What is Anorexia Nervosa?
Today is the first day of National Eating Disorders Awareness Week, and I’ve been wanting to do something special for it. As such, I’ve been compiling research on the six major DSM-identified eating disorders (along with one OSFED disorder), and I plan on releasing one of these each day for this week. This might be a tall order, but I will do my best to keep up with it and deliver the best material I can. I hope you all enjoy; I plan on expanding on each of these and possibly even turning them into their own individual reference books, but we’ll see.
The order to these will predictably follow that of a standard literature review, albeit totally condensed so that it is actually readable and somewhat user-friendly. While you don’t need an extensive background in the sciences to understand what I’ll be saying here and in subsequent posts, it will be a good bit heavier than most of my other blogs.
Now, without further ado, let’s start with our first eating disorder, and my area of academic specialty: Anorexia nervosa.
Definition and Diagnosis
Anorexia nervosa (AN) is probably the eating disorder most of us have heard of before. It is a disorder of extremely low body weight, food restriction, and distorted body image (though we’ll be challenging that last point).
To be diagnosed with Anorexia Nervosa, the DSM 5 (APA, 2013) requires 3 qualifications:
Persistent restriction of energy intake leading to significantly low body weight (in the context of what is minimally expected for age, sex, developmental trajectory, and physical health).
Either an intense fear of gaining weight or of becoming fat, or persistent behaviour that interferes with weight gain (even though significantly low weight).
Disturbance in the way one's body weight or shape is experienced, undue influence of body shape and weight on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight.
Further, anorexia nervosa can be broken down into 2 types:
Purging type: During the last 3 months, individual has engaged in recurrent episodes of purging (and/or bingeing) behaviors.
Restricting type: During the last 3 months, individual has not engaged in recurrent episodes of purging (and/or bingeing) behaviors. This subtype pertains more to the “extreme dieting” or fasting modes of restriction.
However, there is emerging evidence that anorexia does not have to do with body image (or, at least, that this is not a primary etiological factor). The work of Shan Guisinger has led us to what we call the flee from famine hypothesis, which we will return to.
Currently, the severity of anorexia is ranked based on BMI (which is not the comprehensive metric we’d like it to be, but suffices as we use it for correlation purposes):
Mild: ≥17 kg/m2
Moderate: 16-17 kg/m2
Severe: 15-16 kg/m2
Extreme: <15 kg/m2
As early as the Hellenistic era, descriptions of religious fasting intended to strip the dieter of tons of weight were described. This practice would go on to sometimes be called anorexia mirabilis. While diseases that looked like anorexia were being treated as early as the 17th century, it was not until late 19th century that it was first identified.
The term “anorexia nervosa” was coined in 1873 by Sir William Gull. “An” means anti, and “orexis” refers to appetite. In this vein, “anorexic” is not only used to refer to the diseases AN, AA, and AM; it is also the scientifically accepted term for any agent that reduces hunger (anorexigenic), as well as any state that involves drastically reduced hunger (i.e. lab rats in a medically induced anorexic state).
In 1978, German psychoanalyst Hilde Bruch published The Golden Cage: The Enigma of Anorexia Nervosa (Bruch, 1978), which was what put anorexia on the map as a mainstream, widely recognized mental illness. It was chiefly Bruch’s theories, posited in that piece, that would shape our understanding of the illness. Unfortunately, a lot of the hypothesis and theories that came out of this are now outdated but not entirely rejected by the medical community.
Between 0.9% and 2% of females, and between 0.1% and 0.3% of males, will develop anorexia nervosa at some point (Stice & Bohon, 2012). Anorexia increases all-cause mortality by as much as tenfold (Smink, van Hoeken & Hoek, 2012).
Etiology and Pathophysiology
Predisposing elements to anorexia include (Gorwood et al., 2016).
Presence of psychiatric family history of eating disorders (Strober et al., 2000)
Presence of personal anxious, depressive, or bipolar disorder (Bould et al., 2015)
Personality traits like perfectionism and rigidity (Treasure, Claudino & Zucker, 2010)
Disturbed family interactions early in life (Jaite et al., 2012)
Family interactions connected w/eating habits (Haycraft, Goodwin & Meyer, 2014; Loth et al., 2014)
Being female (Connan et al., 2003)
Early exposure to stress (i.e. intra-uterine stress and premature birth) (Connan et al., 2003; Treasure, Claudino & Zucker, 2010)
Disrupted personal development (Toyokawa et al., 2012)
Ideal of slimness in society (Garner, 1993)
The rewarding sensation of thinness has been correlated with abnormally high levels of peptides like Agouti-related peptide (AgRP), Neuropeptide Y (NPY), and ghrelin (Tortorella, 2014). On the flip side of this, the abnormal satiety cues in anorexia have been correlated with abnormally low levels of brain-derived neurotrophic factor (BDNF), oxytocin, thyrotropin-releasing hormone (TRH), vasopressin (VP), leptin, and Peptide YY (PYY).
The reward value seen here seems to be inappropriately received, possibly even routing to an anxious (rather than happy) response, as evidenced by studies that gave dopamine-inducing amphetamines to those with AN, which generated an unusually but reliably anxious response (Bailer et al., 2012).
Anorexics may also have a preference for delayed reward (Decker, Figner & Steinglass, 2015). This alteration in reward circuitry is due to a reinforcing effect of starvation, due to:
An increased hedonic feeling of underweight
A decreased positive feeling of normal body weight
One final important feedback alteration to take note of is the dysregulation between input (food intake) and output (exercise) (Gorwood et al., 2016). In line with this, there is evidence for the common trait of hypercortisolemia in anorexics to be a culprit behind their unusual ability and willingness to engage in exhausting physical exercise despite an inappropriately low amount of available substrate in the body (Klein et al., 2007).
