In
a recent post I raised the issue of maybe we should be looking at the
schizophrenia research, given that the condition appears very closely related to
ASD. Then I got rather side tracked by
MR (Mental Retardation), now known as Intellectual Disability, in polite
society. Since schizophrenia is adult-onset,
I thought it might attract some serious research; indeed it does.
It
turns out there may have been more sense than you thought, in my making
“connections” between autism, schizophrenia and MR.
A
striking study has just been published from Trinity College, Dublin. It draws these three conditions together
using genes and makes a remarkable conclusion regarding epigenetics. Epigenetic change has already been highlighted
as a key process behind the development of autism.
The
full paper is not openly available, but below is the abstract and here is a
press release from the University.
De novo mutations in schizophrenia implicate chromatin remodelling and support agenetic overlap with autism and intellectual disability
An
excellent lay person’s summary is available in this article:-
A Single Genetic Variation Is Shared By People With Schizophrenia ,Autism, And Intellectual Disability
Scientists believe some cases of schizophrenia are
caused by gene mutations passed from parents to children with environmental
factors exacerbating the effects of such mutations. Yet researchers also
believe some cases of the mental disorder may be caused by de novo genetic
mutations (DNMs). DNMs are
new defects in genes that occur only in offspring — in such
cases, neither parent possesses the same defects as the child. These mutations
are simple copying errors caused during mechanical DNA replication. They occur
infrequently in every human being during sperm and egg development, but
typically they have no overall impact on human health.
However, when de novo mutations occur in a gene or genes indispensable
for normal development they have devastating consequences. For this reason, McCombie and his colleagues, in an ongoing
collaboration with Dr. Aiden Corvin of Trinity College, Dublin, hypothesized
there may some special link between schizophrenia and DNMs.
For the current study, then, the team enlisted the
help of 42 “trio” families in which the child, but neither parent, was
diagnosed with schizophrenia and/or psychosis. They also enrolled 15 trio
families with a history of psychosis. Then they set to work, searching for de
novo mutations. What did they discover?
Among the 42 affected children in the study, they discovered de novo
mutations in three genes: AUTS2, CDH8, and MECP2. (In prior genetic studies,
mutations on these very same genes have been identified in people with autism.)
Two other mutated genes found in the participants — HUWE1 and TRAPPC9 — have
been similarly linked to people with intellectual disability. Of these five "overlapping" genes,
three — CHD8, MECP2 and HUWE1 — play a role in what scientists call the epigenetic
regulation of transcription. That is, these three genes are involved
in a complex molecular process that determines when and which genes are
switched on or switched off.
"There's a growing awareness of the importance
of epigenetic regulation during brain development, as well as in cognition in
the mature brain," said Dr. Shane McCarthy, a CSHL research investigator
and lead author of the new study. This regulation is the reason why the team’s
discovery is so important — normal brain development depends on these genes. With this study, then, de novo
mutations of these genes have been linked to not just schizophrenia but autism
and intellectual disability as well.
Conclusion
This
is actually all very important.
Epigenetics is a mechanism whereby the environment can affect your genes
(flipping a specific gene, from on to off, or off to on). Epigenetic changes can be inherited and so
pass through the generations. In theory,
it can potentially be reversed. Epigenetic
change is not a good thing; but it seems that in people with autism, key genes
have mutated that make them more prone to such epigenetic change. So this might explain why people with autism
are prone to so many other things (comorbidities) as well. It might also explain why they are autistic
in the first place; they were already at risk, but in addition they were more
vulnerable to any kind of environmental insult.
The number of environmental insults is increasing in modern society and
we are slowly accumulating some of the epigenetic flaws of our ancestors. This might explain the increase in autism,
particularly in modern societies, where environmental insults are more likely.
The
other interesting point is that the five overlapping genes related to autism,
MR and schizophrenia in the study are all new mutations; they were not
inherited from the parents. Many parents,
and indeed pseudo-experts with their therapy “protocols”, often suggest that
autism is nothing to do with genetics and they look for other factors to "blame",
like heavy metals. Parents clearly do
not want to feel autism was their “fault”.
As this study shows, these five critical genetic causes are not
inherited, they are just the result of imperfections in the copying
process. So in the case of these five
genes, parents can accept the scientific evidence without any feeling of guilt.
People
with autism, but no MR, should probably count themselves very lucky indeed.
