Jonathan Mill and colleagues at the Institute of Psychiatry, King’s College, London have scanned the genome of 22 pairs of identical twins. The twins were chosen because one twin in each pair was diagnosed with Schizophrenia or Bipolar Disorder.
The findings produce the strongest evidence yet that gene changes caused by their environment might cause the conditions
The twins had identical DNA. But they showed significant differences in chemical “epigenetic” markings. These are changes that do not alter the sequence of DNA but leave chemical marks on genes that dictate how active they are. These changes were on genes that have been linked with Bipolar Disorder and Schizophrenia.
Mill’s team scanned for differences in the attachment of chemical methyl groups at 27,000 sites in the genome. Genes are normally switched off by Methylation and De-Methylation turns them on.
Regardless of which condition the twin had, the most significant differences,with variations of up to 20% in the amount of Methylation, were in the promoter “switch” for a gene called ST6GALNAC1, which has been linked with Schizophrenia . The function of this gene is not yet fully known but it is thought to add sugars to proteins which could alter the speed or specificity of their usual function
The findings have tallied with another study which involved the screening of post- mortem brain tissue from people who had some form of psychosis. Here the researchers found differences of up to 25% in methylation of the same gene, compared with controls
The twin scans also showed methylation differences in GPR24 a gene previously linked to Bipolar Disorder. One gene called ZNF659 showed over- methylation in people with Schizophrenia and under- methylation in those were were Bipolar. This suggests that the conditions might result from opposing gene activity. (Human Molecular Genetics DOI:10.19098/hmg/ddr416)
Jonathan Mill says “We know these disorders are related, and there are clinical features shared by both. But our scan suggests there are some genes that might be overactive in one disease and underactive in the other.”
Mill says that twins would need to be scanned regularly through life to find out whether epigenetic changes precede the onset of the disorders. Maybe then the alterations could be linked to environmental changes like stressful events or diet, which have been shown to cause inheritable epigenetic changes in mice.
The human studies support the hypothesis that epigenetic mechanisms may drive psychiatric disorders. I think the environment we live in and trauma we endure are key factors in the onset of conditions such as Schizophrenia and Bipolar Disorder and it is certainly well documented that trauma in childhood is a key risk factor for psychosis. I ask the Government to invest more money in mental health research. The current level of 6.5% is simply too low. We should be looking to protect our children and also to widen our understanding of the role of epigenetics in mental health.