Etiologies of Anorexia Nervosa

Anorexia nervosa is an eating disorder characterized by excessive weight loss, and irrational fear of gaining weight and distorted body self-perception. Anorexia nervosa usually developes during adolescence and early adulthood.Due to the fear of gaining weight, people with this disorder restrict the amount of food they intake. This restriction of food intake causes metabolic and hormonal disorders.The terms anorexia nervosa and anorexia are often used interchangeably, however anorexia is simply a medical term for lack of appetite. Anorexia nervosa has many complicated implications and may be thought of as a lifelong illness that may never be truly cured, but only managed over time. Anorexia nervosa is characterized by low body weight, inappropriate eating and obsession with thin figure.

Anorexia nervosa is often coupled with a distorted self image which may be maintained by various cognitive biases that alter how the affected individual evaluates and thinks about her or his body, food and eating. Persons with anorexia nervosa continue to feel hunger, but deny themselves all but very small quantities of food. The average caloric intake of a person with anorexia nervosa is 600–800 calories per day, but extreme cases of complete self-starvation are known.It is a serious mental illness with a high incidence of comorbidity and similarly high mortality rates to serious psychiatric disorders.[7]

Anorexia most often has its onset in adolescence and is most prevalent among adolescent girls. However, more recent studies show that the onset age of anorexia has decreased from an average of 13 to 17 years of age to 9 to 12. While it can affect men and women of any age, race, and socioeconomic and cultural background,Anorexia nervosa occurs in females 10 times more than in males. While anorexia nervosa is quite commonly (in lay circles) believed to be a woman ‘s illness, it should not be forgotten than ten per cent of people with anorexia nervosa are male.

The term anorexia nervosa was established in 1873 by Sir William Gull, one of Queen Victoria’s personal physicians.The term is of Greek origin: an- (ἀν-, prefix denoting negation) and orexis (ὄρεξις, “appetite”), thus meaning a lack of desire to eat.However, while the term “anorexia nervosa” literally means “neurotic loss of appetite” the literal meaning of the term is somewhat misleading. Many anorexics do enjoy eating and have certainly not lost their appetite as the term “loss of appetite” is normally understood; it is better to regard anorexia nervosa as a self-punitive addiction to fasting, rather than a literal loss of appetite.

Causes

Studies have hypothesized that the continuance of disordered eating patterns may be epiphenomena of starvation. The results of the Minnesota Starvation Experiment showed that normal controls exhibit many of the behavioral patterns of anorexia nervosa when subjected to starvation. This may be due to the numerous changes in the neuroendocrine system, which results in a self perpetuating cycle. Studies have suggested that the initial weight loss such as dieting may be the triggering factor in developing AN in some cases, possibly because of an already inherent predisposition toward AN. One study reports cases of AN resulting from unintended weight loss that resulted from varied causes such as a parasitic infection, medication side effects, and surgery. The weight loss itself was the triggering factor

Biological

  • 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. Neonatal complications may also have an influence on harm avoidance, one of the personality traits associated with the development of AN.
  • Genetics: anorexia nervosa is believed to be highly heritable, 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 behavior, 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 anorexia nervosa, but not binge-purge anorexia.Recent studies have advanced the theory that the sex difference in incidence and the common onset at the age of puberty may reflect an abnormal response of the brain to anorexic (feeding suppressing) effects of the female sex hormone, estrogen.This viewpoint has been recently supported by a report that abnormal forms of the estrogen receptor are more common in women with anorexia nervosa of the restricting type.
    • epigenetics: Epigenetic mechanisms: are means by which genetic mutations are caused by environmental effects that alter gene expression via methods such as DNA methylation, these are independent of and do not alter the underlying DNA sequence. They are heritable, as was shown in the Överkalix study, but also may occur throughout the lifespan, and are potentially reversible. Dysregulation of dopaminergic neurotransmission and Atrial natriuretic peptide homeostasis resulting from epigenetic mechanisms has been implicated in various eating disorders.[62] “We conclude that epigenetic mechanisms may contribute to the known alterations of ANP homeostasis in women with eating disorders.
    • serotonin dysregulation;particularly high levels in those 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 might reduce serotonin levels at these critical sites and ward off anxiety. Other studies of the 5HT2A serotonin receptor (linked to regulation of feeding, mood, and anxiety), suggest that serotonin activity is decreased at these sites. There is evidence that both personality characteristics associated with AN, and disturbances to the serotonin system are still apparent after patients have recovered from anorexia.
  • 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 behavior 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 AN and some comorbid disorders such as major depression.Exercise increases levels of BDNF
  • leptin and ghrelin; leptin is a hormone produced primarily by the fat cells in white adipose tissue of the body it has an inhibitory (anorexigenic) effect on appetite, by inducing a feeling of satiety. Ghrelin is an appetite inducing (orexigenic) 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 anorexia nervosa and bulimia nervosa.
  • cerebral blood flow (CBF); neuroimaging studies have shown reduced CBF in the temporal lobes of anorectic patients, which may be a predisposing factor in the onset of AN.
  • autoimmune system; Autoantibodies against neuropeptides such as melanocortin have been shown to affect personality traits associated with eating disorders such as those that influence appetite and stress responses.
  • Infections: Some people are hypothesized to have developed anorexia abruptly as a reaction to a streptococcus or mycoplasma infection. PANS is an acronym for Pediatric acute-onset neuropsychiatric syndrome, a hypothesis describing children who have abrupt, dramatic onset of obsessive-compulsive disorder (OCD) or anorexia nervosa coincident with the presence of two or more neuropsychiatric symptoms.[76]
  • Nutritional deficiencies
    • Zinc deficiency may play a role in anorexia. It is not thought responsible for causation of the initial illness but there is evidence that it may be an accelerating factor that deepens the pathology of the anorexia. A 1994 randomized, double-blind, placebo-controlled trial showed that zinc (14 mg per day) doubled the rate of body mass increase compared to patients receiving the placebo.

