January 16, 2007

Genetic Studies Show DISC1 Gene Likely a Player in Schizophrenia

The DISC1 gene, whose variation has been linked to a 50% increase in the risk of developing schizophrenia, has again made the news.

An article published in the Schizophrenia Research Forum reports on three new studies, two molecular and one genetic, that strengthen the case for the involvement of DISC1 in the development of schizophrenia. The DISC1 gene appears to be involved in neuronal outgrowth. Neuronal outgrowth refers to the many connections made between neurons during development. Variation in the DISC1 gene can lead to disruption of neuronal outgrowth.

Together the three papers indicate that failures of axonal transport (axons allow one neuron to communicate with another, and tracts of axons make up "white matter"; axonal transport refers to movement of cell contents from one neuron to the next through the axon) due to the variation in the DISC1 gene either during development or beyond, may be a key facet of schizophrenia.

Thanks to Flooby for pointing out this article.

Read the Article: DISC1 Delivers—Genetic, Molecular Studies Link Protein to Axonal Transport
Original Sources:
J Neurosci 2007 Jan 3 ; 27(1):15-26
Hum Mol Genet 2006 Dec 21
J Neurosci 2007 Jan 3 ; 27(1):4-14.

More about the DISC1 Gene:
Schizophrenia Genetics among Top Scientific Breakthroughs of 2005
UCLA Schizophrenia Genetics Discoveries
Damaged gene & Schizophrenia Predisposition (DISC1)


Research on the genetics behind schizophrenia is going on at lightning speed and gathering a lot of momentum. Several recent studies, now this one, have given DISC a more prominent role. But other studies have found other genes associated with the disorder. Fact is, since schizophrenia is a group of symptoms, it's also quite likely to not be associated with one gene alone.

Recently, studies of 'endophenotypes' have shown over 130 genes/gene breakage/defect (not defect in the usual sense, but a kind of a minor mistake when the gene repicates) are associated with schizophrenia.

'Endophenotypes' were defined for schizophrenia because one is very unlikely to find 'a gene' for a complex behaviorally described disorder like schizophrenia, which consists of many different symptoms, and underlying each type of symptom, a type of brain function, and underlying that function, a group of specific functions, measurable, definable, 'endophenotypes'. And those endophenotypes, relating to one or more genes.

All these 130 genes associated with these endophenotypes fall into only six general categories, though, each category related to nerve growth, development and activity of neurotransmitters. Intriguingly, these genes may all have one thing in common - being 'FS', sensitive to folate.

Consider this. Recently, a study was conducted to find disorders and illnesses that had the SAME epidemiological pattern as schizophrenia does (occurance in the population, rates of inheritance, etc). Guess which disorder has the same epidemiological pattern as schizophrenia.

Hint...hint...it's a disorder that is Folate Sensitive.

Posted by: slc at January 17, 2007 11:00 AM

Here this is stated on an article linked to this site - I was lambasted for saying same here several months ago.

"First of all - its important to understand that when schizophrenia researchers talk about "environment" they have a very broad definition that basically includes everything other than "genes" or genetic factors. So, whereas the typical person might think of their "environment" as their house, or their neighborhood - scientists trying to understand the factors that influence the development of schizophrenia define environment to include everything from the social, nutritional, hormonal and chemical environment in the womb of the mother during pregnancy, up to the social dynamics and stress a person experiences, to street drug use, education, virus exposure, vitamin use, and much, much more. So, when you see the word "environment" used when talking about the causes of schizophrenia - another way to think of it is "everything other than genes". "

"Environment" to a scientist or researcher doesn't mean simply "environment around your house and area", but much more - viruses, en utero environment, etc.

Posted by: slc2 at January 17, 2007 12:27 PM

That is an interesting connection you made between the DISC1 gene and Folate (& alzheimers) since both are implicated in neuronal development, or lack thereof.

Bottom line is as people, we can only do the best we can - eat healthy, take food supplements, exercise, try to avoid toxic chemicals, air pollution, etc, live a low-key, low stress life (learn Zen Buddhism?), stay away from viruses (?)... and since life happens as it happens, pray that scientists figure this out and comes up with tangible, immediate, and practical solutions.

Figuring out women needed extra folate to avoid some cases of spina bifida in their offspring was a big plus. If taking it longer during pregnancy can prevent some more cases of schizophrenia that will be a plus also.

Likely, scientists will come up with (and are coming up with) many different answers because there are many different causes, and we are likely looking at many different illnesses.

