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Anorexia Nervosa
Evolution and Anorexia Nervosa
Biochemical insights into self-starvation
Posted June 23, 2012
One of my teachers at Children's Hospital characterized anorexia nervosa as "a desperate disease." On the inpatient unit where the (mostly) young women were hospitalized, it was difficult to find one who would stay still. They were forbidden to exercise, but during groups would move their legs and fidget constantly to burn calories. Quite a feat, as some of them still had dangerously low blood pressure and body temperature from the self-induced starvation. Often purging and starvation were combined (though this combination would be more correctly called "eating disorder not otherwise specified" or "anorexia nervosa, bingeing-purging subtype" than strict anorexia nervosa), and they had to be watched in the bathroom to prevent purging or claiming constipation in order to get laxatives.
My evolutionary psychiatry interest has always been in how psychiatric disorders have changed over the past 100 years of rapidly changing lifestyle and diet. Anorexia nervosa is one of those illnesses that was exceedingly rare until 50 years ago, then escalated rapidly and finally leveled off for about the past 20 years, though those who are affected encompass more children and more men now than ever before. My educated guess is that only a small percentage of us are capable of starving ourselves outright without being under lock and key, and that vulnerable population shows symptoms earlier and earlier in life as societal pressures and the obesogenic environment increases.
All full-blown eating disorders remain relatively rare, though in total they are more common than schizophrenia and bipolar I disorder. Anorexia afflicts about 0.5% of women and 0.1% of men. Bulimia around 1-3% of women (also 0.1% of men), and binge eating disorder 3.3% of women and 0.8% of men. Anorexia nervosa remains the most deadly of all psychiatric disorders, with a 5-10% death rate within 10 years of developing the symptoms, and an 18-20% death rate within 20 years.
In 10-20% of patients, the disorder is short-lived. In 20-30% it is chronic and unremitting. The most seriously affected are at greatest risk for hypothyroidism, loss of bone density, electrolyte disturbances, low blood cell counts, amenorrhea, suicide, and death.
Anorexia is endemic in the fashion industry, to the point where models are now being airbrushed to add curves. Another model, Isabelle Caro, died at age 28 of anorexia, and Ana Reston of Brazil died at age 20, still modeling with a BMI of less than 14.
Photo of Isabelle Caro from Wikipedia
The current state of the art treatment of anorexia begins with refeeding, mostly because we know that semi-starvation itself causes obsessions, depression, and fixation on food. In the hospital, patients work closely with dietitians, trying to learn how to eat a healthy amount and to establish a better relationship with food. While medicines that promote weight gain are prescribed, antidepressants and other agents are fairly useless in a starvation situation.
But what makes these young ladies (and children, and young men and boys) susecptible to the illness in the first place? Could it be a survival mechanism gone wrong? Recently, a friend sent me this paper: Role of the evolutionarily conserved starvation response in anorexia nervosa. It is a fascinating piece, with an in-depth consideration of biology, evolution, and insulin.
The authors speculate that "AN [anorexia nervosa] may be caused by defects in the evolutionarily conserved response to food and nutrient shortage associated with reduced calorie intake."
In anorexia, the physiology of starvation is paramount. Both brain and peripheral metabolism responses come into play, orchestrated by the brain and the endocrine system. The goal of the starvation response is to conserve energy, delay growth, preserve ATP (the "gasoline" used by our cells to keep things running) by increasing efficiency of energy metabolism, and to minimize oxidative damage. In starvation, changes in the hypothalamus of the brainstem result in a fall in blood insulin levels and a suppression of other anorexogenic factors. Once a metabolic state called ketosis occurs with the depletion of glycogen stores, there is an increase in output from the sympathetic nervous system and stimulation of food-seeking behaviors. These multiple pathways explain why fasting can be healthy for some when used carefully, but also stressful.
One of the major biochemical pathways activated is the IGF-1/FOXO response (an insulin growth factor 1 pathway). That means anorexia nervosa could arise when there is defective regulation in the starvation pathway, similar to how insulin deficiency (due to insulin resistance) is a factor in type II diabetes. Meaning there is a lot going on with respect to home life, environment, stress, and temperament in eating disorders, but only a select few have the genetic capability to deliberately starve themselves is response to the environment, and those few may have differences in the IGF-1/FOXO pathway. The researchers were able to find some yeast, fruit flies, worms, and mice with defects in that pathway who tend to restrict food and develop more slowly (or, alternatively, eat more and spontaneously gain weight), and who have genetic differences in the IGF-1/FOXO pathway.
Evidence for genetic vulnerability to anorexia includes the fact that eating disorders are highly heritable. (Uruguayan model Luisel Ramos and her sister both died from anorexia in recent years). When doing genome-wide linkage analysis of families with eating disorders, many components of the starvation response pathway are located in highly suspect genetic areas. In practical terms, the increased impetus on thinness and subsequent dieting brings out the reinforcing starvation response as a result of the genetic vulnerability. A single episode of excessive caloric restriction seems to bring out long-term changes in the neurotransmitter production mediated by FOXO.
Thus caloric restriction and weight loss predispose to additional episodes of dieting, especially in susceptible individuals wih defective regulation of their starvation response, or with perseverative bias in behavior, reflected in obsessive thoughts and compulsivity.
How do these general ideas affect treatment? Family therapy, distress tolerance, and cognitive behavioral therapy around distorted body image are all cornerstones of therapy for eating disorders, along with the refeeding.
Should we use insulin to treat anorexia? Well, the reactive hypoglycemia and other risks are problematic. A more sophisticated approach is to use IGF-1 itself--it can increase appetite and reverse bone loss seen in anorexia. Long term treatment tends to result in hyperplasia of the lymphatic tissue, tumor promotion, and excess accumulation of body fat.
Better that we never begin dieting in the first place. Skipping the processed foods and ensuring there are plenty of healthy fat and nutrients for the brain and muscles seems like the optimal and common sensical approach in that regard. I'm not sure what to do about the fashion industry.
Before and after treatment for Anorexia Nervosa, 1894
Copyright Emily Deans, MD