The gut microbiome also plays an important role in the pathophysiology of AN. Deviation of microbiota (Guidoum, 2013), as well as increase in M. smithii (directly involved in energy efficiency, via increasing the conversion rate of nutrients yielding calories [aka they can eat less and derive more calories]) have been observed in AN subjects (Armougom, 2009).
One final point worth mentioning is the mothering vs. migrating hypothesis alluded to earlier, more formally known as the flee from famine hypothesis. Shan Guisinger led some of the landmark research here, and her site explains a lot of it. To summarize, the theory here has to do with our evolutionary migration patterns. Tens of thousands of years ago, nomadic humans would have stuck together in small tribes of 20-40. Within these tribes, there would need to be at least one member who - upon the stimulus of food scarcity, brought on by going through territories where no food could be found - could actually develop food aversion and strength/energy in spite of food. This trait would go on to manifest in modern day anorexia nervosa.
Guisinger argues that the overemphasis of therapeutic approaches, as well as the misguided notions of a “mothering” etiology of anorexia (that the disease is caused by overly controlling mothers), are in large part the barriers to improving anorexia remission rates. As the deadliest psychiatric disorder we know of, she posits that moving towards a more biology-based etiology, presumably leading us to focusing more on proper refeeding strategies and less on CBT/DBT lessons, would yield more desirable prognoses.
Below is a pictorial overview of the pathophysiology of AN.
A global model of AN (Gorwood et al., 2016):
Selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Cymbalta, are notoriously ineffective in the treatment of AN (Attia et al., 1998; Walsh et al., 2006). And while standard therapy models like cognitive-behavioral therapy (CBT) and behavioral therapy (BT) are generally effective for broadly treating mood disorders (Burns, 1999), they are not effective for promising remission of AN symptoms (McIntosh et al., 2005). Family therapy too, though not a completely useless model, seems to be ineffective as a first line treatment of AN symptoms (Geist et al., 2000).
One important factor in predicting remission of symptoms is feeling empowered (Aardoom et al., 2014; Gabay, 2016). In contrast to this, when patients experience their stays in treatment as akin to imprisonment, rates of remission predictably went down (Wright, 2010; Ramjan & Gill, 2012).
So then, if standard therapeutic models, family therapy, and pharmacological treatments are not promising, what is the answer? Well, proper refeeding seems to be at the top of this list. I did a talk on this with Danny Lennon on the Sigma Nutrition Radio podcast, which you can find here. Check that out for more in-depth discussion into the factors that go into refeeding syndrome, how much of a risk refeeding syndrome actually is, different clinical approaches to refeeding, and my own hypothesis about the understated efficacy of “high-fat rapid refeeds,” which I thoroughly believe could be the answer to treating late-stage anorexia nervosa.
Unfortunately, refeeding requirements can vary greatly and can be hard to accurately estimate. This is the case for three primary reasons: REE overshooting, NEAT feedback, and gut microbiome alterations.
Resting energy expenditure (REE) starts low at beginning of refeeding and then “overshoots” baseline amounts over time, which can of course distort how well we can predict caloric requirements for recovering patients (Dempsey et al., 1984).
Just as obese individuals have shown to decrease non-exercise activity thermogenesis (NEAT) - which involves involuntary movements like posture adjustments, shivering, leg-shaking, etc. - in response to weight loss regimens, anorexic individuals have shown to increase NEAT in response to weight gain regimens (Belak et al., 2017). This means even with proper food intake during the restoration period, NEAT can increase and change the individual’s total daily energy expenditure (TDEE), so that even more food is then needed. Whether dietary thermogenesis - the caloric expenditure involved in mechanical digestion, metabolism, absorption, and excretion of food - increases as well as a physiologically tricky means of constantly upping energy requirements has so far only been hypothesized but never proven.
Chronic restriction can have adverse effects on the gut microbiome, leading to inefficient conversion of nutrients into calories over time.* This could partly explain why standard TDEE equations are usually under what anorexic patients actually need to weight restore (Fetissov, 2017).
*This would still allow the earlier hypothesis of anorexics having an enhanced ability to convert nutrients to calories to be true, as this speaks to the effects of starvation, not the initial hallmark traits of the disease
As stated earlier, AN has the highest mortality rate of all psychiatric illnesses (Harris & Barraclough, 1998). We see extremely high rates of relapse here, even after long-term treatment (Zipfel et al., 2000). As many as 30-50% of anorexics in inpatient care require readmission within 12 months (Mayer, 2001). One major issue is how commonly patients enter treatment with a total lack of motivation (Halmi et al., 2005).
We can classify…
Partial remission as: Healthy body weight has been restored, but either fear of gaining weight and behaviors that inhibit proper weight gain or disturbances in self-perception of weight and shape are still persistent issues.
Full remission as: All criteria of anorexia have been improved to baseline.
For more resources, check out...
NEDA - The largest national eating disorder advocacy forum, which regularly hosts outreach events, funds important research, and directly helps those affected via their helpline.
ANAD (National Association of Anorexia and Related Disorders) - Non-profit corporation that advocates for and seeks to spread awareness of eating disorders, especially anorexia nervosa and bulimia nervosa.
AED (Academy for Eating Disorders) - Organization that specializes in ensuring the professional standards of eating disorder research, treatment, and information.
NEDA’s Helpline number is: 1-800-931-2237
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