Epigenetic clue to schizophrenia and bipolar disorder

Schizophrenia and bipolar disorder are known to occur significantly more often in some families than in others, so some genetic component is rather likely. Particular genes that seem to be involved have even been identified. But at the same time, it often happens that in pairs of identical twins, having identical DNA, one twin may have the disorder while the other does not. So there must be other factors besides strict genetics involved – diet, lifestyle, stress, or infectious diseases, for example.

The task would then be to determine the mechanisms through which such environmental factors act. The mechanisms could still be genetic, if an environmental factor has epigenetic effects, as many do. One of the most studied epigenetic mechanisms is DNA methylation, in which a methyl group is added added at specific places within the DNA. In particular, if a spot in the promoter region for some gene is methylated, expression of the gene is inhibited. But if the methylation is removed, expression of the gene (which might be in a mutated form) is enabled.

The research reported here studied pairs of identical twins in which only one of the pair had schizophrenia or bipolar disorder (or both). Scans of the genomes of each twin found significant differences in methylation patterns occurring in the promoter regions of genes that had already been linked to the psychiatric disorder that was present.

Although that provides very strong indications of genes that might be targeted to relieve the disorder, the question of what environmental factors caused the differences in methylation still remains. This is especially of interest, since it’s known that methylation patterns can be inherited.

Epigenetic clue to schizophrenia and bipolar disorder – New Scientist

Regardless of which condition the twin had, the most significant differences, with variations of up to 20 per cent in the amount of methylation, were in the promoter “switch” for a gene called ST6GALNAC1, which has been linked with schizophrenia. Although the function of the gene isn’t fully established, it is thought to add sugars to proteins, which could alter the speed or specificity of their usual function.

The findings tallied with another study which involved screening post-mortem brain tissue from people who had had some form of psychosis. The researchers found differences of up to 25 per cent in methylation of the same gene compared with controls.

Further reading:

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder


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