoparathyroidism;
- electrocardiogram (EKG or ECG): measures electrical activity of heart can be used to detect various disorders such as hyperkalemia;
- neuroimaging; via the use of various techniques such as PET scan, MRI and SPECT imaging.
PATHOGENESIS
Studies have suggested that the initial weight loss such as dieting may be the triggering factor in developing NA in some cases, possibly due to an already inherent predisposition toward NA.
Biological
About genetic origin, NA is believed to be highly inheritable, with estimated inheritance rates ranging from 56% to 84%. Association studies have been performed, studying 128 different polymorphisms related to 43 genes including genes involved in regulation of eating behaviour, motivation and reward mechanics, personality traits and emotion. Consistent associations have been identified for polymorphisms associated with agouti related peptide, brain derived neurotrophic factor, catechol-o-methyl transferase, SK3 and opioid receptor delta-1. In one study, variations in the norepinephrine transporter gene promoter were associated with restrictive NA, but not binge-purge anorexia.
As far as concern acquired origin many causes have to be mentioned.
Obstetric complications: various prenatal and perinatal complications may factor into the development of AN such as maternal anemia, diabetes mellitus, preeclampsia, placental infarction, and neonatal cardiac abnormalities. Many endocrinal and neuroendocrinal dysregulation are involved. Dopamine and serotonin pathways has been implicated in the aetiology, pathogenesis and pathophysiology of NA: serotonin dysregulation, resolving in particularly high levels in those areas in the brain with the 5HT1A receptor – a system linked to anxiety, mood and impulse control. Starvation has been hypothesized to be a response to these effects, as it is known to lower tryptophan and steroid hormone metabolism, which might reduce serotonin levels at these critical sites and ward off anxiety.
Brain-derived neurotrophic factor (BDNF) is a protein that regulates neuronal development and neuroplasticity, it also plays a role in learning, memory and in the hypothalamic pathway that controls eating behaviour and energy homeostasis. BDNF amplifies neurotransmitter responses and promotes synaptic communication in the enteric nervous system. Low levels of BDNF are found in patients with NA and some comorbid disorders such as major depression.
Leptin and ghrelin; leptin is a hormone produced primarily by the fat cells in white adipose tissue of the body it has an inhibitory effect on appetite (it’s an anorexigenic hormon), by
inducing a feeling of satiety. Ghrelin is an appetite inducing hormone produced in the stomach and the upper portion of the small intestine. Circulating levels of both hormones are an important factor in weight control. While often associated with obesity both have been implicated in the pathophysiology of NA and bulimia nervosa.
Other factors influencing the development of NA are cerebral blood flow, as far neuroimaging studies have shown reduced CBF in the temporal lobes of anorectic patients, the presence of
auto-antibodies against neuropeptides such as melanocortin, that have been shown to affect personality traits associated with eating disorders such as those that influence appetite and stress responses. Finally nutritional deficiencies (for example Zinc deficiency) are associated; it is not thought responsible for causation of the initial illness but there is evidence that it may be an accelerating factor of the pathology.
Environmental
Sociocultural studies have highlighted the role of cultural factors, such as the promotion of thinness as the ideal female form in Western industrialized nations, particularly through the media.
Gender, ethnicity and socio-economic status were large influences on the chance of developing anorexia. People in professions where there is a particular social pressure to be thin (such as models and dancers) are much more likely to develop anorexia during the course of their career.
There is a high rate of reported child sexual abuse experiences in clinical groups of who have been diagnosed with anorexia. Although prior sexual abuse is not thought to be a specific risk factor for anorexia, those who have experienced such abuse are more likely to have more serious and chronic symptoms.
Social and psychological causes
An important risk factor is live in a family where there are people suffering of the same disease or where there are serious problems in communication and emotional expression. In that case the disease is a way “to communicate without words” with the family, a way to have attention, to have care.
An important feature of anorexic patients is the incapacity of accept their body. They have a wrong idea of the reality and so they see their body like something deformed. This perception is called
dismorphophobia and it’s a psychopathological symptom that needs a specific therapy.
THERAPY
Treatment for NA tries to address three main areas
- restoring the person to a healthy weight;
- treating the psychological disorders related to the illness;
- reducing or eliminating behaviours or thoughts that originally led to the disordered eating.
