The term anorexia is of Greek origin: an (privation or lack of) and orexis (appetite) thus meaning a lack of desire to eat. 
A person who is suffering from anorexia nervosa is referred to as 'anorexic' or (less commonly) as 'an anorectic'. "Anorectic" is the noun form, whereas "anorexic" is the adjectival form.
The term "anorectic" can also refer to any drug that suppresses appetite.
"Anorexia nervosa" is frequently shortened to "anorexia" in both the popular media and scientific literature. This is technically incorrect, as strictly speaking "anorexia" refers to the medical symptom of reduced appetite.
In popular culture, and especially with anorexics themselves, the term is often shortened to "ana" to avoid sounding clinical and impersonal. "Pro-ana" groups often use the terms "ana" and "mia" (referring to bulimia nervosa) to describe their conditions, as it has less negative connotations than the full medical term.
Diagnosis and clinical features
The criteria for diagnosing anorexia are from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD).
Although biological tests can aid the diagnosis of anorexia, the diagnosis is based on a combination of behavior, reported beliefs and experiences, and physical characteristics of the patient. Anorexia is typically diagnosed by a clinical psychologist, psychiatrist, medical doctor or other qualified clinician.
Notably, diagnostic criteria are intended to assist clinicians, and are not intended to be representative of what an individual sufferer feels or experiences in living with the illness.
The full ICD-10 diagnostic criteria for anorexia nervosa can be found here, and the DSM-IV-TR criteria can be found here.
To be diagnosed as having Anorexia Nervosa, according to the DSM-IV-TR, a person must display:
A. Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g., weight loss leading to maintenance of body weight less than 85% of that expected; or failure to make expected weight gain during period of growth, leading to body weight less than 85% of that expected).
B. Intense fear of gaining weight or becoming fat, even though underweight.
C. 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.
D. In postmenarcheal females, amenorrhea, i.e., the absence of at least three consecutive menstrual cycles. (A woman is considered to have amenorrhea if her periods occur only following hormone, e.g., estrogen, administration
* Restricting Type: during the current episode of Anorexia Nervosa, the person has not regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas)
* Binge-Eating/Purging Type: during the current episode of Anorexia Nervosa, the person has regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas).
The ICD-10 criteria are similar, but in addition, specifically mention: i) 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); ii) physiological features, including "widespread endocrine disorder involving hypothalamic-pituitary-gondola axis is manifest in women as amenorrhea and in men as loss of sexual interest and potency. There may also be elevated levels of growth hormones, raised cortisol levels, changes in the peripheral metabolism of thyroid hormone and abnormalities of insulin secretion"; and iii) if the onset is before puberty, development is delayed or arrested.
There are a number of features, that although not necessarily diagnostic of anorexia, have been found to be commonly (but not exclusively) present in those with this eating disorder. 
* Distorted body image
* Intense fear about becoming overweight
* Self-evaluation largely, or even exclusively, in terms of their shape and weight
* Pre-occupation or obsessive thoughts about food, weight and appearance
* Cognitive impairment
* Low self-esteem and self-efficacy
* Clinical depression or chronically low mood
* Obsessive Compulsive Disorder or other Anxiety Disorders
* Moodiness or 'mood swings'
Interpersonal and social
* Lack of concentration that may reflect in poor school performance
* Withdrawal from previous friendships and other peer-relationships
* Deterioration in relationships with the family
* Withdrawal from previously enjoyed social events
* Extreme weight loss
* Endocrine disorder, leading to cessation of periods in girls (amenorrhea)
* Starvation symptoms, such as reduced metabolism, slow heart rate (bradycardia), hypotension, hypothermia and anemia
* Growth of baby-fine hair over the body
* Abnormalities of mineral and electrolyte levels in the body
* Zinc deficiency
* Often a reduction in white blood cell count
* Reduced immune system function
* Body mass index less than 17.5 in adults, or 85% of expected weight in children
* Possibly with pallid complexion and sunken eyes
* Creaking joints and bones
* Collection of fluid in ankles during the day and around eyes during the night
* Very dry/chapped lips due to malnutrition
