[Paleopsych] Economist: Psychiatric disorders and immunity: Molecular self-loathing

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Psychiatric disorders and immunity: Molecular self-loathing

    Sep 29th 2005

    Anorexia and bulimia may be autoimmune diseases--and so may several
    other 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, that 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 bulimia.

    Shooting the messenger

    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

    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

    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 confusing 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 Helicobacter 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-pathological 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 caused 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 they 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.

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