For the first task, diet and nutrition changes are due: it’s necessary to introduce into the body of 1500-1800 kcal per day. It is also necessary to reduce bone loss using vitamin D and
calcium, to supplement zinc, essential fatty acid and micronutrients to reach a healthy weight. A refeeding syndrome has been reported in 6% of hospitalized patients and can include congestive
heart failure and pedal edema, a prolonged QT interval with arrhythmia, tachycardia, and sudden cardiac death. Electrolyte disturbances such as hypokalemia and hypophosphatemia require immediate
attention. Slower refeeding will minimize the risk of major complications with refeeding.
For the second, some specific medication are considered: olanzapine has been shown to be effective in treating certain aspects of NA including to help raise the body mass index and reduce obsessive behaviour, including obsessional thoughts about food. It is discussed the use of selective serotonin reuptake inhibitors, also known as the new generation antidepressants SSRI. Corticosteroids are used, such as prednisolone (to an extent of 15-30 mg daily) or equivalent, dexamethasone (with lower dose: 2-4 mg daily).
Finally, psychotherapy intervention are requested. As far as concern this aspect, different approaches are possible and used:
- cognitive behavioral therapy (CBT) : is an evidence based approach which in studies to date has shown to be useful in adolescents and adults with anorexia. There are many subcategories of
approaches(Rational emotive behavior therapy, Cognitive Therapy, Rational living therapy…)
- cognitive remediation therapy (CRT): is a cognitive rehabilitation therapy designed to improve neurocognitive abilities such as attention, working memory, cognitive flexibility and planning, and executive functioning which leads to improved social functioning.
- family therapy: various forms of family therapy have been proven to work in the treatment of adolescent AN including “Conjoint family therapy” (CFT), in which the parents and child are seen together by the same therapist, “separated family therapy” (SFT) in which parents and child attend therapy separately with different therapists.
Some experimental medical therapy are under study: a treatment with dronabinol, a synthetic form of the main psychoactive compound extracted from the resin of the Cannabis sativa (delta-9-THC), is currently the subject of a clinical trial for use in the treatment of NA, the study is slated to end in 2011. A ghrelin treatment has also to be mentioned: pilot studies have been concluded in the use of ghrelin infusion for the inhospital treatment of patients with NA. The results showed positive effect in the reduction of the associated gastrointestinal symptoms, an increase in appetite and energy intake without adverse effects.
PROGNOSYS
Although eating disorders among all is the one with the highest mortality, anorexia rarely leads to death (the deaths by suicide are also logged, and come to a peak of 5%).
Most women, after five years of clinical care, has managed to overcome the state of chronic illness, coming after the full recovery.
COMPLICATIONS
Complications of NA are many and include disorders that range in the most of the human body systems.
Psychiatric
Depression (from 25% to 80% according to many trials); anxiety (from 20% to 65%, especially at the beginning of the disease); symptom of abuse of alcohol and drugs.
Dermatological
Cutaneous xerosis, livedo reticuaris, seborrhoic dermatitis, acne, pellagra; cheeks may become swollen due to enlargement of the salivary glands caused by excessive vomiting; nails fragility and
lesions; cheiliteis and angular stomatitis; lanugo: soft, fine hair grows on face and body; Russell’s sign scarring on knuckles due to sticking fingers down throat to force vomiting.
Gastrointestinal
Tooth lesions (loss of enamel and dentine to masticatory and acid reflux due to prolonged vomiting); lesions in esophageal and motility disorders; delayed gastric emptying; constipation or diarrhoea; changes in colon, pancreas and liver.
Endocrinological
Amenorrhoea; ipercortisolism and Cushing’ Syndrome; hypoglycaemia from an excess of glucagon; activation of the hypothalamic-pituitary-adrenal axis; off of the hypothalamic-pituitary-gonadal; hypothyroidism resulting state of decay.
Blood and electrolyte balance
Leukopenia , due to IGF-I deficit; anemia and thrombocytopenia; Zn deficit; hyponatriemia; hypokaliemia; edema.
Metabolism
Ketosis and ketonuria; abnormal lipid with increased cholesterol; hypoproteinemia with azotemia; impaired glucose tolerance; metabolic alkalosis hypochloraemic; decreased magnesium; hypercarotenemia.
Muscle and skeletal
Decrease of bones mineral density, osteopenia and osteoporosis; joint hypotrophy and hypotonia, myopathy and spontaneous fractures.
Central and peripheral neurological disorders
Insomnia, seizures, peripheral neuropathy, brain atrophy, optic neuropathy and intolerance to cold: frequently complains of being cold due to loss of insulating body fat or poor circulation due to
extremely low blood pressure; body temperature lowers (hypothermia) in effort to conserve energy.