* Poor circulation, resulting in common attacks of 'pins and needles' and purple extremities
* In cases of extreme weight loss, there can be nerve deterioration, leading to difficulty in moving the feet
* Headaches, due to malnutrition
* Thinning of the hair
* Nails become more brittle
* Constantly feeling "cold"
* Food restriction
* Excessive exercise
* Secretive about eating or exercise behavior
* Possible self-harm, substance abuse or suicide attempts
* Very sensitive to references about body weight
* Become very angry when forced to eat "forbidden" foods
Diagnostic issues and controversies
The distinction between the diagnoses of anorexia nervosa, bulimia nervosa and eating disorder not otherwise specified (EDNOS) is often difficult to make in practice and there is considerable overlap between patients diagnosed with these conditions. Furthermore, seemingly minor changes in a patient's overall behavior or attitude (such as reported feeling of 'control' over any bingeing behavior) can change a diagnosis from 'anorexia: binge-eating type' to bulimia nervosa. It is not unusual for a person with an eating disorder to 'move through' various diagnoses as his or her behavior and beliefs change over time
Additionally, it is important to note that an individual may still suffer from a health- or life-threatening eating disorder (e.g., subclinical anorexia nervosa or EDNOS) even if one diagnostic sign or symptom is still lacking. For example, a substantial number of patients diagnosed with EDNOS meet all criteria for diagnosis of anorexia nervosa, but lack the three consecutive missed menstrual cycles needed for a diagnosis of anorexia.
Another controversy lies in what feminist writers such as Susie Orbach and Naomi Wolf have criticized the medical focus of extreme dieting and weight-loss as locating the problem within the affected women, rather than in a society that imposes concepts of unreasonable and unhealthy thinness as a measure of female beauty.
Causes and contributory factors
It is clear that there is no single cause for anorexia and that it stems from a mixture of social, psychological and biological factors. Current research is commonly focused on explaining existing factors and uncovering new causes. However, there is considerable debate over how much each of the known causes contributes to the development of anorexia. In particular, the contribution of perceived media pressure on women to be thin has been especially contentious.
Physiological factors are as follows:
Family and twin studies have suggested that genetic factors contribute to about 50% of the variance for the development of an eating disorder and that anorexia shares a genetic risk with clinical depression. This evidence suggests that genes influencing both eating regulation, and personality and emotion, may be important contributing factors.
Several rodent models of anorexia have been developed which largely involve subjecting the animals to various environmental stressors or using gene knockout mice to test hypotheses about the effects of certain genes on related behavior. These models have suggested that the hypothalamic-pituitary-adrenal axis may be a contributory factor, although the models have been criticized as food is being limited by the experimenter and not the animal, and these models cannot take into account the complex cultural factors known to affect the development of anorexia nervosa.
There are strong correlations (but not proven causation) between the neurotransmitter serotonin and various psychological symptoms such as mood, sleep, emesis (vomiting), sexuality and appetite. A recent review of the scientific literature has suggested that anorexia is linked to a disturbed serotonin system  particularly to high levels at areas in the brain with the 5HT1A receptor - a system particularly 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, in turn, might reduce serotonin levels at these critical sites and, hence, ward off anxiety. In contrast, studies of the 5HT2A serotonin receptor (linked to regulation of feeding, mood, and anxiety), suggest that serotonin activity is decreased at these sites. One difficulty with this work, however, is that it is sometimes difficult to separate cause and effect, in that these disturbances to brain neurochemistry may be as much the result of starvation, than continuously existing traits that might predispose someone to develop anorexia. There is evidence, however, that both personality characteristics (such as anxiety and perfectionism) and disturbances to the serotonin system are still apparent after patients have recovered from anorexia  suggesting that these disturbances are likely to be causal risk factors.
Recent studies also suggest anorexia may be linked to an autoimmune response to melanocortin peptides which influence appetite and stress responses.
