Schizophrenia research, the good news and the bad news
If you are an identical twin whose twin is schizophrenic, your chances of getting schizophrenia is 40%, if you are just a fraternal twin your chance is 15%, amazingly much higher than the 1% chance the rest of us have, because that’s the incidence in the general population.
So to find out what causes schizophrenia, study the genes of schizophrenics and compare them to those without it. [ Neuron vol. 103 pp. 203 – 216 ’19 ] First off — the Psychiatric Genomics Consortium (PGC) has identified well over 100 (genomic loci) loci with a significant genome-wide association with risk for schizophrenia. This means that unlike cystic fibrosis (where over 1,700 disease associated mutations have been found in the causative gene),and despite the genetics schizophrenia is not going to be due to one gene.
The good news is that serious money and attention to the genomes of schizophrenics is being paid.The paper reports the latest results from the horribly named BrainSeq. This is a precompetitive initiative launched by the Liber Institute for Brain Development (LIBD) with heavy big pharma involvement (Eli Lilly, Johnson and Johnson, Hoffman-LaRoche, AstraZenica). The LIBD has over 1,900 human postmortem neuropsychiatric disease and control samples. They are mapping all sorts of genetic information (DNA sequences, RNA sequencing, DNA epigenetics (cytosine methylation) etc. etc.)
The bad news is what this research is telling us. The paper looked in differences in messenger RNA (mRNA) levels in two areas of the brain in 286 schizophrenics and 265 normal controls. mRNA levels are a marker for gene expression, levels of the proteins coded for by the mRNA would be better, but is presently beyond our technology (when you are looking at the whole genome, as they were).
Well, out of our 20,000 or so protein coding genes, they found 48 differently expressed (by schizophrenics compared to normals) in one area (the hippocampus) and 245 in another (the dorsolateral prefrontal cortex). That’s not a big deal, the two areas of the brain have rather different neurons and organization.
The bad news is there was almost no overlap between the 48 and the 245. So although schizophrenics express their genome differently than normals, the expression varies in brain areas. It would be great if there was some overlap, so then the genes differentiating schizophrenics from normal could be intensively studied.
The work also casts a shadow over a lot of earlier work, in which gene expression in schizophrenic brain was studied either in one area (or in ground up whole brain), and the results were assumed to be applicable to the brain as a whole. They aren’t. Back to the drawing board.