Christopher Badcock outlines a new theory that
resolves some long-standing contradictions in explaining mental illness
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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 disorders (ASDs) 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 ASDs are
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. ASDs
can also be caused by thalidomide, where it affects about 5 per cent of those
with birth defects attributable to this cause.
At first sight, 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 Christopher Badcock (Reader in Sociology at the LSE) and Bernard
Crespi (Killam Research Professor in the Department of Biosciences, Simon
Fraser University) published a paper in The Journal of Evolutionary Biology
setting out the theory in relation to autism. Later this year the world’s leading
peer-review journal in its field, Behavioral and Brain Sciences, will publish a
second paper along with 23 expert commentaries and the authors’ replies which
extends the idea to psychoses like schizophrenia.
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:
Autism/Asperger’s syndrome
|
Psychosis/Paranoid schizophrenia
|
gaze-monitoring deficits
|
delusions of being watched/spied on
|
apparent deafness/insensitivity to voices
|
hallucination of and hyper-sensitivity to voices
|
deficits in interpreting others’ intentions
|
erotomania/delusions of persecution
|
deficits in appreciating shared-attention/groups
|
delusions of conspiracy
|
theory of mind deficits
|
magical ideation/delusions of reference
|
deficit in sense of personal agency/episodic memory
|
megalomania/delusions of grandeur
|
literalness/inability to deceive
|
delusional self-deception
|
pathological single-mindedness
|
pathological ambivalence
|
early onset
|
late onset
|
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.
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,
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 ASDs 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 ASDs or PSDs 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:
Mentalistic Cognition
|
Mechanistic Cognition
|
psychological interaction with self and others
|
physical interaction with nature and objects
|
uses social, psychological, and political skills
|
uses mechanical, spatial, and engineering skills
|
deficits in autism, augmented in women
|
accentuated in autism, augmented in men
|
voluntaristic, subjective, particularistic
|
deterministic, objective, universal
|
abstract, general, ambivalent
|
concrete, specific, single-minded
|
verbal, metaphoric, conformist
|
visual, literal, eccentric
|
top-down, holistic, centrally-coherent
|
bottom-up, reductionistic, field-independent
|
epitomized in literature, politics, and religion
|
epitomized in science, engineering, and technology
|
‘pseudo-science’: astrology, alchemy, creationism
|
‘hard science’: astronomy, chemistry, Darwinism
|
nurtured: culturally- and personally-determined
|
natural: factually- and genetically-determined
|
belief-based therapies: placebos, faith-healing, psychotherapy etc.
|
physical effect-based therapies: drugs, surgery, physiotherapy, etc.
|
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 ASDs. 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, PSDs—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 ASDs, the contrary conditions—starvation during
pregnancy and/or early life—could be predicted to increase the risk of PSDs, 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.
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 ASDs afflict 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 very rare. However,
there is evidence of both 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. Twentythree
experts are only the start: Nature’s comment will be decisive and, thanks to
rapid progress in genomics, should not be long in coming.
Christopher Badcock (with thanks to Bernard Crespi)
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