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.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. People 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.

Anorexia nervosa is more likely to occur in a person’s pubertal years, especially for girls. Female students are 10 times more likely to suffer from anorexia nervosa than male students. According to a survey of 1799 Japanese female high school students, “85% who were a normal weight wanted to be thinner and 45% who were 10–20% underweight wanted to be thinner.”Teenage girls concerned about their weight and who believe that slimness is more attractive among peers trend to weight-control behaviors. Teen girls are learning from each other to consume low-caloric, low-fat foods and diet pills. This results in lack of nutrition and a greater chance of developing anorexia nervosa.

It has also been noted that anorexia nervosa is more likely to occur in populations in which obesity is more prevalent. It has been suggested that anorexia nervosa results from a sexually selected evolutionary drive to appear youthful in populations in which size becomes the primary indicator of age.

There is also evidence to suggest that patients who have anorexia nervosa can be characterised by alexithymia and also a deficit in certain emotional functions. A research study showed that this was the case in both adult and adolescent anorexia nervosa patients.

There is a high rate of reported child sexual abuse experiences in clinical groups of who have been diagnosed with anorexia. The connection between eating disorders and abuse has been convincingly evidenced by a number of studies, including one published in Epidemiology (and strengthened by blind hypothesis survey), which showed in a comparison of women with no history of eating disorders, women with a history of eating disorders were twice as likely to have reported childhood sexual abuse.While the joint effect of both physical and sexual abuse resulted in a nearly 4-fold risk of eating disorders that met DSM-IV criteria.It is thought that links between childhood abuse and sexual abuse are complex, such as by influencing psychologic processes that increase a woman’s susceptibility to the development of an eating disorder, or perhaps by producing changes in psychobiologic process and neurotransmitting function, associated with eating behaviour.

Recent efforts have been made to dispel some of the myths around anorexia nervosa and eating disorders, such as the misconception that families, in particular mothers, are responsible for their daughter developing an eating disorder.

Relationship to autism

Relationship between anorexia nervosa and autism, a large-scale longitudinal study into teenage-onset anorexia nervosa conducted in Sweden confirmed that 23% of people with a long-standing eating disorder are on the autism spectrum.Those on autism spectrum tend to have a worse outcome, but may benefit from the combined use of behavioural and pharmacological therapies tailored to ameliorate autism rather than anorexia nervosa per se.Other studies, most notably research conducted at the Maudsley Hospital, UK, furthermore suggest that autistic traits are common in people with anorexia nervosa; shared traits include, e.g., poor executive function, autism quotient score, central coherence, theory of mind, cognitive-behavioural flexibility, emotion regulation and understanding facial expressions.

The autism spectrum make up the cognitive endophenotype underlying anorexia nervosa and appealed for increased interdisciplinary collaboration.A pilot study into the effectiveness Cognitive Behaviour Therapy, which based its treatment protocol on the hypothesised relationship between anorexia nervosa and an underlying autistic like condition, reduced perfectionism and rigidity in 17 out of 19 participants

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