Anorexia nervosa pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]


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.[1]

Physiological Factors

Genetic Factors

Family and twin studies have suggested that genetic factors contribute to about 50% of the variance for the development of an eating disorder[2] and that anorexia shares a genetic risk with clinical depression.[3] 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.[4] These models have suggested that the hypothalamic-pituitary-adrenal axis may be a contributory factor, although the models have been criticised 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.

Neurobiological Factors

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,[5] 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,[6] 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.[7]

Nutritional Factors

Zinc deficiency causes a decrease in appetite that can degenerate in anorexia nervosa (AN), appetite disorders and, notably, inadequate zinc nutriture. The use of zinc in the treatment of anorexia nervosa has been advocated since 1979 by Bakan. At least five 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 AN.[8] 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.[8]

Psychological Factors

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[9] 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.[10] 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.[11]

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.[12]

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.[13]

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[14] (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.[15] 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.

Fairburn and colleagues psychological model of anorexia

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.

Professor Chris Fairburn, of the University of Oxford and his colleges have created a 'transdiagnostic' model,[16] 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 behavioral 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 industrialised 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.[17] 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,[18] and further research has suggested that those with anorexia have much higher contact with cultural sources that promote weight-loss.[19]

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 countries. 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.[20]

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.[21]

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 by former sufferers, and some by professionals. The majority of such sites support a medical view of anorexia as a disorder to be cured, 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.[22] 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.[23]


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  8. 8.0 8.1 Neurobiology of Zinc-Influenced Eating Behavior | [1]
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