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Wednesday, December 23, 2009

Good News for Armchair Neuropathologists

Ever wanted to crack the mysteries of the brain? Dreamed of discovering the cause of mental illness?

Well, now, you can - or, at any rate, you can try - and you can do it from the comfort of your own home, thanks to the new Stanley Neuropathology Consortium Integrative Database.

Just register (it's free and instant) and you get access to a pool of data derived from the Stanley Neuropathology Consortium brain collection. The collection comprises 60 frozen brains - 15 each from people with schizophrenia, bipolar disorder, and clinical depression, and 15 "normals".

In a Neuropsychopharmacology paper announcing the project, administrators Sanghyeon Kim and Maree Webster point out that
Data sharing has become more important than ever in the biomedical sciences with the advance of high-throughput technology and web-based databases are one of the most efficient available resources to share datasets.
The Institute's 60 brains have long been the leading source of human brain tissue for researchers in biological psychiatry. Whenever you read about a new discovery relating to schizophrenia or bipolar disorder, chances are the Stanley brains were involved. The Institute provide slices of the brains free of charge to scientists who request them, and they've sent out over 200,000 to date.

Until now, if you wanted to find out what these scientists discovered about the brains, you'd have to look up the results in the many hundreds of scientific papers where the various results were published. If you knew where to look, and if you had a lot of time on your hands. The database collates all of the findings. That's a good idea. To ensure that they get all of the results, the Institute have another good idea:
Coded specimens are sent to researchers with the code varying from researcher to researcher to ensure that all studies are blinded. The code is released to the researcher only when the data have been collected and submitted to the Institute.
The data we're provided about the brains is quite exciting, if you like molecules, comprising 1749 markers from 12 different parts of the brain. Markers include levels of proteins, RNA, and the number and shape of various types of cells.

It's easy to use. While waiting for my coffee to brew, I compared the amount of the protein GFAP76 in the frontal cortex between the four groups. There was no significant difference. I guess GFAP76 doesn't cause mental illness - darn. So much for my Nobel Prize winning theory. But I did find that levels of GFAP76 were very strongly correlated with levels of another protein, "phosphirylated" (I think they mean "phosphorylated") PRKCA. You read it here first.

In the paper, Kim and Webster used the Database to find many differences between normal brains and diseased brains, including increased levels of dopamine in schizophrenia, and increased levels of glutamate in depression and bipolar. And decreased GAD67 proteins in the frontal cortex in bipolar and schizophrenia. And decreased reelin mRNA in the frontal cortex and cerebellum in bipolar and schizophrenia. And...

This leaves open the vital questions of what these differences mean, as I have complained before. And the problem with giving everyone in the world the results of 1749 different tests, and letting us cross-correlate them with each other and look for differences between 4 patient groups, is that you're making possible an awful lot of comparisons. With only 15 brains per group, none of the results can be considered anything more than provisional, anyway - what we really need are lots more brains.

But this database is still a welcome move. This kind of data pooling is the only sensible approach to doing modern science, and it's something people are advocating in other fields of neuroscience as well. It just makes sense to share results rather than leaving everyone to do there own thing in near-isolation from each other, now that we have the technology to do so. In fact, I'd say it's a... no-brainer.

ResearchBlogging.orgKim, S., & Webster, M. (2009). The Stanley Neuropathology Consortium Integrative Database: a Novel, Web-Based Tool for Exploring Neuropathological Markers in Psychiatric Disorders and the Biological Processes Associated with Abnormalities of Those Markers Neuropsychopharmacology, 35 (2), 473-482 DOI: 10.1038/npp.2009.151

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