Cardiovascular
Bradicardia, especially when the lost of weight is important (due to vagal hypertonus, at night the frequency drops below 40 beats per minute; hypotension, (due to dehydration, the reduction of
pump rate, the decrease of wall thickness of the myocardium); cardiac atrophy; mitral valve prolapse; pericardial effusion; prolonged and altered QT interval; ventricular arrhythmia; sudden death; stroke.
A focus on cardiovascular complications
QT Interval Prolongation and Heart Rate
Prolongation of the QT interval is the most worrying complications of NA, because it appears to predict and anticipate the onset of certain cardiac arrhythmias and sudden death. It could be due to heart atrophies, that would cause such histologic changes (myocytolysis, fat and mononuclear infiltration, collagen deposition) in the muscle that impairment of myocardial blood flow can take place and problems with the phase of repolarization may occurr. Actually, heart atrophy is not satisfactfully explained, being hypothesized that its origin is due to a compensatory mechanisms for the hypovolemia, in order to guarantee preload. Most of the studies concluded that the measured outcome (mean QT interval, corrected QT, QT dispersion) are increased in NA patient, while some studies did not found any difference between patient and controls. A possible confounding factor has been identification in the selection of the patient, that might had not discriminated between female having a diagnosis of NA and female with a non pathological low BMI (20 kg/m2). A study incorporated this theory into the study design, in which three groups of sixteen women had been compared. The first group was made by women with eating disorder-induced starvation, the second with sixteen women of normal weight and the third with sixteen women who were constitutionally thin (BMI kg/m2). The results showed a significantly longer QTd in the anorexic group when compared both with the thin and control group. This controversy, anyway, seems to be finally resolved by one cross-study that looked at the effect of treatment in this disease and whether or not these risks can be reversed. In this, QT interval in patients with NA has been compared before and after treatment. The study showed that there was in fact a significant prolongation of the QT interval in patients with anorexia and also a significant reversion to normal after sufficient treatment (refeeding) of the disease.
Bradycardia
Depressed heart rate variability is another predictor of sudden cardiac death, especially in patients with congestive heart failure and coronary artery disease. It seems to be, from many
studies, that sinus bradycardia is one of the most frequent arrhythmias found in patients with NA.
Several theories exists for why bradycardia is so common in these patients. It has been hypothesized that the slow heart rate is an effect of vagal hyperactivity in an attempt to decrease the
amount of cardiac work by reducing cardiac output. While the true mechanism remain unclear, plausible hypothesis have been proposed (electrolyte loss, drug effects, decrease in glycogen content of
the myocardial cells, cellular atrophy) and some findings (decreased level of T3 in the anorexic group, as in people with chronic malnutrition) have been found.
Myocardial mass modification and hemodynamics
Many studies have shown that strict caloric deprivation has significant effects on cardiac structure and function.
Echocardiographic findings showed that diastolic and systolic left ventricular internal dimension, left ventricular mass, left ventricular mass index, and cardiac output were all significantly
reduced in patients with NA, and thus cardiac index. Another study found that left ventricular septal thickness was also decreased. However, posterior wall thickness, and ejection fraction were similar in patients with anorexia and control subjects. Some patients demonstrated a prolapsed mitral valve.
According to the hypothesis that an increase or decrease in body weight is associated with an increase or decrease in cardiac mass, after refeeding, many of these cardiac abnormalities improved with the exception of the mitral valve prolapse, which persisted after treatment but showed no clinical significance. Despite the increased incidence of hypotension in the anorexic patient, peripheral resistance seemed to be very higher than normal.
Remains uncertain whether the decrease in left ventricular mass is secondary to malnutrition or simply a reduction in preload.
REFERENCE
Definition
National Library of Medicine – Medical Subject Headings Anorexia nervosa (consulted on 20th February 2011)
Epidemiology, classification, symptoms, diagnosis, pathogenesis, therapy and complications
* Wikipedia, english version. Anorexia nervosa. (consulted on 21th February 2011)
* Wikipedia, italian versione. Anoressia nervosa". (consulted on 21th February 2011)
* Furlan PM, Picci RL. Dispense di psichiatria
Cardiovascular complications
Casiero D, Frishman WH. Cardiovascular complications of eating disorders. Cardiology Review 2006 Sep-Oct;14(5):227-31.
This work has been made by Chiara Arrigoni and Enrico Boero.
