Hunger, fullness, and the brain

Many of the neurochemical differences in people with anorexia seem to be related to changes in the brain circuitry that moderate hunger and satiety. It's more complex than that, but there's little doubt that this changes are hugely important in anorexia and ANY eating disorder.

Researchers at Duke University recently released a study about the relationship of a brain enzyme to appetite. This particular enzyme helped to make ghrelin, a hormone that signals fullness. When a mutation caused this pathway to be blocked, no ghrelin was produced and the mice at significantly less and, shocker of shockers, they lost weight.

The study was, of course, framed in the context of weight loss. To some extent, this makes sense; after all, weight loss was one of the primary results in the mice. But this is being touted as a new finding to "combat obesity." Indeed, the first sentence of the press release was:

Imagine being able to tone down appetite and promote weight loss, while improving the body's ability to handle blood sugar levels.

But appetite and weight regulation are likely more complex than this. I would ask several major questions should research be done in humans: is maintaining a lower weight than appropriate any better than being at a higher weight that has been determined by your genes? And what happens when you stop taking the pill that blocks the ghrelin pathway? I would think you would gain the weight back, but I'm sure the pharmaceutical industry would just love this fact.

One should also note the links to Duke's well-known weight loss center on the page with the press release.

What struck me, however, was the possible relationship with this gene mutation and anorexia. Abnormalities in levels of ghrelin and leptin (which functions as the opposite of ghrelin and stimulates fullness) have been found in people with anorexia. I've been asked a lot (usually with a tone of wonderment): how can you eat so little for such a long period?

Hell if I know. But maybe my brain does.

Certainly, people with eating disorders still feel hunger and fullness. Yet they might feel hunger less often and fullness faster once the chain of events gets started. Before my eating disorder started, I think I ate pretty normally. I had my quirks--one of my favorite snack was pretzels mixed with mini marshmallows--but I think I felt hunger and fullness just fine, thank you very much. But then the weight loss started. Just a little bit. And all of those abilities went a-flyin' out the window.

Of course, eating disorders are likely far too complicated for one gene or one enzyme. There's almost certainly much more going on than that. But finding these genetic differences may help determine who is at risk, and better ways to treat the illness.

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2 comments:

fighting_forever said...

There are so many problems with the studies done into the brain chemistry (or other physical aspects) of people with eating disorders. The main one is that no one can be sure which causes the other.

Do people become anorexic because their leptin and ghrelin levels are out of ballance? Or do the hormones get messed up because the person's stopped eating?

They can only do studies into people who have or have had disorders. They can't do the studies into people who will develop disorders, so they can't know for sure which way round it is. Which is why it's stupid for these research centres to start declaring they've found a weapon against obesity whenever they find some chemical which is connected to hunger.

On the other hand, this press release is a lot better than some I've read about research into weight loss.

Jane said...

I agree with fighting forever that's is tricky to tease apart which came first. Sensitivities do seem to improve with recovery which offers hope (study 1). Brain scans seem to show differences from controls persists post recovery (study 2). Interesting stuff. I love reading your blog!

J Psychiatr Res. 2008 Apr 16 [Epub ahead of print] Links
Gustatory and olfactory sensitivity in patients with anorexia and bulimia in the course of treatment.

Aschenbrenner K, Scholze N, Joraschky P, Hummel T.
Department for Psychosomatic Medicine, University of Dresden Medical School, Fetscherstra├če 74, 01307 Dresden, Germany; Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstra├če 74, 01307 Dresden, Germany; Affective Sensory Neuroscience Laboratory, The John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
BACKGROUND: The majority of studies on taste and smell in eating disorders have revealed several alterations of olfactory or gustatory functions. Aim of this prospective study was to employ detailed olfactory and gustatory testing in female subjects of three homogenous groups - anorexia nervosa, bulimia nervosa and healthy controls - and to look at the effects of treatment on these measures. METHODS: Sixteen hospitalized female patients with anorexia (restricting type, mean age [M]=24.5 years), 24 female patients with bulimia (purging type, M=24.3 years) as well as 23 healthy controls (M=24.5 years) received olfactory ("Sniffin' Sticks") and gustatory testing ("Taste Strips"). Group differences in olfactory and gustatory sensitivity, body mass index (BMI), the Beck depression inventory, the eating attitudes test (EAT), and the influence of therapy on gustatory and olfactory function were investigated. RESULTS: (1) Group differences were present for odor discrimination and overall olfactory function with anorexic patients having the lowest scores. (2) Regarding taste function, controls scored higher than patients with anorexia. (3) At admission small but significant correlations were found between overall olfactory function and body weight (r(63)=0.35), BMI (r(63)=0.37), and EAT score (r(63)=-0.27). Similarly, (4) the taste test score correlated significantly with body weight (r(63)=0.48), and BMI (r(63)=0.45). Finally, (5) at discharge overall olfactory and gustatory function were significantly higher compared to admission in anorexic patients. CONCLUSIONS: As compared to healthy controls and bulimic patients our results show lowered olfactory and gustatory sensitivities in anorexic patients that improved with increasing BMI and decreasing eating pathology in the course of treatment.

Neuropsychopharmacology. 2008 Feb;33(3):513-23. Epub 2007 May 9. Links
Altered insula response to taste stimuli in individuals recovered from restricting-type anorexia nervosa.

Wagner A, Aizenstein H, Mazurkewicz L, Fudge J, Frank GK, Putnam K, Bailer UF, Fischer L, Kaye WH.
Department of Psychiatry, School of Medicine, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Anorexia nervosa (AN) is an illness characterized by aversion to ingestion of normally palatable foods. We examined whether there is a primary disturbance of taste processing and experience of pleasure using a sucrose/water task in conjunction with functional magnetic resonance imaging (fMRI). To avoid confounding effects of illness, 16 women recovered from restricting-type AN were compared to 16 control women (CW). We used a region of interest-based fMRI approach to test the idea that individuals with AN have differential neural activation in primary and secondary taste cortical regions after sucrose and water administration. Compared to CW, individuals recovered from AN showed a significantly lower neural activation of the insula, including the primary cortical taste region, and ventral and dorsal striatum to both sucrose and water. In addition, insular neural activity correlated with pleasantness ratings for sucrose in CW, but not in AN subjects. Altered taste processing may occur in AN, based on differences in activity in insular-striatal circuits. These data provide the first evidence that individuals with AN process taste stimuli differently than controls, based on differences in neural activation patterns.

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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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nour·ish: (v); to sustain with food or nutriment; supply with what is necessary for life, health, and growth; to cherish, foster, keep alive; to strengthen, build up, or promote



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