Our physiology is shaped in part by our genes, and how those genes are expressed. Many things can influence gene expression and function, including epigenetic changes, which do not alter the sequence of DNA, but can have a significant impact on gene activity. Epigenetic influences can include changes in the structure of DNA, and how various parts of it may or may not be available to the cell; or chemical tags that attach to DNA and affect whether or not a gene is expressed. Two new studies have linked epigenetic changes in development with mental conditions including schizophrenia and autism.
In one study, reported in Cell Genomics, researchers assessed methyl tags on DNA in almost 1,000 human brains of many different ages. The researchers were particularly interested in the cortical regions of these donated, post-mortem brains, since that region is related to memory, behavior, perception, and other higher-order functions.
This research indicated that the methylation status of DNA in cortical brain cells changes significantly before birth, which helps activate certain pathways that are crucial to cortical development. Neurons also begin to show patterns of methylation in early development that are different from other brain cells. It seems that certain epigenetic characteristics are important to the creation of specific types of brain cells. If this process goes awry, neurodevelopmental disorders may arise.
"By analyzing how chemical changes to DNA shape the brain across the human lifespan, we've uncovered important clues about why neurodevelopmental conditions like autism and schizophrenia may develop. Our findings highlight that their roots may lie very early on in brain development,” said the first author of this study, Alice Franklin of the University of Exeter.
In an unrelated report published in Molecular Psychiatry, researchers confirmed previous studies that have shown that maternal infections during pregnancy are linked to an increased risk of neurodevelopmental disorders in offspring. This study revealed that this link could be due to epigenetic changes.
The researchers used a mouse model to show that certain epigenetic changes had arisen in pregnant (rodent) mothers that had infections, which led to cognitive changes in pups that were associated with schizophrenia.
This work indicated that during infection, the rat immune system affected epigenetic patterns and molecules that are related to epigenetic changes in fetuses. In those fetuses, certain genes that have previously been linked to schizophrenia were shown to have different methylation patterns.
Sources: University of Exeter, Cell Genomics, Molecular Psychiatry
