Biological Basis of Anorexia Nervosa

Most of us are at least familiar with the name of this life-altering affliction, commonly referred to solely as “anorexia”. Anorexia is a Latin-derived word meaning “lack of” (an-) “appetite” (orexigenic). Other websites provide a detailed description of the disease, including behaviors and symptoms. Herein, I want to explain the biology behind this deadly psychiatric disorder and dispel some common myths.

Is Anorexia Nervosa An Addiction?

An addiction may be defined as a progressive narrowing of the things that bring one pleasure, leading to severe dysfunction in one’s life. Although debated, anorexia can, in some senses, be thought of as an addiction*, as the avoidance of food (and fascination thereof) gradually becomes one of the only things to bring pleasure, at the expense of most other activities and interactions. Similar to neuro-biochemical changes experienced by individuals addicted to alcohol, biochemical changes occur in the brain of an individual with anorexia, causing food avoidance to become extremely rewarding (as drugs become rewarding to those with substance abuse disorders). While there are fundamental differences between anorexia nervosa and substance abuse (Barbarich-Marsteller et al., 2015), and while the point of this article is not to debate the precise definition of what does or does not constitute an “addiction,” it may be helpful to think of anorexia as an addiction, whereby an individual is unlikely to be able to simply “stop” the detrimental behavior purely through willpower.

So What Causes Anorexia?

In a fascinating study, Madra & Zeltser showed that approximately 40% of mice with a genetic predisposition to anxiety (conferred by a variant in a specific gene, the BDNF-Val66Met allele) and exposed to social isolation stress and caloric restriction would exhibit severe self-imposed dietary restriction, sometimes to the point of death. Furthermore, the Val66Met genotype markedly increased the likelihood and severity of abnormal feeding behavior triggered by caloric restriction, but only when caloric restriction was imposed in the peri-pubertal period. Incidence of anorexic behavior was also dependent on juvenile exposure to social stress and could be extinguished by adolescent handling. (Madra & Zeltser, 2016) While there is also undoubtedly a cultural component to this disorder, case descriptions of anorexia nervosa date back to the middle of the 19th century when thinness was not as widely desirable, suggesting that factors other than culture are important in the pathogenesis of this disorder. Familial studies suggest that first-degree relatives of individuals with anorexia nervosa have an approximately ten-fold greater lifetime risk of having anorexia nervosa than relatives of unaffected individuals, with twin studies demonstrating that a considerable portion of observed familial aggregation is due to additive genetic factors. (Barbarich-Marsteller et al., 2015)

It’s Not Solely About Control

We hear it all the time—that individuals struggling with an eating disorder are trying to exercise some thread of control in a life that is full of chaos, and controlling food is a way to try to find this balance. I’m here to tell you that it’s not solely about control. While individuals with eating disorders are more likely to experience OCD or anxiety, which in and of themselves are often related to control-like behaviors, eating disorders stem from a biological aversion to food. If you don’t or have never experienced an eating disorder, imagine for a moment that feeling of anxiety you may feel when you realize that you forgot something important—maybe you forgot to pick your kid up from school, or forgot your spouse’s birthday, or maybe missed an important meeting at work. You freeze, right? Suddenly paralyzed, stomach sinking and fear tightening your throat. Now imagine feeling this every time you’re around food, an overwhelming sense of anxiety that floods through your body. Looking for a door, looking for an exit—you’ll do almost anything not to feel this way.

It May Be About Emotion Regulation

While this is my personal experience, and maybe yours as well, it’s not just anec-data. In fact, studies have demonstrated that for individuals who have recovered from anorexia nervosa, amphetamine-induced dopamine release is associated with greater anxiety, compared to the dopamine associated feelings of euphoria experienced by individuals who haven’t had an eating disorder. (Bailer et al., 2012) For most people, food consumption—which is associated with dopamine release in the brain—is normally highly pleasurable. (Roitman et al., 2004) However, individuals with anorexia may experience this food-derived dopamine as highly anxiety inducing, and thus dietary restraint/starvation may be an effective means of reducing anxiety.

