Wired for Hunger

A post on the DANA Foundation blog, titled "Wired for Hunger," looks at obesity, how the body regulates hunger and satiety, and what happens when these systems malfunction. But that's not the real interesting part. The interesting part was the sidebar on anorexia. It was both interesting and scientifically astute, with some testable hypotheses and potential interventions for anorexia. I'm copying it in its entirety here because I really think its worth reading.

Anorexia Nervosa: A Mortal Clash between Reward and Hunger

Few disorders reveal the power of the brain’s cognitive circuitry more clearly than anorexia nervosa, a psychiatric disorder characterized by extreme undereating, loss of body weight, hyperactivity and hypothermia. Compared with other psychiatric conditions, this disorder has the highest mortality rate. We theorize that, in cases of anorexia nervosa, the brain’s ancient evolutionary wiring for adapting happily to low food availability is inappropriately activated and finds itself in a life-threatening battle with other brain signals demanding action to obtain nourishment.

One clue to the intensity of this clash is the elevated level of physical activity in patients with anorexia nervosa, a symptom that people have reported for more than 100 years. Several studies have established a relationship between obsessive-compulsive characteristics and exercise frequency in women with strenuous daily exercise routines and in hospitalized female patients with anorexia nervosa.16 In the patient group, preoccupation with weight was associated with both the frequency of exercise and pathological attitudes toward it. Addictive and obsessive-compulsive personalities contributed to excessive exercise because of their obligatory, pathological thoughts promoting it. Among anorexia nervosa patients, those who exercise excessively have more bulimic symptoms, higher levels of general psychopathology about eating and a greater degree of body dissatisfaction, anxiety, somatization (physical symptoms with a psychological origin), depression and irritability.

Scientists view the tendencies toward mental alertness and continued normal-to-high activity levels (despite insufficient nutrition and weight loss) as being relatively unique to anorexia nervosa patients, versus individuals who experience semi-starvation due to causes such as illness, chemotherapy or famine. For both of these tendencies, the most plausible explanation is activation of evolutionarily old circuitry leading to reward upon reduced energy intake.

A final clue is another characteristic of anorexia nervosa patients: 90 percent are women, mainly in their late teens. This leads us to propose that a cellular mechanism, in association with the changing hormonal milieu that is characteristic of anorexia nervosa patients, unifies and orchestrates activation of key brain circuits, which in turn leads to the behavioral and endocrine manifestation of anorexia nervosa. Our hypothesis is that anorexia nervosa occurs following shifts in the circulating hormones ghrelin, leptin and estradiol, which alter key groups of neurons. These alterations bring about sex-specific structural and functional changes in particular circuits of the midbrain that transmit the chemical dopamine to communicate. Dopamine then triggers a reward response in the prefrontal cortex and hypothalamus to undereating and overexercise.

We further hypothesize that rolling back this shift in reward response could reverse anorexia nervosa, and that either eliminating ghrelin signaling or suppressing the number of available long-chain free fatty acids in the brain could accomplish this. Neuronal cells normally activated by ghrelin use these acids for energy; thus, eliminating the fatty acids would silence the ghrelin-activated neuronal population. Patients who received controlled leptin and estrogen replacement therapy also might see their anorexic symptoms diminish. Moreover, we predict that if doctors help at-risk patients maintain estradiol and/or leptin levels during the initial phase of disease, the patients will be less likely to undergo the shift in reward responses that leads to anorexia nervosa.


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Cathy (UK) said...

An interesting set of hypotheses... So, in summary, the hypotheses are as follows:

1. Energy deprivation/starvation reduces the circulating levels of oestradiol and leptin, while increasing circulating ghrelin levels. In certain, susceptible people (to anorexia nervosa = AN)these endocrine changes activate reward centres in the brain which makes starvation rewarding and 'addictive'.

2. Whereas energy deprivation normally reduces the urge to be physically active, people susceptible to AN respond unusually to starvation by increasing their physical activity (and have a tremendous urge to be active). In turn, this increase in activity exacerbates the endocrine responses to starvation (i.e. further reduces leptin and oestradiol levels and the knock-on effects of these changes).

3. On the basis of 1 and 2 above, prevention of the circulating declines in oestradiol and leptin, in conjunction with prevention of the rise in circulating ghrelin consentration (or blocking ghrelin activity in the brain) will prevent or dampen the reward response to starvation and exercise - and so prevent/reverse AN.

So here are my thoughts:

There have been many studies of the effects of oestradiol administration to patients with AN which have been undertaken with the objective of investigating changes in bone turnover and bone density. None of these studies have reported a reversal of anorexic symptomology. (It is also known that oestradiol administration is largely inefficacious in the prevention or reversal of bone loss in AN).

Studies have shown that leptin administration to active, underweight women with hypothalamic amenorrhoea (i.e. no periods due to energy deprivation) can reverse hypothalamic adaptations to starvation. The problem however, is that the exogenous leptin further reduces appetite.

The idea of blocking central ghrelin action is interesting and I need to do a literature search to determine if there are any studies in this field.

I don't wish to write a complete essay here..., but I do see a number of practical and ethical issues relating to the testing of the aforementioned hypotheses.

And, in actuality, all of these biochemical and neurophysiological changes could be prevented by early intervention through re-feeding, which is more ethical and practical than treatment with exogenous hormone analogues...

Abby said...

I can't take the scholarly, scientific angle that Cathy can, but I just have to add that in some twisted way, this makes me feel "justified" in my thoughts and (maladaptive) behaviors.

My OCD is a driving force, and I often don't even understand myself how I can be such a hyper freak when I am truly probably so depleted. Others see it as "motivation" or willpower to exercise, when really it's just such an addictive need to do it--driven more out of desperation.

Although I knew a majority of the info here, it does slightly help to know there is an actual biological factor lurking behind the disorder, if that makes any sense. It doesn't justify it, but it almost gives me something to hold up as "proof" that I'm not nuts.

If I were open to people about my disorder, I would forward this post on to everyone to read.

balancingontwofeet said...

A fantastic find. Seeing articles such as this help me to physiologically understand what I have gone through with anorexia. It confirms again that this is really a physical illness with psychological symptoms.

I am however wary of the thought that artificial leptin and estrogen could work to halt the disease. It was long though that the estrogen from birth control pills would work as well as natural estrogen in order to halt bone deterioration, but it has been more recently found that this is not the case. I would suspect the same might be true for what these researchers would like to do with the hormones. IN the end there is no replacement for what our bodies naturally produce.

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I'm a science writer, a jewelry design artist, a bookworm, a complete geek, and mom to a wonderful kitty. I am also recovering from a decade-plus battle with anorexia nervosa. I believe that complete recovery is possible, and that the first step along that path is full nutrition.

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