Edge 266—November 20, 2008
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According to the so-called imprinted brain theory, the paradoxes can be explained in terms of the expression of genes, and not simply their inheritance. Imprinted genes are those which are only expressed when they are inherited from one parent rather than the other. The classic example is IGF2, a growth factor gene only normally expressed when inherited from the father, but silent when inherited from the mother. According to the most widely-accepted theory, genes like IGF2 are silenced by mammalian mothers because only the mother has to pay the costs associated with gestating and giving birth to a large offspring. The father, on the other hand, gets all the benefit of larger offspring, but pays none of the costs. Therefore his copy is activated. The symbolism of a tug-of-war represents the mother's genetic self-interest in countering the growth-enhancing demands of the father's genes expressed in the foetus—the mother, after all, has to gestate and give birth to the baby at enormous cost to herself.
THE IMPRINTED BRAIN THEORY
According to a recent New York Times Science Times article ("In a Novel Theory of Mental Disorders, Parents’ Genes Are in Competition" by Benedict Carey, November 10, 2008) Christopher Badcock and Bernard Crespi have presented a new theory that purports to resolve some long-standing contradictions in explaining mental illness.
Edge wrote to Badcock, an early member of the Edge community, to ask him for a summary of his new theory for our readers.
"At first sight," he wrote back in an email, "it would seem that no single theory could explain these seemingly contradictory facts—and certainly not an evolutionary or genetic one—but an attempt is underway to do exactly that which has just passed its first major test. In 2006 Bernard Crespi (Killam Research Professor in the Department of Biosciences, Simon Fraser University) and I published a paper in The Journal of Evolutionary Biology setting out the theory in relation to autism. Earlier this year Behavioral and Brain Sciences published a second paper along with 23 expert commentaries and the authors' replies which extends the idea to psychoses like schizophrenia. More recently still, Nature has published our essay on the theory ("Battle of Sexes May Set The Brain", 28 August 2008)."
CHRISTOPHER BADCOCK is a Reader in Sociology at the London School of Economics and the author of PsychoDarwinism and Evolutionary Psychology: A Clinical Introduction.
THE IMPRINTED BRAIN THEORY
What causes mental illnesses like schizophrenia and autism? We have long known that both tend to run in families and that if one of two identical twins has such a disorder, there is a much higher than average probability that the other will too. Autism is sometimes associated with genetic syndromes, such as Rett, Down, and Turner's, Phenylketonuria, and Tuberous Sclerosis. The clearest single-gene cause of autism spectrum disorder (ASD) is Fragile X syndrome, with a wide range of severity in symptoms and 25-47 per cent of affected males meeting the criteria for autism. But neither autism nor schizophrenia obeys classical Mendelian laws of inheritance in the way that Cystic Fibrosis or some types of colour blindness do.
However, there is also good evidence for social, environmental causes of mental illnesses. 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. Those with 4 out of 5 measured indicators of hardship had an almost 3-fold greater risk of schizophrenia than those with none. Where ASD is concerned, the exponential increase in diagnoses since the 1980s has prompted some to suggest environmental or social causes: most controversially, childhood vaccines like MMR. Autism can certainly result from ethanol or valproic acid poisoning during the mother's pregnancy, and in the 1964 rubella epidemic in the USA, the rate of incidence of autism exceeded 7 per cent at a time when the normal rate of diagnosis was not much more than a tenth of one per cent. ASD can also be caused by thalidomide, where it affects about 5 per cent of those with birth defects attributable to this cause.
The figure illustrates the idea. According to the so-called imprinted brain theory, the paradoxes can be explained in terms of the expression of genes, and not simply their inheritance. Imprinted genes are those which are only expressed when they are inherited from one parent rather than the other. The classic example is IGF2, a growth factor gene only normally expressed when inherited from the father, but silent when inherited from the mother. According to the most widely-accepted theory, genes like IGF2 are silenced by mammalian mothers because only the mother has to pay the costs associated with gestating and giving birth to a large offspring. The father, on the other hand, gets all the benefit of larger offspring, but pays none of the costs. Therefore his copy is activated. The symbolism of a tug-of-war represents the mother's genetic self-interest in countering the growth-enhancing demands of the father's genes expressed in the foetus—the mother, after all, has to gestate and give birth to the baby at enormous cost to herself.
