Comments on: Split brains, autism and schizophrenia

By: kjmtchl

kjmtchl — Mon, 15 Aug 2011 15:23:03 +0000

Not SNPs – mutations! Proper screw-up-your-protein mutations only found in one or two people. There are several examples in this paper and more in Song et al.: http://www.ncbi.nlm.nih.gov/pubmed/18164685 and another by Song et al:
http://www.ncbi.nlm.nih.gov/pubmed/20850505

By: pconroy

pconroy — Mon, 15 Aug 2011 15:13:03 +0000

Does anyone know the relevant SNP’s involved?

By: kjmtchl

kjmtchl — Sat, 13 Aug 2011 18:39:07 +0000

Mike, in this case the translocation truncates the DISC1 protein, suggesting it could be a gain-of-function phenotype, but actually very little of that mutant protein is made and all the evidence suggests it is simply haploinsufficiency that causes the phenotype. Some of the mutations found in this study, and one by Song et al in a schizophrenia sample are amino acid changes or splice site changes predicted to have a deleterious effect on protein function. And the main ones in this study are two different deletions, again in heterozygous mode.

By: Mike McK

Mike McK — Fri, 12 Aug 2011 16:37:30 +0000

There are some things that are not immediately apparent.

Such a translocation can result in transcript fusions between genes on each side of the breaks. This is notable in some cancers. Given the original version is such mutation and generates the phenotypes as a +/translocation heterozygote there might well be a gain-of-function phenotype.

Alternatively it could be a haplo-insufficiency.

Is it know if there are deletion or early stop codon mutations in disc1 that give the same array of phenotypes shown in the original translocation allele?

By: majkinetor

majkinetor — Thu, 11 Aug 2011 13:36:30 +0000

I didn’t find anything useful about surgical removal of callosum. There is one paper that looks like summary of sympthoms if you have full access – “Corpus callosotomy in children and the disconnection syndromes: a review”. Its definitely not the same as if it never developed, however, there must be some overlap of symptoms of the 2 phenomena, given the function of CC in the brain.

About Piracetam – yes, it thought that it influences corpus. You can see more info here:

http://agingcorpus.wordpress.com/2006/10/10/piracetam/

By: kjmtchl

kjmtchl — Thu, 11 Aug 2011 11:50:02 +0000

Thanks for your comment. I think there is good reason to expect people who have had their corpus callosum surgically cut in adulthood to show quite different effects from those in which it never developed in the first place. Suddenly not having the tract is very different from the brain having developed with it never having been there. But clearly it is testable – my impression is that split brain patients do not show psychiatric symptoms. (Though it has other effects).

I would be interested to hear more about Piracetam and its “effects on corpus callosum” – does that mean it affects the functional connectivity between the hemispheres?

By: majkinetor

majkinetor — Thu, 11 Aug 2011 11:32:50 +0000

Looks like testable in certain degree on corpus callosotomy patients.

Besides that, on the positive side, Piracetam is known to improve cognitive performance in schizophrenia. It also helps in autism. One of the hypothetical explanations of its beneficial effects on brain are its effects on corpus callosum.