Zinc deficiency causes a decrease in appetite -- which could degenerate in anorexia nervosa. Appetite disorders, in turn, cause malnutrition and, notably, inadequate zinc nutriture. The use of zinc in the treatment of anorexia nervosa has been advocated since 1979 by Bakan. At least 5 trials showed that zinc improved weight gain in anorexia. A 1994 randomized, double-blind, placebo-controlled trial showed that zinc (14 mg per day) doubled the rate of body mass increase in the treatment of anorexia. Deficiency of other nutrients such as tyrosine and tryptophan (precursors of the monoamine neurotransmitters norepinephrine and serotonin, respectively), as well as vitamin B1 (thiamine) could contribute to this phenomenon of malnutrition-induced malnutrition.
There has been a significant amount of work into psychological factors that suggests how biases in thinking and perception help maintain or contribute to the risk of developing anorexia.
Anorexic eating behavior is thought to originate from feelings of fatness and unattractiveness and is maintained by various cognitive biases that alter how the affected individual evaluates and thinks about their body, food and eating.
One of the most well-known findings is that people with anorexia tend to over-estimate the size or fatness of their own bodies. A recent review of research in this area suggests that this is not a perceptual problem, but one of how the perceptual information is evaluated by the affected person. Recent research suggests people with anorexia nervosa may lack a type of overconfidence bias in which the majority of people feel themselves more attractive than others would rate them. In contrast, people with anorexia nervosa seem to more accurately judge their own attractiveness compared to unaffected people, meaning that they potentially lack this self-esteem boosting bias.
People with anorexia have been found to have certain personality traits that are thought to predispose them to develop eating disorders. High levels of obsessionality (being subject to intrusive thoughts about food and weight-related issues), restraint (being able to fight temptation), and clinical levels of perfectionism (the pathological pursuit of personal high-standards and the need for control) have been cited as commonly reported factors in research studies.
It is often the case that other psychological difficulties and mental illnesses exist alongside anorexia nervosa in the sufferer. Clinical depression, obsessive compulsive disorder, substance abuse and one or more personality disorders are the most likely conditions to be comorbid with anorexia, and high-levels of anxiety and depression are likely to be present regardless of whether they fulfill diagnostic criteria for a specific syndrome.
Research into the neuropsychology of anorexia has indicated that many of the findings are inconsistent across studies and that it is hard to differentiate the effects of starvation on the brain from any long-standing characteristics. Nevertheless, one reasonably reliable finding is that those with anorexia have poor cognitive flexibility  (the ability to change past patterns of thinking, particularly linked to the function of the frontal lobes and executive system).
Other studies have suggested that there are some attention and memory biases that may maintain anorexia. Attentional biases seem to focus particularly on body and body-shape related concepts, making them more salient for those affected by the condition, and some limited studies have found that those with anorexia may be more likely to recall related material than unrelated material.
Although there has been quite a lot of research into psychological factors, there are relatively few theories which attempt to explain the condition as a whole.
Fairburn and colleagues have created a 'transdiagnostic' model  in which they aim to explain how anorexia, as well as related disorders such as bulimia nervosa and ED-NOS are maintained. Their model is developed with psychological therapies, particularly cognitive behavior therapy, in mind, and so suggests areas where clinicians could provide psychological treatment.
Their model is based on the idea that all major eating disorders (with the exception of obesity) share some core types of psychopathology which help maintain the eating disorder behavior. This includes clinical perfectionism, chronic low self-esteem, mood intolerance (inability to cope appropriately with certain emotional states) and interpersonal difficulties.
Social and environmental factors
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. A recent epidemiological study of 989,871 Swedish residents indicated that gender, ethnicity and socio-economic status were large influences on the chance of developing anorexia, with those with non-European parents among the least likely to be diagnosed with the condition, and those in wealthy, white families being most at risk. A classic study by Garner and Garfinkel demonstrated that those in professions where there is a particular social pressure to be thin (such as models and dancers) were much more likely to develop anorexia during the course of their career  and further research has suggested that those with anorexia have much higher contact with cultural sources that promote weight-loss.
Although anorexia nervosa is usually associated with Western cultures, exposure to Western media is thought to have led to an increase in cases in non-Western counties. However, it is notable that other cultures may not display the same 'fat phobic' worries about becoming fat as those with the condition in the West, and instead may present with low appetite with the other common features. 