Mental disorders can be located along a dimension of mentalism (aka 'theory-ofmind,' 'folk-psychology' or 'people skills') defined as our evolved ability to comprehend others' actions and behaviour in purely mental terms (such as intention, belief, desire, emotion etc.). Autistics, notoriously, are poor where mentalistic skills like inferring intention or understanding false belief are concerned. ASDs therefore belong on the hypo-mentalistic side of the continuum. However, what we would now term psychotic spectrum disorders (PSDs) can be typified as hyper-mentalistic: paranoid schizophrenics, for example, symptomatically over-interpret intention either positively in erotomania (delusions that others are in love with you) or negatively in delusions of persecution. They also entertain bizarre false beliefs about themselves and others, and generally exhibit excessive mentalism, often enshrined in quasi-religious or mystical delusions. Indeed, the symptoms and signs of autism and psychoses like paranoid schizophrenia exhibit a remarkable pattern of antithesis:
The concepts of hypo- and hyper-mentalism readily explain the last item: age of onset. Typically, this is early childhood for autism but late adolescence or adulthood for schizophrenia: a difference which up until now has lacked an obvious explanation. But the fact that you have to develop normal mentalistic skills before you can over-develop them to the point of psychosis readily explains why the mentalistic deficits of autism are apparent in childhood and why the hyper-mentalism of psychosis can only become fully apparent much later. Mentalism appears to be the key to social behaviour because autistics are notably non-social in the sense that they typically lack social skills and have impoverished social lives with few if any friends, little interest in group activities, and muted emotional responses such as empathy and interest in others. Consequently their behaviour often seems callous, childish, or self-centred. However, mammals as a whole show a notable sex-difference in social behaviour to which human beings are no exception. In general, females have been found to be more sociable, co-operative, and nurturing than males — particularly among primates. This may explain why the mother's genes appear to promote mentalism in human beings and why the father's seem to motivate more self-interested behaviour. From an evolutionary point of view, every one of a mother's offspring carries an equal complement of her genes (half of them). But uncertainty of paternity—the bane of mammals thanks to internal, unseen fertilization—means that the genes of a father have no necessary reason to find themselves in any of a woman's other children: Mother's baby. Father's? Maybe! The result is that, from an evolutionary and genetic point of view, paternallyactive genes do not have the same self-interest in family cohesion and social cooperation that the mother's characteristically do. Why should the father's encourage his offspring to co-operate with those of the mother's other mates?
Nevertheless, paternal genes do have a more positive cognitive bias of their own: what you might call mechanistic cognition. This is the mode of cognition that we have evolved to interact with the physical, non-human, natural environment, and stands in contrast to mentalistic cognition, which evolved to facilitate social contact and cognition in relation to other people. Significantly, autistics often show compensations for their mentalistic deficits in mechanistic cognitive skills, one of the most common being calendar calculation (such as knowing the date of Easter in any year you care to name), rote memorization, and maths skills. Indeed, the attraction of like-minded people with mechanistic cognitive configurations is probably part of the explanation for the remarkably high incidence of ASD in Silicon Valley, California, and in the Cambridge area in the UK—both places with high levels of employment in maths-, computer- and science-based industries.
If we have evolved two parallel cognitive systems rather than just one, they appear to vary in the same way that vulnerability to ASD or PSD does: more paternal influence predisposes to mentalistic deficits, but mechanistic compensations; and more maternal influence is the converse. A counter-intuitive prediction of this model corroborated by some recent clinical findings is that hyper-mentalism should go with mechanistic deficits in exactly the same way that autistic hypo-mentalism goes with mentalistic deficits. Indeed, this model also suggests that if there are autistic savants with outstanding skills in mechanistic aspects of cognition, there ought also to be psychotic ones with the opposite, mentalistic ones. However, the very same excellence in mentalism would make such psychotic savants much less noticeable than their autistic counterparts, whose deficits immediately identify them as odd, socially-isolated, and eccentric. Psychotic savants, by contrast, can be expected to be deeply embedded in successful social networks, and found at the centre of excellence in such things as religious and ideological evangelism; literary and theatrical culture; litigation and the law; hypnosis, faith-healing, and psychotherapy; fashion and advertising; politics, public-relations and the media; commerce, confidence-trickery, and fraud of all kinds. The following table gives some idea of the inverted symmetry to be found between mentalistic and mechanistic cognition:
According to this way of looking at things, development can be pushed to either extreme by any factors that affect gene expression either before or after birth. Valproic acid is known to do this, as is thalidomide and other environmental causes of autism. Where purely genetic factors are concerned, the theory proposes that increased expression of paternal genes like IGF2 will predispose to autism—and expression of that gene is now known to be enhanced in individuals with ASD. This will result in the features listed in the figure: higher birth weight, an increased vulnerability to cancer (which is another expression of over-growth), and a larger brain in childhood with more white matter. Furthermore, increased nutrition would mimic the effect of genes like IGF2 and predispose to growth, perhaps explaining part of the recent exponential increase in milder ASDs such as Asperger's syndrome. Indeed, the fact that birth-weights of new-born babies in Vienna rose an unprecedented amount during the 1920s perhaps partly explains why Asperger was to discover the autistic syndrome named after him during the next couple of decades. And because all fathers are male the new theory can also be reconciled with the extreme male brain theory of autism, which persuasively argues that ASDs can often be linked to increased testosterone exposure in utero and to the more lateralized brain characteristic of males.
