AUTISM is a strange condition. Sometimes its symptoms of
“social blindness” (an inability to read or comprehend the emotions of others)
occur alone. This is dubbed high-functioning autism, or Asperger’s syndrome.
Though their fellow men and women may regard them as a bit odd,
high-functioning autists are often successful (sometimes very successful)
members of society. On other occasions, though, autism manifests as part of a
range of cognitive problems. Then, the condition is debilitating. What is
common to those on all parts of the so-called autistic spectrum is that they
are more often men than women—so much more often that one school of thought
suggests autism is an extreme manifestation of what it means, mentally, to be
male. Boys are four times more likely to be diagnosed with autism than girls
are. For high-functioning autism, the ratio is seven to one.
Moreover, what is true of autism is true, to a lesser
extent, of a lot of other neurological and cognitive disorders. Attention
deficit hyperactivity disorder (ADHD) is diagnosed around three times more
often in boys than in girls. “Intellectual disability”, a catch-all term for
congenital low IQ, is 30-50% more common in boys, as is epilepsy. In fact,
these disorders frequently show up in combination. For instance, children
diagnosed with an autistic-spectrum disorder often also receive a diagnosis of
ADHD.
Autism’s precise causes are unclear, but genes are
important. Though no mutation which, by itself, causes autism has yet been
discovered, well over 100 are known that make someone with them more vulnerable
to the condition.
Most of these mutations are as common in women as in men, so
one explanation for the divergent incidence is that male brains are more
vulnerable than female ones to equivalent levels of genetic disruption. This is
called the female-protective model. The other broad explanation, social-bias
theory, is that the difference is illusory. Girls are being under-diagnosed
because of differences either in the ways they are assessed, or in the ways
they cope with the condition, rather than because they actually have it less.
Some researchers claim, for example, that girls are better able to hide their
symptoms.
The weaker sex
To investigate this question, Sebastien Jacquemont of the
University Hospital of Lausanne and his colleagues analysed genetic data from
two groups of children with cognitive abnormalities. Those in one group, 800
strong, were specifically autistic. Those in the other, 16,000 strong, had a
range of problems.
Dr Jacquemont has just published his results in the American
Journal of Human Genetics. His crucial finding was that girls in both groups
more often had mutations of the sort associated with abnormal neural
development than boys did. This was true both for copy-number variants (CNVs,
which are variations in the number of copies in a chromosome of particular
sections of DNA), and single-nucleotide variants (SNVs, which are alterations
to single genetic letters in the DNA message).
On the face of it, this seems compelling evidence for the
female-protective model. Since all the children whose data Dr Jacquemont
examined had been diagnosed with problems, if the girls had more serious
mutations than the boys did, that suggests other aspects of their physiology
were covering up the consequences. Females are thus, if this interpretation is
correct, better protected from developing symptoms than males are. And, as
further confirmation, Dr Jacquemont’s findings tally with a study published
three years ago, which found that CNVs in autistic girls spanned more genes
(and were thus, presumably, more damaging), than those in autistic boys.
The counter-argument is that if girls are better at hiding
their symptoms, only the more extreme female cases might turn up in the
diagnosed groups. If that were true, a greater degree of mutation might be
expected in symptomatic girls as a consequence. However, Dr Jacquemont and his
colleagues also found that damaging CNVs were more likely to be inherited from
a child’s mother than from his or her father. They interpret this as further
evidence of female-protectedness. Autistic symptoms make people of either sex
less likely to become parents. If mothers are the source of the majority of
autism-inducing genes in children, it suggests they are less affected by
them.
None of this, though, explains the exact mechanism that
makes boys more susceptible than girls. On this question, too, there are two
predominant theories. The first is that males are more sensitive because they
have only one X-chromosome. This makes them vulnerable to mutations on that
chromosome, because any damaged genes have no twin to cover for them. One
cognitive disorder, fragile-X syndrome, is indeed much more common in men for
this reason. Dr Jacquemont’s study, however, found only a limited role for
X-chromosome mutations. That suggests the genetic basis of the difference is
distributed across the whole genome.
The other kind of explanation is anatomical. It is based on
brain-imaging studies which suggest differences between the patterns of
internal connection in male and female brains. Male brains have stronger local
connections, and weaker long-range ones, than do female brains. That is similar
to a difference seen between the brains of autistic people and of those who are
not. The suggestion here is that the male-type connection pattern is somehow
more vulnerable to disruption by the factors which trigger autism and other
cognitive problems. Why that should be, however, remains opaque.
From the print edition: Science and technology
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