ERMAHGERD! ERVALANCH! ERVs in schizophrenia and bipolar disorder


I have a love/hate relationship with the ERV-[insert brain/CNS disorder] 'connection'.  Labs from all over the world, with independent protocols and patient cohorts, see there is something going on with, for example, ERVs and multiple sclerosis.  So there is *something* going on there, we just arent sure what yet.  Sometimes I think the researchers are on the right track, and sometimes I think subsequent papers are a backslide, but *something* is going on.

I am totally sympathetic to the folks who do research with brains and other precious body tissues. Im 'lucky' with my form of HIV research-- I just need a draw of blood and Im good to go.  But the folks studying HIV in the brain do not have this luxury.  They must use animal models or individuals who have donated their bodies to science.  Its not like you can round up groups of patients and cut out chunks of brains for analysis.

Likewise the people who want to study ERVs and schizophrenia/bipolar disorder/MS/ALS cant just take a slice of brain out of their patients and get to work.  So, they draw blood?

I cannot figure out why the first ERV/'brain disease' group decided to test their hypothesis in blood cells.  Yes, its easy to draw blood. But why would they think there was any connection between what was going on in the blood and what is going on in the brain? Maybe they thought a malfunction in circulating immune cells caused them to target brain tissues... I dont know.

But like I said, labs from all over have observed an increase in ERV transcription and translation in blood, and also in the brains of individuals with MS and ALS.

Hell, wayward ERV expression in blood cells might just be a lucky side-effect. If we can solidify the link between ERV expression and  schizophrenia, and blood cells can be used as a marker of disease instead of like, brain biopsies, that would be just fine.

But without a firm connection, an understanding of whats going on, I have to sigh when I see a Nature-grade paper using ERV expression in blood.  And thats what these folks did.

Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder


You have to start somewhere, I know. And if they got positive results, it would justify looking in patient brains for ERV expression, like what was done with MS and ALS. I get it. But still... *sigh*

Well, they did see elevated ERV RNA in schizophrenic and bipolar patient blood!

... Though some patients had 'normal' levels of ERV RNA, and some health controls had high levels of ERV RNA.

ERV expression isnt sufficient to 'cause' either of these diseases on its own, nor is it necessary for these diseases to develop.

If we want to use a blood test for ERV expression to give us a hint towards proper diagnosis of any of these diseases, we need to keep in mind that a negative result would not rule out disease, nor would a positive result point to disease with 100% certainty.

They also made an interesting observation-- Patients with schizophrenic and bipolar disorder had 1) fewer copies of related ERVs in their genome than healthy controls, and 2) little differences between the sequences that were active in diseased vs healthy.

It might not be a blood test for these diseases at all in the future-- but a genetic test. Do you have the 'wrong' number of the 'wrong' ERVs in your genome?

Even diagnoses then isnt set in stone-- these two particular mental disorders do not have a clear genetic link. Its not that simple, we know that. But it might be the wrong ERVs, exposed to the wrong environment, at the wrong time.  Some kind of genetic test would at least give us a heads-up, though.


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Having done work on Alzheimer's, brain samples can be extremely difficult to get and not only did we want old person brains but also fetal brains too to look at DNA methylation profiles, which are just short of impossible.

Different copy number of HERV-W in different people implies that some sites are polymorphic for it. I thought HERV-K was the only one with polymorphic sites.

By Preston Garrison (not verified) on 11 Feb 2013 #permalink

I found this blog very interesting because although multiple sclerosis and schizophrenia are two distinct diseases they both have been discussed for ERVS. I believe there should be more in depth investigation on how people could be able to study schizophrenia and multiple sclerosis and see if testing their blood cells are legitimate. I believe this post is important because there should be a genetic test that would give us hope on being able to test and study these mental disorders to be able to find out what causes these disorders. I believe ERV’s are the first step people should take and investigate to be able to find further information for disorders that answers can’t be found by just removing blood.

By Viviana Vasquez (not verified) on 12 Feb 2013 #permalink

I would love to hear your analysis of this recent In Vivo publication of research by Whittemore Peterson Institute for Neuro-Immune Disease.

Plasmacytoid Dendritic Cells in the Duodenum of Individuals Diagnosed with Myalgic Encephalomyelitis Are Uniquely Immunoreactive to Antibodies to Human Endogenous Retroviral Proteins