anorexia/ocd research crossover

[Guest guest]

Thought the board might be interested in this research (from

Karolinska institute in Sweden, which is pioneering anorexia

treatment with a behavioral as opposed to psychodynamic model)

which has implications for OCD and tourettes as well as anorexia. The

articles suggest that permeability of the blood brain barrier may

allow autoantibodies to do damage, I don't know if the PANDAS theory

has also suggested that mechanism...

The Economist magazine, dated 1-7 October 2005

Science & Technology section

Psychiatric disorders and immunity:

Molecular self-loathing: Anorexia and bulimia may be autoimmune

diseases -- and so may several psychiatric illnesses

Sometimes, the immune system works in mysterious ways. During an

infection one of its roles is to produce antibodies designed to

attack and eliminate the invading bugs. However, in certain unlucky

individuals the body also develops so-called autoantibodies which

attack its own tissue, sometimes with devastating effects. The result

is known as an autoimmune disease, two well-known examples of which

are type-1 diabetes and multiple sclerosis. But there is a widespread

suspicion among researchers in the field that a lot more diseases

than these have an autoimmune component. In particular, they think, a

number of illnesses usually labelled as " psychiatric " are actually,

at bottom, the result of autoimmunity.

Until now, the suspicion has been based on correlations between

certain sorts of infection and certain sets of psychiatric symptoms.

But work just published in the Proceedings of the National Academy of

Sciences by Serguei Fetissov of the Karolinska Institute in Stockholm

and his colleagues has tied the connection more tightly for two

psychiatric eating disorders -- anorexia nervosa and bulimia nervosa.

Dr Fetissov's work suggests that abnormal levels of autoantibodies

against hormones called melanocortins are a crucial part of the cause

of these two diseases. Melanocortins are small protein molecules that

carry messages between nerve cells in the brain. They are involved in

regulating a variety of complex behaviours, including social

interactions, stress responses and -- most importantly in this

context -- food intake. So it is easy to see how interfering with

them could cause anorexia and bulimi.

Shooting the messinger

To test this idea, Dr Fetissov and his colleagues analysed blood

serum from three groups of women (both anorexia and bulimia are more

common in women than in men). One of these groups consisted of people

diagnosed as anorexic. The second was composed of individuals

diagnosed as bulimic. The third contained people with no eating

disorder.

The researchers looked to see whether there was any relationship

between the levels of autoantibodies to melanocortins in these women

and their expression of particular psychological traits -- such

as " Drive for thinness " , " Body dissatisfaction " and " Perfectionism " --

which are associated with eating disorders and which can be measured

using a specially designed scoring system.

What they found was intriguing. There was not one relationship, but

two. The level of autoantibodies to melanocortins was positively

correlated with anorexia, but it was inversely correlated with

bulimia. These opposite correlations make sense. Although both

disorders are associated with depression and self-doubt, anorexia

involves a constant refusal to eat, whereas bulimia is a " diet-binge-

purge disorder " that includes periods of excessive consumption. The

molecular triggers of the two could thus easily be opposites.

The ultimate cause of the altered levels of autoantibody in anorexics

and bulimics is unresolved as yet. However, according to the

researchers, a clue may lie in the fact that micro-organisms, too,

work in mysterious ways. In the world of bacteria and viruses, a

strategy called molecular mimicry is common. In this, pathogens

evolve to produce pieces of protein similar to those of their hosts,

as a way of consufins that host's immune system. But the immune

system is not always fooled, and in making antibodies to

the " camouflage " proteins it sometimes turns out weapons that also

attack the useful proteins that are being mimicked.

Two common gut bacteria, Escherichia coli and Heliobacter pylori, and

also the influenza-A virus, are particularly adept at playing the

evasive game of molecular mimicry, and the team is now looking at

possible connections between different gut bacteria and

autoantibodies against melanocortins to see if they can pin down

which, if any, of these bugs might be responsible.

That is not to say, even if Dr Fetissov's idea is correct, that

autoimmunity is the whole story. Both anorexia and bulimia are known

to go hand in glove with particular personality characteristics which

are not directly related to the disease. In anorexics, striving for

perfection and conscientiousness are common non-pthologicla traits.

In bulimics, such traits include risk-taking behaviour and problems

with impulse control. So there appear to be predisposing factors at

work, as well as the triggering effect of the autoantibodies.

Nevertheless, given the range of behaviours regulated by

melanocortins and other, similar, messenger molecules, the suspicions

that other psychiatric disorders -- in particular, obsessive-

compulsive disorder -- are partly or wholly the product of a similar

process seem entirely plausible. Dr Fetissov's work also adds weight

to the idea that two other neurological diseases, schizophrenia and

Tourette's syndrome, have an autoimmune component. In the case of

these diseases, the damage seems to be casued irreversibly in the

womb, suggesting that any autoantibodies involved are attacking

structural molecules rather than messengers (attacks on structural

molecules are the cause of multiple sclerosis, though tthey involve a

different part of the immune system). That gives little hope for

treatment. But in the case of anorexia, bulimia, and possibly,

obsessive-compulsive disorder Dr Fetissov's work opens a new line of

thinking about how these diseases might be treated.

Autoantibodies Tied to Psychological Traits in Eating Disorders

NEW YORK (Reuters Health) Sept 30 - There are associations between

levels of autoantibodies to alpha-melanocyte-stimulating hormone

(alpha-MSH) and traits such as body dissatisfaction in patients with

anorexia nervosa and bulimia nervosa. Alpha-MSH is involved in both

the stress response and appetite control, Swedish researchers point

out in the September 26th PNAS Early Edition.

Dr. Serguei O. Fetissov of the Karolinska Institutet in Stockholm and

colleagues observe that the findings suggest that dysfunction of the

melanocortin system mediated by these autoantibodies may be involved

in eating disorders.

Dr. Fetissov and his team had previously found alpha-MSH

autoantibodies in anorexia and bulimia patients and in controls. In

the current study, the researchers investigated levels of

autoantibodies to alpha-MSH as well as to oxytocin and vasopressin in

a different group, including 12 patients with anorexia, 42 with

bulimia, and 41 healthy controls.

Some healthy patients showed higher autoantibody levels than patients

with eating disorders, the researchers found, making it clear that

elevated levels of autoantibodies do not cause the disease. However,

Dr. Fetissov and his team write, it is possible that an increase in

blood-brain permeability caused by stressful events could make the

normally harmless autoantibodies pathogenic.

The researchers found significant correlations between levels of

autoantibodies to alpha-MSH and scores on the Eating Disorder

Inventory-2 (EDI-2). Most defining traits of the eating disorders

were linked to levels of autoantibodies to alpha-MSH. " Remarkably, "

say the investigators these correlations were opposite in anorexia

and bulimia patients.

Correlations between levels of autoantibodies to other neuropeptides

and EDI-2 subscale scores also were seen in these patients, but few

such associations were noted in controls.

" Further investigation of this previously undescribed concept in

animal models, " the investigators conclude, could clarify the role of

neuropeptide autoantibodies, with the aim of developing novel

treatments for eating disorders.