Anorexia nervosa (AN) is a disorder with no proven treatment that is effective in reversing core symptoms, and it may have the highest mortality rate of any psychiatric illness. It is a very difficult disorder to treat, in part, because those with AN often lack motivation to engage in treatment. Many people in today’s society diet frequently and want to lose weight, but very few develop AN. Considerable evidence suggests that heritability contributes to the development of an eating disorder. It may be that genes code for certain temperament traits in childhood, such as perfectionism, anxiety, obsessiveness, that create a susceptibility for the development of AN during adolescence.
Recent studies offer new understanding of alterations of neural circuitry that may contribute to development of AN. In particular, findings from these studies suggest how individuals with AN can severely restrict their caloric intake for years. In contrast, most people have difficulty adhering to a diet for a long period of time, and experience a high rate of recidivism after they lose weight. How are individuals with AN able to ignore signals regarding hunger that otherwise motivate eating, even when they are severely emaciated?
Understanding such questions may lead to the development of more effective treatments targeted at the underlying mechanisms of the disorder. For example, future treatments could address the neural circuitry of reward and the modulation of salient stimuli, such as food, as well as the circuitry contributing to anxious temperament or self-awareness of body states.
One reason that it is difficult to get persons with AN to gain and maintain weight is because little in life is more rewarding to them than starvation. Clinically, individuals with AN have long been noted to be anhedonic and ascetic, and able to sustain not only the self-denial of food but also most comforts and pleasures in life.1 Behavioral studies show that individuals with AN have an enhanced ability to delay reward (ie, show less reduction in the value of a monetary reward over time) compared to healthy cohorts and this ability to delay reward may help them to maintain persistent food restriction.2
Persons with AN may be unable to appreciate rewarding stimuli because they are preoccupied with consequences.3 Thus, an altered balance between reward and inhibition appears to be a hallmark of AN. In fact, a recent review showed that persons with AN tend to have low reward reactivity but a high sensitivity to punishment in both the ill and recovered states.4 Imaging data support this hypothesis and suggest that altered reward sensitivity and increased behavioral inhibition in AN are related to underactive limbic (reward) circuitry and overactive executive (inhibition) neural circuitry.5,6 Clinically, this bias is likely to interfere with motivation as well as the ability to learn from experience. That is, ill persons with AN tend to perceive their actions as incorrect or flawed and are highly sensitive to criticism, rather than being able to appropriately proportion reward and punishment in order to learn from experience.
Dr Kaye is Director of the Eating Disorders Program and Professor in the department of psychiatry at the University of California, San Diego, School of Medicine.
1. Frank G, Bailer UF, Henry S, et al. Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11C]raclopride. Biol Psychiatry. 2005;58:908-912.
2. Steinglass J, Albano A, Simpson H, et al. Fear of food as a treatment target: exposure and response prevention for anorexia nervosa in an open series. Int J Eat Disord. 2012;45:615-621.
3. Halmi K, Agras WS, Crow S, et al. Predictors of treatment acceptance and completion in anorexia nervosa. Arch Gen Psychiatry. 2005;62:776-781.
4. Harrison A, O’Brien N, Lopez C, Treasure J. Sensitivity to reward and punishment in eating disorders. Psychiat Res. 2010;177:1-11.
5. Bischoff-Grethe A, McCurdy D, Grenesko-Stevens E, et al. Altered brain response to reward and punishment in adolescents with anorexia nervosa. Psychiat Res. 2013;214:331-340.
6. Wagner A, Aizenstein H, Venkatraman M, et al. Altered reward processing in women recovered from anorexia nervosa. Am J Psychiatry. 2007;164:1842-1849.
7. Tchanturia K, Davies H, Roberts M, et al. Poor cognitive flexibility in eating disorders: examining the evidence using the Wisconsin Card Sorting Task. PLoS One. 2012;7:e28331.
8. Cloninger C, Przybeck T, Svrakic D, Wetzel R. The Temperament and Character Inventory (TCI): A Guide to Its Development and Use. St. Louis: Center for Psychobiology of Personality; 1994:19-28.
9. Kaye W, Wierenga C, Bailer U, et al. Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci [Special Issue on Neural Control of Appetite]. 2013;36:110-120.
10. Kaye W, Wierenga C, Bailer U, et al. Does a shared neurobiology for foods and drugs of abuse contribute to extremes of food ingestion in anorexia and bulimia nervosa? Biol Psychiatry. 2013;73:836-842.
11. Eagle D, Wong J, Allan M, et al. Contrasting roles for dopamine D1 and D2 receptor subtypes in the dorsomedial striatum but not the nucleus accumbens core during behavioral inhibition in the stop-signal task in rats. J Neuroscience. 2011;31:7349-7356.
12. Simon N, Montgomery K, Beas B, et al. Dopaminergic modulation of risky decision-making. J Neuroscience. 2011;31:17460-17470.
13. Bailer U, Narendran R, Frankle W, et al. Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa. Int J Eat Disord. 2012;45:263-271.
14. Oberndorfer T, Frank G, Fudge J, et al. Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa. Am J Psychiatry. 2013;170:1143-1151.
15. Wagner A, Aizenstein H, Frank GK, et al. Altered insula response to a taste stimulus in individuals recovered from restricting-type anorexia nervosa. Neuropsychopharmacol. 2008;33:513-523.
16. Kaye W, Strober M, Klump KL. Neurobiology of eating disorders. In: Martin A, Scahill L, Charney DS, Leckman JF, Eds. Pediatric Psychopharmacology, Principles & Practice. New York: Oxford University Press; 2003:224-237.
17. Steinglass J, Sysko R, Mayer L, et al. Pre-meal anxiety and food intake in anorexia nervosa. Appetite. 2010;55:214-218.
18. Frank G, Kaye W. Current status of functional imaging in eating disorders. Int J Eat Disord. 2012;45:723-736.
19. Small D. Individual differences in the neurophysiology of reward and the obesity epidemic. Int J Obes. 2009;33(Suppl 2):S44-48.
20. Le Grange D, Lock J. Family-Based Treatment of Adolescent Anorexia Nervosa: The Maudsley Approach. http://www.maudsleyparents.org/whatismaudsley.html. Accessed February 14, 2014.