There is a high-rate of child sexual abuse experiences in those who have been diagnosed with anorexia (up to 50% in those admitted to inpatient wards, with a lesser prevalence among people treated in the community). Although prior sexual abuse is not thought to be a specific risk factor for anorexia (although it is a risk factor of mental illness in general), those who have experienced such abuse are more likely to have more serious and chronic symptoms. 
In recent years, the internet has enabled anorexics and bulimics to contact and communicate with each other outside of a treatment environment, with much lower risks of rejection by mainstream society. A variety of websites exist, some run by sufferers, some former sufferers, and some by professionals. The majority of such sites support a medical view of anorexia as a disorder to be cured or actively in recovery, although some people affected by anorexia have formed online pro-ana communities that reject the medical view and argue that anorexia is a 'lifestyle choice', using the internet for mutual support, and to swap weight-loss tips. Such websites were the subject of significant media interest, largely focusing on concerns that these communities could encourage young women to develop or maintain eating disorders, and many were taken offline as a result.
Anorexia is thought to have the highest mortality rate of any psychiatric disorder, with approximately 10% of those who are diagnosed with the disorder eventually dying due to related causes.  The suicide rate of people with anorexia is also higher than that of the general population and is thought to be the major cause of death for those with the condition. Anorexia is also considered difficult to treat. A recent review suggested that less than one-half recover fully, one-third improve, and 20% remain chronically ill.
Incidence, prevalence and demographics
The majority of research into the incidence and prevalence of anorexia has been done in Western industrialized countries, so results are generally not applicable outside these areas. However, recent reviews  of studies on the epidemiology of anorexia have suggested an incidence of between 8 and 13 cases per 100,000 persons per year and an average prevalence of 0.3% using strict criteria for diagnosis. These studies also confirm the view that the condition largely affects young adolescent females, with females aged between 15 and 19 making up 40% of all cases. Furthermore, the majority of cases are unlikely to be in contact with mental health services. As a whole, about 90% of people with anorexia will be female.
The first line treatment for anorexia is nutrition rehabilitation for immediate weight gain to decrease the starvation symptoms, especially with those who have particularly serious conditions that require hospitalization. In particularly serious cases, this may be done as an involuntary hospital treatment under mental health law, where such legislation exists. In the majority of cases, however, people with anorexia may be treated voluntarily in inpatient and residential treatment centers (24/7 care) or outpatient partial hospitalization programs, with input from physicians, psychiatrists, clinical psychologists and other mental health professionals.
A recent clinical review has suggested that nutrition rehabilitation and psychotherapy is an effective form of treatment and can lead to restoration of weight, return of menses among female patients, and improved psychological and social functioning when compared to simple support or education programs. However, this review also noted that there are only a small number of randomized controlled trials on which to base this recommendation, and no specific type of psychotherapy seems to show any overall advantage when compared to other types. Family therapy has also been found to be an effective treatment for adolescents with anorexia  and in particular, a method developed at the Maudsley Hospital is widely used for child and adolescents and found to maintain improvement over time.
It is important to note that many recovering underweight persons (who are more or less forced against their will into recovery by parents or other relatives) often initially harbor a hateful dislike for those who they feel to be robbing them of their treasured emaciation. Often when well-meaning friends or relatives compliment the recoveree on how much healthier they look, the recoveree's mind replaces "healthy" with "fat." Eventually, these individuals, when successfully nourished and treated, are grateful for the attention others paid when they could not do it for themselves.
Drug treatments, such as SSRI or other antidepressant medication, have not found to be generally effective for either treating anorexia or in some studies preventing relapse although it has also been noted that there is a lack of adequate research in this area. However, more recently prozac given when the patient has reached a BMI of 20 has shown to be successful in preventing relapse. It is common, however, for antidepressants to be prescribed, often with the intent of trying to treat the associated anxiety and depression, especially if anxiety and depression were present prior to the malnourishment. Also, neuroleptics or anti-psychotics at low doses are showing promising effects.
- ^ a bBirmingham CL, Su J, Hlynsky JA, Goldner EM, Gao M. (2005) The
mortality rate from anorexia nervosa. Int J Eat Disord, 38 (2), 143-6.