Sometimes it seems like we are looking at a net full of sea life, and just calling them "fish". One method to fillet the "fish" is not going to work on the sea urchins, the swordfish, the octopus, etc... even though they are all in the same net. That's how I see "schizophrenia". They are all caught in the same net, and we call it all "schizophrenia".


Posted by: Jeanie at January 17, 2007 05:06 PM

Susan though undoubtedly scientists use the word in a broader though not more accurate way, when 'environment' is talked about as having an effect it is often within the context of genetics v environment as in the so called stress-diathesis model= living conditions/family interactions and how that impacts on mental health.

That is not to deny or dispute that researchers/scientists can and do use 'environment' in a perfectly legitimate broader context or to imply that those 'broader' environmental
factors do not come into play as possible factors in causing schizophrenia.

So though you did not deserve to be so 'lambasted' and you have made a valid point i think it would be wrong for you to adopt a retrospective 'look i was right and you were wrong' stance that does not stand up to close scrutiny.

That aside i am pleased to see you back.Your contribution is valued by me even though I may not always agree with your conclusions.

Re 'folate sensitivity' is this what you are referring to ? http://www.springerlink.com/content/p00520r6p7181885/

If not please let us know the disorder in question as i am intrigued as to what
it could be.

Posted by: Tim at January 17, 2007 05:23 PM

The article recently posted about Homocysteine Elevated Prenatal Homocysteine May Raise Schizophrenia Risk" hinted at Folate sensitivity in that prenatal exposure to raised homosysteine levels (which can be caused by Folate deficiency) may increase risk of schizophrenia.

But Alzheimer's also, as CopperKettle pointed out below that post, has been found to be connected with Folate deficiency... or at least slowed with Folate increase. ( See: Higher Folate Levels Linked To Reduced Risk For Alzheimer's Disease )

Posted by: Jeanie at January 17, 2007 05:53 PM

The relationship to folate is interesting on a number of levels, and may explain the elevated risk of cardiovascular problems in schizophrenia. Choline and folate
availability are implicated in spina bifida as well. Interestingly, a recent finding indicates that in some instances, the fetus is unable to metabolize(?) choline -- spina bifida can occur even when the mother's dietary intake is adequate. This would suggest that risk for spina bifida is increased by both
inadequate dietary intake and/or genetic anomoly, much like famine and schizophrenia. The choline finding (genetic) in spina bifida reminds me of a
preliminary finding reported at a MH conference in Oct. 2005(?) indicating that
fatty acid metabolization was impaired in schizophrenia; again, adequate intake did not guarantee availability of the nutrient. Finally, the folate link may tie
somewhat to the vascular dysfunction hypothesis of a few years ago. I am so thankful for progress !

Posted by: flooby at January 17, 2007 07:32 PM

Actually, the disorder with the same epidemiological profile as schizophrenia isn't alzheimers. The disorder pinpointed in that article was Neural Tube Disorders, such as spina bif.

Genetic research is exploding in new areas and finally answering questions about disorders that have been confusing and mystifying for a very long time. It is far more sophisticated work and is building on recent technical improvements that are going to take us ahead light years. These aren't 'genes for schizophrenia' in the usual sense. These are genes that for example, code for a single agonist, or one tiny part of the growth of a certain group of nerve cells...and these genes get deletions or the like...'DISC' means 'disrupted in Schizophrenia' - the genes are normal, but then have deletions and changes. And the idea is that these deletions and changes can be due to folate. Other authors caution that with 130 or so genes being involved, the genes themselves may interact, too. It is quite likely that people with more severe illness and more symptoms have had more genes disrupted, so more agonists are disturbed, more axonal development is disturbed, etc.

This explains both the disappointing earlier genetic research, the 'low rate of inheritance', and the appearance of 'multifactoral causality' of schizophrenia. It also offers greater hope than ever before, for treatment and prevention.

Posted by: slc at January 17, 2007 07:47 PM

There's an ongoing study measuring the effects of homocysteine-lowering vitamins (folate, B6, and B12) in schizophrenic patients: The purpose of this study is to determine whether individuals with schizophrenia who will take a high dose of the B-vitamins folate, B12 and pyridoxine, may experience improvement in their symptoms

Posted by: CopperKettle at January 18, 2007 01:28 AM

Dear commenters,

This is not the forum for personal discussions - please take them to other venues such as the web site's discussion areas. This comment area is only for commentary directly related to the blog news posting. In the future, personal discussions will be removed.


Posted by: szadmin at January 18, 2007 11:40 AM

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