What really causes anorexia?

here's a rule of thumb in biology that if something is evolutionarily conserved it means it must have survival value. That means there must be a gene for it. What does this say about eating disorders, which are strongly inherited?

The standard way of finding a gene is a genome-wide association study (GWAS). But finding a gene for a disorder doesn't necessarily imply causation. In a metabo-psychiatric disorder like anorexia, a GWAS would identify genes that code for self-esteem, genes for body image, genes for regulating food intake, and genes for personality type. Low self-esteem is practically a euphemism for low social status, so a GWAS would find genes correlated with that as well.

It sounds impossible. But the thinking among geneticists is that correlation is the first step to identifying causation. The challenge is that we don't have a good understanding of how the mind works, so we don't know what causes anorexia. In this article, I'll discuss some recent hypotheses.

You eat sixteen calories and what do you get? Another day older and deeper in metabolic debt

Evolutionary Psychology

In 2019 Frontiers In Psychology dedicated a whole section to “new perspectives to unlock the current impasse in treating anorexia nervosa (AN).” Because anorexia is strongly inherited, one approach is evolutionary psychology, and these researchers have come up with several theories.

1. The thrifty genotype hypothesis The upper level of adiposity is set by the risk of predation, while the lower level is set by the need to avoid starvation. Since the risk of predation is lower today, genes coding for obesity are more prevalent. This could explain obesity but not anorexia.

2. The intrasexual competition hypothesis ^[1,2]. As women age, they tend to gain body mass, signaling the impending closure of their reproductive window. Thus women compete to maintain a youthful slimness to obtain higher social status.

   This is supported by the fact that eating disorders tend to be contagious among friendship groups. Moreover, studies have shown that women consistently think thinner female figures are more attractive than what men prefer ^[3]. It's an example of how any differences between men and women become sexualized and therefore tend to be exaggerated whenever possible.

   Rantala et al.^[1] put it this way: humans evolved to signal their reproductive potential via their physical appearance, but also to eat as much as possible when food is available. When food is abundant, the individual is torn between opposing incentives: food rewards and mating rewards.

3. The reproductive suppression hypothesis This theory speculates that since childbirth is riskier for small women, there might be survival value for them in delaying or even preventing repro­ductive ability. This theory hasn't received as much attention as it deserves. It's consistent with the fact that, while anorexics say they're trying to improve their appearance, they're also delaying the onset of menstruation and impairing their sexual attractiveness, and they often express distaste about becoming an adult.

These hypotheses don't explain why only a fraction of women develop eating disorders, or why their obsession is so strong they often starve to death. Patients exhibit many OCD traits including checking weight and obsessively exercising. Women with OCD have a 16-fold higher rate of anorexia, and stress induces both OCD and AN. These patients may use dieting as a way to alleviate anxiety.

The GWAS studies identified some potential therapeutic targets, such as copy number variations in contactin 4 and contactin 6, which are immunoglobulin cell adhesion molecules involved in neurodevelopment.^[4] Mutations in these proteins are found in AN patients ^[5]. A big GWAS study found eight more risk loci including CADM1 (cell adhesion molecule 1), MGMT (O-6-methylguanine-DNA methyltransferase), FOXP1 (forkhead box P1), and PTBP2 (polypyrimidine tract binding protein 2) ^[6]. It is far too early to say how these genes contribute to AN, what their function may be, or whether they support any of the evolutionary hypotheses listed above.

Limitations of the reductive approach

The unstated assumptions in this reductive approach are: (1) humans don't have access to their biological programming, so they rationalize it, and (2) identifying genes that correlate with a disorder may lead to treatments that work despite our lack of understanding. Scientists recognize that these theories fail to capture the role of personality, ambition, and other intangible factors, but the belief is that if AN is inherited, there must be a gene or set of genes that act as risk factors. We could then create mice with these mutations. If they became anorexic, it would be strong evidence of causality.

The weakness of evolutionary psychology theories is that they are purely explanatory and don't provide us with a pathway to treatment. By contrast, biochemical and genetic analyses cannot determine whether things like elevated stress hormones and immune system dysreg­ulation are causes of AN or the effects of extreme fasting. And neither theory takes the human mind into account.

These aren't limitations of science, but of technology. Today we can identify gene mutations and correlate them with what we observe in the patient. What we need is a way of measuring simultaneously what every cell and every molecule in a living human brain is doing, where it's going, and what it means to the patient. We also need to understand the human mind. Although it sounds like arrogance when we dismiss things we don't understand as irrelevant, it's really just an admission that science is limited by what we can measure.

Another theory invokes the now-fashionable topic of gut microbiota. This may sound implausible, but intestinal bacteria are increasingly believed to play important roles in multiple sclerosis, migraine headache, Parkinson's disease, and many other neurological disorders. There are also reports of so-called auto­immune anorexia nervosa ^[7] following an infection. It may sound crazy, but there's precedent: it's well known that an immune reaction to Lone Star tick bites can produce alpha-gal syndrome, which is a food allergy that causes lifelong aversion to dietary red meat.

What's really happening?

The other unstated assumption is that the only thing that happens in adolescence is hormones. Obviously, this is not true. Adolescence is also when the person's mind starts expanding. For instance, a young person who suddenly realizes that their appearance has to meet certain criteria in order to get love, or who discovers that his childhood friends are all idiots, undergoes as much of a crisis as a biologist who wishes he'd followed his first love of making H-bombs instead of working with those god damn rats all the time. (Not that I know anyone like that.)

In a toxic family environment, an abusive parent could use these theories to avoid culpability and blame ‘bad genes’ inherited from the hated ex-spouse to delegitimize the child's complaints. It's also possible that finding a genetic risk factor or evolutionary explanation will no more cure AN than an antidepressant cures depression; antidepressants only make it harder for the patient to feel the emotion. Medicine is still focused on life-threatening conditions, so the prevailing belief is that if blocking the symptom saves the patient's life it is worthwhile. But we also need to recognize the importance of interpersonal dynamics and the need of the human spirit to find its own way.

This is the dilemma we face. If a patient's symptom is a way of coping with feelings of inadequacy, they're highly motivated to retain it. But as our society grows more authoritarian—taking medicine along with it—it risks crushing the patients' spirit by treating them like bacteria in a petri dish, thereby reinforcing the delusion. These disorders often show up exactly when it's possible for the individual to do something about them. Although it may be much easier said than done, it could be that the best therapy is to help the individual to overcome it by him- or herself.

dec 04 2021, 4:33 am