- ^ a b c d Lask B, and Bryant-Waugh, R (eds) (2000) Anorexia Nervosa
and Related Eating Disorders in Childhood and Adolescence. Hove:
Psychology Press. ISBN 0-86377-804-6.
- ^Katzman DK. (2005) Medical complications in adolescents with anorexia
nervosa: a review of the literature. Int J Eat Disord, 37 Suppl, S52-9.
- ^Legroux-Gerot I, Vignau J, Collier F, Cortet B. (2005) Bone loss
associated with anorexia nervosa. Joint Bone Spine, 72 (6), 489-95.
- ^Palazidou E, Robinson P, Lishman WA. (1990) Neuroradiological and
neuropsychological assessment in anorexia nervosa. Psychol Med, 20
(3), 521-7. PMID 2236361.
- ^Lask B, Gordon I, Christie D, Frampton I, Chowdhury U, Watkins B.
(2005) Functional neuroimaging in early-onset anorexia nervosa. Int
J Eat Disord, 37 Suppl, S49-51. PMID 15852320.
- ^ Costin, Carolyn.~ (1999) The Eating Disorder Sourcebook.
Linconwood: Lowell House. 6.
- ^ a b Gowers S, Bryant-Waugh R. (2004) Management of child and
adolescent eating disorders: the current evidence base and future
directions. J Child Psychol Psychiatry, 45 (1), 63-83. PMID 14959803
- ^ Tiggemann M and Pickering AS. (1996) Role of television in adolescent
women's body dissatisfaction and drive for thinness Int J Eat Disord, Sep;
- ^Klump KL, Kaye WH, Strober M (2001) The evolving genetic
foundations of eating disorders. Psychiatr Clin North Am, 24 (2), 215-25.
- ^Wade TD, Bulik CM, Neale M, Kendler KS. (2000) Anorexia nervosa
and major depression: shared genetic and environmental risk factors.
Am J Psychiatry, 157 (3), 469-71. PMID 10698830.
- ^Siegfried Z, Berry EM, Hao S, Avraham Y. (2003) Animal models in
the investigation of anorexia. Physiol Behav, 79 (1), 39-45.
- ^Kaye WH, Frank GK, Bailer UF, Henry SE, Meltzer CC, Price JC,
Mathis CA, Wagner A. (2005) Serotonin alterations in anorexia and
bulimia nervosa: new insights from imaging studies. Physiol Behav, 85
(1), 73-81. PMID 15869768.
- ^Kaye WH, Bailer UF, Frank GK, Wagner A, Henry SE. (2005) Brain
imaging of serotonin after recovery from anorexia and bulimia nervosa.
Physiol Behav, 86(1-2), 15-7. PMID 16102788.
- ^Fetissov SO, Harro J, Jaanisk M, Jarv A, Podar I, Allik J, Nilsson I,
Sakthivel P, Lefvert AK, Hokfelt T. (2005) Autoantibodies against
neuropeptides are associated with psychological traits in eating
disorders. Proc Natl Acad Sci U S A, 102 (41), 14865-70. PMID 16195379.
- ^ a bNeurobiology of Zinc-Influenced Eating Behavior | 
- ^Rosen JC, Reiter J, Orosan P. (1995) Assessment of body image in
eating disorders with the body dysmorphic disorder examination.
Behav Res Ther, 1, 77-84. PMID 7872941.
- ^ Skrzypek S, Wehmeier PM, Remschmidt H. (2001) Body image
assessment using body size estimation in recent studies on anorexia
nervosa. A brief review. Eur Child Adolesc Psychiatry, 10 (4), 215-21.
- ^Jansen A, Smeets T, Martijn C, Nederkoorn C. (2006) I see what you
see: the lack of a self-serving body-image bias in eating disorders. Br
J Clin Psychol, 45 (1), 123-35. PMID 16480571.
- ^Wonderlich SA, Lilenfeld LR, Riso LP, Engel S, Mitchell JE. (2005)
Personality and anorexia nervosa. Int J Eat Disord, 37 Suppl, S68-71.
- ^ O'Brien KM, Vincent NK. (2003) Psychiatric comorbidity in anorexia and
bulimia nervosa: nature, prevalence, and causal relationships.