Significantly then, PSD—and schizophrenia in particular—are associated with the features listed on the other side of the diagram: low birth weight, a reduced vulnerability to cancer (despite schizophrenics smoking much more!), and smaller adult brains with less white matter. Correspondingly, just as increased nutrition in pregnancy and/or early life might mimic paternally-active genes like IGF2 to predispose to ASD, the contrary conditions—starvation during pregnancy and/or early life—could be predicted to increase the risk of PSD, as we saw they indeed do, at least in the case of schizophrenia. And because all mothers are female, enhanced expression of maternal genes also goes with reduced foetal testosterone and the less lateralized brain typical of women. Indeed, the fact that mammalian females have two X sex chromosomes (XX) by contrast to the male's one (XY) means that X chromosome gene expression is also implicated. In cases where an extra X chromosome is present: X trisomy (XXX) and Klinefelter syndrome (XXY), the presence of the additional X results in brain features similar to those found in schizophrenia, along with a notably increased vulnerability to psychosis, just as the theory would predict.
Another controversial and counter-intuitive prediction of the theory for which there is already much evidence is that, if ASD has increased in modern societies with higher standards of living as it so spectacularly has done, then PSD should be falling. Interestingly in this respect, rates of admission for PSDs like schizophrenia have decreased by between 10 and 57 per cent in England and Wales, Scotland, Denmark, Australia, and New Zealand. Indeed, even Bleuler, who coined the term schizophrenia, noticed a secular decline in his own lifetime, and a recent Canadian study showed a 42 per cent decrease in the number of first-admission schizophrenia cases over 20 years. It found that annual inpatient prevalence rates decreased by 52 per cent between1986 and 1996, with no corresponding change in outpatient rates, regardless of sex. Although total major affective disorders increased, this was due to an increase in major depression, not bipolar disorder, which is now thought to be much more closely allied to schizophrenia than was once believed.
Surprisingly as it may seem, the new theory can even encompass the finding that infectious agents can sometimes be implicated in causing schizophrenia. People infected with the protozoan parasite Toxoplasma gondii are three times more likely to suffer from schizophrenia than those not infected, and so too are catowners. The significance of the latter may lie in the fact that the parasite can only complete the reproductive phase of its life-cycle inside a cat. It achieves this by causing its principal carriers, rats and mice, to lose their fear of cats, and so be much more likely to be eaten by one. Inside the rodent's brain, the parasite attacks the amygdalas, which play the same role in triggering fear-reactions that it does in humans. But when infected rats are treated with anti-psychotic drugs like those given to human schizophrenics the rats' fear of felines returns. Men with Toxoplasma infection tend to be more reckless than normal, and infected people of both sexes are almost three times more likely to be involved in car accidents, and have measurably slowed reaction times. In mice, only paternal genes are expressed in the amygdalas and there is good evidence suggesting that the same is true in humans. This finding suggests the intriguing possibility that an explanation may lie in the parasite suppressing paternally-controlled brain systems like the amygdala to produce an overall preponderance of maternal brain function, which according to the new theory is the fundamental basis of psychosis in general and of schizophrenia in particular. T. gondii, in other words, could be another of those environmental effects portrayed in black in the figure, but one pushing development pathologically towards the psychotic end of the spectrum by sabotaging brain systems built by paternal genes.
Finally, what of normal development? The implication is clear: so-called normality represents a more-or-less balanced expression of genes and environmental developmental influences. However, the fact that all fathers are male and all mothers are female implies that the norms for the sexes are likely to be slightly offset. This would fit with the finding that ASD afflicts more males than females and that men typically do worse on tests of mentalistic competence than do women. Women, on the other hand, would be symmetrically offset to the more mentalistic side of the spectrum, and this might explain why rates of incidence of schizophrenia among family members of women with the disorder are higher than those among family members of men with schizophrenia. And although there is a slightly higher incidence of schizophrenia overall in men, erotomania appears to be a predominantly female pathology, with women suffering more paranoid delusions and hallucinations than men, particularly in late-onset cases.
