Monday, 1 July 2013

The big H and schizophrenia

Frankly I am more than a little interested in all-things homocysteine when it comes to behaviour and psychiatry. Perhaps more readily finding discussion and argument with regards to more physical health complaints as per the literature on homocysteine and cardiovascular disease risk*, the 'big H' ties into quite a lot of other interesting areas such as folic acid and the link with another important amino acid, methionine and all that methylation mumbo-jumbo.
Islands in the CpG stream @ Wikipedia 

With autism in mind, the various investigations looking at homocysteine have been pretty much all one direction: elevated levels detected in various biological fluids** (open-access). I hate to make generalisations about the autisms, but homocysteine does appear to be something in need of more detailed consideration as per another potential elephant in the room.

Today however my interest turns to a paper by Makoto Kinoshita and colleagues*** (open-access version here) who report that their cohort of participants with schizophrenia (n=42) not only presented with significantly elevated levels of plasma total homocysteine but also that this homocysteine load might also affect DNA methylation.

OK, a recap. Homocysteine and methionine take part in a merry dance together which crosses one-carbon metabolism (folic acid) and should eventually result in methionine being converted to SAM which then donates a methyl group for the process of DNA methylation. I've kinda covered this process on a previous post with autism in mind complete with hand drawn diagram by yours truly.

Kinoshita et al used some nifty technology (quantitative high-resolution DNA methylation array) to look at the methylation status of CpG islands (see here) located across whole gene regions based on the analysis of peripheral leukocytes. They concluded that alongside those elevations in homocysteine "plasma total homocysteine might affect DNA methylation across whole gene regions" and when talking about genes which have been linked to schizophrenia, one might be minded to look at methylation outside of more structural changes to the genome.

Outside of what I've already discussed about the big 'H' and methylation, there is another potentially important implication from all this talk about epigenetics and schizophrenia: intervention. I'm taken back for example to some interesting work about folic acid and SNPs in schizophrenia which was discussed on this blog (see here). The question being whether any intervention strategy designed to bring the homocysteine-methionine relationship back into planetary alignment would impact on gene methylation and then on presented symptoms? (Bearing in mind my caveat about not giving medical advice on this blog).

To finish, I can't talk about (CpG) islands without linking to an interpretation of a famous song about islands.... (what's occurring?)


* Wald DS. et al. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002 Nov 23;325(7374):1202.

** Kałużna-Czaplińska J. et al. A focus on homocysteine in autism. Acta Biochim Pol. 2013 Jun 6.

*** Kinoshita M. et al. Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics. 2013 Apr 26;8(6).

---------- Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, & Ohmori T (2013). Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics : official journal of the DNA Methylation Society, 8 (6) PMID: 23774737