Clin Psychol Rev, 23 (1), 57-74. PMID 12559994
- ^Tchanturia K, Campbell IC, Morris R, Treasure J. (2005)
Neuropsychological studies in anorexia nervosa. Int J Eat Disord, 37
Suppl, S72-6. PMID 15852325.
- ^ Cooper MJ (2005) Cognitive theory in anorexia nervosa and bulimia
nervosa: progress, development and future directions. Clin Psychol Rev,
25 (4), 511-31. PMID 15914267.
- ^ Fairburn CG, Cooper Z, Shafran R. (2003) Cognitive behaviour therapy for
eating disorders: a "transdiagnostic" theory and treatment. Behav Res Ther,
41 (5), 509-28. PMID 12711261.
- ^Lindberg L, Hjern A. (2003) Risk factors for anorexia nervosa: a national
cohort study. Int J Eat Disord, 34 (4), 397-408. PMID 14566927
- ^Garner DM, Garfinkel PE. (1980) Socio-cultural factors in the development
of anorexia nervosa. Psychol Med, 10 (4), 647-56. PMID 7208724.
- ^Toro J, Salamero M, Martinez E. (1994) Assessment of sociocultural
influences on the aesthetic body shape model in anorexia nervosa.
Acta Psychiatr Scand, 89 (3), 147-51. PMID 8178671.
- ^Simpson KJ. (2002) Anorexia Nervosa and culture. J Psychiatr Ment
Health Nurs, 9 (1), 65-71. PMID 11896858.
- ^Carter JC, Bewell C, Blackmore E, Woodside DB. (2006) The impact
of childhood sexual abuse in anorexia nervosa. Child Abuse Negl, 30 (3),
257-69. PMID 16524628.
- ^Norris ML, Boydell KM, Pinhas L, Katzman DK. (2006) Ana and the
internet: A review of pro-anorexia websites. Int J Eat Disord, May 23;
Epub ahead of print. PMID 16721839.
- ^Reaves, J. (2001). Anorexia goes high tech. Time (July). Retrieved
7th May 2005 from
- ^Pompili M, Mancinelli I, Girardi P, Ruberto A, Tatarelli R. (2004) Suicide
in anorexia nervosa: a meta-analysis. Int J Eat Disord, 36 (1),
99-103. PMID 15185278
- ^Steinhausen HC. (2002) The outcome of anorexia nervosa in the 20th
century. Am J Psychiatry, 159 (8), 1284-93. PMID 12153817.
- ^Bulik CM, Reba L, Siega-Riz AM, Reichborn-Kjennerud T. (2005)
Anorexia nervosa: definition, epidemiology, and cycle of risk. Int J
Eat Disord, 37 Suppl, S2-9. PMID 15852310.
- ^ Hoek HW. (2006) Incidence, prevalence and mortality of anorexia
nervosa and other eating disorders. Curr Opin Psychiatry., 19 (4), 389-94.
- ^Hay P, Bacaltchuk J, Claudino A, Ben-Tovim D, Yong PY. (2003)
Individual psychotherapy in the outpatient treatment of adults with
anorexia nervosa. Cochrane Database Syst Rev, 4, CD003909.
- ^Lock J, Le Grange D. (2005) Family-based treatment of eating disorders.
Int J Eat Disord, 37 Suppl, S64-7. PMID 15852323.
- ^Le Grange D. (2005) The Maudsley family-based treatment for
adolescent anorexia nervosa. World Psychiatry, 4 (3), 142-6.
- ^Claudino AM, Hay P, Lima MS, Bacaltchuk J, Schmidt U, Treasure J.
(2006) Antidepressants for anorexia nervosa. Cochrane Database
Syst Rev, 1, CD004365. PMID 16437485.
- ^Walsh BT, Kaplan AS, Attia E, Olmsted M, Parides M, Carter JC,
Pike KM, Devlin MJ, Woodside B, Roberto CA, Rockert W. (2006) Fluoxetine
after weight restoration in anorexia nervosa: a randomized
controlled trial. JAMA, 295(22), 2605-12. PMID 16772623.