Saturday, March 29, 2008

A breakthrough in understanding the genetics of schizophrenia -- and perhaps of autism too

A major publication in Science on the genetics of schizophrenia is summarized in Gordon's Notes

Gordon's Notes: What is schizophrenia? Not what we thought.

... note only 15% percent of "schizophrenics" fit this pattern. I'll summarize the key implications:

  • Schizophrenia is not a disease. It's the name given a fairly large number of unique disorders of brain development that have, among their endpoints, social withdrawal, hallucinations, and fixed beliefs.
  • A good number of cases of "autism" and "schizophrenia" are different manifestations of overlapping sets of mutations.
  • There may be"no genes for most instances autism and schizophrenia". There are sets of large scale mutations that are similar between close genetic relatives, but similar appearances are resulting from disorders of quite different components of brain development.
  • One in twenty seemingly normal people have big, ugly looking mutations that ought to be messing up their brain development. Yet they seem "normal". Seventeen in twenty persons with "schizophrenia" do NOT have these nasty scattered "sledgehammer" mutations. (So called because it's as though something took a sledgehammer to the genome.)
  • The age onset of schizophrenia is determined by when the disordered developmental genes are activated. There's a lot of this going on in late teen years. The implication is that the same thing explains why "autism" presents around ages 2-3, and why it can seem to appear fairly suddenly. This may also explain why some conditions seem to improve at other ages. Schizophrenia syndromes often improves in middle age, for example.
  • If every person with autism has a somewhat unique disorder, then treatments and prognosis are also unique. This validates the age old practice of asking someone with a cognitive/psychiatric disorder what treatments have worked for relatives.

I'm seeing a growing consensus that "autism" will turn out to have a similar picture. The trend is clear, autism is also going to turn out to be a diverse collection of disorders of brain development and injury response with diverse genetic causes. These as yet unnamed disorders will turn out to have different prognoses and different therapies.

No comments: