Epigenetic impact on neuropsychiatric disorders
Neuropsychiatric diseases including schizophrenia and bipolar disorder are influenced by epigenetic processes, new research from the United Kingdom shows. Presented in the journal Human Molecular Genetics, this study probed genome-wide epigenetic differences in cases of twins with psychosis. The results could lead to novel treatment approaches. The research was funded in part by the EUTWINSS ('European twin study network on schizophrenia') study, which clinched a Marie Curie Research Training Networks grant worth EUR 2.4 million under the EU's Sixth Framework Programme (FP6).
Past studies linked epigenetic changes in the brain to various biological and cognitive processes including neurogenesis, drug addiction and neurodegeneration. Researchers also identified how epigenetic changes in the brain may play a role in the spectrum of psychiatric disorders such as psychosis.
In the first comprehensive analysis of disease-associated deoxyribonucleic acid (DNA) methylation differences in twins discordant for schizophrenia and bipolar disorder, researchers from the Institute of Psychiatry at King's College London in the United Kingdom discovered no changes in global DNA methylation between affected and unaffected twins. However, they did find a link between twin differences at specific loci across the genome.
'Our hypothesis-free experimental design allowed us to identify disease-associated DNA methylation differences at loci not previously implicated in psychiatric disorders, but we also found evidence for DNA methylation differences at genes previously implicated in psychosis,' the authors of the paper write. 'Pathway analysis of our top loci highlighted a significant enrichment of epigenetic disruption to biological networks and pathways relevant to psychiatric disease and neurodevelopment. Overall, our data provide further evidence to support a role for DNA methylation differences in the aetiology of both schizophrenia and bipolar disorder.'
Their findings suggest that while 70% of the cases of schizophrenia and bipolar disorder are heritable, disease concordance between pairs of twins is far from 100%. This shows that non-genetic factors are involved in the onset of diseases.
'We studied a group of 22 identical twin-pairs, so 44 individuals in all, one of the largest twin studies performed for any complex disease to date,' says the Institute's Dr Jonathan Mill, lead author of the study. 'In each twin-pair, one had either schizophrenia or bipolar disorder. Because we know that twins are genetically identical, we can rule out any genetic cause of illness in the affected twin — the aim of our study was to investigate epigenetic variations associated with these disorders.'
According to the researchers, there is a connection between epigenetic mechanisms and heritable, but reversible, changes in gene expression. It should be noted, however, that no changes occur in the underlying DNA sequence. This is triggered through changes in DNA methylation and chromatin structure.
'Our findings suggest that it is not only genetic variations that are important,' Dr Mill says. 'The epigenetic differences we see may tell us more about the causes or schizophrenia and bipolar disorder, as some alterations were specific to either disease. Importantly, epigenetic processes are potentially reversible, meaning that our research could open up new avenues for the development of novel therapeutic drugs.'
Human Molecular Genetics
Institute of Psychiatry at King's College London
'EU project to determine causes of schizophrenia'