There is a recent study – ‘FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies’ by Tolosa and colleagues (freely available here) which takes a closer look at the possible role of the FOXP2 gene in schizophrenia. This is a complex study which covers a lot of ground and so I’ll focus on a few aspects of the paper. First of all the researchers have chosen the FOXP2 gene which is a very interesting choice for a study as there is a great deal of data to link this gene with language. Clarifying the biology of this relationship though is another matter. What I like about this paper is that the researchers begin by introducing the ideas of Professor Crow. Professor Crow has developed a model of schizophrenia in which cerebral asymmetry and language development play a central role (see reviews here and here). FOXP2 in turn has been linked to language disorders such as dyslexia and verbal dyspraxia and has also been used as a proxy marker for language abilities in the field of paleoarchaeology. Thus the investigation of the FOXP2 gene in schizophrenia has a rich and interesting background. The researchers here looked at both the genes and expression of the genes. In the first case they looked at variants of the FOXP2 genes in a reasonably sized population of 293 people with schizophrenia and 340 controls. In the second case they examined post-mortem brains comparing people who had received a diagnosis of schizophrenia with a control group and this time focusing on the expression of the gene by examining the mRNA. The researchers found that a variation in one region of the FOXP2 gene (rs2253478 SNP located in intron s3) was significantly associated with a score of poverty of speech on one of the questionnaires. This result was significant even after a Bonferroni correction which is used to adjust for chance findings with large numbers of comparisons. The function of this region was unclear. On the other hand, there were several variations that were more likely to occur in the control group than in people with schizophrenia and auditory hallucinations (rs7803667T/rs10447760C/rs923875A/rs2396722C/rs2396753A) and the researchers suggested that these might confer some degree of protection. When analysing the methylation of DNA the researchers found a decrease in the control group in the left parahippocampal region in comparison with the group with a diagnosis of schizophrenia. A higher degree of methylation was assumed to represent a lower degree of RNA expression. The researchers suggest in the future that hippocampal volume might be a useful phenotype to examine.
So the researchers have produced some interesting findings and they point out the limitations of the study in their discussion. The expression part of the study contained a very small sample set while the association study used only two items from the Manchester scale to assess language. Although very interesting, the rs2253478 SNP finding might be due to chance even after the Bonferroni correction and so replication and triangulation with other methods will clarify this further. The hippocampal volume suggestion has other associations of interest and if the researchers are on the right track linking this with hippocampal volume it will have many ramifications reinforcing the importance of further work in this area.
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