A paper published in this week's Nature establishes that genes play a key role in autism (DOI: 10.1038/nature07999). But according to a new theory, the genes involved may explain much more. Indeed, genetics may explain the apparent environmental and social causes of both autism spectrum disorders (ASDs) along with psychotic spectrum disorders (PSDs) such as schizophrenia.*

According to the new theory, both ASD and PSD have a genetic origin in recently-discovered genetic phenomena such as imprinting. This describes the fact that some key genes are normally only expressed from one parent, rather than from both as is the norm. The theory proposes that a bias in favour of the expression of the father's and/or reduction in the expression of the mother's genes may predispose to ASD, with PSD being the other way round. Indeed, any kind of genetic glitch that affects expression in this way can have the same effect. For example, children who inherit both copies of chromosome 15 from the mother are invariably diagnosed with PSD in adult life.

The classic example of an imprinted gene is IGF2, which codes for a growth hormone. Its effect is to make a baby bigger--something that benefits the father's genes invested in it but is at a cost to the mother, who has to gestate and give birth to it. So perhaps not surprisingly, the mother's copy of IGF2 is normally imprinted, or silenced, and only the father's is expressed. IGF2 is up-regulated in ASD, and in Beckwith-Wiedemann syndrome (an over-growth disorder where both parents' IGF2 is expressed) incidence of ASD is seven times normal.

To the extent that rising living standards increase birth-weights and nutrition in childhood, they might be seen as environmental factors that mimic paternally-active growth-enhancing genes like IGF2. Furthermore, there is some evidence that maternal food-intake may affect the expression of such genes in the foetus. This in itself might explain quite a lot of the so-called "autism epidemic" of recent years. Growth-enhancement thanks to higher standards of living in developed countries could be predicted to predispose towards milder forms of ASD such as Asperger's syndrome. Indeed, birth-weights of new-born babies in Vienna rose an unprecedented amount during the 1920s, and perhaps this partly explains why Asperger was to discover the syndrome named after him during the next couple of decades. Again, critics of Kanner's original description of autism have pointed out that he portrayed it as an upper class disorder but that later research--particularly in Sweden--contradicted this and found no clear link to social class. However, it might simply be that during the 1940s the heavier-birth weight effect was mainly seen among upper class people in the USA, but that by the 1980s it had spread to just about everyone in welfare-state Sweden--and today to most people in modern Western societies, where obesity, rather than under-nourishment, has become the primary health problem related to food intake.

If this explanation is correct, it would be a case of nurture via nature rather than the conventional way of putting it: nature via nurture. Indeed, the new theory might also explain the parallel decline in PSD that has been reported. Studies of the Dutch wartime famine and of the Chinese famine of 1959-61 reported increased incidence of schizophrenia among children born just after the events. And a study of 2 million Swedish children born between 1963 and 1983 revealed a significant link between schizophrenia and poverty in childhood. According to the new theory, this is the contrary situation to the autism epidemic: maternal and childhood deprivation mimicking (and perhaps interacting with) maternally-active resource-limiting genes, explaining the link between PSD and poverty-but also the fall in PSD associated with rising standards of living.

Genes, in other words, may have more of a key role in all aspects of mental illness than previously suspected--not least in autism. The finding reported in Nature is likely to be just the tip of this genetic iceberg!

 *Chistopher Badcock is the author of The Imprinted Brain.

 

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