The model appears to rule out anyone suffering from an ASD and a PSD simultaneously, and such co-morbidity does appear to be rare—but is not unknown. However, I know of cases of individuals diagnosed with bipolar disorder who also show unmistakable signs of ASD during their non-manic phases. Indeed, I have research on one individual who suffers from severe gaze-aversion, autistic deficits in a sense of self and social anxiety most of the time, but who becomes comfortable with other people during manic episodes when his sense of self hypertrophies into megalomania with the feeling that he is the returned Jesus Christ! Furthermore, there is evidence of both ASD and PSD in Newton and Beethoven, and incontrovertibly so in the Nobel-prize winning mathematician John Nash. Here the theory predicts that the ASD must come first (typically in childhood) and leave a permanent savant-like basis later built on by hyper-mentalistic tendencies to produce an unusually broadened and dynamically-balanced cognitive configuration: that of true genius.
Such a far-reaching theory as this can be expected to be controversial, and much
remains to be done to work out its detailed implications. But the theory does have
one outstanding merit: it makes clear and profoundly counter-intuitive predictions
about which genes are involved, about how they should be expressed, and about
what effects they should be found to have in the brain and on behaviour. Twenty-three
experts are only the start: Nature's comment will be decisive and, thanks to
rapid progress in genomics and neuroscience, should not be long in coming.
Arnold Trehub on Alva Noë's "The Problem With Consciousness"
What Alva Noe and others with similar views about consciousness seemingly fail to understand is that the very world with which we are dynamically interacting is both a real and a phenomenal world. It is the real world in which our actions must be adaptive and creative, but—and this is the key point—our consciously initiated actions can only be governed by the features of our phenomenal world. It is the phenomenal world that poses the essential problem of conscious experience.
Here's why. The world that you (or I) consciously experience (the phenomenal world) is, in its irreducible form, a global coherent volumetric space in which you are the egocentric origin of all experience and action. The rich and constantly changing content of your phenomenal world cannot exist outside of your phenomenal 3D space that encompasses it. Whatever your conscious experience, it must be an experience of something somewhere in your egocentric phenomenal world. The problem is that humans have no sensory transducers by which to detect and represent the extended coherent 3D space of the world we live in. This means that the brain must have an innate system of biological mechanisms (most likely neuronal) that provide us with a transparent representation of the world from our privileged egocentric perspective. The existence of this conscious egocentric representation of our personal world is a necessary precondition for the kind of active engagement with the world that Alva Noe describes so well.
A final comment. When Noe claims that "… at the present time, we actually can't give any satisfactory explanations about the nature of human experience in terms of the functioning of the brain", it appears that he is unaware of a wealth of recently published findings relating brain events to objective measures of phenomenal experience. My own work argues strongly against Noe's pessimism regarding brain function and human experience.
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November 20, 2008
Essays and Opinion
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November 11, 2008
In a Novel Theory of Mental Disorders, Parents’ Genes Are in Competition
Two scientists, drawing on their own powers of observation and a creative reading of recent genetic findings, have published a sweeping theory of brain development that would change the way mental disorders like autism and schizophrenia are understood.
The theory emerged in part from thinking about events other than mutations that can change gene behavior. And it suggests entirely new avenues of research, which, even if they prove the theory to be flawed, are likely to provide new insights into the biology of mental disease.
At a time when the search for the genetic glitches behind brain disorders has become mired in uncertain and complex findings, the new idea provides psychiatry with perhaps its grandest working theory since Freud, and one that is grounded in work at the forefront of science. The two researchers — Bernard Crespi, a biologist at Simon Fraser University in Canada, and Christopher Badcock, a sociologist at the London School of Economics, who are both outsiders to the field of behavior genetics — have spelled out their theory in a series of recent journal articles. ...
August 28, 2008
A tug-of-war between the mother's and father's genes in the developing brain could explain a spectrum of mental disorders from autism to schizophrenia, suggest Christopher Badcock and Bernard Crespi.
It has long been recognized that mental illnesses such as schizophrenia and autism tend to run in families. But neither disorder obeys classical Mendelian laws of inheritance, making it difficult to pinpoint the genes involved.
We believe that psychiatric illness may be less to do with the genes a mother and father pass down, and more to do with which genes they program for expression. By our hypothesis, a hidden battle of the sexes — where a mother's egg and a father's sperm engage in an evolutionary struggle to turn gene expression up or down — could play a crucial part in determining the balance or imbalance of an offspring's brain. If this proves true, it would greatly clarify the diagnosis of mental disorders. It might even make it possible to reset the mind's balance with targeted drugs. ...
November 19, 2008
ENCELADUS: SECRETS OF SATURN'S STRANGEST MOON
Wrinkled landscapes and spouting jets on Saturn's sixth-largest moon hint at underground waters
By Carolyn Porco
On the Saturnian moon Enceladus, jets of powdery snow and water vapor, laden with organic compounds, vent from the “tiger stripes,” warm gashes in the surface. How can a body just over 500 kilometers across sustain such vigorous activity?
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