In addition to the anxiogenic (anxiety-producing) effects of dopamine in anorexia, this disorder has also been shown to be associated with high levels of baseline serotonin. (Bailer & Kaye, 2011) Elevated levels of serotonin are linked with fear and anxiety (Marcinkiewcz et al., 2016), and starvation may therefore diminish serotonin activity to reduce anxiety. And it’s not just neurotransmitters that exhibit unique functioning in anorexia—these individuals have increased brain activation in areas related to reward processing; activation of the lateral orbitofrontal cortex, in particular, is associated with increased impulse control to reward presentation and is likely the reason individuals with anorexia are able to demonstrate high food-intake control, something others without eating disorders find extremely difficult. (Frank et al., 2012) The continuation of anorexia may also be driven by a slowing of brain activity, particularly in the cerebral cortex (the higher-order structure that allows us to think and feel and be human), stemming from the scarcity of calories. If an individual tends to worry or ruminate, functions allowed for by the prefrontal cortex, a lack of energy may reduce these negative thoughts. In my personal experience, starvation quieted the fear and pain and hurt, blunting the emotions I wasn’t able to tolerate.

Take-Home Message

From what we know about the biological basis of anorexia, alterations in reward processing systems cause food intake to become highly aversive, and food avoidance to be extremely rewarding. While much more research needs to be done in this area, the solution for an individual with anorexia is not simply to “just eat.” Cognitive behavioral therapy, along with nutrition counseling and potentially pharmacotherapy, are necessary to fully address the underlying issue. So next time you hear someone say that people with anorexia are just striving to control something, kindly let them know that, in fact, individuals with anorexia are behaving in a way that allows them to avoid crippling feelings of anxiety.

Notes

*Interestingly, severity of caloric restriction has been found to be a significant predictor of psychostimulant use, independent of diagnostic eating disorder category. (Wiederman & Pryor, 1996)

References

Bailer, U. F., & Kaye, W. H. (2011). Serotonin: Imaging Findings in Eating Disorders. Current Topics in Behavioral Neurosciences, 6, 59–79. https://doi.org/10.1007/7854_2010_78

Bailer, U. F., Narendran, R., Frankle, W. G., Himes, M. L., Duvvuri, V., Mathis, C. A., & Kaye, W. H. (2012). Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa. The International Journal of Eating Disorders, 45(2), 263–271. https://doi.org/10.1002/eat.20937

Barbarich-Marsteller, N. C., Foltin, R. W., & Walsh, B. T. (2011). Does Anorexia Nervosa Resemble an Addiction? Current Drug Abuse Reviews, 4(3), 197–200. https://doi.org/10.2174/1874473711104030197

Frank, G. K., Bailer, U. F., Henry, S. E., Drevets, W., Meltzer, C. C., Price, J. C., Mathis, C. A., Wagner, A., Hoge, J., Ziolko, S., Barbarich-Marsteller, N., Weissfeld, L., & Kaye, W. H. (2005). Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride. Biological Psychiatry, 58(11), 908–912. https://doi.org/10.1016/j.biopsych.2005.05.003

Madra, M., & Zeltser, L. M. (2016). BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to anorexic behavior in mice. Translational Psychiatry, 6(4), e776–e776. https://doi.org/10.1038/tp.2016.35

Roitman, M. F., Stuber, G. D., Phillips, P. E. M., Wightman, R. M., & Carelli, R. M. (2004). Dopamine Operates as a Subsecond Modulator of Food Seeking. The Journal of Neuroscience, 24(6), 1265–1271. https://doi.org/10.1523/JNEUROSCI.3823-03.2004

Wiederman, M. W., & Pryor, T. (1996). Substance use among women with eating disorders. International Journal of Eating Disorders, 20(2), 163–168. https://doi.org/10.1002/(SICI)1098-108X(199609)20:2%253C163::AID-EAT6%253E3.0.CO;2-E